Professional Documents
Culture Documents
1
these additives from the CDC
website in the first pages so
that you can see they are in
fact in the vaccines. In addition
to this if you read the WI-38 and
MRC-5 tissue culture listings from
the CDC Vaccine Additives List
and then read the pages from the
medical supply corporation's
websites you will find undeniable
evidence contained within the
following pages illustrating the
fact that some of the shot
vaccines are made using tissue
from aborted babies.
2
2
2
Vaccine Excipient & Media Summary, Part 2
Excipients Included in U.S. Vaccines, by Vaccine
Includes vaccine ingredients (e.g., adjuvants and preservatives) as well as substances used during the manufacturing process,
including vaccine-production media, that are removed from the final product and present only in trace quantities.
In addition to the substances listed, most vaccines contain Sodium Chloride (table salt).
Vaccine Contains
Aluminum Hydroxide, Amino Acids, Benzethonium Chloride, Formaldehyde
Anthrax (BioThrax)
or Formalin, Inorganic Salts and Sugars, Vitamins
Japanese Encephalitis Formaldehyde or Formalin, Gelatin, Mouse Serum Protein, Polysorbate 80,
(JE-Vax) Thimerosal
Pneumococcal (Prevnar) Aluminum Phosphate, Amino Acid, Soy Peptone, Yeast Extract
Cell Culture Media, Fetal Bovine Serum, Sodium Citrate, Sodium Phosphate
Rotavirus (RotaTeq)
Monobasic Monohydrate, Sodium Hydroxide Sucrose, Polysorbate 80
Adapted from Grabenstein JD. ImmunoFacts: Vaccines & Immunologic Drugs. St. Louis, MO: Wolters Kluwer
Health Inc.; 2009 and individual products’ package inserts.
All reasonable efforts have been made to ensure the accuracy of this information, but manufacturers may change
product contents before that information is reflected here.
Resources
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search Help & Bioassays Resources…
Search: PubMed 6
DNA & RNA
BankItofBioSystems
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Influenza Virus
National Institutes of HealthPopSet Reference Sequence (RefSeq) RefSeqGene Sequence Read Archive (SRA) Sequin tbl2asn Trace Archive All DNA & RNA Resources…
Database
Data & Software
Display Settings: Abstract
Cn3D E-Utilities ProSplign Sequin Splign tbl2asn All Data & Software Resources… Send to:
Domains & Structures
Transgenic Res.Cn3D
2005Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Oct;14(5):569-81.
(VAST) All Domains & Structures Resources…
Production of human serum albumin by sugar starvation induced promoter Related citations
Genes & Expression Amylase gene silencing by RNA interference
and rice cell culture.
improves
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus recombinant
(GEO) hGM-CSF
Database Gene [Plant production
MolOmnibus
Expression Biol. 2008]
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Huang LF, Liu (GEO)
YK, LuDatasets
CA, Hsieh
GeneSL, Yu SM. Omnibus (GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian Inheritance in Man (OMIM)
Expression
Novel gene expression system for plant cells
Institute of Molecular Biology, UniGene
RefSeqGene AcademiaAllSinica,
Genes Taipei 115, Nankang,
& Expression Taiwan, ROC.
Resources… based on induction of alpha-amylase
[J Biol Chem.
promoter
1994]
Genetics & Medicine
Abstract Metabolic regulation of alpha-amylase gene
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance in Man (OMIM) PubMed PubMed Central (PMC)
Human serum albumin (HSA) is the most widely used clinical serum protein. Currently, commercial HSA expression in transgenic cell [Plant
cultures
Mol Biol.
of rice
1993]
PubMed Clinical Queries RefSeqGene All Genetics & Medicine Resources…
can only be obtained from human plasma, due to lack of commercially feasible recombinant protein
Genomes & Maps Review Molecular farming of pharmaceutical
expression systems. In this study, inducible expression and secretion of HSA by transformed rice proteins. [Transgenic Res. 2000]
Database of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus Map Viewer Nucleotide
suspension cell culture was established. Mature form of HSA was expressed under the control of the
Database PopSet ProSplign Sequence Read Archive (SRA) Sequin Splign tbl2asn Trace Archive UniSTS All Genomes
Review &[Progress
Maps Resources…
in purification of human
sucrose starvation-inducible rice alpha Amy3 promoter, and secretion of HSA into the culture medium was
Homology serum albumin]
[Sheng Wu Gong Cheng Xue Bao. 2002]
achieved by using the alpha Amy3 signal sequence. High concentrations of HSA were secreted into
BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) Conserved Domain Database (CDD) Genome ProtMap HomoloGene Protein Clusters All Homology
culture medium in a short time (2-4 days) by sucrose depletion after cell concentrations had reached a See reviews...
Resources…
peak density in culture medium containing sucrose. The recombinant HSA had the same electrophoretic
Literature See all...
mobility as commercial HSA and was stable and free from apparent proteolysis in the culture medium. In
Bookshelf E-Utilities Journals Database MeSH Database PubMed PubMed Central (PMC) PubMed Clinical Queries All Literature Resources…
a flask scale culture with repeated sucrose provision-depletion cycles, HSA was stably produced with
Proteins
yields up to 11.5% of total medium proteins or 15 mg/L per cycle after each sucrose provision-depletion
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) ConservedAll links
Domain fromService
Search this (CD
record
Search) E-
cycle. A bubble column type bioreactor was designed for production of HSA. In the bioreactor scale culture,
Utilities GenBank ProSplign Protein Protein Clusters Reference Sequence (RefSeq) All Proteins Resources… Related Citations
HSA was produced with yields up to 76.4 mg/L 4 days after sucrose depletion. HSA was purified from the
Sequence Analysis Compound (MeSH Keyword)
culture medium to high purity by a simple purification scheme. Enrichment of HSA in culture medium
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) GenBank Genome Workbench Influenza Virus Primer-
simplifies downstream purification, minimizes protease degradation, and may reduce production cost. Gene
BLAST ProSplign Splign All Sequence Analysis Resources…
The combination of a DNA construct containing the alpha Amy3 promoter and signal sequence, and the HomoloGene
Taxonomy
use of a rice suspension cell culture can provide an effective system for the production of recombinant
Taxonomy Taxonomy Browser Taxonomy Common Tree All Taxonomy Resources… Nucleotide (RefSeq)
pharmaceutical proteins.
Training & Tutorials Nucleotide (Weighted)
PMID: 16245148NCBI Education
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& Medicine Genomes &
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MeSH Terms:
Base Sequence
Recent activity
Bioreactors
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Production of human serum albumin by
Cell Proliferation sugar starvation induced promoter and
PubMed
Cell Survival
Culture Media See more...
DNA, Recombinant/genetics
Humans
Oryza sativa/cytology
Oryza sativa/genetics*
Oryza sativa/metabolism*
Plants, Genetically Modified
Plasmids/genetics
Promoter Regions, Genetic
RNA, Messenger/biosynthesis
RNA, Messenger/genetics
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Serum Albumin/biosynthesis*
Serum Albumin/genetics*
Serum Albumin/isolation & purification Generated by www.PDFonFly.com at 12/9/2010 5:06:38 PM
URL: http://www.ncbi.nlm.nih.gov/pubmed/16245148
Sucrose/metabolism
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alpha-Amylases/metabolism
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DNA, Recombinant
RNA, Messenger
Recombinant Proteins
Serum Albumin
Sucrose
alpha-Amylases
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WARNING
This drug should be used primarily for treatment of patients with progressive and potentially life-
threatening fungal infections; it should not be used to treat noninvasive forms of fungal disease
such as oral thrush, vaginal candidiasis and esophageal candidiasis in patients with normal neutro-
phil counts.
EXERCISE CAUTION to prevent inadvertent overdose with AMPHOCIN. Verify the product name
and dosage if dose exceeds 1.5 mg/kg.
DESCRIPTION
AMPHOCIN® (amphotericin B for injection, USP) contains amphotericin B, an antifungal polyene antibi-
otic obtained from a strain of Streptomyces nodosus. Amphotericin B is designated chemically as [1R-
(1R*, 3S*, 5R*, 6R*, 9R*, 11R*, 15S*, 16R*, 17R*, 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R*, 35S*, 36R*,
37S*)] -33-[(3-Amino-3, 6-dideoxy-β-D-mannopyranosyl)-oxy]- 1, 3, 5, 6, 9, 11, 17, 37 -octahydroxy-15, 16,
18-trimethyl-13-oxo-14, 39-dioxabicyclo[33.3.1] nonatriaconta-19, 21, 23, 25, 27, 29, 31-heptaene-36-
carboxylic acid.
Structural formula: OH
OH
H3C O OH
O OH OH OH OH O
HO COOH
CH3
H
H3C
CH3 O
O
NH2 OH
HO
C47H73NO17 MW 924.09
Each vial contains a sterile, nonpyrogenic, lyophilized cake (which may partially reduce to powder
following manufacture) providing 50 mg amphotericin B and 41 mg sodium desoxycholate buffered with
20.2 mg sodium phosphates (consisting of mono and dibasic sodium phosphate, phosphoric acid and
sodium hydroxide). Crystalline amphotericin B is insoluble in water; therefore, the antibiotic is solubilized
by the addition of sodium desoxycholate to form a mixture which provides a colloidal dispersion for
intravenous infusion following reconstitution.
At the time of manufacture the air in the vial is replaced by nitrogen.
CLINICAL PHARMACOLOGY
Microbiology
Amphotericin B shows a high order of in vitro activity against many species of fungi. Histoplasma
capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula,
Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus are all
inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida
albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible.
Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is with-
out effect on bacteria, rickettsiae, and viruses.
Susceptibility Testing
Standardized techniques for susceptibility testing for antifungal agents have not been established and
results of susceptibility studies have not been correlated with clinical outcomes.
Pharmacokinetics
Amphotericin B is fungistatic or fungicidal depending on the concentration obtained in body fluids and
the susceptibility of the fungus. The drug acts by binding to sterols in the cell membrane of susceptible
fungi with a resultant change in membrane permeability allowing leakage of intracellular components.
Mammalian cell membranes also contain sterols and it has been suggested that the damage to human
cells and fungal cells may share common mechanisms.
An initial intravenous infusion of 1 to 5 mg of amphotericin B per day, gradually increased to 0.4 and
0.6 mg/kg daily, produces peak plasma concentrations ranging from approximately 0.5 to 2 mcg/mL.
Following a rapid initial fall, plasma concentrations plateau at about 0.5 mcg/mL. An elimination half-life
of approximately 15 days follows an initial plasma half-life of about 24 hours. Amphotericin B circulating
in plasma is highly bound (>90%) to plasma proteins and is poorly dialyzable. Approximately two thirds
of concurrent plasma concentrations have been detected in fluids from inflamed pleura, peritoneum,
synovium, and aqueous humor. Concentrations in the cerebrospinal fluid seldom exceed 2.5 percent of
those in the plasma. Little amphotericin B penetrates into vitreous humor or normal amniotic fluid.
Complete details of tissue distribution are not known.
Amphotericin B is excreted very slowly (over weeks to months) by the kidneys with two to five percent
of a given dose being excreted in the biologically active form. Details of possible metabolic pathways are
not known. After treatment is discontinued, the drug can be detected in the urine for at least seven
weeks due to the slow disappearance of the drug. The cumulative urinary output over a seven day period
amounts to approximately 40 percent of the amount of drug infused.
INDICATIONS AND USAGE
AMPHOCIN should be administered primarily to patients with progressive, potentially life-threatening
fungal infections. This potent drug should not be used to treat noninvasive fungal infections, such as
oral thrush, vaginal candidiasis and esophageal candidiasis in patients with normal neutrophil counts.
AMPHOCIN is specifically intended to treat potentially life-threatening fungal infections: aspergillosis,
cryptococcosis (torulosis), North American blastomycosis, systemic candidiasis, coccidioidomycosis,
histoplasmosis; zygomycosis including mucormycosis due to susceptible species of the genera Absidia,
Mucor and Rhizopus , and infections due to related susceptible species of Conidiobolus and
Basidiobolus, and sporotrichosis.
AMPHOCIN may be useful in the treatment of American mucocutaneous leishmaniasis, but it is not the
drug of choice as primary therapy.
CONTRAINDICATIONS
This product is contraindicated in those patients who have shown hypersensitivity to amphotericin B
or any other component in the formulation unless, in the opinion of the physician, the condition requir-
ing treatment is life-threatening and amenable only to amphotericin B therapy.
WARNINGS
AMPHOCIN is frequently the only effective treatment available for potentially life-threatening fungal
disease. In each case, its possible life-saving benefit must be balanced against its untoward and
dangerous side effects.
PRECAUTIONS
General
Amphotericin B should be administered intravenously under close clinical observation by medically
trained personnel. It should be reserved for treatment of patients with progressive, potentially life-
threatening fungal infections due to susceptible organisms (see INDICATIONS AND USAGE).
Acute reactions including fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, and
tachypnea are common 1 to 3 hours after starting an intravenous infusion. These reactions are usually
more severe with the first few doses of amphotericin B and usually diminish with subsequent doses.
Rapid intravenous infusion has been associated with hypotension, hypokalemia, arrhythmias, and
shock and should, therefore, be avoided (see DOSAGE AND ADMINISTRATION).
Amphotericin B should be used with care in patients with reduced renal function; frequent monitor-
ing of renal function is recommended (see PRECAUTIONS, Laboratory Tests and ADVERSE REACTIONS). In
some patients, hydration and sodium repletion prior to amphotericin B administration may reduce the
risk of developing nephrotoxicity. Supplemental alkali medication may decrease renal tubular acidosis
complications.
Since acute pulmonary reactions have been reported in patients given amphotericin B during or shortly
after leukocyte transfusions, it is advisable to temporally separate these infusions as far as possible and
to monitor pulmonary function (see PRECAUTIONS, Drug Interactions).
Leukoencephalopathy has been reported following use of amphotericin B. Literature reports have sug-
gested that total body irradiation may be a predisposition.
Whenever medication is interrupted for a period longer than seven days, therapy should be resumed
by starting with the lowest dosage level, e.g., 0.25 mg/kg of body weight, and increased gradually as out-
lined under DOSAGE AND ADMINISTRATION.
Laboratory Tests
Renal function should be monitored frequently during amphotericin B therapy (see ADVERSE
REACTIONS). It is also advisable to monitor on a regular basis liver function, serum electrolytes
(particularly magnesium and potassium), blood counts, and hemoglobin concentrations. Laboratory test
results should be used as a guide to subsequent dosage adjustments.
Drug Interactions
When administered concurrently, the following drugs may interact with amphotericin B:
Antineoplastic agents: may enhance the potential for renal toxicity, bronchospasm and hypotension.
Antineoplastic agents (e.g., nitrogen mustard, etc.) should be given concomitantly only with great caution.
Corticosteroids and Corticotropin (ACTH): may potentiate amphotericin B-induced hypokalemia
which may predispose the patient to cardiac dysfunction. Avoid concomitant use unless necessary to
control side effects of amphotericin B. If used concomitantly, closely monitor serum electrolytes and
cardiac function (see ADVERSE REACTIONS).
Digitalis glycosides: amphotericin B-induced hypokalemia may potentiate digitalis toxicity. Serum
potassium levels and cardiac function should be closely monitored and any deficit promptly corrected.
Flucytosine: while a synergistic relationship with amphotericin B has been reported, concomitant use
may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal
excretion.
Imidazoles (e.g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.): in vitro and animal
studies with the combination of amphotericin B and imidazoles suggest that imidazoles may induce
fungal resistance to amphotericin B. Combination therapy should be administered with caution,
especially in immunocompromised patients.
Other nephrotoxic medications: agents such as aminoglycosides, cyclosporine, and pentamidine may
enhance the potential for drug-induced renal toxicity, and should be used concomitantly only with great
caution. Intensive monitoring of renal function is recommended in patients requiring any combination
of nephrotoxic medications (see PRECAUTIONS, Laboratory Tests).
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Composition Unit 2566
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Amphocin ®
brand of amphotericin B for injection, USP
Skeletal muscle relaxants: amphotericin B-induced hypokalemia may enhance the curariform effect
of skeletal muscle relaxants (e.g., tubocurarine). Serum potassium levels should be monitored and
deficiencies corrected.
Leukocyte transfusions: acute pulmonary toxicity has been reported in patients receiving intravenous
amphotericin B and leukocyte transfusions (see PRECAUTIONS, General).
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term studies in animals have been performed to evaluate carcinogenic potential. There also
have been no studies to determine mutagenicity or whether this medication affects fertility in males or
females.
Pregnancy, Teratogenic Effects, Pregnancy Category B
Reproduction studies in animals have revealed no evidence of harm to the fetus due to amphotericin B
for injection. Systemic fungal infections have been successfully treated in pregnant women with ampho-
tericin B for injection without obvious effects to the fetus, but the number of cases reported has been
small. Because animal reproduction studies are not always predictive of human response, and adequate
and well-controlled studies have not been conducted in pregnant women, this drug should be used dur-
ing pregnancy only if clearly indicated.
Nursing Mothers
It is not known whether amphotericin B is excreted in human milk. Because many drugs are excreted
in human milk and considering the potential toxicity of amphotericin B, it is prudent to advise a nursing
mother to discontinue nursing.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established through adequate and well-
controlled studies. Systemic fungal infections have been successfully treated in pediatric patients with-
out reports of unusual side effects. Amphotericin B for injection when administered to pediatric patients
should be limited to the smallest dose compatible with an effective therapeutic regimen.
ADVERSE REACTIONS
Although some patients may tolerate full intravenous doses of amphotericin B without difficulty, most
will exhibit some intolerance, often at less than the full therapeutic dose.
Tolerance may be improved by treatment with aspirin, antipyretics (e.g., acetaminophen), antihista-
mines, or antiemetics. Meperidine (25 to 50 mg IV) has been shown in some patients to decrease the
duration of shaking chills and fever that may accompany the infusion of amphotericin B.
Administration of amphotericin B on alternate days may decrease anorexia and phlebitis.
Intravenous administration of small doses of adrenal corticosteroids just prior to or during the
amphotericin B infusion may help decrease febrile reactions. Dosage and duration of such corticosteroid
therapy should be kept to a minimum (see PRECAUTIONS, Drug Interactions).
Addition of heparin (1000 units per infusion), and the use of a pediatric scalp-vein needle may lessen
the incidence of thrombophlebitis. Extravasation may cause chemical irritation.
The adverse reactions most commonly observed are:
General (body as a whole): fever (sometimes accompanied by shaking chills usually occurring within
15 to 20 minutes after initiation of treatment); malaise; weight loss.
Cardiopulmonary: hypotension; tachypnea.
Gastrointestinal: anorexia; nausea; vomiting; diarrhea; dyspepsia; cramping epigastric pain.
Hematologic: normochromic; normocytic anemia.
Local: pain at the injection site with or without phlebitis or thrombophlebitis.
Musculoskeletal: generalized pain, including muscle and joint pains.
Neurologic: headache.
Renal: decreased renal function and renal function abnormalities including: azotemia, hypokalemia,
hyposthenuria, renal tubular acidosis; and nephrocalcinosis. These usually improve with interruption of
therapy. However, some permanent impairment often occurs, especially in those patients receiving large
amounts (over 5 g) of amphotericin B or receiving other nephrotoxic agents. In some patients hydration
and sodium repletion prior to amphotericin B administration may reduce the risk of developing nephro-
toxicity. Supplemental alkali medication may decrease renal tubular acidosis.
The following adverse reactions have also been reported:
General (body as a whole): flushing.
Allergic: anaphylactoid and other allergic reactions; bronchospasm; wheezing.
Cardiopulmonary: cardiac arrest; shock; cardiac failure; pulmonary edema; hypersensitivity pneumonitis;
arrhythmias, including ventricular fibrillation; dyspnea; hypertension.
Dermatologic: rash, in particular maculopapular; pruritus.
Gastrointestinal: acute liver failure; hepatitis; jaundice; hemorrhagic gastroenteritis; melena.
Hematologic: agranulocytosis; coagulation defects; thrombocytopenia; leukopenia; eosinophilia; leuko-
cytosis.
Neurologic: convulsions; hearing loss; tinnitus; transient vertigo; visual impairment; diplopia; peripheral
neuropathy; encephalopathy (see PRECAUTIONS); other neurologic symptoms.
Renal: acute renal failure; anuria; oliguria.
Altered Laboratory Findings
Serum Electrolytes: Hypomagnesemia; hypo- and hyperkalemia; hypocalcemia.
Liver Function Tests: Elevations of AST, ALT, GGT, bilirubin, and alkaline phosphatase.
Renal Function Tests: Elevations of BUN and serum creatinine.
OVERDOSAGE
Amphotericin B overdoses can result in cardio-respiratory arrest. If an overdose is suspected, discon-
tinue therapy and monitor the patient’s clinical status (e.g., cardio-respiratory, renal, and liver function,
hematologic status, serum electrolytes) and administer supportive therapy, as required. Amphotericin B
is not hemodialyzable.
Prior to reinstituting therapy, the patient’s condition should be stabilized (including correction of elec-
trolyte deficiencies, etc.).
DOSAGE AND ADMINISTRATION
* * VERIFY PRODUCT NAME AND DOSAGE. * *
CAUTION: Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded.
Amphotericin B overdoses can result in cardio-respiratory arrest (See OVERDOSAGE).
AMPHOCIN should be administered by slow intravenous infusion. Intravenous infusion should be given
over a period of approximately 2 to 6 hours (depending on the dose) observing the usual precautions
for intravenous therapy (see PRECAUTIONS, General). The recommended concentration for intravenous
infusion is 0.1 mg/mL (1 mg/10 mL).
Since patient tolerance varies greatly, the dosage of amphotericin B must be individualized and adjust-
ed according to the patient’s clinical status (e.g., site and severity of infection, etiologic agent, cardio-
renal function, etc.).
A single intravenous test dose (1 mg in 20 mL of 5% dextrose solution) administered over 20 to 30
minutes may be preferred. The patient’s temperature, pulse, respiration, and blood pressure should be
recorded every 30 minutes for 2 to 4 hours.
In patients with good cardio-renal function and a well tolerated test dose, therapy is usually
initiated with a daily dose of 0.25 mg/kg of body weight. However, in those patients having severe and
rapidly progressive fungal infection, therapy may be initiated with a daily dose of 0.3 mg/kg of body
weight. In patients with impaired cardio-renal function or a severe reaction to the test dose,
therapy should be initiated with smaller daily doses (i.e., 5 to 10 mg).
Depending on the patient’s cardio-renal status (see PRECAUTIONS, Laboratory Tests), doses may grad-
ually be increased by 5 to 10 mg per day to final daily dosage of 0.5 to 0.7 mg/kg.
There are insufficient data presently available to define total dosage requirements and duration of
treatment necessary for eradication of specific mycoses. The optimal dose is unknown. Total daily dosage
may range up to 1.0 mg/kg per day or up to 1.5 mg/kg when given on alternate days.
Sporotrichosis: Therapy with intravenous amphotericin B for sporotrichosis has ranged up to nine
months with a total dose up to 2.5 g.
Aspergillosis: Aspergillosis has been treated with amphotericin B intravenously for a period up to
11 months with a total dose up to 3.6 g.
Rhinocerebral phycomycosis: This fulminating disease, generally occurs in association with diabetic
ketoacidosis. It is, therefore, imperative that diabetic control be restored in order for treatment with
AMPHOCIN to be successful. In contradistinction, pulmonary phycomycosis, which is more common in
association with hematologic malignancies, is often an incidental finding at autopsy. A cumulative dose
of at least 3 g of amphotericin B is recommended to treat rhinocerebral phycomycosis. Although a total
dose of 3 to 4 g will infrequently cause lasting renal impairment, this would seem a reasonable minimum
where there is clinical evidence of invasion of deep tissue. Since rhinocerebral phycomycosis usually
follows a rapidly fatal course, the therapeutic approach must necessarily be more aggressive than that
used in more indolent mycoses.
PREPARATION OF SOLUTIONS
Reconstitute as follows: An initial concentrate of 5 mg amphotericin B per mL is first prepared by
rapidly expressing 10 mL Sterile Water for Injection, USP without a bacteriostatic agent directly into the
lyophilized cake, using a sterile needle (minimum diameter: 20 gauge) and syringe. Shake the vial imme-
diately until the colloidal solution is clear. The infusion solution, providing 0.1 mg amphotericin B per mL,
is then obtained by further dilution (1:50) with 5% Dextrose Injection, USP of pH above 4.2. The pH of
each container of Dextrose Injection should be ascertained before use. Commercial Dextrose Injection
usually has a pH above 4.2; however, if it is below 4.2, then 1 or 2 mL of buffer should be added to the
Dextrose Injection before it is used to dilute the concentrated solution of amphotericin B. The recom-
mended buffer has the following composition:
Dibasic sodium phosphate (anhydrous) 1.59 g
Monobasic sodium phosphate (anhydrous) 0.96 g
Water for Injection, USP qs 100.0 mL
The buffer should be sterilized before it is added to the Dextrose Injection, either by filtration through
a bacterial retentive stone, mat, or membrane, or by autoclaving for 30 minutes at 15 lb pressure (121°C).
CAUTION: Aseptic technique must be strictly observed in all handling, since no preservative or
bacteriostatic agent is present in the antibiotic or in the materials used to prepare it for administration.
All entries into the vial or into the diluents must be made with a sterile needle. Do not recon-
stitute with saline solutions. The use of any diluent other than the ones recommended or the
presence of a bacteriostatic agent (e.g., benzyl alcohol) in the diluent may cause precipitation of
the antibiotic. Do not use the initial concentrate or the infusion solution if there is any
evidence of precipitation or foreign matter in either one.
An in-line membrane filter may be used for intravenous infusion of amphotericin B; however, the
mean pore diameter of the filter should not be less than 1.0 micron in order to assure passage
of the antibiotic dispersion.
HOW SUPPLIED
AMPHOCIN®
(amphotericin B for injection, USP)
NDC 0013-1405-44, 50 mg vial, 5 packs.
Available as single vials providing 50 mg of amphotericin B as a yellow to orange lyophilized cake (which
may partially reduce to powder following manufacture).
Storage
Prior to reconstitution, AMPHOCIN should be stored under refrigeration 2° to 8°C (36° to 46°F),
protected against exposure to light. Retain in carton until time of use. The concentrate (5 mg ampho-
tericin B per mL after reconstitution with 10 mL Sterile Water for Injection, USP) may be stored in the
dark, at room temperature for 24 hours, or at refrigerator temperatures for one week with minimal loss
of potency and clarity. Any unused material should then be discarded. Solutions prepared for intravenous
infusion (0.1 mg or less amphotericin B per mL) should be used promptly after preparation and should
be protected from light during administration.
% only
Manufactured for: Pharmacia & Upjohn Company, a subsidiary of
Pharmacia Corporation, Kalamazoo, MI 49001, USA
By: Cardinal Health, Albuquerque, NM 87109, USA
Revised September 2003 817 168 003
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Composition Unit 2566
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ITEM SIZE FOLDED SIZE DRAWING #
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SUBSTANCE PROFILES
Toxicological Data on Ingredients: Brilliant Green LD50: Not available. LC50: Not available.
Potential Acute Health Effects: Hazardous in case of skin contact (irritant, permeator), of eye contact (irritant), of ingestion,
of inhalation.
Potential Chronic Health Effects:
Hazardous in case of skin contact (irritant, permeator), of eye contact (irritant), of ingestion, of inhalation. CARCINOGENIC
EFFECTS: Not available. MUTAGENIC EFFECTS: Not available. TERATOGENIC EFFECTS: Not available.
DEVELOPMENTAL TOXICITY: Not available. The substance is toxic to lungs. Repeated or prolonged exposure to the
substance can produce target organs damage.
Eye Contact:
Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least 15
minutes. Cold water may be used. Get medical attention.
p. 1
Skin Contact:
In case of contact, immediately flush skin with plenty of water. Cover the irritated skin with an emollient. Remove contaminated
clothing and shoes. Cold water may be used.Wash clothing before reuse. Thoroughly clean shoes before reuse. Get medical
attention.
Serious Skin Contact:
Wash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek medical attention.
Inhalation:
If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical
attention.
Serious Inhalation: Not available.
Ingestion:
Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious
person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight clothing such as a collar,
tie, belt or waistband.
Serious Ingestion: Not available.
Small Spill:
Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading water on
the contaminated surface and dispose of according to local and regional authority requirements.
Large Spill:
Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on the
contaminated surface and allow to evacuate through the sanitary system.
Precautions:
Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the residue under
a fume hood. Ground all equipment containing material. Do not breathe dust. Wear suitable protective clothing. In case of
p. 2
insufficient ventilation, wear suitable respiratory equipment. If you feel unwell, seek medical attention and show the label when
possible. Avoid contact with skin and eyes.
Storage: Keep container tightly closed. Keep container in a cool, well-ventilated area.
Engineering Controls:
Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended
exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants
below the exposure limit.
Personal Protection:
Splash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case of a Large Spill:
Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used to avoid
inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this
product.
Exposure Limits: Not available.
p. 3
Instability Temperature: Not available.
Conditions of Instability: Not available.
Incompatibility with various substances: Not available.
Corrosivity: Non-corrosive in presence of glass.
Special Remarks on Reactivity: Not available.
Special Remarks on Corrosivity: Not available.
Polymerization: Will not occur.
Waste Disposal:
p. 4
Massachusetts RTK: Brilliant Green TSCA 8(b) inventory: Brilliant Green
Other Regulations: OSHA: Hazardous by definition of Hazard Communication Standard (29 CFR 1910.1200).
Other Classifications:
WHMIS (Canada): CLASS D-2A: Material causing other toxic effects (VERY TOXIC).
DSCL (EEC): R36/38- Irritating to eyes and skin.
HMIS (U.S.A.):
Health Hazard: 2
Fire Hazard: 1
Reactivity: 0
Personal Protection: E
National Fire Protection Association (U.S.A.):
Health: 2
Flammability: 1
Reactivity: 0
Specific hazard:
Protective Equipment:
Gloves. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Wear appropriate respirator
when ventilation is inadequate. Splash goggles.
The information above is believed to be accurate and represents the best information currently available to us. However, we
make no warranty of merchantability or any other warranty, express or implied, with respect to such information, and we assume
no liability resulting from its use. Users should make their own investigations to determine the suitability of the information for
their particular purposes. In no event shall ScienceLab.com be liable for any claims, losses, or damages of any third party or for
lost profits or any special, indirect, incidental, consequential or exemplary damages, howsoever arising, even if ScienceLab.com
has been advised of the possibility of such damages.
p. 5
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Final report on the safety assessment of EDTA, calcium disodium EDTA,
Genes & Expression Review Final report on the safety assessment
diammonium EDTA, dipotassium EDTA, disodium EDTA, TEA-EDTA, of Glycyrrhetinic Acid,Gene
Potassium
[Int Glycyrrhetinate,
J Toxicol. 2007]
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tetrasodium EDTA, tripotassium EDTA, trisodium EDTA, HEDTA, and
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trisodium HEDTA. Review Final report of the safety assessment of
RefSeqGene UniGene All Genes & Expression Resources… Alcohol Denat., including SD Alcohol
[Int J Toxicol.
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Lanigan RS, Yamarik
Genetics TA.
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Review Safety assessment of Salicylic Acid,
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance in Man (OMIM) PubMed PubMed Central (PMC)
Abstract Butyloctyl Salicylate, Calcium [Int
Salicylate,
J Toxicol.
C12-15
2003]
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ethylenediamine triacetic acid) and its trisodium salt are substituted amines. These ingredients function of Methylparaben, Ethylparaben,
[Int Propylparaben,
J Toxicol. 2008]
Database of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus Map Viewer Nucleotide
as chelating agents in cosmetic formulations. The typical concentration of use of EDTA is less than 2%,
Review &Final
Database PopSet ProSplign Sequence Read Archive (SRA) Sequin Splign tbl2asn Trace Archive UniSTS All Genomes Mapsreport of the safety assessment of
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with the other salts in current use at even lower concentrations. The lowest dose reported to cause a toxic L-Ascorbic Acid, Calcium Ascorbate,
[Int J Toxicol. 2005]
Homology
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Key Points
Formaldehyde is a colorless, flammable, strong-smelling chemical that is used in building materials and to
produce many household products (see Question 1).
Formaldehyde sources in the home include pressed-wood products, cigarette smoke, and fuel-burning
appliances (see Question 2).
When exposed to formaldehyde, some individuals may experience various short-term effects (see
Question 3).
Formaldehyde has been classified as a known human carcinogen (cancer-causing substance) by the
International Agency for Research on Cancer and as a probable human carcinogen by the U.S.
Environmental Protection Agency (see Question 4).
Research studies of workers exposed to formaldehyde have suggested an association between
formaldehyde exposure and several cancers, including nasopharyngeal cancer and leukemia (see Question
5).
1. What is formaldehyde?
Formaldehyde is a colorless, flammable, strong-smelling chemical that is used in building materials and to
produce many household products. It is used in pressed-wood products, such as particleboard, plywood,
and fiberboard; glues and adhesives; permanent-press fabrics; paper product coatings; and certain
insulation materials. In addition, formaldehyde is commonly used as an industrial fungicide, germicide,
and disinfectant, and as a preservative in mortuaries and medical laboratories. Formaldehyde also
occurs naturally in the environment. It is produced in small amounts by most living organisms as part of
normal metabolic processes.
According to a 1997 report by the U.S. Consumer Product Safety Commission, formaldehyde is
normally present in both indoor and outdoor air at low levels, usually less than 0.03 parts of
formaldehyde per million parts of air (ppm). Materials containing formaldehyde can release
formaldehyde gas or vapor into the air. One source of formaldehyde exposure in the air is automobile
tailpipe emissions.
During the 1970s, urea-formaldehyde foam insulation (UFFI) was used in many homes. However, few
homes are now insulated with UFFI. Homes in which UFFI was installed many years ago are not likely
to have high formaldehyde levels now. Pressed-wood products containing formaldehyde resins are often
a significant source of formaldehyde in homes. Other potential indoor sources of formaldehyde include
cigarette smoke and the use of unvented fuel-burning appliances, such as gas stoves, wood-burning
stoves, and kerosene heaters.
Although the short-term health effects of formaldehyde exposure are well known, less is known about
its potential long-term health effects. In 1980, laboratory studies showed that exposure to formaldehyde
could cause nasal cancer in rats. This finding raised the question of whether formaldehyde exposure
could also cause cancer in humans. In 1987, the U.S. Environmental Protection Agency (EPA)
classified formaldehyde as a probable human carcinogen under conditions of unusually high or prolonged
exposure (1). Since that time, some studies of humans have suggested that formaldehyde exposure is
associated with certain types of cancer. The International Agency for Research on Cancer (IARC)
classifies formaldehyde as a human carcinogen (2).
5. What have scientists learned about the relationship between formaldehyde and cancer?
Since the 1980s, the National Cancer Institute (NCI), a component of the National Institutes of Health,
has conducted studies to determine whether there is an association between occupational exposure to
formaldehyde and an increase in the risk of cancer. The results of this research have provided EPA and
the Occupational Safety and Health Administration (OSHA) with information to evaluate the potential
health effects of workplace exposure to formaldehyde.
The long-term effects of formaldehyde exposure have been evaluated in epidemiologic studies (studies
that attempt to uncover the patterns and causes of disease in groups of people). One type of
epidemiologic study is called a cohort study. A cohort is a group of people who may vary in their
exposure to a particular factor, such as formaldehyde, and are followed over time to see whether they
develop a disease. Another kind of epidemiologic study is called a case-control study. Case-control
studies begin with people who are diagnosed as having a disease (cases) and compare them to people
without the disease (controls), trying to identify differences in factors, such as exposure to
formaldehyde, that might explain why the cases developed the disease but the controls did not.
Several NCI surveys of professionals who are potentially exposed to formaldehyde in their work, such
as anatomists and embalmers, have suggested that these individuals are at an increased risk of leukemia
and brain cancer compared with the general population. However, specific work practices and
exposures were not characterized in these studies. An NCI case-control study among funeral industry
workers that characterized exposure to formaldehyde also found an association between increasing
formaldehyde exposure and mortality from myeloid leukemia (3). For this study, carried out among
funeral industry workers who had died between 1960 and 1986, researchers compared those who had
died from hematopoietic and lymphatic cancers and brain tumors with those who died from other
causes. (Hematopoietic or hematologic cancers such as leukemia develop in the blood or bone marrow.
Lymphatic cancers develop in the tissues and organs that produce, store, and carry white blood cells
that fight infections and other diseases.) This analysis showed that those who had performed the most
embalming and those with the highest estimated formaldehyde exposure had the greatest risk of myeloid
leukemia. There was no association with other cancers of the hematopoietic and lymphatic systems or
with brain cancer.
A number of cohort studies involving workers exposed to formaldehyde have recently been completed.
One study, conducted by NCI, looked at 25,619 workers in industries with the potential for occupational
formaldehyde exposure and estimated each worker’s exposure to the chemical while at work (4). The
results showed an increased risk of death due to leukemia, particularly myeloid leukemia, among
workers exposed to formaldehyde. This risk was associated with increasing peak and average levels of
exposure, as well as with the duration of exposure, but it was not associated with cumulative exposure.
An additional 10 years of data on the same workers were used in a follow-up study published in 2009
(5). This analysis continued to show a possible link between formaldehyde exposure and cancers of the
hematopoietic and lymphatic systems, particularly myeloid leukemia. As in the initial study, the risk was
highest earlier in the follow-up period. Risks declined steadily over time, such that the cumulative excess
risk of myeloid leukemia was no longer statistically significant at the end of the follow-up period. The
researchers noted that similar patterns of risks over time had been seen for other agents known to
cause leukemia.
A cohort study of 11,039 textile workers performed by the National Institute for Occupational Safety
and Health (NIOSH) also found an association between the duration of exposure to formaldehyde and
leukemia deaths (6). However, the evidence remains mixed because a cohort study of 14,014 British
industry workers found no association between formaldehyde exposure and leukemia deaths (7).
Generated by www.PDFonFly.com at 12/9/2010 9:39:05 PM
URL: http://www.cancer.gov/cancertopics/factsheet/Risk/formaldehyde/print
Formaldehyde undergoes rapid chemical changes immediately after absorption. Therefore, some
scientists think that formaldehyde is unlikely to have effects at sites other than the upper respiratory
tract. However, some laboratory studies suggest that formaldehyde may affect the lymphatic and
hematopoietic systems. Based on both the epidemiologic data from cohort and case-control studies and
the experimental data from laboratory research, NCI investigators have concluded that exposure to
formaldehyde may cause leukemia, particularly myeloid leukemia, in humans.
In addition, several case-control studies, as well as analysis of the large NCI industrial cohort (5), have
found an association between formaldehyde exposure and nasopharyngeal cancer, although some other
studies have not. Data from extended follow-up of the NCI cohort found that the excess of
nasopharyngeal cancer observed in the earlier report persisted (8).
Earlier analysis of the NCI cohort found increased lung cancer deaths among industrial workers
compared with the general U.S. population. However, the rate of lung cancer deaths did not increase
with higher levels of formaldehyde exposure. This observation led the researchers to conclude that
factors other than formaldehyde exposure might have caused the increased deaths. The most recent
data on lung cancer from the cohort study did not find any relationship between formaldehyde exposure
and lung cancer mortality.
In 1987, OSHA established a Federal standard that reduced the amount of formaldehyde to which
workers can be exposed over an 8-hour workday from 3 ppm to 1 ppm. In May 1992, the standard was
amended, and the formaldehyde exposure limit was further reduced to 0.75 ppm.
The EPA recommends the use of “exterior-grade” pressed-wood products to limit formaldehyde
exposure in the home. These products emit less formaldehyde because they contain phenol resins, not
urea resins. (Pressed-wood products include plywood, paneling, particleboard, and fiberboard and are
not the same as pressure-treated wood products, which contain chemical preservatives and are intended
for outdoor use.) Before purchasing pressed-wood products, including building materials, cabinetry, and
furniture, buyers should ask about the formaldehyde content of these products. Formaldehyde levels in
homes can also be reduced by ensuring adequate ventilation, moderate temperatures, and reduced
humidity levels through the use of air conditioners and dehumidifiers.
The following organizations can provide additional resources that readers may find helpful:
The EPA offers information about the use of formaldehyde in building materials and household
products. The EPA can be contacted at:
The U.S. Consumer Product Safety Commission (CPSC) has information about household products that
contain formaldehyde. CPSC can be contacted at:
The Federal Emergency Management Agency (FEMA) has information about formaldehyde exposure
levels in mobile homes and trailers supplied by FEMA after Hurricane Katrina. FEMA can be contacted
at:
The Occupational Safety and Health Administration (OSHA) has information about occupational
exposure limits for formaldehyde. OSHA can be contacted at:
Selected References
1. U.S. Environmental Protection Agency, Office of Air and Radiation. Report to Congress on Indoor
Air Quality, Volume II: Assessment and Control of Indoor Air Pollution, 1989.
2. International Agency for Research on Cancer (June 2004). IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans Volume 88 (2006): Formaldehyde, 2-Butoxyethanol and 1-tert-
Butoxypropan-2-ol. Retrieved October 5, 2010,
from: http://monographs.iarc.fr/ENG/Monographs/vol88/index.php.
3. Hauptmann M, Stewart PA, Lubin JH, et al. Mortality from lymphohematopoietic malignancies and
brain cancer among embalmers exposed to formaldehyde. Journal of the National Cancer Institute
2009; 101(24):1696–1708. [PubMed Abstract 1]
4. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from lymphohematopoietic
malignancies among workers in formaldehyde industries. Journal of the National Cancer Institute
2003; 95(21):1615–1623. [PubMed Abstract 2]
5. Beane Freeman L, Blair A, Lubin JH, et al. Mortality from lymphohematopoietic malignancies among
workers in formaldehyde industries: The National Cancer Institute Cohort. Journal of the National
Cancer Institute 2009; 101(10):751–761. [PubMed Abstract 3]
6. Pinkerton LE, Hein MJ, Stayner LT. Mortality among a cohort of garment workers exposed to
formaldehyde: An update. Occupational Environmental Medicine 2004; 61:193–200. [PubMed
Abstract 4]
7. Coggon D, Harris EC, Poole J, Palmer KT. Extended follow-up of a cohort of British chemical
workers exposed to formaldehyde. Journal of the National Cancer Institute 2003; 95(21):1608–
1615. [PubMed Abstract 5]
8. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from solid cancers among
workers in formaldehyde industries. American Journal of EpidemiologyGenerated
2004; 159(12):1117–1130.
by www.PDFonFly.com at 12/9/2010 9:39:05 PM
URL: http://www.cancer.gov/cancertopics/factsheet/Risk/formaldehyde/print
[PubMed Abstract 6]
###
We offer comprehensive research-based information for patients and their families, health professionals,
cancer researchers, advocates, and the public.
Glossary Terms
bone marrow (bone MAYR-oh)
The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and
platelets.
brain tumor
The growth of abnormal cells in the tissues of the brain. Brain tumors can be benign (not cancer) or
malignant (cancer).
cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer
cells can also spread to other parts of the body through the blood and lymph systems. There are several
main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal
organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective
or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow,
and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and
multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system
cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
carcinogen (kar-SIN-o-jin)
chemical (KEH-mih-kul)
A research study that compares a particular outcome (such as lung cancer) in groups of individuals who
are alike in many ways but differ by a certain characteristic (for example, female nurses who smoke
compared with those who do not smoke).
The total amount of a substance or radiation that a person is exposed to over time. Cumulative exposure
to a harmful substance or radiation may increase the risk of certain diseases or conditions.
disinfectant (DIS-in-fek-tunt)
Any substance or process that is used primarily on non-living objects to kill germs, such as viruses,
bacteria, and other microorganisms that can cause infection and disease. Most disinfectants are harsh
chemicals but sometimes heat or radiation may be used.
follow-up
Monitoring a person's health over time after treatment. This includes keeping track of the health of people
who participate in a clinical study or clinical trial for a period of time, both during the study and after the
study ends.
An agency in the U.S. federal government whose mission is to protect public health by making sure that
food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug
Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and
that blood for transfusions and transplant tissue are safe. Also called FDA.
formaldehyde (for-MAL-deh-hide)
fungicide (FUN-jih-side)
Any substance used to kill fungi (plant-like organisms that do not make chlorophyll), such as yeast and
molds.
germicide (JERM-ih-side)
Any substance or process that kills germs (bacteria, viruses, and other microorganisms that can cause
infection and disease). Also called microbicide.
inhalation
In medicine, refers to the act of taking a substance into the body by breathing.
Research done in a laboratory. A laboratory study may use special equipment and cells or animals to find
out if a drug, procedure, or treatment is likely to be useful in humans. It may also be a part of a clinical
trial, such as when blood or other samples are collected. These may be used to measure the effect of a
drug, procedure, or treatment on the body.
leukemia (loo-KEE-mee-uh)
Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood
cells to be produced and enter the bloodstream.
Cancer that forms in tissues of the lung, usually in the cells lining air passages. The two main types are
small cell lung cancer and non-small cell lung cancer. These types are diagnosed based on how the cells
look under a microscope.
metabolic (MEH-tuh-BAH-lik)
Having to do with metabolism (the total of all chemical changes that take place in a cell or an organism to
produce energy and basic materials needed for important life processes).
mortality (mor-TA-lih-tee)
The state of being mortal (destined to die). Mortality also refers to the death rate, or the number of deaths
in a certain group of people in a certain period of time. Mortality may be reported for people who have a
certain disease, live in one area of the country, or who are of a certain gender, age, or ethnic group.
myeloid (MY-eh-loyd)
Having to do with or resembling the bone marrow. May also refer to certain types of hematopoietic
(blood-forming) cells found in the bone marrow. Sometimes used as a synonym for myelogenous; for
example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.
Cancer that forms in tissues of the nasopharynx (upper part of the throat behind the nose). Most
nasopharyngeal cancers are squamous cell carcinomas (cancer that begins in flat cells lining the
nasopharynx).
nausea
A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side
effect of some types of cancer therapy.
organ
A part of the body that performs a specific function. For example, the heart is an organ.
phenol (FEE-nol)
Generated by www.PDFonFly.com at 12/9/2010 9:39:05 PM
URL: http://www.cancer.gov/cancertopics/factsheet/Risk/formaldehyde/print
A very poisonous chemical substance made from tar and also found in some plants and essential oils
(scented liquid taken from plants). Phenol is used to make plastics, nylon, epoxy, medicines, and to kill
germs. Also called carbolic acid.
The organs that are involved in breathing. These include the nose, throat, larynx, trachea, bronchi, and
lungs. Also called respiratory system.
scientist
A person who has studied science, especially one who is active in a particular field of investigation.
statistically significant
Describes a mathematical measure of difference between groups. The difference is said to be statistically
significant if it is greater than what might be expected to happen by chance alone. Also called significant.
throat (throte)
The hollow tube inside the neck that starts behind the nose and ends at the top of the trachea (windpipe)
and esophagus (the tube that goes to the stomach). The throat is about 5 inches long, depending on body
size. Also called pharynx.
tissue (TISH-oo)
A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood
and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes,
monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.
Table of Links
1 http://www.ncbi.nlm.nih.gov/pubmed/19933446
2 http://www.ncbi.nlm.nih.gov/pubmed/14600094
3 http://www.ncbi.nlm.nih.gov/pubmed/19436030
4 http://www.ncbi.nlm.nih.gov/pubmed/14985513
5 http://www.ncbi.nlm.nih.gov/pubmed/14600093
6 http://www.ncbi.nlm.nih.gov/pubmed/15191929
7 http://www.cancer.gov/cancertopics/understandingcancer/cancer
8 http://www.cancer.gov/cancertopics/wyntk/overview
9 http://www.cancer.gov/cancertopics/wyntk/leukemia
10 http://www.cancer.gov/cancertopics/types/leukemia
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and rice cell culture.
improves
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Database Gene [Plant production
MolOmnibus
Expression Biol. 2008]
in
Huang LF, Liu (GEO)
YK, LuDatasets
CA, Hsieh
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Resources… based on induction of alpha-amylase
[J Biol Chem.
promoter
1994]
Genetics & Medicine
Abstract Metabolic regulation of alpha-amylase gene
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance in Man (OMIM) PubMed PubMed Central (PMC)
Human serum albumin (HSA) is the most widely used clinical serum protein. Currently, commercial HSA expression in transgenic cell [Plant
cultures
Mol Biol.
of rice
1993]
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can only be obtained from human plasma, due to lack of commercially feasible recombinant protein
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expression systems. In this study, inducible expression and secretion of HSA by transformed rice proteins. [Transgenic Res. 2000]
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suspension cell culture was established. Mature form of HSA was expressed under the control of the
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in purification of human
sucrose starvation-inducible rice alpha Amy3 promoter, and secretion of HSA into the culture medium was
Homology serum albumin]
[Sheng Wu Gong Cheng Xue Bao. 2002]
achieved by using the alpha Amy3 signal sequence. High concentrations of HSA were secreted into
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culture medium in a short time (2-4 days) by sucrose depletion after cell concentrations had reached a See reviews...
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Accepted for publication: March 2003 One has published the first epidemiological evidence
showing a direct association between thimerosal-
Keywords Autism, mental retardation, speech disorders,
VAERS. containing childhood vaccines and neurodevelopmental
disorders in children [1, 2]. It has been shown that there
Summary was from a 2–6-fold statistically significant increased
incidence of neurodevelopment disorders following an
The prevalence of autism in the US has risen from 1 in additional 75–100 microgram dosage of mercury from
2500 in the mid-1980s to 1 in 300 children in the mid-
1990s. The purpose of this study was to evaluate whether thimerosal-containing childhood vaccines in compari-
mercury from thimerosal in childhood vaccines contributed son to thimerosal-free childhood vaccines [1]. One has
to neurodevelopmental disorders. Neurodevelopmental dis- also shown that there were dose-response curves
order dose-response curves for increasing mercury doses of demonstrating a close correlation between increasing
thimerosal in childhood vaccines were determined based
mercury doses from childhood vaccines and childhood
upon examination of the Vaccine Adverse Events Reporting
System (VAERS) database and the 2001 US’ Department neurodevelopmental disorders [2].
of Education Report. The instantaneous dosage of mercury The purpose of this study was to extend previous
children received in comparison to the Food and Drug studies and integrate statistical and dose-response
Administration (FDA)’s maximum permissible dose for the curve methodologies into a single analysis evaluating
oral ingestion of methylmercury was also determined. The
dose-response curves showed increases in odds ratios of mercury doses from childhood vaccines and childhood
neurodevelopmental disorders from both the VAERS and neurodevelopmental disorders. In the first part of this
US Department of Education data closely linearly correlated study, the dose-response was evaluated of increasing
with increasing doses of mercury from thimerosal-containing mercury doses from thimerosal-containing Diphtheria-
childhood vaccines and that for overall odds ratios statistical Tetanus-acellular Pertussis (DTaP) vaccine in compar-
significance was achieved. Similar slopes and linear regression
coefficients for autism odds ratios in VAERS and the US ison to thimerosal-free DTaP vaccines for neuro-
Department of Education data help to mutually validate developmental disorders from 1997–2001, based upon
each other. Controls employed in the VAERS and US examination of the Vaccine Adverse Events Reporting
Department of Education data showed minimal biases. The System (VAERS) database. Secondly, the 2001 US’
evidence presented here shows that the occurrence of neuro-
Department of Education Report [3] was evaluated on
developmental disorders following thimerosal-containing
childhood vaccines does not appear to be coincidental. the prevalence of neurodevelopmental disorders and the
average dosage of mercury that children received as part
of their childhood immunization schedules in birth
cohorts in comparison to a baseline measurement. The
Introduction final part of this analysis studied the instantaneous
Thimerosal is an organic mercury compound. It is dosage of mercury children received in comparison to
metabolized to ethylmercury and thiosalicylate and has the Food and Drug Administration (FDA)’s maximum
been present since the 1930s as a preservative in many permissible dose for the oral ingestion of methylmer-
vaccines and pharmaceutical products to prevent bac- cury as part of the 2002 recommended childhood immu-
terial and fungal contamination. nization schedule. It was determined by the FDA in
1999 that, under the recommended childhood immuni-
zation schedule, infants might be exposed to cumulative
Authors: David A. Geier, President, MedCon, Inc.; Mark R.
Geier, MD, PhD (author for correspondence; e-mail: doses of ethylmercury that exceed some federal safety
mgeier@erols.com), President, The Genetic Centers of guidelines established for oral ingestion of methylmer-
America, 14 Redgate Ct., Silver Spring, MD 20905, USA. cury [4].
Pediatric Rehabilitation ISSN 1363–8491 print/ISSN 1464–5270 online # 2003 Taylor & Francis Ltd
http://www.tandf.co.uk/journals
DOI: 10.1080/1363849031000139315
D. A. Geier and M. R. Geier
98
Neurodevelopmental disorders
9
R2 = 0.95
99
D. A. Geier and M. R. Geier
3.5
R = 0.96 Table 1 A summary of the instantaneous mercury exposure levels of
US infants at various times in comparison to the maximum daily FDA
Odds Ratio ± Standard Error
established limits.
3
Dose in g Average child’s
2.5 from permissible FDA
childhood dose in g (average
2
Age (months) vaccines weight in Kg)
1.5
0 12.5 0.330 (3.30)
1 Instantaneous relative excess — 9.5
2 62.5 0.486 (4.86)
0.5 Instantaneous relative excess — 32
4 62.5 0.654 (6.54)
0 Instantaneous relative excess — 24
0 50 100 150 200 6 50 0.780 (7.80)
Instantaneous relative excess — 16
Mercury Dose (micrograms) 15 50 1.05 (10.5)
Instantaneous relative excess — 12
Figure 4 Autism disabilities reported in comparison to the average 60 25 1.86 (18.6)
mercury dosage form thimerosal in childhood vaccines Instantaneous relative excess — 3.2
24
Odds Ratio ± Standard Error
8 Discussion
4 It is clear from the analysis shown in table 1 that US
infants and children are exposed to mercury levels from
0
their childhood immunization schedule that exceed the
0 50 100 150 200
FDA established maximum permissible levels for the
Mercury Dose (micrograms) daily oral ingestion of methylmercury. The fact that
Figure 5 Speech disorders reported in comparison to the average
mercury in the vaccines is given by injection rather
mercury dosage form thimerosal in childhood vaccines than by oral ingestion only makes the exposure levels
worse because Geier et al. [9] showed that the distri-
bution of foreign particles in mice reached several-logs
It was found that administration of thimerosal- higher concentration in organs following intravenous or
containing DTaP vaccines slightly raised the odds ratios intramuscular injections than via oral ingestion.
of febrile seizure, fever, pain, oedema and vomiting con- The dose-response curves (figures 1–5) show that the
trol adverse events compared to thimerosal-free DTaP increases in odds ratios of neurodevelopmental dis-
vaccines, but the increased relative risks did not corre- orders from both the VAERS and US Department of
late with the mercury dose children received (data not Education data closely linearly correlated with increas-
shown). Similarly, the odds ratios of visual impairment, ing doses of mercury from thimerosal-containing child-
deaf-blindness and orthopaedic impairment control hood vaccines and that for the overall odds ratios
disabilities in comparison to the mercury concentration examined statistical significance was achieved. In
that children received from thimerosal contained in addition, similar slopes and linear regression coefficients
their childhood vaccines did not correlate with the were observed for the odds ratios for autism from
increasing doses of mercury the children received VAERS and the US Department of Education data,
(data not shown). helping to mutually validate the data from each of
Table 1 shows the instantaneous mercury exposure of these independent sources.
US infants at various times as part of their childhood The lack of correlation between acute events and
immunization schedule in comparison to the FDA increasing mercury exposure levels in the VAERS
established limits. This table shows that the instanta- data argues against reporting bias or differences in the
neous relative excess mercury that US children received vaccines themselves and argues for the specific effects of
from their childhood immunizations ranged from 3.2– thimerosal on neurodevelopmental disorders. Likewise,
100
Neurodevelopmental disorders
the lack of correlation between visual impairments, was not necessary for neurotoxicity. It has been deter-
deaf-blindness and orthopaedic impairments and the mined that that brain preferentially takes up mercury
increasing mercury exposure levels in the US 5–7 times greater than the blood [15, 16]. The reason for
Department of Education data, again, argues for the this stems from the fact that thimerosal contains the
specific effects of thimerosal in childhood vaccines on ethylmercury radical attached to the sulphur atom of
the prevalence of autism and speech disorders. In addi- the thiol group of salicylic acid. Generally, mercuric
tion, because thimerosal-containing and thimerosal-free ions bind tightly but reversibly to thiol ligands [17]. It
DTaP vaccines were examined for the same years in the is likely, therefore, that the ethylmercury cation will
VAERS database, popular presentations in the media dissociate from the thiosalicylic acid moiety immedi-
regarding vaccine reactogenecitis or yearly inherent ately after injection to bind to the surrounding thiol
population difference should have had limited effects ligands present in great excess in tissue proteins [15].
upon the data examined. The concept of ethylmercury deposition in tissues
It has been shown that there may have been signifi- fairly rapidly following administration of thimerosal
cant concentrations of mercury once present in Rhogam from vaccines is suggested by a recent publication by
and mercury continues to be present in seafood and Pichichero et al. [18]. The authors examined the concen-
other pharmaceuticals [2]. These other sources of mer- trations of mercury in the blood, urine and stool from
cury, while potentially significant, probably had a lim- 3–28 days following thimerosal-containing vaccines in
ited effect on the results of this study because the 40 full-term infants aged 6 months and younger in
populations analysed were large and there should comparison to 21 control infants receiving thimerosal-
have been equal exposure to other sources of mercury free vaccines. The mean mercury doses of the infants
among the populations examined. exposed to thimerosal were 45.6 mg (range 37.5–62.5)
In addition, recent studies have analysed the preva- for 2 month-olds and 111.3 mg (range 87.5–175.0) for
lence of autism from the mid-1980s through the mid- 6 month-olds. Blood mercury in thimerosal-exposed 2
1990s and determined that the prevalence of autism has month-old infants ranged from less than 3.75 to
risen from one in 2500 children in the mid-1980s to 20.55 nmol/L; in 6 month-old infants all values were
one in 300 children in 1996 [10–12]. These studies have lower than 7.50 nmol/L. Only 15 blood samples from
confirmed that the rise in the prevalence in autism controls contained quantifiable mercury. Concen-
reflects genuine phenomena and is not the result of trations of mercury were low in the urine after vaccina-
population migration, differences in autism diagnoses tion, but were high in the stools of thimerosal-exposed
or other potential confounders. This suggests that the 2 month-old infants (mean 82 ng/g dry weight) and in
autism raises observed in this study reflect genuine 6 month-old infants (mean 58 ng/g dry weight). The
phenomena that is occurring in the US population. authors estimated that the blood half-life of ethylmer-
The 2001 IOM report has concluded the hypothesis cury was 7 days (95% confidence interval of 4–10 days).
that exposure to thimerosal-containing vaccines could The study was unable to determine the ultimate disposi-
be associated with neurodevelopmental disorders is bio- tion of most of the mercury with which infants were
logically plausible [7]. Bernard et al. [13] have compared injected.
the similar biological abnormalities commonly found in
autism and the corresponding pathologies arising from
Conclusion
mercury exposure. Distinct similarities were found
between autism and mercury exposure in their effects This study provides additional epidemiological
upon biochemistry, the immune system, the central evidence for a link between increasing mercury from
nervous system structure, neuro-chemistry and neuro- thimerosal-containing childhood vaccines and neuro-
physiology. Magos et al. [14] compared the effects of the developmental disorders and shows that children
administration of similar doses of ethylmercury and received doses of mercury in their childhood vaccines
methylmercury in rats. They determined that there that are in excess of the FDA permissible dose. In light
was little difference in the neurotoxicites of ethyl- of literature supporting the biologic mechanisms for
mercury and methylmercury treated rats when effects mercury induced neurotoxicity, the concentration of
on the dorsal root ganglia or coordination disorders mercury in thimerosal-containing childhood vaccines
were compared. The authors also determined that being in excess of the Federal Safety Guidelines for
microgram quantities of organic-mercury alone in the the oral ingestion of mercury and previous epidemio-
rat brain were in some cases associated with neurotoxi- logical studies showing overall statistically significant
city indicating that the presence of inorganic mercury and dose-response effects from mercury contained in
101
D. A. Geier and M. R. Geier
thimerosal-containing childhood vaccines, the occur- 7. Institute of Medicine (US): Immunization safety review:
Thimerosal-containing vaccines and neurodevelopmental dis-
rence of neurodevelopmental disorders following orders (Washington, DC: National Academy Press), 2001.
thimerosal-containing childhood vaccines does not 8. Diem, K. and Lentner, C. (editors): Geigy scientific tables
appear to be coincidental. It is suggested that, in light (Ardsley, NY: Geigy Pharmaceuticals), 1974.
9. Geier, M. R., Trigg, M. E. and Merril, M. R.: Fate of bacter-
of the results of this and previous studies, thimerosal iophage in non-immune germ-free mice. Nature, 246: 221–222,
should be removed immediately from all childhood 1973.
vaccines. 10. Burd, L., Fisher, W. and Kerbeshian, J.: A prevalence study of
pervasive developmental disorders in North Dakota. Journal of
the American Academy of Childhood and Adolescent Psychiatry,
26: 700–703, 1987.
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University of Utah epidemiologic survey of autism: prevalence.
1. Geier, M. R. and Geier, D. A.: Neurodevelopmental disorders American Journal of Psychiatry, 146: 194–199, 1989.
following thimerosal-containing childhood vaccines. Experimental 12. Yeargin-Allsopp, M., Rice, C., Karapurkar, T. et al.:
Biology and Medicine, in press. Prevalence of autism in a US metropolitan area. Journal of the
2. Geier, M. R. and Geier, D. A.: Thimerosal in childhood America Medicine Association, 289: 49–55, 2003.
vaccines, neurodevelopment disorders, and heart disease in the 13. Bernard, S., Enayati, A., Redwood, L. et al.: Autism: a
United States. Journal of American Physicians and Surgeons, 8: novel form of mercury poising. Medical Hypothesis, 56: 462–
6–11, 2003. 471, 2001.
3. Department of Education (US): Annual report to Congress on 14. Magos, L., Brown, A. W., Sparrow, S. et al.: The comparative
the implementation of the individuals with disabilities education act, toxicology of ethyl- and methylmercury. Archives of Toxicology,
23rd annual report (Washington, DC: Office of Special Education 57: 260–267, 1985.
Programs); A-14, 2001. 15. Clarkson, T. W.: The three faces of mercury. Environmental
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thimerosal use in childhood vaccines. Pediatrics, 107: 1147– 16. Cernichiari, E., Brewer, R. G., Myers, J. et al.: Monitoring
1154, 2001. methylmercury during pregnancy: maternal hair predicts fetal
5. Niu, M. T., Rhodes, A., Salive, M. et al.:. Comparative safety brain exposure. Neurotoxicology, 16: 705–710, 1995.
of two recombinant hepatitis B vaccines in children: data from the 17. Carty, A. J. and Malone, S. F.: The chemistry of mercury in
Vaccine Adverse Events Reporting System (VAERS) and Vaccine biological systems. In: J. O. Nriagu (editor) The biogeochemistry
Safety Datalink (VSD). Journal of Clinical Epidemiology, 51: 503– of mercury in the environment (New York: Elsevier/North
510, 1998. Holland), pp. 433–459, 1979.
6. Centers for Disease Control and Prevention: Live births 18. Pichichero, M. E., Cernichiari, E., Lopreiato, J. et al.:
by age of mother and race: United States, 1933–98. http:// Mercury concentrations and metabolism in infants receiving vac-
www.cdc.gov/nchs/data/natality/mage33tr.pdf; Visited 1 January cines containing thimerosal: a descriptive study. Lancet, 360:
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102
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necrosis of the hypothalamus along with behavioral abnormalities. In the present study the behavioral Temporal and spatial expression of
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Maps Resources…
the components of spontaneous locomotor activity but, after apomorphine challenge, marked decreases blind study and review.[Food Chem Toxicol. 1993]
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changes in the extinction and relearning phases. The results indicate that exposure to MSG in early life in
Bookshelf E-Utilities Journals Database MeSH Database PubMed PubMed Central (PMC) PubMed Clinical Queries All Literature Resources…
rats could lead to subtle behavioral aberrations in late adulthood.
Proteins
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Receptors, N-Methyl-D-Aspartate
Sodium Glutamate
Apomorphine
Medical:
Movement Disorders - MedlinePlus Health Information Generated by www.PDFonFly.com at 12/9/2010 10:07:47 PM
URL: http://www.ncbi.nlm.nih.gov/pubmed/10771161?dopt=Citation
Learning Disorders - MedlinePlus Health Information
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Neonatal exposure to monosodium glutamate induces cell death and
Genes & Expression Neonatal exposure to monosodium L-glutamate
dendritic hypotrophy in rat prefrontocortical pyramidal neurons. induces lossDatabase
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A.P. 7-70, C.P. 58261, Morelia, Michoaoán, Mexico. igonbur@hotlaim.com
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Domains & Structures
[Enhancing effects of Herpesvirus hominis on
Cn3D
Sheng Li Xue Bao. Conserved
1994 Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Feb;46(1):44-51. sodium glutamate [Zhongguo
neurotoxicity]
Yao Li Xue Bao. 1994]
(VAST) All Domains & Structures Resources…
[Transplacental neurotoxic effects of monosodium glutamate on structures Effects of maternal oral administration of
Genes & Expression
and functions of specific brain areas of filial mice] monosodium glutamate at a late [Brain
stage
Res.
of 1997]
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene Expression Omnibus
[Article in Chinese] Exogenous
(GEO) Datasets Gene Expression Omnibus (GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian glutamate enhances
Inheritance in glutamate
Man (OMIM)
RefSeqGene UniGene All Genes & Expression
Gao J, Wu J, Zhao XN, Zhang WN, Zhang YY, Zhang ZX. Resources… receptor subunit expression
[Neuroendocrinology.
during selective
1998]
Substances:
Sodium Glutamate
Calcium
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[Characterization of an experimental model of
Cn3D Conserved
Arch Med Res. 1995;26 Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Spec No:S127-32. monosodium- glutamate-induced
[Arch Invest Medconvulsions
(Mex). 1990]
(VAST) All Domains & Structures Resources…
Chronobiological variations in the convulsive effect of monosodium L- Monosodium-L-glutamate-induced convulsions-
Genes & Expression
glutamate when administered to adult rats. -I. Differences in seizure pattern
[Gen Pharmacol.
and duration
1984]
of
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UniGene All Genes &Neurológicas, Hospital de Especialidades, Centro Médico Nacional
Expression Resources… changes in uptake and release [Epilepsy
of Res. 1989]
Siglo XXI, Instituto Mexicano del Seguro Social, México, D.F.
Genetics & Medicine Monosodium glutamate neonatal treatment as a
Abstract seizure and
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance excitotoxic
in Man model.PubMed
(OMIM) PubMed [BrainCentral
Res. 2010]
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Monosodium L-glutamate Queries
(MSG) RefSeqGene
when All Genetics
administered & Medicine Resources…
intraperitoneally (i.p.) to rodents induces convulsions Review The significance of excursions above
Genomes & Maps
and has been used as a model to study various aspects of status epilepticus of multifocal origin. There the ADI. Case study:
[Regulmonosodium
Toxicol Pharmacol.
glutamate.
1999]
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are circadian variations Structural
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to convulsions Genome
induced Genome factors
by various Project Genome
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were used as controls, also being injected at 07:00, 15:00 and 23:00 h. One group was injected with NaCI
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the experimental group.PubMed
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following injections in the three groups of animals. Neither signs of brain hyperexcitability, nor convulsions
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when rats were injected at 07:00 h was shorter than that seen at 15:00 and 23:00 h. No significant
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seizures per hour and their intensity were significantly greater when animals were injected at 07:00 h than Recent activity
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Locomotor and learning deficits in adult rats
Variation exposed to monosodium-L-glutamatePubMed ...
PMID: 8845636 [PubMed - indexed
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of Genomic Structural Variation (dbVar) Database of Genotypes and Phenotypes (dbGaP) Database of Single Nucleotide Polymorphisms (dbSNP) SNP
Submission Tool All Variation Resources… Neonatal exposure to monosodium
glutamate induces cell death and dendritic
PubMed
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All How To Chemicals & Bioassays DNA & RNA Data & Software Domains & Structures Genes & Expression Genetics & Medicine Genomes &
MeSH Terms: See more...
Maps Homology Literature Proteins Sequence Analysis Taxonomy Training & Tutorials Variation
Animals
Circadian Rhythm/physiology* My NCBI Sign In
Convulsants/toxicity*
Drug Administration Schedule
Evaluation Studies as Topic
Male
Rats
Rats, Wistar
Reaction Time/drug effects
Sodium Glutamate/toxicity*
Substances:
Convulsants
Sodium Glutamate
Toxicological Data on Ingredients: Sodium deoxycholate LD50: Not available. LC50: Not available.
Eye Contact: Check for and remove any contact lenses. Do not use an eye ointment. Seek medical attention.
Skin Contact:
After contact with skin, wash immediately with plenty of water. Gently and thoroughly wash the contaminated skin with running
water and non-abrasive soap. Be particularly careful to clean folds, crevices, creases and groin. Cover the irritated skin with an
emollient. If irritation persists, seek medical attention. Wash contaminated clothing before reusing.
p. 1
Serious Skin Contact: Not available.
Inhalation: Allow the victim to rest in a well ventilated area. Seek immediate medical attention.
Serious Inhalation: Not available.
Ingestion:
Do not induce vomiting. Loosen tight clothing such as a collar, tie, belt or waistband. If the victim is not breathing, perform
mouth-to-mouth resuscitation. Seek immediate medical attention.
Serious Ingestion: Not available.
Small Spill:
Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading water on
the contaminated surface and dispose of according to local and regional authority requirements.
Large Spill:
Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on the
contaminated surface and allow to evacuate through the sanitary system.
Precautions:
Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the residue under a
fume hood. Ground all equipment containing material. Do not breathe dust. Avoid contact with eyes Wear suitable protective
clothing In case of insufficient ventilation, wear suitable respiratory equipment If you feel unwell, seek medical attention and
show the label when possible.
Storage:
Keep container dry. Keep in a cool place. Ground all equipment containing material. Keep container tightly closed. Keep in a
cool, well-ventilated place. Combustible materials should be stored away from extreme heat and away from strong oxidizing
agents.
p. 2
Section 8: Exposure Controls/Personal Protection
Engineering Controls:
Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended
exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants
below the exposure limit.
Personal Protection:
Splash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case of a Large Spill:
Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used to avoid
inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this
product.
Exposure Limits: Not available.
p. 3
Special Remarks on Reactivity: Not available.
Special Remarks on Corrosivity: Not available.
Polymerization: No.
Waste Disposal:
p. 4
DSCL (EEC): R36- Irritating to eyes.
HMIS (U.S.A.):
Health Hazard: 2
Fire Hazard: 1
Reactivity: 0
Personal Protection: E
National Fire Protection Association (U.S.A.):
Health: 2
Flammability: 1
Reactivity: 0
Specific hazard:
Protective Equipment:
Gloves. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Splash goggles.
The information above is believed to be accurate and represents the best information currently available to us. However, we
make no warranty of merchantability or any other warranty, express or implied, with respect to such information, and we assume
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p. 5
He a lt h 3
1 1
F ir e
3 0
Re a c t iv it y 0
Pe rson a l H
P r o t e c t io n
Toxicological Data on Ingredients: 2-Phenoxyethanol: ORAL (LD50): Acute: 1260 mg/kg [Rat]. DERMAL (LD50): Acute:
5000 mg/kg [Rabbit].
p. 1
Eye Contact:
Check for and remove any contact lenses. Immediately flush eyes with running water for at least 15 minutes, keeping eyelids
open. Cold water may be used. Do not use an eye ointment. Seek medical attention.
Skin Contact:
After contact with skin, wash immediately with plenty of water. Gently and thoroughly wash the contaminated skin with running
water and non-abrasive soap. Be particularly careful to clean folds, crevices, creases and groin. Cold water may be used.
Cover the irritated skin with an emollient. If irritation persists, seek medical attention. Wash contaminated clothing before
reusing.
Serious Skin Contact:
Wash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek immediate medical
attention.
Inhalation: Allow the victim to rest in a well ventilated area. Seek immediate medical attention.
Serious Inhalation: Not available.
Ingestion:
Do not induce vomiting. Examine the lips and mouth to ascertain whether the tissues are damaged, a possible indication that
the toxic material was ingested; the absence of such signs, however, is not conclusive. Loosen tight clothing such as a collar,
tie, belt or waistband. If the victim is not breathing, perform mouth-to-mouth resuscitation. Seek immediate medical attention.
Serious Ingestion: Not available.
Small Spill:
Dilute with water and mop up, or absorb with an inert dry material and place in an appropriate waste disposal container.
Finish cleaning by spreading water on the contaminated surface and dispose of according to local and regional authority
requirements.
Large Spill:
Absorb with an inert material and put the spilled material in an appropriate waste disposal. Finish cleaning by spreading water
on the contaminated surface and allow to evacuate through the sanitary system.
p. 2
Precautions:
Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the residue under
a fume hood. Ground all equipment containing material. Do not ingest. Do not breathe gas/fumes/ vapour/spray. In case
of insufficient ventilation, wear suitable respiratory equipment If ingested, seek medical advice immediately and show the
container or the label. Avoid contact with skin and eyes
Storage:
Keep container dry. Keep in a cool place. Ground all equipment containing material. Keep container tightly closed. Keep in a
cool, well-ventilated place. Combustible materials should be stored away from extreme heat and away from strong oxidizing
agents.
Engineering Controls:
Provide exhaust ventilation or other engineering controls to keep the airborne concentrations of vapors below their respective
threshold limit value. Ensure that eyewash stations and safety showers are proximal to the work-station location.
Personal Protection:
Splash goggles. Lab coat. Vapor respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case of a Large Spill:
Splash goggles. Full suit. Vapor respirator. Boots. Gloves. A self contained breathing apparatus should be used to avoid
inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this
product.
Exposure Limits: Not available.
p. 3
Section 10: Stability and Reactivity Data
Waste Disposal:
p. 4
Section 15: Other Regulatory Information
The information above is believed to be accurate and represents the best information currently available to us. However, we
make no warranty of merchantability or any other warranty, express or implied, with respect to such information, and we assume
no liability resulting from its use. Users should make their own investigations to determine the suitability of the information for
their particular purposes. In no event shall ScienceLab.com be liable for any claims, losses, or damages of any third party or for
lost profits or any special, indirect, incidental, consequential or exemplary damages, howsoever arising, even if ScienceLab.com
has been advised of the possibility of such damages.
p. 5
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Medicine BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) E-Utilities GenBank Genome Workbench ClearNucleotide
Influenza Virus
National Institutes of HealthPopSet Reference Sequence (RefSeq) RefSeqGene Sequence Read Archive (SRA) Sequin tbl2asn Trace Archive All DNA & RNA Resources…
Database
Data & Software
Display Settings: Abstract
Cn3D E-Utilities ProSplign Sequin Splign tbl2asn All Data & Software Resources… Send to:
Domains & Structures
Cn3D Conserved
Exp Biol Med (Maywood). Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
2003 Jun;228(6):660-4.
(VAST) All Domains & Structures Resources… Related citations
Neurodevelopmental disorders after thimerosal-containing vaccines: a brief
Genes & Expression
communication. Neurodevelopmental disorders following
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene
thimerosal-containing Expression
childhood Omnibus
[Int J Toxicol. 2004]
Geier MR, Geier DA. Datasets Gene Expression Omnibus (GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian Inheritance in Man (OMIM)
(GEO)
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Spring, Maryland 20905,Resources…
USA. mgeier@erols.com An assessment of the impact of thimerosal on
RefSeqGene UniGene Genes & Expression
childhood neurodevelopmental
[Pediatr
disorders.
Rehabil. 2003]
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Comment in: & Medicine
A meta-analysis
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in Man (OMIM) assessment
PubMed PubMed Central (PMC)
Exp Biol Med (Maywood). 2003 Oct;228(9):991-2; discussion 993-4. of neurodevelopmental[Neuro
disorders
Endocrinol
following
Lett. 2006]
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Genomes & Maps
Abstract Review Thimerosal-containing vaccines and
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We were initially highly of Genomicthat
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tetanus, and acellular pertussis (DTaP) vaccines in comparison with thimerosal-free DTaP vaccines. The
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vasculitis (RR Taxonomy Taxonomy
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NCBI Education Page NCBI Handbook NCBI Help disorders
Manual NCBI News Science Primer All Training Compound (MeSH Keyword)
vaccines. An association between neurodevelopmental and thimerosal-containing DTaP& Tutorials Resources…
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vaccines was found, but additional studies should be conducted to confirm and extend this study. Substance (MeSH Keyword)
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Neurodevelopmental disorders after
MeSH Terms: thimerosal-containing vaccines: a brief
PubMed
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Neurologic Diseases - MedlinePlus Health Information
Developmental Disabilities - MedlinePlus Health Information
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Domains & Structures
The African polio vaccine-acquired immune
Cn3D
Med Hypotheses. 1994Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Jun;42(6):347-54. deficiency syndrome connection.
[Med Hypotheses. 1997]
(VAST) All Domains & Structures Resources…
Polio vaccines and the origin of AIDS. Origin of AIDS: contaminated polio vaccine
Genes & Expression
Elswood BF, Stricker RB. theory refuted. [Nature. 2004]
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene Expression Omnibus
University of California San Francisco,
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Genetics & Medicine Review AIDS as a zoonosis? Confusion over
Med Hypotheses. 1995 Mar;44(3):226.
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NCBI Education Page NCBI Handbook NCBI Help Manual NCBI News Science Primer All Training & Tutorials Resources… activity
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Acquired Immunodeficiency Syndrome/epidemiology
Database of Genomic Structural Variation (dbVar) Database of Genotypes and Phenotypes (dbGaP) Database of Single Nucleotide Polymorphisms (dbSNP) SNP
Polio vaccines and the origin of AIDS.
Acquired Immunodeficiency Syndrome/history
Submission Tool All Variation Resources… PubMed
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Evidence of SV40 infections in hospitalized
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History, 20th Century See more...
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Macaca/microbiology
Neoplasms, Experimental/microbiology
Poliovirus Vaccine, Inactivated/adverse effects*
Poliovirus Vaccine, Inactivated/history
Poliovirus Vaccine, Oral/adverse effects
Poliovirus Vaccine, Oral/history
Simian Acquired Immunodeficiency Syndrome/microbiology
Simian immunodeficiency virus/isolation & purification
Simian virus 40/isolation & purification
Simian virus 40/pathogenicity
Zoonoses
Substances:
Poliovirus Vaccine, Inactivated
Poliovirus Vaccine, Oral
Generated by www.PDFonFly.com at 12/10/2010 11:22:44 AM
URL: http://www.ncbi.nlm.nih.gov/pubmed/7935079
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Medical:
Human Herpesvirus-8 - HIV InSite
AIDS - MedlinePlus Health Information
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BioSystems PubChem BioAssay PubChem Compound PubChem Structure Search PubChem
Limits Substance
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search Help & Bioassays Resources…
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Medicine BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) E-Utilities GenBank Genome Workbench ClearNucleotide
Influenza Virus
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Display Settings: Abstract
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2009 Feb Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
15;66(4):345-7.
(VAST) All Domains & Structures Resources… Related citations
Neurotoxicity in patients treated with intravenous polymyxin B: Two case
Genes & Expression
reports. Parenteral polymyxin B use in patients with
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Databasegram-negative
multidrug-resistant Gene
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2008]
Weinstein L, Doan(GEO)TL, Smith Gene
Datasets MA. Expression Omnibus (GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian Inheritance in Man (OMIM)
Division of Infectious Diseases, Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, Combination therapy with polymyxin B for the
RefSeqGene UniGene All Genes & Expression Resources…
USA. treatment of multidrug-resistant
[J Antimicrob Chemother.
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2004]
Genetics & Medicine
Pharmacokinetics
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance of intravenous
in Man (OMIM) polymyxin
PubMed PubMed B in
Central (PMC)
Abstract
critically ill patients. [Clin Infect Dis. 2008]
PURPOSE: Two PubMed
casesClinical Queries neurotoxicity
of reversible RefSeqGene Allassociated
Genetics & with
Medicine Resources… of intravenous
the administration
Genomes & Maps
polymyxin B are described. Review Polymyxin B for the treatment of
multidrug-resistant
Database of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus [J Antimicrob
pathogens:Chemother.
Map Viewer Nucleotide a critical review.
2007]
SUMMARY: In the first case, a 60-year-old, obese, white woman with a medical history of recurring urinary
Database PopSet ProSplign Sequence Read Archive (SRA) Sequin Splign tbl2asn Trace Archive UniSTS All Genomes
Review &Successful
Maps Resources…
treatment of ceftazidime-
tract infections, nephrolithiasis, and chronic renal insufficiency was admitted for parenteral antibiotics for
Homology resistant Klebsiella pneumoniae
[Clin Infect
ventriculitis
Dis. 1999]
dysuria and hematuria despite outpatient management with oral antibiotics. Her urinalysis revealed pyuria
BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) Conserved Domain Database (CDD) Genome ProtMap HomoloGene Protein Clusters All Homology
and large blood content. The corresponding urine culture contained >or=100,000 colony-forming units/mL See reviews...
Resources…
of multidrug-resistant (MDR) Klebsiella pneumoniae. The patient was treated with polymyxin B at 20,000
Literature See all...
units/kg i.v. as a loading dose and then 10,000 units/kg i.v. daily based on her renal function. The patient
Bookshelf E-Utilities Journals Database MeSH Database PubMed PubMed Central (PMC) PubMed Clinical Queries All Literature Resources…
experienced oral paresthesia that resolved upon discontinuation of the infusion with no further
Proteins
complications. In the second case, a 57-year-old white man with hypertension and ascending cholangitis
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) ConservedAll links
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was admitted. He required percutaneous drainage of an infected pancreatic cyst and received polymyxin B
Utilities GenBank ProSplign Protein Protein Clusters Reference Sequence (RefSeq) All Proteins Resources… Related Citations
at 25,000 units/kg i.v. as a loading dose and then 15,000 units/kg i.v. daily in addition to imipenem-
Sequence Analysis
cilastatin based on the sensitivities of two organisms (Escherichia coli and MDR K. pneumoniae) isolated Compound (MeSH Keyword)
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) GenBank Genome Workbench Influenza Virus Primer-
from the abdominal drainage. For his pancreatic abscess, the patient received a prolonged course of Substance (MeSH Keyword)
BLAST ProSplign Splign All Sequence Analysis Resources…
polymyxin B, which was well tolerated for the first four weeks. On day 30 of the polymyxin B, the patient
Taxonomy
reported oral and lower extremity paresthesias. The symptoms resolved upon discontinuation of the
Taxonomy Taxonomy Browser Taxonomy Common Tree All Taxonomy Resources…
polymyxin B. Recent activity
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NCBI Handbook of Help
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How To tumors. PubMed
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MeSH Terms:
Anti-Bacterial Agents/adverse effects*
Female
Gram-Negative Bacterial Infections/drug therapy*
Humans
Injections, Intravenous
Male
Middle Aged
Neurotoxicity Syndromes/etiology*
Polymyxin B/adverse effects*
Substances:
Anti-Bacterial Agents
Polymyxin B
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To reduce the development of drug-resistant bacteria and maintain the effectiveness of Polymyxin and other antibacterial drugs, Polymyxin B for Injection
USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
WARNING
CAUTION: WHEN THIS DRUG IS GIVEN INTRAMUSCULARLY, INTRAVENOUSLY AND/OR INTRATHECALLY, IT
SHOULD BE GIVEN ONLY TO HOSPITALIZED PATIENTS, SO AS TO PROVIDE CONSTANT SUPERVISION BY A
PHYSICIAN.
RENAL FUNCTION SHOULD BE CAREFULLY DETERMINED AND PATIENTS WITH RENAL DAMAGE AND NITROGEN
RETENTION SHOULD HAVE REDUCED DOSAGE. PATIENTS WITH NEPHROTOXICITY DUE TO POLYMYXIN B SULFATE
USUALLY SHOW ALBUMINURIA, CELLULAR CASTS, AND AZOTEMIA. DIMINISHING URINE OUTPUT AND A RISING
BUN ARE INDICATIONS FOR DISCONTINUING THERAPY WITH THIS DRUG.
NEUROTOXIC REACTIONS MAY BE MANIFESTED BY IRRITABILITY, WEAKNESS, DROWSINESS, ATAXIA, PERIORAL
PARESTHESIA, NUMBNESS OF THE EXTREMITIES, AND BLURRING OF VISION. THESE ARE USUALLY ASSOCIATED
WITH HIGH SERUM LEVELS FOUND IN PATIENTS WITH IMPAIRED RENAL FUNCTION AND/OR NEPHROTOXICITY.
THE CONCURRENT OR SEQUENTIAL USE OF OTHER NEUROTOXIC AND/OR NEPHROTOXIC DRUGS WITH
POLYMYXIN B SULFATE, PARTICULARLY BACITRACIN, STREPTOMYCIN, NEOMYCIN, KANAMYCIN, GENTAMICIN,
TOBRAMYCIN, AMIKACIN, CEPHALORIDINE, PAROMOMYCIN, VIOMYCIN, AND COLISTIN SHOULD BE AVOIDED.
THE NEUROTOXICITY OF POLYMYXIN B SULFATE CAN RESULT IN RESPIRATORY PARALYSIS FROM
NEUROMUSCULAR BLOCKADE, ESPECIALLY WHEN THE DRUG IS GIVEN SOON AFTER ANESTHESIA AND/OR
MUSCLE RELAXANTS.
USAGE IN PREGNANCY: THE SAFETY OF THIS DRUG IN HUMAN PREGNANCY HAS NOT BEEN ESTABLISHED.
DESCRIPTION
Polymyxin B Sulfate is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aerosporous). Polymyxin B sulfate is the sulfate salt
of Polymyxins B1 and B2, which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillacea). It has a potency of not less
than 6000 polymyxin B units per mg, calculated on the anhydrous basis. The structural formulae are:
Each vial contains 500,000 polymyxin B units for parenteral or ophthalmic administration.
Polymyxin B for Injection is in powder form suitable for preparation of sterile solutions for intramuscular, intravenous drip, intrathecal, or ophthalmic use.
In the medical literature, dosages have frequently been given in terms of equivalent weights of pure polymyxin B base. Each milligram of pure polymyxin B
base is equivalent to 10,000 units of polymyxin B and each microgram of pure polymyxin B base is equivalent to 10 units of polymyxin B.
Aqueous solutions of polymyxin B sulfate may be stored up to 12 months without significant loss of potency if kept under refrigeration. In the interest of
safety, solutions for parenteral use should be stored under refrigeration and any unused portion should be discarded after 72 hours. Polymyxin B sulfate
should not be stored in alkaline solutions since they are less stable.
CLINICAL PHARMACOLOGY
Polymyxin B sulfate has a bactericidal action against almost all gram-negative bacilli except the Proteus group. Polymyxins increase the permeability of
bacterial cell wall membranes. All gram-positive bacteria, fungi, and the gram-negative cocci, N gonorrhoeae and N meningitidis, are resistant.
Susceptibility plate testing: If the Kirby-Bauer method of disc susceptibility testing is used, a 300-unit polymyxin B disc should give a zone of over 11 mm
when tested against a polymyxin B susceptible bacterial strain.
Polymyxin B sulfate is not absorbed from the normal alimentary tract. Since the drug loses 50 percent of its activity in the presence of serum, active blood
levels are low. Repeated injections may give a cumulative effect. Levels tend to be higher in infants and children. The drug is excreted slowly by the
kidneys. Tissue diffusion is poor and the drug does not pass the blood brain barrier into the cerebrospinal fluid. In therapeutic dosage, polymyxin B
sulfate causes some nephrotoxicity with tubule damage to a slight degree.
CONTRAINDICATIONS
This drug is contraindicated in persons with a prior history of hypersensitivity reactions to polymyxins.
PRECAUTIONS
See “WARNING” box.
Prescribing Polymyxin B for Injection USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to
provide benefit to the patient and increase the risk of the development of drug-resistant bacteria.
Baseline renal function should be done prior to therapy, with frequent monitoring of renal function and blood levels of the drug during parenteral therapy.
Avoid concurrent use of a curariform muscle relaxant and other neurotoxic drugs (ether, tubocurarine, succinylcholine, gallamine, decamethonium and
sodium citrate) which may precipitate respiratory depression. If signs of respiratory paralysis appear, respiration should be assisted as required, and the
drug discontinued. As with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi.
If superinfection occurs, appropriate therapy should be instituted.
ADVERSE REACTIONS
See “WARNING” box.
Nephrotoxic reactions: Albuminuria, cylinduria, azotemia, and rising blood levels without any increase in dosage.
Neurotoxic reactions: Facial flushing, dizziness progressing to ataxia, drowsiness, peripheral paresthesias (circumoral and stocking glove), apnea due to
concurrent use of curariform muscle relaxants, other neurotoxic drugs or inadvertent overdosage, and signs of meningeal irritation with intrathecal
administration, e.g., fever, headache, stiff neck and increased cell count and protein cerebrospinal fluid.
Other reactions occasionally reported: Drug fever, urticarial rash, pain (severe) at intramuscular injection sites, and thrombophlebitis at intravenous
injection sites.
HOW SUPPLIED
POLYMYXIN B FOR INJECTION USP, 500,000 polymyxin B units per vial is available in single vial cartons NDC# 39822-0166-5.
Storage recommendations:
Before reconstitution: Store at controlled room temperature 20° to 25°C (68° to 77°F). Protect from light. Retain in carton until time of use.
After reconstitution: Product must be stored under refrigeration, between 2° to 8°C (36° to 46°F) and any unused portion should be discarded after 72
hours.
Manufactured for:
X-Gen Pharmaceuticals, Inc.
Northport, NY 11768
6-DPMX-05
PRODUCT INFO
INJECTION,
POWDER,
Dosage
Product Code 39822-0166 LYOPHILIZED,
Form
FOR
SOLUTION
Route Of DEA
INTRAMUSCULAR, INTRATHECAL, INTRAVENOUS, OPHTHALMIC
Administration Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
polymyxin b sulfate (polymyxin b) Active 500000 UNITS In 1 VIAL
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 39822-0166-5 1 VIAL In 1 CARTON contains a VIAL
1 1 VIAL In 1 VIAL This package is contained within the CARTON (39822-0166-5)
Resources
All Resources Chemicals & Bioassays
BioSystems PubChem BioAssay PubChem Compound PubChem Structure Search PubChem
Limits Substance
Advanced All Chemicals
search Help & Bioassays Resources…
Search: PubMed 6
DNA & RNA
BankItofBioSystems
U.S. National Library Search
Medicine BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) E-Utilities GenBank Genome Workbench ClearNucleotide
Influenza Virus
National Institutes of HealthPopSet Reference Sequence (RefSeq) RefSeqGene Sequence Read Archive (SRA) Sequin tbl2asn Trace Archive All DNA & RNA Resources…
Database
Data & Software
Display Settings: Abstract
Cn3D E-Utilities ProSplign Sequin Splign tbl2asn All Data & Software Resources… Send to:
Domains & Structures
Cn3D
Ann Allergy Asthma Conserved
Immunol. Domain
2005 Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Dec;95(6):593-9.
(VAST) All Domains & Structures Resources… Related citations
Polysorbate 80 in medical products and nonimmunologic anaphylactoid
Genes & Expression Anaphylactoid reactions in two patients after
reactions. omalizumab administration
[Allergyafter
Asthma
successful
Proc. 2007]
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene Expression Omnibus
Coors EA, Seybold
(GEO)H, Merk HF,
Datasets Mahler
Gene V.
Expression Omnibus (GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian Inheritance in Man (OMIM)
[Anaphylactic and anaphylactoid reactions
Department of Dermatology,
RefSeqGeneFriedrich-Alexander
UniGene All Genes University of Erlangen-Nuremberg,
& Expression Resources… Erlangen, Germany. occurring during anaesthesia
[Ann Fr Anesth
in France.
Reanim. 2004]
Genetics & Medicine
Abstract Anaphylaxis to viscotoxins of mistletoe (Viscum
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance in Man (OMIM) PubMed PubMed Central (PMC)
BACKGROUND: Polyoxyethylene-sorbitan-20-monooleate (also known as polysorbate 80 and Tween 80) is album) extracts.
[Ann Allergy Asthma Immunol. 2005]
PubMed Clinical Queries RefSeqGene All Genetics & Medicine Resources…
a solubilizing agent ubiquitously used in nutritives, creams, ointments, lotions, and multiple medical Review Polysorbates 20 and 80 used in the
Genomes & Maps
preparations (e.g., vitamin oils, vaccines, and anticancer agents) and as an additive in tablets. Whereas its formulation of protein biotherapeutics:
[J Pharm Sci.
structure
2008]
Database of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus Map Viewer Nucleotide
relevance as a contact allergen has declined during the past decades, it is of current relevance as a
Review &Anaphylaxis
Database PopSet ProSplign Sequence Read Archive (SRA) Sequin Splign tbl2asn Trace Archive UniSTS All Genomes induced by the
Maps Resources…
"hidden" inductor of anaphylactoid reactions. carboxymethylcellulose
[Ann Allergycomponent
Asthma Immunol.
of injectable
1995]
Homology
OBJECTIVE: To identify
BLAST polysorbate
(Basic 80 (generally
Local Alignment believed
Search Tool) to(Stand-alone)
BLAST be an inert vehicle) as Domain
Conserved an inductor of a (CDD)
Database severeGenome ProtMap HomoloGene Protein Clusters All Homology
See reviews...
anaphylactoid Resources…
reaction.
Literature See all...
METHODS: Skin prick testing, enzyme-linked immunosorbent assay, IgE immunoblotting, and flow
Bookshelf
cytometric detection E-Utilities Journals
of basophil Database
activation MeSH Database
were performed PubMedand
in controls PubMed Central (PMC)
in a patient with aPubMed
medicalClinical Queries All Literature Resources…
history Proteins
of anaphylactic shock due to intravenous administration of a multivitamin product during pregnancy.
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) ConservedCited
Domainby 2 PubMed
Search Central
Service (CD articles
Search) E-
RESULTS: Polysorbate 80 was identified as the causative agent for the anaphylactoid reaction of
Utilities GenBank ProSplign Protein Protein Clusters Reference Sequence (RefSeq) All Proteins Resources… Anaphylaxis following quadrivalent human
nonimmunologic origin in the patient. Polysorbate specific IgE antibodies were not identified in enzyme- papillomavirus vaccination. [CMAJ. 2008]
Sequence Analysis
linked immunosorbent assay and immunoblot examinations, confirming the nonimmunologic nature of
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) GenBank Genome Workbench
The human Influenza Virus
papillomavirus Primer-
vaccine and risk of
the anaphylactoid reaction.
BLAST ProSplign Splign All Sequence Analysis Resources… anaphylaxis. [CMAJ. 2008]
CONCLUSIONS:
Taxonomy Polysorbate 80 is a ubiquitously used solubilizing agent that can cause severe
nonimmunologic anaphylactoid
Taxonomy Taxonomy reactions.
Browser Taxonomy Common Tree All Taxonomy Resources…
Training & Tutorials
PMID: 16400901 [PubMed - indexed for MEDLINE] All links from this record
NCBI Education Page NCBI Handbook NCBI Help Manual NCBI News Science Primer All Training & Tutorials Resources…
Related Citations
Variation
MeSH Terms, Substances Compound (MeSH Keyword)
Database of Genomic Structural Variation (dbVar) Database of Genotypes and Phenotypes (dbGaP) Database of Single Nucleotide Polymorphisms (dbSNP) SNP
MeSH Terms: Submission Tool All Variation Resources… Substance (MeSH Keyword)
How To
Anaphylaxis/chemically induced* Cited in PMC
All How To Chemicals & Bioassays DNA & RNA Data & Software Domains & Structures Genes & Expression Genetics & Medicine Genomes &
Anaphylaxis/immunology
Maps Homology Literature Proteins Sequence Analysis Taxonomy Training & Tutorials Variation
Basophils/immunology
Enzyme-Linked Immunosorbent Assay Recent activity My NCBI Sign In
Female Turn Off Clear
Flow Cytometry Polysorbate 80 in medical products and
Humans nonimmunologic anaphylactoid reactions.
PubMed
Substances:
Pharmaceutical Preparations
Polysorbates
Surface-Active Agents
Vitamins
Immunoglobulin E Generated by www.PDFonFly.com at 12/10/2010 12:24:00 PM
URL: http://www.ncbi.nlm.nih.gov/pubmed/16400901
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Figure 2. (A) Neurodevelopment disorders and heart disease conditions reported following thimerosal-containing DTwcP in
comparison to thimerosal-free DTaP vaccines for increasing mercury dosage that children received from thimerosal; (B) Control
adverse events reported acutely following thimerosal-containing DTwcP in comparison to thimerosal-free DTaP vaccines for increasing
mercury dosage from thimerosal
guidelines for the oral ingestion of containing DTaP vaccines slightly raised DTaP vaccines for different mercury doses.
methylmercury, ranging from 2.7 to 37-fold the rate of adverse events compared to We found that administration of
at a given age. thimerosal-free DTaP vaccines, but the thimerosal-containing DTwcP vaccines
Figure 1A plots the relative risk of increased relative risks did not correlate significantly raised the rate of adverse
speech disorders, autism, and heart arrest with the total amount of mercury the events compared to thimerosal-free DTaP
reported after thimerosal-containing DTaP children received. vaccines, but the increased relative risks did
in comparison to thimerosal-free DTaP Figure 2A shows the relative risk of not correlate with the total amount of
vaccines for increasing doses of mercury. speech disorders, autism, and heart arrest mercury the children received.
We found that the data points for each reported after thimerosal-containing Figures 3A-B show the prevalence of
condition closely followed exponential DTwcP in comparison to thimerosal-free autism and speech disorders as a function of
distributions. DTaP vaccines for increasing dosage of the mercury dose that children received
Figure 1B plots the relative risks of mercury. We found that the data points from thimerosal contained in their child-
febrile seizure, fever, pain, edema, and hood vaccines. We found that the condi-
closely followed exponential distributions.
vomiting reported after thimerosal- tions analyzed closely followed linear
Figure 2B shows the relative risk of distributions with an increase of about one
containing DTaP in comparison to febrile seizure, fever, pain, edema, and case of autism per 100,000 children for
thimerosal-free DTaP vaccines. We found vomiting after thimerosal-containing every microgram present in childhood
that administration of thimerosal- DTwcP in comparison to thimerosal-free vaccines and about one case of speech
disorders per 1,000 children for every 3 µg thimerosal-containing DTaP and DTwcP ments, as shown in Figure 3C.
of mercury present in childhood vaccines. have higher rates of speech disorders, The lack of correlation between acute
Figure 3C shows the prevalence of the autism, and heart arrest overall, but also events and increasing mercury exposure
control disabilities of visual impairment, that the relative risk of each of these levels in the VAERS data argues against
deaf-blindness, and orthopedic impairment disorders correlated with increasing doses reporting bias or differences in the vaccines
as a function of the mercury dose that of mercury contained in childhood themselves and argues for the specific
children received from thimerosal con- vaccines, as illustrated in Figures 1A and effects of thimerosal on neurodevelopment
tained in their childhood vaccines. We 2A. Figures 1B and 2B show that exposure disorders and heart disease. Likewise, the
found that the prevalence of these condi- to increasing doses of mercury is not lack of correlation between visual impair-
tions did not correlate with the increasing correlated to acute vaccine adverse events ments, deaf-blindness, or orthopedic
total amount of mercury the children including febrile seizures, fever, pain, impairments and the increasing mercury
received. edema, or vomiting. exposure levels in the US Department of
Our demonstration of a significant Education data also argues for the specific
Discussion overall increase in the relative risks of acute effects of thimerosal in childhood vaccines
It is clear from our analysis, shown in adverse events following DTwcP vaccine on the prevalence of autism and speech
Table 1, that US infants are exposed to when compared to thimerosal-free DTaP disorders.
mercury levels from their childhood vaccine is not surprising since our previous As an additional epidemiological
immunization schedule that far exceed the studies have shown that DTwcP vaccines confirmation of our findings, we analyzed
EPA and FDA-established maximum are far more reactogenic than DTaP the CDC's Phase I Thimerosal Vaccine
permissible levels for the daily oral vaccines.1 5 , 1 However,
6
we observed that Safety Datalink (VSD) data.1 7 We found
ingestion of methylmercury. The fact that only those events for which causation by this data showed that the increasing relative
mercury in the vaccines is given by thimerosal is biologically plausible were risk of developmental neurologic disorder,
injection rather than by oral ingestion only found to be correlated with the mercury autism, speech disorder, and attention
makes the exposure levels worse because levels children received in their vaccines. deficit disorder all closely followed
Geier et al. showed that the distribution of Our analyses of a completely independ- exponential distributions with increasing
foreign particles in mice reached several- ent source, the US Department of mercury levels from the thimerosal that
logs higher concentration in organs Education's report on the prevalence of children received as part of their childhood
following intravenous or intramuscular various childhood disease among school immunizations.
injections than via oral ingestion.1 4 children of various ages, showed autism We conducted a MEDLINE (1966-
Our previous studies comparing DTaP and speech disorders were correlated with 2003) search for the terms merthiolate and
with and without thimerosal have shown a increasing mercury from childhood thimerosal and found almost 1,500
statistically and clinically significant vaccines, as shown in Figures 3A-B. No references, primarily about various adverse
increase in neurodevelopment disorders in correlation was seen between increasing outcomes following exposure. Of particu-
those vaccinated with thimerosal- mercury exposure from childhood vaccines lar interest, Bernard et al. have compared
containing vaccines.8 Our current study not and the prevalence of visual impairments, the similar biological abnormalities
only shows that those vaccinated with deafness-blindness, or orthopedic impair- commonly found in autism and the
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The role of SV40 in malignant mesothelioma and other human malignancies.
Genes & Expression Review [SV40: a possible co-carcinogen of
Pershouse MA, Heivly S, Girtsman
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Database of (GEO)
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Montana, Missoula, Montana 59812, USA. mark.pershouse@umontana.edu SV40 multiple tissue infection and asbestos
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area for Res.
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2007]
Genetics & Medicine
Abstract
SV40 enhances the risk of malignant
SV40 is a DNABookshelf Database
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as a contaminant Viewer Online
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vaccine in Man (OMIM) PubMed
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PubMed Central (PMC)
exposedRes.
to 2005]
PubMed Clinical Queries RefSeqGene All Genetics & Medicine Resources…
preparations. Some estimates suggest that millions of people are currently infected with the virus. The
Genomes
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primary Review Animal models of malignant
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Virus Map Viewer Nucleotide [Inhal Toxicol. 2006]
some rodent models. It has also been detected in a similar spectrum of human tumors. However,
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demonstrate Sequin incidence
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populations. To date, over 60 reports from 49 different laboratories have shown SV40 sequences in 40 and mesothelioma. [Curr Opin Pulm Med. 2008]
BLASTcancer
tissues from human (Basic Local Alignment
patients. Search Tool)
Six studies, BLAST
however, (Stand-alone)
have Conserved
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Display Settings: Abstract
Cn3D E-Utilities ProSplign Sequin Splign tbl2asn All Data & Software Resources… Send to:
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Cn3D
Hum Pathol. 1999 Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Dec;30(12):1496-502.
(VAST) All Domains & Structures Resources… Related citations
Evidence of SV40 infections in hospitalized children.
Genes & Expression Molecular evidence of simian virus 40 infections
Butel JS, JafarBioSystems
S, Wong C,Database
Arrington
of AS, Opekun
Genotypes AR,
and Finegold (dbGaP)
Phenotypes MJ, Adam E.
E-Utilities in children.
GenBank Gene Gene Expression Omnibus [J InfectOmnibus
(GEO) Database Gene Expression Dis. 1999]
Collaborators (GEO)
(1) Datasets Gene Expression Omnibus (GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian Inheritance in Man (OMIM)
Lack of serologic evidence for prevalent simian
Butel JS. RefSeqGene UniGene All Genes & Expression Resources… virus 40 infection in humans.
[J Natl Cancer Inst. 2003]
Genetics
Department & Medicine
of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Detection of polyomavirus SV40 in tonsils from
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance in Man (OMIM) PubMed PubMed Central (PMC)
immunocompetent children. [J Clin Virol. 2008]
Abstract PubMed Clinical Queries RefSeqGene All Genetics & Medicine Resources…
SimianGenomes
virus 40 &(SV40)
Maps is known to have contaminated poliovirus vaccines used between 1955 and 1963. Review Is there a role for SV40 in human
Accumulating Database
reports have described the presence of SV40 DNA in human tumors and normal tissues, cancer? [J Clin Oncol. 2006]
of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus Map Viewer Nucleotide
although the significance of human infections by SV40 is unknown. We investigated whether unselected
Database PopSet ProSplign Sequence Read Archive (SRA) Sequin Splign tbl2asn Trace Archive UniSTS All Genomes Review &Association between SV40 and non-
Maps Resources…
hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent.
Homology Hodgkin's lymphoma. [Leuk Lymphoma. 2003]
Serum samples were(Basic
BLAST examined
Local for SV40 neutralizing
Alignment antibody
Search Tool) BLAST using a specific
(Stand-alone) plaque
Conserved reduction
Domain Databasetest; of Genome ProtMap HomoloGene Protein Clusters All Homology
(CDD)
337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was See reviews...
Resources…
significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-
Literature See all...
positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA
Bookshelf E-Utilities Journals Database MeSH Database PubMed PubMed Central (PMC) PubMed Clinical Queries All Literature Resources…
sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the
Proteins
antibody-positive patients.BLAST
BioSystems This study, usingAlignment
(Basic Local 2 independent
Search assays, shows
Tool) BLAST the presence
(Stand-alone) of Link
BLAST SV40(BLink) ConservedCited
Domainby 8 PubMed
Search Central
Service (CD articles
Search) E-
infections in children born after
Utilities GenBank 1980. We
ProSplign conclude
Protein Protein that SV40
Clusters causes Sequence
Reference natural infections in humans.
(RefSeq) All Proteins Resources… Polyomavirus infection and its impact on renal
Sequence Analysis function and long-term outcomes
[Transplantation.
after lung2009]
PMID: 10667429 [PubMed - indexed for MEDLINE]
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) GenBank Genome Workbench
Polyomavirus Influenza
shedding Virus
in the Primer-
stool of healthy
adults. [J Clin Microbiol. 2009]
PublicationBLAST
Types,ProSplign
Splign All Sequence Analysis Resources…
MeSH Terms, Substances, Grant Support
Taxonomy
Viral regulatory region effects on vertical
Publication Types:
Taxonomy Taxonomy Browser Taxonomy Common Tree All Taxonomy Resources… transmission of polyomavirus SV40 [Virology.
in 2009]
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All How To Chemicals & Bioassays DNA & RNA Data & Software Domains & Structures Genes & Expression GeneticsCited
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Child, Preschool
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Humans Evidence of SV40 infections in hospitalized
children. PubMed
Infant
Kidney Transplantation High incidence of SV40-like sequences
detection in tumour and peripheral blood c...
PubMed
Male
Papillomavirus Infections/diagnosis Expression of the simian virus 40 large
Papillomavirus Infections/epidemiology* tumor antigen (Tag) and formation of Tag...
PubMed
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Domains & Structures
SV40 DNA in human osteosarcomas shows
Oncogene. 1996Cn3D Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Aug 1;13(3):527-35. sequence variation among T-antigen
[Int J Cancer.
genes.1997]
(VAST) All Domains & Structures Resources…
SV40-like sequences in human bone tumors. SV40 sequences in human osteosarcoma of
Genes & Expression
Carbone M, Rizzo P, Procopio A, Giuliano M, Pass HI, Gebhardt MC, Mangham C, Hansen M, Malkin DF, German origin. [Anticancer Res. 2000]
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene Expression Omnibus
Bushart G, Pompetti F, Picci P,
(GEO) Datasets GeneLevine AS, Bergsagel
Expression JD, Garcea
Omnibus (GEO) ProfilesRL. Different
Genome Workbench HomoloGene Map Viewer Online simian
Mendelian virus 40
Inheritance genomic
in Man (OMIM)regions and
Department of Pathology,
RefSeqGeneUniversity
UniGene of All
Chicago,
GenesIllinois 60637, USA.
& Expression Resources… sequences homologous with SV40 [Cancer.
large T2002]
Genetics & Medicine Review Evidence for and implications of SV40-
Abstract
like sequences
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance in human
in Man (OMIM) mesotheliomas
[Dev
PubMed Biol Stand.
PubMed Centraland
1998]
(PMC)
Simian virus 40 (SV40) is a monkey virus that induces ependymomas, choroid plexus tumors,
PubMed Clinical Queries RefSeqGene All Genetics & Medicine Resources…
mesotheliomas, osteosarcomas, sarcomas and true histiocytic lymphomas when injected in hamsters. Review Simian virus 40 DNA sequences in
Genomes & Maps human brain and bone tumours.
[Dev Biol Stand. 1998]
Recently, approximately 60% of human ependymomas, choroid plexus tumors and mesotheliomas were
Database of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus Map Viewer Nucleotide
reported to contain and express SV40-like sequences (N. Engl. J. Med., 1992, 36, 988-993; Oncogene,
Database PopSet ProSplign Sequence Read Archive (SRA) Sequin Splign tbl2asn Trace Archive UniSTS All Genomes & Maps Resources… See reviews...
1994, 9, 1781-1790). In this study the presence of SV40-like sequences was investigated in additional
Homology See all...
types of human tumors. Initially, 200 tumor and normal tissue DNA samples were analysed by
BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) Conserved Domain Database (CDD) Genome ProtMap HomoloGene Protein Clusters All Homology
polymerase chain reaction (PCR) with primers that amplify a 574 base pair region of SV40 large T antigen
Resources…
(Tag), which includes the Rb-pocket binding domain and the intron of Tag. PCR amplification and
Literature Cited by 19 PubMed Central
Southern blot hybridization with a probe specific for SV40 Tag revealed that 18/200 samples contained
Bookshelf E-Utilities Journals Database MeSH Database PubMed PubMed Central (PMC) PubMed Clinical Queries All Literature Resources…
articles
SV40-like sequences and, unexpectedly, 11/18 were from patients with osteosarcomas. Additional DNA
Proteins Role of SV40 integration site at chromosomal
samples from bone tumors were then analysed. In 40/126 osteosarcomas, and 14/34 other bone-related
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) Conservedinterval
Domain1q21.1
Search in
Service (CD Search)
immortalized E- Res.cells.
[Cancer
CRL2504 2009]
tumors, Tag sequences could be amplified. Sequence analysis of the DNA amplified from seven different
Utilities GenBank ProSplign Protein Protein Clusters Reference Sequence (RefSeq) All Proteins Resources…
tumors confirmed that the amplified sequences corresponded to SV40 Tag, with some demonstrating Review Osteosarcoma development and stem
Sequence Analysis cell differentiation. [Clin Orthop Relat Res. 2008]
deletions in the intron region but not in the Rb-pocket binding domain. The extent of SV40 genome
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) GenBank Genome Workbench Influenza Virus Primer-
sequences present in the DNA samples was further analysed in two osteosarcomas. PCR amplification, Review Small tumor antigen of
BLAST ProSplign Splign All Sequence Analysis Resources…
Southern blot hybridization, and sequence analysis revealed that these samples also contained polyomaviruses: role in viral[Jlife
Cell
cycle
Physiol.
and cell
2008]
Taxonomy
sequences for the carboxy-terminal domain of Tag, the viral regulatory region, and the VP1 capsid protein.
Taxonomy Taxonomy Browser Taxonomy Common Tree All Taxonomy Resources… See all...
These results indicate that SV40-like sequences are present in human bone tumors.
Training & Tutorials
NCBI Education
PMID: 8760294 [PubMed Page
- indexed NCBI Handbook NCBI Help Manual NCBI News Science Primer All Training & Tutorials Resources…
for MEDLINE]
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Types, MeSH Structural
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How To
Research Support,
All How Non-U.S.
To Chemicals Gov't DNA & RNA Data & Software Domains & Structures Genes & Expression Genetics & Medicine Genomes &
& Bioassays
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Bone Neoplasms/genetics* SV40-like sequences in human bone
tumors. PubMed
Bone Neoplasms/virology*
DNA, Neoplasm/analysis* See more...
DNA, Viral/analysis*
Genome, Viral
Humans
Molecular Sequence Data
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Influenza Virus
National Institutes of HealthPopSet Reference Sequence (RefSeq) RefSeqGene Sequence Read Archive (SRA) Sequin tbl2asn Trace Archive All DNA & RNA Resources…
Database
Data & Software
Display Settings: Abstract
Cn3D E-Utilities ProSplign Sequin Splign tbl2asn All Data & Software Resources… Send to:
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Domains & Structures
Review Cell and molecular biology of simian
Cn3D
Virology. 2004 Jan Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
5;318(1):1-9. virus 40: implications for
[J human
Natl Cancer
infections
Inst. 1999]
and
(VAST) All Domains & Structures Resources…
Simian virus 40 infection in humans and association with human diseases: Evidence against a role for SV40 in human
Genes & Expression
results and hypotheses. mesothelioma. [Cancer Res. 2005]
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene Expression Omnibus
Barbanti-Brodano G,Datasets
(GEO) Sabbioni S, Martini
Gene F, Negrini
Expression OmnibusM,(GEO)
Corallini A, Tognon
Profiles GenomeM. Natural
Workbench HomoloGene Map Viewer Online isolates
Mendelian of simian
Inheritance virus
in Man 40 from
(OMIM)
Department of Experimental
RefSeqGeneand Diagnostic
UniGene Medicine,
All Genes Section ofResources…
& Expression Microbiology, Center of Biotechnology, University of immunocompromised monkeys display [J Virol. 1998]
Ferrara, I-44100, Ferrara, Italy.
Genetics & Medicine Review The biological activities of simian virus
Abstract 40 large-T
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance antigen
in Man [Monaldi
and
(OMIM) its possible
PubMedArch Chest
PubMed oncogenic
Dis. 1998]
Central (PMC)
Simian virus 40 PubMed
(SV40) Clinical Queries RefSeqGene
is a monkey virus that wasAll Genetics
introduced & Medicine Resources…
in the human population by contaminated [SV40 as a possible cofactor in the
Genomes & Maps
poliovaccines, produced in SV40-infected monkey cells, between 1955 and 1963. Epidemiological etiopathogenesis of [G mesothelioma
Ital Med Lav and
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each tumour. TheBookshelf E-Utilities
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ABSTRACT. Simian virus 40 (SV40), a monkey polyomavirus that is believed to Email this article to a
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Current Issue
ABSTRACT
Search This Journal Simian virus 40 in human cancers☆
FULL TEXT
Articles In Press
ac b c FULL-TEXT PDF (165 KB)
Browse All Issues Regis A Vilchez, MD , Claudia A Kozinetz, PhD, MPH , Amy S Arrington , Charles
GET FULL TEXT
R Madden, PhDc , Janet S Butel, PhDc
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Info for Advertisers control groups in some reports have made it difficult to assess their reliability. BOOKMARK ARTICLE
RSS
Methods
Studies were included in this analysis if they met the following criteria: original studies
of patients with primary brain tumors and bone cancers, malignant mesothelioma, or
non-Hodgkin’s lymphoma; the investigation of SV40 was performed on primary cancer
specimens; the analysis included a control group; and the same technique was used
for cases and controls. Included reports were published from 1975 to 2002.
Results
More periodicals:
Thirteen studies fulfilled the criteria for the investigation of primary brain cancers (661
FIND A PERIODICAL
tumors and 482 control samples). Specimens from patients with brain tumors were
FIND A PORTAL almost four times more likely to have evidence of SV40 infection than were those from
GO TO PRODUCT CATALOG controls (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 2.6 to 5.8). The
association was even stronger for mesothelioma (OR = 17; 95% CI: 10 to 28; based on
15 studies with 528 mesothelioma samples and 468 control samples) and for bone
cancer (OR = 25; 95% CI: 6.8 to 88; based on four studies with 303 cancers and 121
control samples). SV40 DNA was also more frequent in samples from patients with
non-Hodgkin’s lymphoma (OR = 5.4; 95% CI: 3.1 to 9.3; based on three studies with
301 cases and 578 control samples) than from controls.
Conclusion
These results establish that SV40 is associated significantly with brain tumors, bone
cancers, malignant mesothelioma, and non-Hodgkin’s lymphoma. Studies are needed
to assess current prevalence of SV40 infections.
Requests for reprints should be addressed to Regis A. Vilchez, MD, Department of Medicine, Section of Infectious Diseases, Baylor
College of Medicine, BCM 286, Room N1319, One Baylor Plaza, Houston, Texas 77030, USA
☆
This study was supported in part by the Baylor Center for AIDS Research Core Support Grant AI36211 from the
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland. Dr. Vilchez is the recipient of the 2001
Junior Faculty Development Award from GlaxoSmithKline, Generated by www.PDFonFly.com
Philadelphia, at 12/10/2010
Pennsylvania, and the 2002 11:07:20 AM
Translational
URL: http://www.amjmed.com/article/S0002-9343(03)00087-1/abstract
Research Award from the Leukemia & Lymphoma Society, White Plains, New York. The funding sources had no
role in study design; the collection, analysis, or interpretation of data; and the preparation, review, or approval of
the manuscript.
PII: S0002-9343(03)00087-1
doi:10.1016/S0002-9343(03)00087-1
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Mar 24.
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A two-phased population epidemiological study of the safety of thimerosal-
Genes & Expression Neurodevelopmental disorders following
containing vaccines: a follow-up analysis.
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene
thimerosal-containing Expression
childhood Omnibus
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Geier DA, Geier MR. Datasets Gene Expression Omnibus (GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian Inheritance in Man (OMIM)
(GEO)
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(OMIM) PubMedofPubMed
thimerosal on(PMC)
Central
BACKGROUND: Thimerosal is an ethylmercury-containing preservative in vaccines. Toxicokinetic studies neurodevelopmental
[J Toxicol
disorders
Environ reported
Health A. 2006]
PubMed Clinical Queries RefSeqGene All Genetics & Medicine Resources…
have shown children received doses of mercury from thimerosal-containing vaccines (TCVs) that were in
Genomes & Maps Review Thimerosal-containing vaccines and
excess of safety guidelines. Previously, an ecological study showing a significant association between autistic
Database of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus Map spectrum disorder: a critical
Viewer Nucleotide [Pediatrics.
review 2004]
of
TCVs and neurodevelopmental disorders (NDs) in the US was published in this journal.
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Review &An Maps Resources…
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MATERIAL/METHODS:
Homology A two phased population-based epidemiological study was undertaken. Phase one childhood vaccines. [Pediatrics. 2001]
evaluated reported
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Resources…
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Literature administered from 1997 through 2001. Phase two evaluated the automated Vaccine Safety See all...
Datalink (VSD)Bookshelf
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MeSH TCVs at
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Taxonomy Taxonomy Browser Taxonomy Common Tree All Taxonomy Resources…
CONCLUSIONS: This study showed that exposure to mercury from TCVs administered in the US was a
Training & Tutorials
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Thimerosal
Effective Date: 22-Dec-1999
Eli Lilly and Company
Material Safety Data Sheet
Section 1 - Chemical Product and Company
Manufacturer's Emergency Phone:
Manufacturer:
1-317-276-2000
Eli Lilly and Company
CHEMTREC:
Lilly Corporate Center
1-800-424-9300 (North America)
Indianapolis, IN 46285
1-703-527-3887 (International)
Mercury - (Alkyl compounds, as Hg) PEL 0.01 mg/m3 TWA, 0.4 mg/m3 ceiling. (Aryl compounds, as
Hg) TLV 0.1 mg/m3 TWA (skin). BEI 35 micrograms total inorganic mercury per gram of creatinine
sampled in urine before the shift. BEI 15 micrograms of total inorganic mercury per liter of blood
sampled at the end of shift at the end of workweek.
UK- (Alkyl compounds, as Hg) Exposure Standard 0.01 mg/m3 TWA, 0.03 mg/m3 STEL (skin).
Ireland - (Alkyl compounds, as Hg) Occupational Exposure Limit 0.01 mg/m3 TWA, 0.03 mg/m3
15-minute STEL (skin).
Thimerosal
France - (Alkyl compounds as Hg) Occupational Exposure Limits 0.01 mg/m3 (VME) TWA (skin).
Germany - (Organic mercury compounds, as Hg) TRGS 900 Limit Value 0.01 mg/m3 TWA, 15-minute
limit not to exceed 4 times MAK (skin).
Emergency Overview
Special
R = Reproductive
A = Allergen
Emergency Overview Effective Date: 08-Dec-1999
Primary Physical and Health Hazards: Skin Permeable. Toxic. Mutagen. Irritant (eyes).
Allergen. Nervous System and Reproductive Effects.
Caution Statement: Thimerosal may enter the body through the skin, is toxic, alters genetic material,
may be irritating to the eyes, and causes allergic reactions. Effects of exposure may include numbness
of extremities, fetal changes, decreased offspring survival, and lung tissue changes.
Under normal use and handling conditions, no protective equipment is required. The following is
recommended for a production setting:
Respiratory Protection: Use an approved HEPA-filtered or supplied-air respirator.
Eye Protection: Chemical goggles and/or face shield.
Thimerosal
Chronic Exposure
Thimerosol is a mercuric compound. Toxicity data for thimerosal and mercury are presented.
Target Organ Effects: Thimerosal - Kidney effects (tubule necrosis), lung effects (tissue changes).
Mercury - Nervous system effects (insomnia, tremor, anorexia, weakness, headache), liver effects
(jaundice, digestive effects (hypermotility, diarrhea).
Other Effects: Thimerosal - Decreased weight gain.
Reproduction: Thimerosal - Decreased offspring survival.
Mercury - Changes in sperm production, decreased offspring survival, and offspring nervous system
effects including mild to severe mental retardation and motor coordination impairment.
Sensitization: No applicable information found.
Mutagenicity: Thimerosal - Mutagenic in mammalian cells. Not mutagenic in bacterial cells.
ICAO/IATA:
Proper Shipping Name: Mercury compound, solid, n.o.s. (Thimerosal)
UN/NA: UN2025
Hazard Class: 6.1
Packing Group: III
IMO:
Proper Shipping Name: Mercury compound, solid, n.o.s. (Thimerosal)
UN/NA: UN2025
Hazard Class: 6.1
Packing Group: III
Additional Information: Label: 6.1
U.S. Regulations
Thimerosal
TSCA - Yes
CERCLA - Name on list is mercury compounds.
SARA 302 - Not on this list
SARA 313 - Name on list is mercury compounds. De minimis = 1%
OSHA Substance Specific - No
California Proposition 65 (Cancer/Reproductive) - Name on developmental list is mercury and mercury
compounds.
EU Regulations
EC Classification
T+ (Very Toxic)
N (Dangerous for the Environment)
Risk Phrases
R 26/27/28 - Very toxic by inhalation, in contact with skin and if swallowed.
R 33 - Danger of cumulative effects.
R 50/53 - Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic
environment.
Safety Phrases
S 13 - Keep away from food, drink and animal feedingstuffs.
S 28 - After contact with skin, wash immediately.
S 36 - Wear suitable protective clothing.
Thimerosal
S 45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label where
possible).
S 60 - This material and its container must be disposed of as hazardous waste.
S 61 - Avoid release to the environment. Refer to special instructions/Safety data sheets.
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Medicine BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) E-Utilities GenBank Genome Workbench ClearNucleotide
Influenza Virus
National Institutes of HealthPopSet Reference Sequence (RefSeq) RefSeqGene Sequence Read Archive (SRA) Sequin tbl2asn Trace Archive All DNA & RNA Resources…
Database
Data & Software
Display Settings: Abstract
Cn3D E-Utilities ProSplign Sequin Splign tbl2asn All Data & Software Resources… Send to:
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Domains & Structures
Review Ocular sensitivity to thimerosal: a
Cn3D
Dermatol Clin. 1990 Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
Jan;8(1):161-4. problem with hepatitis B vaccine?
[South Med J. 1990]
(VAST) All Domains & Structures Resources…
Reactions to thimerosal in hepatitis B vaccines. Asthma and urticaria after hepatitis B
Genes & Expression
Rietschel RL, Adams RM. vaccination. [West J Med. 1987]
BioSystems Database of Genotypes and Phenotypes (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database Gene Expression Omnibus
Department of Dermatology, Ochsner
(GEO) Datasets GeneClinic, New Orleans,
Expression OmnibusLouisiana. Thiomersal
(GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelianallergy andinvaccination
Inheritance Man (OMIM) reactions.
RefSeqGene UniGene All Genes & Expression Resources… [Contact Dermatitis. 1988]
Abstract
Genetics & Medicine Hypersensitivity to thiomersal in hepatitis B
Hypersensitivity to thimerosal in vaccines has been reported to induce persistent local reactions, urticarial
vaccine. in Man (OMIM) PubMed PubMed
Bookshelf Database of Genotypes and Phenotypes (dbGaP) Influenza Virus Map Viewer Online Mendelian Inheritance [Lancet.
Central1991]
(PMC)
and generalized exanthematic eruptions, and, in the case of the hepatitis B vaccine, urticaria with asthma.
PubMed Clinical Queries RefSeqGene All Genetics & Medicine Resources…
The authors describe two cases of extensive reactions, one in a patient who did not form antibodies to the Review Allergic reactions to Merthiolate
Genomes & Maps (Thimerosal). [Cutis. 1981]
principal vaccine antigen. Although not all thimerosal-sensitive patients develop adverse reactions to
Database of Genomic Structural Variation (dbVar) Genome Genome Project Genome Workbench Influenza Virus Map Viewer Nucleotide
vaccines containing this material, there is a potential risk, and the reactions can be very long lasting.
Database PopSet ProSplign Sequence Read Archive (SRA) Sequin Splign tbl2asn Trace Archive UniSTS All Genomes & Maps Resources… See reviews...
Homology
PMID: 2137393 [PubMed - indexed for MEDLINE] See all...
BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) Conserved Domain Database (CDD) Genome ProtMap HomoloGene Protein Clusters All Homology
PublicationResources…
Types, MeSH Terms, Substances
Literature Cited by 3 PubMed Central articles
Publication Types:
Bookshelf E-Utilities Journals Database MeSH Database PubMed PubMed Central (PMC) PubMed Clinical Queries All Literature Resources…
Vaccination and rheumatoid arthritis.
CaseProteins
Reports
[Ann Rheum Dis. 2002]
BioSystems BLAST (Basic Local Alignment Search Tool) BLAST (Stand-alone) BLAST Link (BLink) Conserved Domain Search Service (CD Search) E-
MeSH Terms: Utilities GenBank ProSplign Protein Protein Clusters Reference Sequence (RefSeq) All Proteins Resources… Pulmonary and cutaneous vasculitis following
hepatitis B vaccination. [Thorax. 1993]
AdultSequence Analysis
Review Workbench
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Influenza hepatitis
Virus Primer-B
Biopsy
vaccination. [CMAJ. 1992]
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Dermatitis, Contact/etiology Splign All Sequence Analysis Resources…
Taxonomy
Dermatitis, Contact/pathology
Taxonomy Taxonomy Browser Taxonomy Common Tree All Taxonomy Resources…
Ethylmercury Compounds/adverse effects*
Training & Tutorials All links from this record
Hepatitis B Vaccines
NCBI Education Page NCBI Handbook NCBI Help Manual NCBI News Science Primer All Training & Tutorials Resources…
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Submission Tool All Variation Resources…
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How To Cited in PMC
Patch
AllTests/methods
How To Chemicals & Bioassays DNA & RNA Data & Software Domains & Structures Genes & Expression Genetics & Medicine Genomes &
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Ethylmercury Compounds thimerosal-containing vaccines: a brief
PubMed
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Influenza Virus
National Institutes of HealthPopSet Reference Sequence (RefSeq) RefSeqGene Sequence Read Archive (SRA) Sequin tbl2asn Trace Archive All DNA & RNA Resources…
Database
Data & Software
Display Settings: Abstract
Cn3D E-Utilities ProSplign Sequin Splign tbl2asn All Data & Software Resources… Send to:
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Cn3D Conserved
Toxicol Appl Pharmacol. 2005 AprDomain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment Search Tool
15;204(2):109-21.
(VAST) All Domains & Structures Resources… Related citations
Immunosuppressive and autoimmune effects of thimerosal in mice.
Genes & Expression Methyl mercury-induced autoimmunity in mice.
Havarinasab S, HäggqvistDatabase
BioSystems B, BjörnofE,Genotypes
Pollard KM,
andHultman P. (dbGaP) E-Utilities GenBank Gene Gene Expression Omnibus (GEO) Database
Phenotypes [Toxicol
GeneAppl Pharmacol.
Expression 1999]
Omnibus
Department of Molecular and Clinical
(GEO) Datasets Gene Medicine, Molecular
Expression Omnibusand(GEO)
Immunological Pathology
Profiles Genome (AIR), Linköping
Workbench University,
HomoloGene MapSE-Viewer Online Mendelian Inheritance in Man (OMIM)
581 85 Linköping, Sweden. The immunosuppressive effect of
RefSeqGene UniGene All Genes & Expression Resources… methylmercury does not preclude [Toxicology.
development
2005]
Genetics & Medicine
Abstract
Dose and Hg species determine the T-helper
Bookshelf
The possible health Database
effects of theoforganic
Genotypes and Phenotypes
mercury compound (dbGaP) Influenza
thimerosal Virus Map Viewer Online Mendelian Inheritance in Man (OMIM) PubMed PubMed Central (PMC)
(ethylmercurithiosalicylate), cell activation in murine autoimmunity.
[Toxicology. 2007]
which is rapidlyPubMed Clinical to
metabolized Queries RefSeqGene
ethylmercury All Genetics
(EtHg), & Medicine
have recently been Resources…
much debated and the effect of this
Genomes & Maps Review Organic mercury compounds and
compound on the immune system is largely unknown. We therefore studied the effect of thimerosal by
autoimmunity. [Autoimmun Rev. 2005]
Database
treating A.SW (H-2s) of Genomic
mice, Structural
susceptible Variationof
to induction (dbVar) Genome Genome
autoimmunity by heavy Project Genome
metals, with Workbench
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lymph node expression of IL-2 and IL-15 mRNA was increased after 2 days, and of IL-4 and IFN-gamma
mRNA after 6 and BLAST 14 (Basic
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of splenocytes, Database T (CDD)
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as Ig-secreting cells decreased. A strong immunostimulation superseded after 30 days
Literature See all...
treatment with increase in splenic weight, number of splenocytes including T and B cells and Ig-secreting
cells, and Th2-Bookshelf
as well as E-Utilities Journals Database
Th-1-dependent serumMeSH Database PubMed
immunoglobulins. PubMed Central
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antibodies (ANoA) Clinical Queries All Literature Resources…
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targeting the 34-kDa nucleolar protein fibrillarin, and systemic immune-complex deposits developed. The
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and B10.S BLASTalso(Basic Local Alignment
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Sequence Analysis persistent changes in mu [Neurochem
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in
haplotype (t1), did not develop ANoA, linking the susceptibility to H-2. Thimerosal-treated H-2s mice
homozygous for BioSystems BLAST (Basic
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BLAST ProSplign Splign All Sequence Analysis Resources…
CD28-/-), did not develop ANoA, which showed that the autoimmune response is T-cell dependent. Using [Am J Public Health. 2008]
Taxonomy
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induction of ANoATaxonomy TaxonomyThe
by thimerosal. Browser Taxonomy
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thimerosal (EtHg) and application of different cell
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mercury occurred after 14 days treatment and was 81 microg Hg/g. EtHg made up 59% and
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inorganic mercury of the renal mercury. In NCBI Help Manual
conclusion, the NCBI
organic News Sciencecompound
mercury Primer All Training & Tutorials Resources…
thimerosal
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has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg,
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How To
due to the inorganic mercury derived from the metabolism of ethyl mercury. Related Citations
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& Medicine Genomes &
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PMID: 15808517 [PubMedLiterature
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for MEDLINE]
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GENSAT
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Substances:
Antibodies, Antinuclear
Antigens, CD80
Immunoglobulin G
Immunoglobulin Light Chains
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RNA, Messenger
Receptors, Cytokine
Interleukin-4
Thimerosal
Interferon-gamma
Research Materials:
D1Lac.Cg-Il4<tm1Cgn>/J - Jackson Laboratory JAX®Mice Database
NOD.129S2(B6)-Cd28<tm1Mak>/JbsJ - Jackson Laboratory JAX®Mice Database
NOD.Cg-Il10<tm1Cgn> Il4<tm1Cgn>/DvsJ - Jackson Laboratory JAX®Mice Database
NOD.Cg-Il10<tm1Cgn> Il4<tm1Cgn>/Dvs - Jackson Laboratory JAX®Mice Database
NOD.129P2(B6)-Il4<tm1Cgn>/DvsJ - Jackson Laboratory JAX®Mice Database
STOCK Es1<e> Foxn1<nu>/J - Jackson Laboratory JAX®Mice Database
C3.129S7(B6)-Ifng<tm1Ts>/J - Jackson Laboratory JAX®Mice Database
J:NU - Jackson Laboratory JAX®Mice Database
Miscellaneous:
Mouse Genome Informatics (MGI)
You are here: NCBI > Literature > PubMed Write to the Help Desk
Thimerosal (Merthiolate) is an ethylmercury-containing pharmaceutical compound that is 49.55% mercury and that
was developed in 1927. Thimerosal has been marketed as an antimicrobial agent in a range of products, including
topical antiseptic solutions and antiseptic ointments for treating cuts, nasal sprays, eye solutions, vaginal spermi-
cides, diaper rash treatments, and perhaps most importantly as a preservative in vaccines and other injectable bio-
logical products, including Rho(D)-immune globulin preparations, despite evidence, dating to the early 1930s,
indicating Thimerosal to be potentially hazardous to humans and ineffective as an antimicrobial agent. Despite this,
Thimerosal was not scrutinized as part of U.S. pharmaceutical products until the 1980s, when the U.S. Food and
Drug Administration finally recognized its demonstrated ineffectiveness and toxicity in topical pharmaceutical prod-
ucts, and began to eliminate it from these. Ironically, while Thimerosal was being eliminated from topicals, it was
becoming more and more ubiquitous in the recommended immunization schedule for infants and pregnant women.
Furthermore, Thimerosal continues to be administered, as part of mandated immunizations and other pharmaceuti-
cal products, in the United States and globally. The ubiquitous and largely unchecked place of Thimerosal in phar-
maceuticals, therefore, represents a medical crisis.
We thank Dr. Paul G. King for his invaluable help on the chemistry of mercurials and federal regulations, and for his general review
of this article.
This study was supported by the non-profit Institute of Chronic Illnesses (Silver Spring, MD) through a grant from the Brenen Horn-
stein Autism Research & Education (BHARE) Foundation (Elk Grove, IL).
David A. Geier has been a consultant in vaccine/biologic cases before the no-fault National Vaccine Injury Compensation Program
(NVICP) and in civil litigation. Dr. Mark Geier has been an expert witness and a consultant in vaccine/biologic cases before the no-fault
NVICP and in civil litigation.
Address correspondence to Mark R. Geier, MD, PhD, 14 Redgate Ct., Silver Spring, MD 20905, USA. E-mail: mgeier@comcast.net
575
576 D. A. GEIER ET AL.
Downloaded By: [Geier, David] At: 23:30 29 November 2007
for Disease Control and Prevention (CDC) reported, “Thimerosal (or thiomersal) has been used for
a long time as an effective preservative in some vaccines, and a number of pharmaceutical and cos-
metic products. It has both bactericidal and fungicidal properties and has effectively been applied
to prevent contamination of opened, multidose containers . . . Thimerosal has been used for >60
years in infant vaccines and in other applications and has not been associated with adverse health
effects in the general population . . . Hence there is no stringent reason to stop the use of Thimero-
sal-containing vaccines in current immunization programs worldwide. The balance of risks and ben-
efits of these vaccines is very clearly positive” (p. 954–955).
Offit and Jew (2003), reported, “However, no data exist on the capacity of low-dose, chronic
exposure to ethylmercury to harm the developing nervous system . . . Parents should be reassured
that quantities of mercury . . . contained in vaccines are likely to be harmless on the basis of expo-
sure studies in humans or experimental studies in animals” (p. 1395, p. 1399).
It appears that government regulators in many cases did not analyze the potential impact of
mercury upon the fetuses and infants who were being exposed. In fact, alarmingly, they were not
even responsible for initially calculating the cumulative amount of mercury contained in the immu-
nization schedule. This article is a historical review of the literature concerning Thimerosal and its
ethylmercury breakdown product.
These statements and conclusions by Powell and Jamieson (1931) have been cited over
many decades, and continue to this day, to be cited in defense of the questionable claims that
Thimerosal had a low potential toxicity in humans. Upon closer inspection, however, it is appar-
ent that significant information regarding the clinical trial experience with Thimerosal was not
published.
First, in their article, Powell and Jamieson (1931) failed to reveal that the subjects evaluated by
Smithburn and his colleagues (1930) had, in fact, had meningitis, and were not healthy, a revelation
that would have called into question Powell and Jamieson’s conclusions regarding the nontoxicity
of Thimerosal. It should be noted that Powell and Jamieson (1931) provided a table in which the
22 subjects injected with Thimerosal were identified. These subjects, based upon the information
provided in the table, received massive doses of mercury from intravenous administration of
Thimerosal. The table notes that approximately one-third of the patients were followed for only 1 d
after the therapy. The table failed to note, however, that most probably this follow-up period was so
short because these individuals died. The table also noted only one patient was followed for 62 d.
This maximum follow-up length of 62 d was far too short to accurately discern any chronic damage
produced by the mercury, because mercury toxicity manifests fully only several months after expo-
sure. The study was also flawed because any neurological and/or other damage observed was likely
attributed to the meningitis rather than the Thimerosal exposure. Additionally, Powell and Jamieson
(1931) specifically commented that they evaluated patients, in particular, for shock or anaphylaxis-
type immediate reactions to the administration of Thimerosal. It is important to note that these
outcomes are not typical of mercury toxicity in humans.
Second, it is also apparent that Powell and Jamieson (1931) failed to emphasize their disturbing
animal toxicity data. In fact, Powell and Jamieson (1931) had already determined that administra-
tion of low milligram doses of Thimerosal per kilogram body weight in several different animals was
acutely toxic and resulted in significant numbers of animals dying within days of exposure.
Regarding the reported conclusions reached by Powell and Jamieson (1931), it was even com-
mented that “Considering the type of patient involved, one might question these observations [the
appearance of no deleterious action] as providing adequate indication of any harmful effects of high
doses of Merthiolate in humans, in particular, more long term effects” (Subcommittee on Human
Rights and Wellness, p. 58).
Kharasch (1932) filed a new patent application in an effort to acknowledge the potential
dangers of the germicide/antiseptic he had developed. Kharasch (1932) stated in this second
patent, “I will describe my invention more specifically in connection with that one of such com-
pounds which is now in most general use. That is sodium ethyl mercuri-thiosalicylate, which is
known on the market as Merthiolate.” According to Kharasch (1932), when Thimerosal “is first
made, it is entirely bland, both to the skin and mucous membrane. However, it is found that on
standing . . . the solution loses its blandness and acquires certain burning properties; which make its
use as an antiseptic and bactericide less desirable.” In describing the chemical basis for Thimerosal’s
ability to acquire “certain burning properties,” Kharasch (1932) detailed an important discovery
regarding the decomposition products of Thimerosal. Kharasch (1932) recorded that if “such for
instance as for sodium ethyl mercuri-thiosalicylate, is allowed to stand, there is a dissociation of a
few of the molecules at the bond between the sulphur and the ethyl mercury radical, producing a
small quantity of resultant ions” and that, “However, on account of the invariable presence of oxy-
gen, and of a catalyst such as copper, the sulphur-containing ion. . .is oxidized to the di-thio com-
pound . . . The formation of the di-thio compound removes these sulphur-containing ions from the . . .
mixture . . . so that progressively more ionization of the alky mercuric sulphur compound occurs . . .
This process results in an excess of the mercuri ions such as C2H5−Hg++ —which react with the
hydroxyl ions present in the solution to form C2H5−Hg++−−OH.” Subsequently, Kharasch (1932)
went onto describe in the patent that the C2H5−Hg++−−OH breakdown product of Thimerosal
might mediate adverse reactions in humans. These observations are important because they dem-
onstrate knowledge that Thimerosal would break down, in fairly rapid order, to produce ethylmer-
cury hydroxide and thiosalicylate, and that the ethylmercury breakdown product was the one
mediating Thimerosal toxicity.
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Nonetheless, Marks et al. (1932) from the Lilly Research Laboratories reported, “Merthiolate
(sodium ethyl mercuri thiosalicylate), an organic mercurial compound, seems to fulfill the require-
ments of a satisfactory disinfectant . . . This compound has been shown to possess active germicidal
properties, maintaining its effectiveness in the presence of media most nearly resembling the
tissues, such as serum agar and white clot or fibrin agar. It is readily soluble, possesses definite pen-
etration properties, and does not precipitate serum proteins. Merthiolate has a low degree of toxicity
for animals and human beings, does not hemolyze red blood cells, and does not injure sensitive bac-
terial antigens and antibodies. It has been found to stimulate tissue cell growth and healing” (p. 443).
By the 1930s, Thimerosal was promoted for uses beyond topical antiseptic application. For
example, Jamieson and Powell (1931) described Thimerosal as an efficient preservative in biological
products.
While the applications for Thimerosal were increasing, Kharasch (1935) later applied for a third
patent for “organo-mercuri-sulfur compounds.” In this patent, Kharasch’s acknowledgment of
Thimerosal’s ineffectiveness and adverse effects in clinical practice exceeds all of his previous state-
ments: “It is the object of my invention to stabilize more effectively than has heretofore been done
certain antiseptic and bactericidal . . . compounds, which without such stabilization tend to form
disassociation products and to thereby both lose their effectiveness as antiseptic germicides and to
develop certain medicinally undesirable properties.”
In 1935, some of the first serious safety concerns were raised regarding Thimerosal. Specifically,
researchers reported a “reaction in about 50% of the dogs injected with serum containing dilutions
of Merthiolate, varying in 1 in 40000 to 1 in 5000, and we have demonstrated conclusively that
there is no connection between the lot of serum and the reaction. In other words, Merthiolate is
unsatisfactory as a preservative for serum intended for use on dogs.” They also noted, regarding the
reactions observed in dogs following administration of Thimerosal-containing serums, that “in some
instances, the reaction is extremely severe.” It was concluded, “I might say that we have tested Mer-
thiolate on humans and find that it gives a more marked . . . reaction than does phenol or tricresol”
(Subcommittee on Human Rights and Wellness, p. 34–35). Additionally, Salle and Lazarus (1935)
determined that Thimerosal was 35.3 times more toxic for embryonic cells than for the bacterial
cells that Thimerosal was supposed to kill.
Soon after this 1935 publication by Salle and Lazarus, Cummins (1937) documented in the
literature the first reports of Thimerosal-induced poisonings in animal model systems. Specifically,
he described, “two sets of 7 flasks each were treated with an amount of Merthiolate varying in dilu-
tion from 1 to 100 to 1 in 10 million of the medium in each series. . . The guinea-pigs inoculated
with 1 c.cm. of the mixtures after 24 hours all died; the first of Merthiolate poisoning” (p. 962).
Welch (1939), of the U.S. FDA, expanded the evaluation of the toxic action of potential preser-
vatives, including Thimerosal, in mammalian tissue culture experiments. Welch (1939), when com-
paring the relative toxicity of Thimerosal with other germicide compounds such as phenol or
iodine, determined that Thimerosal was, by several orders of magnitude, the most toxic compound
tested.
In addition, Welch and Hunter (1940), again of the U.S. FDA, continued their previous
research by reporting on the toxicity indices of germicides with human and guinea pig blood. The
researchers determined the toxicity indexes for each germicide tested, by comparing the highest
dilution producing inhibition in human cells or in guinea pig cells with the highest dilution that was
bactericidal for staphylococci. Their experiments showed that Thimerosal was, in fact, considerably
more toxic for human cells than bacterial cells (toxicity index=5.7). Furthermore, it was observed,
among the 10 germicides tested, that Thimerosal had the ninth worst toxicity index. With regard to
Thimerosal, the researchers concluded, “It becomes obvious then that if any antiseptic destroys the
function of the leukocyte much more readily than it kills bacteria there is little hope that it act
efficiently as a chemotherapeutic agent” (p. 136).
Kinsella (1941) described a cases series of 13 patients with bacterial endocarditis that received
Thimerosal treatment. It was observed that all patients receiving the Thimerosal treatment died, and
that following autopsy, some of the patients were determined to have died of mercury poisoning
from the Thimerosal treatment. For example, one report recorded, “Female, aged 23. Onset: Sore
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throat treated with sulfanilamide. Later fever and pain the left chest. Examination: Systolic murmur
second i.c.s left. Blood cultures: Non-hemolytic strep. 37 times 50 colonies per c.c. Clinical
Diagnosis: Subacute bacterial endocarditis pulmonic valve (congenital). Treatment: Merthiolate.
Autopsy: Healing pulmonary endarteritis—mercury poisoning” (p. 985). In light of determination
that the treatment with Thimerosal produced mercury poisoning in humans, the suggestion was
made to significantly limit Thimerosal exposure in humans due to its toxicity and potential hazards.
Despite the aforementioned concerns, however, large amounts of Thimerosal were purchased
by the United States Government, for use in the war effort, from 1941 to 1945. During this time,
the U.S. Army scrutinized the use of Thimerosal as a preservative in blood products. On 20 February
1941, the National Institutes of Health issued minimum requirements for normal human plasma,
indicating that a sufficient amount of a suitable preservative should be added to the product
(Kendrick, 1989).
In the first of several meetings of the Subcommittee on Blood Substitutes of the U.S. Army, it
was noted that the Blood Transfusion Association of New York found Thimerosal unsatisfactory as a
preservative (Kendrick, 1989). Specifically, it considered the instance from 1940 in which a large
percentage of liquid plasma containing 1:10,000 Thimerosal, which had been collected in New
York City, arrived in Britain, contaminated with viable organisms (Kendrick, 1989). At that time, a
publication that questioned Thimerosal as a “preservative” concluded:
In a recent study of protein sulfhydryl groups Hellerman, Chinard and Deitz point out that organo-
metallic compounds of the type R-Hg-X . . . form poorly dissociated protein mercaptides by combina-
tion of the organic mercurial with proteins and thiol groups. According to Fildes the formation of
such mercaptides is the basis for the bacteriostatic action of mercury. Such sulfhydryl groups are
present, however, not only in bacteria but in plasma and other proteins. Bacteriostatic action of such
organomercuric compounds in the presence of serum is therefore largely prevented by competition
of reactive groups on the serum proteins for the mercury. This presumably is the basis of the finding
that the ‘activity of a mercurial antiseptic in serum is reduced to 0.33–0.0007 percent of its activity in
saline.’ Ignoring these chemical facts can be responsible for very serious occurrences, such as the
arrival in England of plasma ‘preserved’ with 1:10,000 Merthiolate containing viable micro-
organisms . . . In our experience 1:10,000 Merthiolate has not been able to insure the sterility of
stored liquid plasma. The contaminations reported in this paper in plasma-saline mixture containing
1:10,000 Merthiolate are sufficient to be an argument against its use. The material found to be
contaminated when tested after its arrival in England is further evidence that 1:10,000 Merthiolate
cannot be considered the ideal preservative. (p. 1253)
Weighing these concerns, some of the subcommittee members argued that plasma was best
stored without any preservative at all; however, a recommendation to this effect was waived when
the subcommittee realized that commercial firms were not inclined to process plasma without a
preservative. Then, at the 3 November 1941 meeting of the subcommittee, Veldee reported on a
review of the literature, which had been delegated to Weiss and himself. He informed the subcom-
mittee that Thimerosal apparently had some bacteriostatic value and possibly some bactericidal
value. Nonetheless, Weiss was not willing to accept Thimerosal as a preservative unless a maximum
limit was set on the dosage of plasma due to toxicity concerns. He also stipulated that the symptoms
of mercurial poisoning must be published on the label of the can. The Fifth Revision of Minimum
Requirements for Liquid or Dried Plasma, 8 January 1945, stated, “There is no preservative bacteri-
cidal to all probable contaminants in concentrations not dangerously toxic in the maximum human
dose.” Subsequently, the Sixth through Ninth Revisions (15 April 1949 through 15 May 1952) pro-
hibited use of a preservative (Gibson, 1976; Kenrick, 1989).
Concurrently, Ellis (1943) published an article on the possible danger of using Thimerosal in
ophthalmic ointments. In his report evaluating this use of Thimerosal, Ellis (1943) observed,
“Merthiolate is capable of causing an inflammation of the mucous membrane in patients,” (p. 266)
and made a very strong recommendation, based upon his clinical experience and that of several
other physicians, considering the adverse effects of Thimerosal use. He disputed the acceptance of
Thimerosal in medicine. Referencing the potential ability of Thimerosal to produce permanent
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damage in the patient during clinical use, Ellis proposed, “it may be advisable to withdraw this prod-
uct from the market” (p. 266). It is important to note that this recommendation was made more than
6 decades ago, after Thimerosal had been on the market for only approximately 10 years.
Ellis (1947) continued his work on Thimerosal, and subsequently reported on an even larger
case series of patients experiencing adverse reactions following application of Thimerosal. Based
upon his further clinical experiences, as well as those of his medical colleagues, Ellis (1947) once
again strongly rebuked those advocating the continued use of Thimerosal in clinical medicine, stat-
ing, “it may be dangerous to inject a serum containing Merthiolate into a patient” (p. 213).
Subsequently, Cogswell and Shown (1948) reported, “We have had recently the occasion to
observe a patient with a severe reaction to tincture of Merthiolate . . . which manifested a local and
general reaction” (p. 42). The authors also stated, “The patient was warned never again to use Mer-
thiolate solutions” (p. 43). Placing the experience of this patient in a larger perspective, the authors
stated, “Many severe reactions have been reported following the use of mercurial ointments and a
lesser number due to antiseptics containing mercurials” (p. 42). Cogswell and Shown (1948) even
dared to condemn their colleagues for their myopia in wrongly evaluating the therapeutic effects of
Thimerosal in the clinical setting:
When a reaction does result, it is important that it be recognized and the application of the drug ceased.
Many of the reported cases are similar in that in spite of a reaction to Merthiolate, its use was being con-
tinued as a means of therapy to alleviate the result of the application. Hollander reported on a nurse
who had severe dermatitis venenata for over two years due to continuous self medication with tincture
of Merthiolate. Improvement was noted on discontinuing its use . . . reaction should be recognized to
prevent further applications of the drug which would exacerbate or accentuate the illness. (p. 43)
Morton et al. (1948), under a grant from the Council on Pharmacy and Chemistry of the
American Medical Association, published an article on the bacteriostatic and bactericidal actions of
some mercurial compounds on hemolytic streptococci. They reported:
The label on a bottle of ‘Solution Merthiolate, 1:1,000, Stainless’ purchased as recently as June 1947
states that it is ‘a stable, stainless, organic mercury compound of high germicidal value, particular in
serum and other protein media.’ It is not highly germicidal and especially does not possess high ger-
micidal value in the presence of serum and other protein mediums. The loss of antibacterial activity
of mercurials in the presence of serum proves their incompatibility with serum . . . The comparative
in vitro studies on mercurochrome, metaphen and Merthiolate on embryonic tissue cells and bacterial
cells by Salle and Lazarus cannot be ignored. These investigators found that metaphen, Merthiolate and
mercurochrome were 12, 35 and 262 times respectively more toxic for embryonic tissue cells than
for Staphylococcus aureus. Nye and Welch also found the same three mercurial compounds more
toxic for leukocytes than for bacterial cells. Not only is there direct toxic action of the mercurial com-
pounds on the cellular and humoral components of the animal body, but there is also the possibility
of sensitization. (p. 41)
Engley (1950) of the Biological Department, Chemical Corps, Camp Detrick, published an evalua-
tion of mercurial compounds as antiseptics and judged mercurials to be inadequate as antiseptics:
Mercurial compounds have not enjoyed a peaceful career as antibacterial chemicals since their pop-
ularization as germicides over sixty years ago (Kock, 1891) . . . During the ensuing years, other work-
ers, using various techniques, have also shown that the antibacterial activity of mercurials is only
slowly bactericidal and mainly bacteriostatic. This bacteriostasis is even nullified by the presence of
many types of sulfur-containing compounds, including sulfides (Geppert, 1889), (Hunt, 1937),
thioglycollate (Marshall, Gunnison, and Luxen, 1941), body fluids such as plasma (Johnson and
Meleney, 1942), and other organic matter (Green and Birkeland, 1944). (p. 197)
Furthermore, and of even greater concern, was Engley’s conclusion that mercurials, such as Thime-
rosal, “are ineffective in vivo and may be more toxic for tissue cells than bacterial cells, as shown in
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mice (Nungester and Kempf, 1942) (Saber, 1942) (Spaulding and Bondi, 1947), tissue culture (Salle
and Catlin, 1947), and embryonic eggs (Witlin, 1942) (Green and Birkeland, 1944), and with leuco-
cytes (Welch and Hunter, 1940)” (p. 197).
Davisson et al. (1956) from the Lilly Research Laboratories reported on a molecular mechanism
for Thimerosal induced cellular toxicity. Specifically, they described that the cellular toxicity of
Thimerosal was the result of “partial ionization of the compound to go give a low but effective level
of ethyl mercuri ion (C2H5Hg+), which blocks enzymatic processes by combining with sulfhydryl
groups on the enzymes” (p. 8).
Subsequently, Engley (1956) presented a paper to the 42nd midyear meeting of the Chemical
Specialties Manufacturer’s Association in Chicago. Engley overtly questioned the acceptance of
Thimerosal as a preservative in vaccines and other pharmaceuticals products by stating:
The use of mercurials as preservatives in vaccines and antisera is of considerable interest. These
chemicals are added to protect against the introduction of organisms in multi-use containers in par-
ticular. We have always wondered about their efficacy in that both vaccines and antisera contain
reactive groups to tie up these compounds. In a series of continuing experiments over the past sev-
eral years we have begun to evaluate various preservatives in serum and vaccines under conditions
of use. Employing stock vaccines and serum with and without preservatives and stored at varying
lengths of time a contaminating dose of representative sporeformer (Bacillus subtilis) in the spore
stage gram negative rod (E. coli) and gram positive coccus (S. aureus) were added. While the mercu-
rial preservatives had good activity on initial addition, after storage of three, six or more months
decreasingly less to negligible residual activity appeared to be left, indicating that the chemical was
tied up by the protein of the biological or otherwise inactivated. A check on a series of over one
thousand bottles of various biologicals from clinics obtained after use revealed that up to five percent
contained micro-organisms. This would suggest that once these biologicals are in the hands of users a
problem still exists. Regarding preservatives, one of the real problems existing in hospitals and clinics
is the need for good preservatives in the routine eye dilators and nasal preparations of the deconges-
tant type. Routine checks of these indicate a high percentage of contaminated solutions. In one
instance we had direct evidence of upper respiratory cross-infection from the use of a common nasal
dropper preparation in a clinic. (p. 205, 223)
Engley (1956) then gave an evaluation of the relative toxicity of mercurials, such as Thimerosal,
by stating:
The toxicity of chemicals used as drugs on or in the body has been of considerable interest since man
first began exposing himself to various chemicals many years ago. Unfortunately there have not been
good techniques for toxicity determinations of certain types of chemicals which might be really indic-
ative of toxicity for humans . . . Graph 15 compares mercurial compounds and shows how they fit in
with other compounds in toxicity . . . Mercurochrome appears to be the least toxic ranging down
through Merthiolate . . . One point should be made here. Bichloride of mercury has always been
pointed out as an extremely toxic mercurial and the organic mercurials were supposed to be much
less toxic but according to these data we find bichloride right in the middle of the organic mercurials
in regard to cell toxicity . . . mercurial antiseptics proved to be more toxic than the antibiotics in
common usage. (p. 223–225)
Finally, it should be noted, with respect to the toxicity experiments undertaken by Engley (1956),
that he determined Thimerosal was significantly toxic to human tissue culture cells at a
concentration of 10 ppb.
malformation of the seedlings of corn and other cereals” (p. 95). He subsequently went onto
describe based upon his series of experiments:
In corn seedlings grown from nontreated seed, the leaf primordial and apical meristem of the
coleoptile have the structure characteristic of meristematic tissues. The cells are small, polygonal,
compactly arranged, and of uniform size. These cells are strictly uninucleate . . . Seedlings from treated
seeds exhibit varying degrees of distortion of cells, tissues and organs in proportion to the severity of
the gross external symptoms . . . The formation of new cells and new leaf primordial cases, the exist-
ing cells continuing their excessive irregular enlargement . . . The cells of the hypertrophied tissues of
corn seedlings were found to be multinucleate. The number of nuclei in a cell varies from one to
more than 10 . . . The ‘giant nuclei’ are clearly polyploid. (p. 95)
One of the earliest studies to evaluate the effects of ethylmercury on animals was published in
1950 (Trakhtenberg, 1950). In this study, the toxicity of the ethylmercury compounds was exam-
ined in mice. White mice were exposed to ethylmercury compound vapor, and the animals were
subsequently observed for clinical signs of toxicity and mortality. Those studies found:
Acute exposure to the organic mercury compounds caused symptoms indicative of serious respira-
tory and nervous system disruption: labored respiration, cyanosis of the nose, tail and ears, and hind
limb paralysis. All animals died 6 to 15 hours after exposure . . . In the chronic study, the central ner-
vous system was the main site of involvement. Mice exposed to the organic compounds showed a
hind limb paralysis that gradually spread to the front limbs. Death occurred by day 38. (p. 13–17)
On the October’ Collective Farm in Tatishchevo District, 383 of 414 swine of various ages were
affected during August (1967), the acute period; 121 died and 145 in the agonal state had to be
slaughtered. By November, another 44 animals had died. On the Fedorov’ State Farm in Marx
District, 211 of 444 swine were affected . . . The first signs of poisoning appeared in suckling pigs and
fatling gilts 20 to 25 d after beginning feeding on the treated grain; in sows, the signs appeared in 30
to 40 d. At first, the animals refused food and water and became restless. There was some nasal
mucous secretion. Then weakness in the hind limbs appeared, with different types of movement
coordination disorder. Some animals showed spinal involvement. Signs of neural disorders were
quite clear, including muscular tremors, convulsional jerking of the extremities and titanic contrac-
tions of the pelvic musculature. As the conditions worsened, the animals lay on their stomachs or
sides, developing varying degrees of paralysis with loss of pain sensation, rapid breathing, etc. The
younger swine almost all died within 3 to 6 d after the symptoms started; the sows’ condition persisted
longer until death (6 to 11 d) and 40 to 45% of the affected animals died. In some instances, the swine
suffered the above symptoms, including partial or complete loss of vision, for 2 to 3 months. The
autopsy findings were initially the same in all the animals, the most constant changes being noted in
the intestines. The intestinal mucous membrane was covered with dryish, dirty yellow or brownish-
green deposits connected to the underlying tissue . . . The fact of a delay in the appearance of symp-
toms following Granosan must be taken into account in diagnosing organomercury poisonings. The
clinical symptoms and pathological-anatomical changes in mass poisonings of swine with Granosan
to a great extent recall the course of infectious diseases . . . so that mercury poisoning should be
eliminated during a differential diagnosis. (Birbin et al., 1968, p. 60–61)
Additionally, heavy losses were reported to have occurred in a poultry-yard due to feed treated
with ethylmercury (Tishkov et al., 1968). The clinical symptoms observed in chickens on the last
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day before death were depression, spasm, paralysis of the limbs, swollen heads, and elevated
temperature. It was observed that mercury residues were detectable in the kidneys, liver, muscles,
skin, brains, lungs, hearts, ovaries, and eggs, and depending on the duration and intensity of the
exposure, mercury residues could be detected in the chicken tissues for as long as 120 d after the
poisoning.
Oharazawa (1968) published a study examining the ability of ethylmercury exposure during
pregnancy to induce fetal damage in mice. He observed that injection of ethylmercury during
pregnancy significantly reduced the weights of developing fetuses in utero and produced significant
increases in fetal malformations and the incidence of unstable chromosomes characterized as
polyploidy, chromatid gaps, or fragmented, in comparison to unexposed controls.
By 1971, researchers had become more sophisticated, evaluating the effects of ethylmercury on
several successive generations of offspring. Goncharuk (1971) administered an ethylmercury
compound to albino rats, and subsequently, these animals were mated. Investigations were made
of the sexual cycle, and the viability, physical development, and fertility of the progeny of the first
and second generations. It was observed that females that had been previously exposed to the
ethylmercury compound became pregnant only on the fourth or fifth occasion when they were
placed with males when in estrus, whereas nonexposed control females became impregnated on
the first or second mating. The number of offspring per litter was significantly smaller in the animals
treated with the ethylmercury compound than in controls. It was also observed that young rats from
mothers that had been previously exposed to the ethylmercury compound died significantly more
frequently than controls. Observations of the first-generation progeny revealed a lag in weight
growth in comparison to controls, especially during the first and second months of extrauterine life.
In addition, the first-generation progeny had birth weights that exceeded those of the control group,
and studies of skeletal ossification in the young rats revealed a large number of cases with retarda-
tion of the appearance and development of ossification centers in bones of the fore and hind paws.
Studies of the organs and tissues of the first generation progeny revealed mercury in the stomach
and intestine at birth and in the first week of life, apparently on account of the entry of mercury
through the placental barrier and by way of their mother’s milk. Subsequently, it was noted that the
first-generation progeny of mothers that had been previously exposed to the ethylmercury com-
pound had significantly reduced fertility in comparison to controls. The second generation progeny
had low viability, lagged in their weight growth, and were retarded with respect to ossification in
several cases. Finally, it was then observed when mating the second generation progeny that there
was a significant decrease in fertility in comparison to the control group.
A later study on pheasants by the Bureau of Sport Fisheries and Wildlife, Patuxent Wildlife
Research Center, concluded that ethylmercury compound exposure at a level equivalent to 12.5
ppm mercury was lethal to adult animals and at 4.2 ppm mercury impaired reproduction in the
species (Spann et al., 1972). These researchers also reported:
Mukai (1972), with a grant from the U.S. National Institutes of Health, reported on an animal
model of ethylmercury-cysteine-induced encephalopathy using mice. Mukai (1972) observed:
Mice injected intraperitoneally with EMC (Ethyl Mercuri-S-Cysteine) labeled with tritium showed the
typical neurologic symptoms of mercury poisoning. Administration of EMC in a concentration of
0.3 mg/0.5 mL saline per day for at least eight days was a prerequisite for significant accretion of EMC
in the central nervous system. The extent and distribution of cell damage were highly predictable,
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and selective necrosis of the small granular neurons in the koniocrotex, and neostriatum was a
constant finding. Autoradiographic study has suggested that the astroglial cell compartment plays a
role in conveying the mercury complex into neurons. (p. 102)
Subsequent research by Tryphonas and Nielsen (1973), which was sponsored by the Medical
Research Council of Canada, not only showed that ethylmercury produced a consistent and pre-
dictable pattern of encephalopathy, but also that it induced severe developmental toxicity at very
low doses. It was described:
Ethylmercuric chloride (EMC) w(as) used to produce chronic alkylmercurial poisoning in young pigs.
A dosage of 0.19 to 0.76 mg. of Hg/kg. of body weight per day was used . . . The resulting toxicosis
was primarily related to the nervous system, in which neuronal necrosis followed by secondary
gliosis, capillary endothelial proliferation, and additional neuronal necrosis due to developing degen-
erative arteriopathy in the blood vessels supplying injured gray matter were seen. In other systems,
degeneration of hepatocytes and renal tubular cells were commonly occurring lesions in pigs . . .
edema of the mescolon, necrosis of the epithelium, and degenerative arteriopathy in the submucosa
were seen most consistently in the esophagus and large intestine of pigs . . . The results proved that . . .
EMC, if fed at low concentrations . . . were highly poisonous . . . Finally, since the alkylmercurial
moiety is absorbed and stored as such for considerable lengths of time in . . . cells, the public health
implications . . . cannot be overlooked. (p. 379, 391)
Furthermore, Wright et al. (1973) from the U.S. Department of Agriculture evaluated the toxi-
cokinetics of mercury in the tissues of cattle and sheep administered ethylmercury. These researchers
showed that significant levels of mercury were detectable in multiple organs including the blood,
kidney, liver, and muscle for significant lengths of time following exposure to ethylmercury.
Additionally, these researchers found that mercury crossed the blood-brain barrier, and resulted in
significant levels of mercury in the brain for more than 20 wk (>140 d) following administration of
the last dose of this ethlymercury compound. In another study that examined swine administered
ethylmercury, it was found that significant levels of mercury were detectable for more than 8 mo
(>240 d) following administration of the last dose of the ethylmercury (Saley, 1970).
Yonaha et al. (1975), from the National Institute of Hygienic Sciences, also evaluated the
uptake, retention, and toxicity of ethylmercury in several organs, when administered to mice. These
researchers reported:
Ethylmercury chloride was highly incorporated into the brain . . . It may be presumed that manifesta-
tions of symptoms after exposure of organic mercury compounds is not merely related to mercury
levels and not always in need of organic forms in the brain . . . The clinical signs and pathological
findings caused by methylmercury compounds in animal experiments were known to be similar to
Minamata disease manifested in human. At the same time, the symptoms in cats, calves, and mice
poisoned by ethylmercury compounds were similar to those in methylmercury compounds. Further,
as reported by Sebe, et al., alkylmercury compounds having short carbon chains (C1-C3) bring about
the specific neurotoxicity and the signs of poisoning in rats. (p. 1718)
Poisoning by a fungicide used for seed-borne diseases of cereals, ethyl mercury p-toluene sulfona-
nilide (Granoson M, Dupont) is described. It affected a large number of farmers and their families
who used the dressed seed in the preparation of home-made bread. Many systems were involved,
including the kidneys, the gastrointestinal tract, the skin, the heart, and the muscles, but involve-
ment of the nervous system was the most constant with disturbance of speech, cerebellar ataxia,
and spasticity. Mental abnormalities were occasionally observed . . . In 1956 many cases of mercury
poisoning were observed in the North of Iraq, and more than 100 cases were admitted to Mosul
Hospital with 14 deaths. In 1960, many farmers from the central part of Iraq were affected and 221
patients were admitted to one hospital in Baghdad. Other patients went to other hospitals. (Jalili &
Abbasi, 1961, p. 303)
Later, a significant series of patients in Russia was observed to suffer from serious toxic out-
comes following ingestion of ethylmercury and occupational exposure to ethylmercury (Shustov &
Syganova, 1970; Nizov & Shestakov, 1971). Early signs of exposure included general weakness,
pains, tachycardia, and headache. Thereafter, it was observed that appetite decreased until, at last,
food was refused; there was also nausea, liquid stool, disordered sleep, decreased memory, and
pain in the extremities. Most of the patients recovered, but death was observed following exposure
in some of the patients. Such case studies clearly demonstrate the severe toxicity of this compound
to humans and document its effect on multiple systems of the human body due to acute exposure.
Not only acute exposure, however, but also low-dose exposure has produced significant
impairment in human beings, a fact documented by Mukhtarova (1977). Mukhtarova (1977) exam-
ined the late after-effects upon the nervous system following chronic low-dose exposure to ethylm-
ercury. The researcher reported:
Paramount in the historical scientific record of exposures to ethylmercury compounds are the
first reports of human fetal poisonings. Bakulina (1968) described in a study on a human fetal
poisoning:
Granosan (ethylmercury chloride) is capable of passing through the placental barrier and penetrating
into the fetus, causing in the organs of the latter grave pathological changes. The permeability of the
placental barrier for organic mercury compounds finds its confirmation in the presence of mercury in
the placenta and organs of the fetus . . . Breast feeding was found to be conducive to accumulation
of mercury in the organism of newborns, since the mothers’ milk, as a rule, disclosed the presence of
this element. A very important point was that fetal intoxication was possible for as long as 3–4 years
after the mother poisoned. (p. 63)
By the early 1970s, researchers developed an overall clinical picture of ethylmercury poisoning
in fetuses following large-scale ethylmercury poisoning episodes (Mal’tsev, 1972; Ramanauskayte &
Baublis 1973).
Ramanauskayte and Baublis (1973) stated that, after exposure to ethylmercury-treated seeds:
Intrauterine poisoning in infants was observed(.) . . . (C)hildren on the whole are more susceptible to
mercury than adults(.) . . . Serious functional disorders of the central nervous system, hydrocephalus,
cerebral paralysis, and spasms were observed in infants. Toxic encephalomyeloradiculoneuritis with
prevalence of the syndromes of lesions of the cerebral cortex, brain stem, cerebellum, myelitis, periph-
eral neurites, lesions of the motor centers, of the pyramidal tracts, and encephalitis with irregular alpha-
rhythm were observed . . . Epilepsy lasting up to 2 years was observed in 10% of all cases. Prevalence of
vegetoneurotic syndromes, tachycardia, bradycardia, arrhythmia, acrocyanosis, liability of the arterial
pressure, and reduction of the blood cholinesterase activity were found in older children with chronic
poisoning. The lesions of the liver, kidney, heart and gastrointestinal tract were much less pronounced
than those of the central nervous system. Sodium thiosulfate, glutamic acid, vitamin B and C com-
plexes, glucose, and diuresis are essential for detoxification. (Ramanauskayte & Baublis, 1973, p. 56–60)
examined at this conference was the metabolic fate of ethylmercury salts, with a specific emphasis
on Thimerosal, in humans. That committee reported:
The toxic nature of ethylmercury has been considered to be fairly similar to that of methylmercury
salts. In the recommendations of the international committee on Maximum Allowable Concentration
for mercury and its compounds, ethylmercury was grouped with methylmercury. Reports on human
intoxication with ethylmercury salts have usually reported symptoms similar to those of methylmer-
cury, which is accentuated by the typical neurological symptoms, although there have been a few
reports that noted slightly different symptoms from the typical features of methylmercury poisoning.
In acute experiments on animals, ethylmercury has an LD50 similar to that of methylmercury salts and
a high neurotoxicity similar to that of methylmercury. (p. 209–210)
By using methods for estimating the inorganic and total mercury content of biological specimens, the
metabolism of ethylmercury salts was studied in man and animals. The [carbon–mercury bond] C−Hg of
ethylmercury salts was able to break fairly rapidly and to a great extent in men, who were patients and
were transfused with a commercial product of human plasma containing 0.01% (Thimerosal) sodium
ethylmercurithiosalicylate, and also in mice injected subcutaneously or intravenously with ethylmercu-
rithiosalicylate solution. The increasing level of inorganic mercury and its percentage to total mercury
content in the brain were quite distinguishable with post-injection time in mice, which resulted in longer
biological half-time of total mercury than that reported for methylmercury injection. (p. 209)
Itoi and his colleagues (1972) conducted a series of experiments to evaluate the reproductive
toxicity of Thimerosal in rabbits. They observed that injection of increasing doses of Thimerosal
(from 0.02 to 0.2% solutions) into pregnant rabbits resulted in significantly increased numbers of
dead fetuses (up to 18% of fetuses died following exposure) and increased fetal congenital anoma-
lies (up to 9.1% of fetuses developed congenital anomalies following exposure) in comparison to
rabbits injected with physiological saline.
Axton (1972) also reported on a series of 6 patients (4 children and 2 adults), 5 of whom died
following injection with chloramphenicol preserved with abnormally high levels of Thimerosal. He
reported that there was something wrong with the chloramphenicol injections. This problem was
first suspected on 23 October 1969, following the appearance of skin necrosis over the injection
sites in 4 children, and the drug was withdrawn from the pediatric wards. Preliminary investigation
of the vials used, for pH, concentration of chloramphenicol, and bacteriology, revealed no abnor-
mality. Heavy metal contamination was not considered at this stage.
Case 1 was the first to die (6 November 1969), and on the morning of his death, the combina-
tion of albuminuria and glycosuria with mental symptoms suggested poisoning, possibly by a heavy
metal. The suspicion was supported by the necropsy findings later in the day (large swollen
kidneys). Reference was again made to the local manufacturers of the chloramphenicol, and it was
discovered that 0.51 kg of Thimerosal was used in the preparation of one thousand 1-g vials of
chloramphenicol. The correct amount should have been 0.51 g. The amount of Thimerosal in each
vial was 1000 times too much.
The FDA undertook a comprehensive review of the safety and effectiveness of over-the-counter
(OTC) medicines in 1974. As one facet of this review, a panel of experts was assembled to review
the safety and efficacy of OTC drugs containing mercury. The Advisory Review Panel on OTC
Miscellaneous External Drug Products began its slow-paced review in 1975.
Independently of the FDA’s review, Gasset et al. (1975), under a grant from the US National
Institutes of Health, examined mercury distribution following administration of Thimerosal to
animals. They stated, “A comparison of topical and subcutaneous administration of Thimerosal to
rabbits shows that a substantial concentration of mercury was present in blood and tissues of the
treated animals and their offspring. Thimerosal was found to cross the blood-brain and placenta
barriers” (p. 52). These researchers also determined that administration of Thimerosal caused a
dose-dependent significant increase in fetal mortality.
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Blair et al. (1975) also examined mercury distribution and form following administration of
Thimerosal to animals. In 1975, the authors reported that squirrel monkeys were dosed intranasally
with saline or Thiomersal (sodium ethylmercurithiosalicylate, 0.002% w/v) daily for 6 mo. The total
amounts of Thiomersal given during the 6 month period were 418 μg (low-dose group) and 2280
μg (high-dose group). This was equivalent to 207 μg mercury and 1125 μg mercury. The dose
differential was achieved by more frequent administration to the high-dose group. Mercury concen-
trations were significantly raised over control values in brain, liver, muscle, and kidneys, but not
blood. Concentrations were highest in kidneys, moderate in liver and lowest in brain and muscle.
Much of the mercury was present in the inorganic form (37–91%). The authors concluded that
“accumulation of mercury from chronic use of thiomersal-preserved medicines is viewed as a
potential health hazard for man” (p. 171).
The U.S. Veterans Administration and the U.S. National Institutes of Health funded research
published by Van Horn et al. (1977) that examined the toxic effects of Thimerosal on human tissue
culture cells. These authors commented:
Parry (1977) utilized yeast cultures for the detection of environmental mutagens using a fluctua-
tion test. He described:
A microbial fluctuation test, modified for the detection of environmental mutagens has been
evaluated using a number of strains of the yeast Saccharomyces cerevisiae. Auoxtrophic diploid
cultures of yeast which produce prototrophic colonies by both mitotic gene conversion and
mutation have been extensively utilized for the detection and evaluation of chemicals showing
genetic activity. A number of the yeast strains utilized were shown to be suitable for use in the
fluctuation test . . . The yeast strains respond to doses of mutagens at least a 100-fold lower than
that required in a conventional short exposure treat and plate experiment. In experiments involv-
ing the induction of mitotic gene conversion at the tryptophan-5 and histidine-4 loci in the flucu-
ation test significant increases in prototrophic cells were produced in the presence of . . . the
preservative Thiomersal (0.0001 μg/mL) . . . The results demonstrate that the fluctuation test pro-
vides an extremely sensitive assay for the detection of chemicals which show genetic activity in
yeast at non-toxic concentrations. (p. 165)
It should be noted that Parry (1977) observed Thimerosal induced significant genetic alterations in
yeast cells at a level <1 ppb.
Fagan et al. (1977) published a case series of children who were apparently poisoned by
Thimerosal. Fagan et al. (1977) reported, in a study funded by the National Institute of Environ-
mental Health Sciences of the U.S. National Institutes of Health, that between 1969 and 1975,
13 cases of exomphalos were treated by Thimerosal. The authors analyzed the mercury content
in tissues from 10 of the patients who had died. Upon reviewing the test results, the researchers
stated:
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The results showed that Thiomersal can induce blood and organ levels of organic mercury which are
well in excess of the minimum toxic levels in adults and fetuses . . . Although Thiomersal is an ethyl
mercury compound, it has similar toxicological properties to methyl mercury and the long-term
neurological sequelae produced by the ingestion of either methyl or ethyl mercury-based fungicides
are indistinguishable. (p. 962–963)
The authors also emphasized, “the fact that mercury readily penetrates intact membranes and is
highly toxic seems to have been forgotten. Equally effective and far less toxic broad-spectrum anti-
fungal and antibacterial . . . antiseptics are currently available” (p. 964).
Also published in 1977 were the results of a large-scale prospective human epidemiological
study (the Collaborative Perinatal Project of the National Institute of Neurological and Communicative
Disorders and Stroke, the U.S. Public Health Service, and the U.S. FDA) on drug exposures during
pregnancy and their association with birth defects (Heinonen et al., 1977). This study reported:
Between 1958 and 1965, under the auspices of the National Institute of Neurological and Commu-
nicative Disorders and Stroke, a prospective study of over 50,000 pregnancies was undertaken with
the main objective of determining whether there are factors during pregnancy or delivery that are
related to the risk of cerebral palsy or other neurological outcomes. This study ultimately became
known as the Collaborative Perinatal Project. Among many items of data obtained, drug use was
recorded during pregnancy, and birth defects identified in the children were recorded subsequently.
With the growing realization that drugs are sometimes teratogenic, it became mandatory to evaluate
the data from the perspective . . . The purpose of this book is to present data on drugs used by
50,282 gravidae in relation to birth defects identified in children. (p. viii)
The measure of association presented is a standardized relative risk (SRR) with its 95% confidence
limits. The SRR is the ratio of the observed number to the expected number of malformed children.
Since the SRR takes into account potential confounding variables, it represents the best estimate of
the relationship between a drug and a malformation . . . Finally, thiomersal . . . was associated with
malformations overall and with uniform malformations. (p. 299, 313)
Specifically, it was determined that Thimerosal exposure during the first 4 mo of pregnancy was
associated with a statistically significant increased risk (SRR=2.69) for birth defects.
Anundi et al. (1979) described a molecular mechanism by which Thimerosal exposure rapidly
induced cellular oxidative stress and subsequent cellular lysis following glutathione depletion, and
that the addition of cysteine could reverse the cellular toxicity of Thimerosal. Specifically, it was
determined:
Compounds are known which interact with lipids and proteins in such a way that both lipid peroxi-
dation and protein alkylation have been considered a cause of toxicity . . . it has become evident that
(glutathione) GSH protects against protein alkylation and that electrophilic compounds which
deplete GSH may alkylate proteins. The main point in this communication is that cellular damage
following GSH depletion may be explained by lipid peroxidation which destroys the cell before the
alkylation of proteins, as a component of cellular damage, is expressed. (p. 45–46)
In 1980, the FDA’s Advisory Review Panel on OTC Miscellaneous External Drug Products finally
delivered its report to the FDA. It reviewed 18 products containing mercury and found them all
either unsafe or ineffective for their stated purpose of killing bacteria to prevent infections. In terms
of effectiveness, the panel stated, “mercury compounds as a class are of dubious value for anti-
microbial use” (Subcommittee on Human Rights and Wellness, 2003, p. 61). They also stated,
“Mercury inhibits the growth of bacteria, but does not act swiftly to kill them” (Subcommittee on
Human Rights and Wellness, 2003, p. 61). In fact, the panel cited a study, conducted in 1935, on
the effectiveness of Thimerosal in killing staphylococcus bacteria on chick heart tissue. The study
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determined that Thimerosal was 35 times more toxic to the heart tissue it was meant to protect than
to the bacteria it was meant to kill. In terms of safety, the panel cited a number of studies demon-
strating the highly allergenic nature of Thimerosal and related organic mercury products. For exam-
ple, it cited a Swedish study that showed that 10% of school children, 16% of military recruits, and
18% of twins, and 26% of medical students had hypersensitivity to Thimerosal. They stated that
while organic mercury compounds, like Thimerosal, were initially developed to decrease the toxic-
ity of the mercury ion, Thimerosal was actually found to be more toxic than bi-chloride of mercury
for certain human cells (Subcommittee on Human Rights and Wellness, 2003, p. 61). By way of
summary, “The Panel concludes that Thimerosal is not safe for OTC topical use because of its
potential for cell damage if applied to broken skin, and its allergy potential. It is not effective as a
topical antimicrobial because its bacteriostatic action can be reversed” (Subcommittee on Human
Rights and Wellness, 2003, p. 61).
Despite the fact that the FDA expert committee found Thimerosal and other ethylmercury com-
pounds to be unsafe and ineffective for OTC products in 1980, the process to remove mercurials
from these products was excruciatingly slow. As a first step in the process, the agency published
Advanced Notice of Proposed Rules or Notice of Proposed Rules, publicizing the recommendations
of their Advisory Panel on OTC Miscellaneous External Drug Products to ban Thimerosal and other
mercurial-containing products in 1980, 1982, 1990, 1991, 1994, and 1995. No action was taken
on any of these occasions (Subcommittee on Human Rights and Wellness, 2003). Decisive action
from the FDA on the issue of mercury in OTC products would not come until 1998, 18 years after
its Advisory Panel first acknowledged Thimerosal’s “lack of safety” in topical ointments
(Subcommittee on Human Rights and Wellness, 2003).
For many years, Merthiolate has been known to have anti-microbial activity. When it was first intro-
duced as an anti-microbial preservative, little information about the fundamental biological effects of
organic mercury compounds was available. We should like to suggest that Merthiolate should now
be regarded as an inappropriate preservative for anti-lymphocytic globulin preparations and other
materials which are intended for administration to human subjects. (p. 333)
During a study of the properties of two antisera which had been prepared against human
lymphoid cells, the present author found that one of the antisera was cytotoxic to lymphoid and
non-lymphoid cells(.) . . . This effect was attributable to the organomercurial compound Merthi-
olate, which had been added to the (antilymphocyte serum) ALS as a preservative . . . In the
opinion of the present author, Merthiolate should no longer be added to ALS or other materials
which are intended for use in human subjects. Tissue accumulation of mercury has been
observed. (p. 91)
It was reported in 1983, in an article titled “Mercury Poisoning in Child Treated with Aqueous
Merthiolate,” that administration of Thimerosal resulted in a child dying from mercury toxicity
(Anonymous, 1983). The article stated, “The Ohio Board of Pharmacy has received an investigative
report from the Ohio Department of Health’s Division of Epidemiology regarding the death of a
21-month old child due to mercury poisoning. The investigation strongly implicated the Thimerosal
solution as ‘the source of mercury’ that subsequently resulted in the child’s death since no other
source could be identified” (p. 523).
Kravchenko et al. (1983) questioned the use of Thimerosal in vaccines and its inexplicable
acceptance in light of mounting scientific evidence demonstrating its inherent toxicity. These
researchers found: “Our experiments show that Merthiolate in 1:10,000 titer can not only damage
cells in culture but also change their properties. . . Increased sensitivity to this mercury compound
has been frequently noted in medical literature, and deserves particularly close attention. Although
there are numerous clinical studies confirming Merthiolate’s damaging action on humans, [medical
and biological preparations] MBP preservation with it continues and is even recommended by
WHO” (p. 87–92). In regard to the use of Thimerosal in vaccines, the researchers concluded, “All of
the above show that Merthiolate usage for MBP manufacturing is inadmissible, especially in pediatrics
. . . . Vaccines must contain only specific substances, free of ballast. There is no way that cell
damage can cause not harmful sequelae in the body” (p. 87–92).
Hekkens et al. (1983) undertook an evaluation of the effectiveness of some preservatives in
inactivated human vaccines by application of the test described in the United States Pharmaco-
poeia (USP) XIX. These researchers described that five recommended strains as well as three strains
isolated from vaccines were used as test strains. It was observed that vaccines preserved with
Thimerosal did not fully meet the requirements for a vaccine preservative according to the criteria
established by the USP XIX.
Royhans et al. (1984) reported on mercury toxicity following pediatric Thimerosal ear irriga-
tions. With regard to the danger posed by mercurials, the researchers were expansive in stating:
Although aqueous Merthiolate has been used for years as a topical antiseptic, a recent review of its
use by the Food and Drug Administration resulted in its classification as ‘less than effective.’ Further-
more, two of the ingredients (Thimerosal and borate) in Merthiolate are toxic if absorbed or injected . . .
Symptoms of organic mercury poisoning chiefly involve the central nervous system, including
paresthesia of the mouth, lips, tongue, and extremities; speech disorders, with difficulty in articulat-
ing words; difficulty in swallowing; salivation; neurasthenia; inability to recall basic information;
emotional instability; ataxia; clumsiness; stupor; and coma . . . Reactions to mercury depend to a
large extent on the form of the chemical agent; its absorption, storage, and excretion; duration of
exposure; and individual susceptibility. Both inorganic and dissociable organic mercurials appear to
act by the same mechanism. Mercury ion reacts with sulfhydryl groups to form mercaptides, which
inactivate sulfhydryl enzymes and interfere with cellular metabolism . . . The blood–brain barrier, is
also more permeable to organic than inorganic mercury. There are definite individual differences in
sensitivity to the effects of mercurials. Some patients tolerate prolonged exposure without symptoms;
others have significant systemic signs and neurological disability with much less exposure. The
mercury in Merthiolate is a thiosalicylate compound that is converted to inorganic mercury more
rapidly than is methyl mercury. The organic compound itself is also easily absorbable, and undergoes
widespread tissue distribution. Toxicity may be related both to the biotransformation into inorganic
mercury and to the unchanged compound, both of which cause degenerative changes in the brain,
especially in the visual cortex and cerebellum, and proliferative changes throughout the cerebellar
cortex. (p. 311–312)
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Winship (1985, p. 171) reported, “Multi-dose vaccines and allergy-testing extracts contain a mer-
curial preservative, usually 0.01% Thimerosal, and may present problems occasionally in practice. It
is, therefore, now accepted that multi-dose injection preparations are undesirable and that preserva-
tives should not be present in unit-dose preparations.”
Stetler et al. (1985) from the U.S. CDC also evaluated the use of Thimerosal as a preservative in
vaccines and found it to be unsatisfactory. The authors reported that Thimerosal was ineffective as a
vaccine preservative, and that giving more mercury than was present in a single Thimerosal-containing
vaccine might pose a health hazard to vaccine recipients. Evaluating the effectiveness of Thimerosal
as a preservative in vaccines, the authors stated: “Laboratory experiments in this investigation have
shown up to 2 weeks’ survival of at least one strain of group A Streptococcus in multidose DTP
(Diphtheria-Tetanus-Pertussis) vials. The manufacturer’s preservative effectiveness tests showed that
at 4°C, 4.5% of the challenge Streptococcus survived 14 d after inoculation into a multi-dose DTP
vaccine vial. At currently used concentrations, Thimerosal is not an ideal preservative” (p. 302–303).
The authors also made specific reference to the toxicity of Thimerosal: “However, because Thime-
rosal is an organic mercurial compound, higher concentrations might reduce vaccine potency or
pose a health hazard to recipients” (p. 303). Their recommendations regarding the use of multi-
dose vials with a Thimerosal preservative were as follows: “The Thimerosal preservative present in
DTP vaccine requires substantial time to kill organisms and cannot be relied upon to prevent trans-
mission of bacteria under conditions of practice when a vial is used over a short period. Instead, the
most important means of preventing abscesses secondary to DTP vaccination is to prevent contam-
ination by careful attention to sterile technique” (p. 303).
Furthermore, Cox and Forsyth (1988) recommended, “However, severe reactions to thiomersal
demonstrate a need for vaccines with an alternative preservative” (p. 229).
Digar et al. (1987) expanded the knowledge base regarding the marked toxicity of Thimerosal
to the developing fetus. The researchers reported:
A single dose of 0.1 mg of Ethyl-mercury-thiosalicylate (Thimerosal) was injected into the yolk sac of
chick embryos . . . Embryos were collected . . . It was found that 0.1 mg dose of Thimerosal was
lethal in 46.46%. Gross malformations like syndactyly, thinning of the abdominal wall, visceroptosis
and scanty feather, during Organogensis as well as in the later period, have been noted in 36.03% . . .
Significant change in the weight of embryo, crown–rump length, body and wing lengths were also
observed . . . However, there was no gross reduction in the size of brain as compared to that of the
control. The high incidence of lethality and malformations prove that organic mercury was transmit-
ted from the yolk sac to the embryo. The deleterious effects of mercurials on cells and tissues seem to
be due to action on a wide spectrum of enzymes by the organic mercury both on the surface and
within the cell. The enzymes particularly involved are−Na−K activated ATPase and also sulfhydryl
groups. Goldwater reported that mercury disrupts the normal function of mitochondria and
lysosomes. (p. 153, 157)
Withrow and his colleagues (1989), from the U.S. FDA, in keeping with the expanding circle of
scientists and physicians expressing ever-increasing concerns in regard to the use of Thimerosal as a
preservative, evaluated the cytotoxicity and mutagenicity of Thimerosal at preservative levels in a
tissue culture system. These researchers reported:
It is known that Thimerosal . . . present in lens care solutions sometimes cause(s) ocular irritation in
contact lens users. For example, Coward et al. (1984) reported that 33% of patients using lens care
solutions with Thimerosal . . . experienced solution intolerance . . . In vitro studies have shown that
preservatives are toxic to cultured human and rat corneal epithelial cells and toxic to isolated rabbit
corneas, and to intact rabbit eyes. (p. 385)
Additionally, these researchers described the impact of Thimerosal at the cellular level:
Cell survival and mutagenesis were measured using the L5178Y mouse lymphoma (TK +/−) system.
Cells were exposed to varying amounts of preservatives for 1 h at 37°C, and then aliquots were
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irradiated with UVA radiation (during the exposure to the preservative). Cells were then assayed for
survival, and for mutagenesis at the thymidine kinase (TK) locus. In concentrations commonly found
in ophthalmic solutions . . . Thimerosal (was) toxic to cells, and Thimerosal was slightly mutagenic.
When cells were exposed to preservative and UVA radiation. . .the mutagenic activity of Thimerosal
was enhanced. (p. 385)
Nascimento et al. (1990) not only reported on a death following Thimerosal ingestion but also
warned of the widespread danger which Thimerosal posed. Specifically, they reported, “A case of
mercurial poisoning caused by ingestion of an organic mercurial compound, Thimerosal, found in
local antiseptic solutions. The clinical picture consisted of grave neurological symptoms which were
not reversed by penicillamine and resin administration despite rapid plasma level reduction of mer-
cury. We call attention to this case because of the widespread availability of antiseptic solutions
containing mercurial compounds” (p. 218).
Aberer (1991) reviewed the continued use of mercury in medicine. In his article, Aberer (1991)
was comprehensive in declaring the extent of the problem that Thimerosal represented in pharma-
ceutical products: “The presence of mercury in over-the-counter drugs for the eye, ear, nose,
throat, and skin; in bleaching creams; as preservative in cosmetics, tooth pastes, lens solutions, vac-
cines, allergy test and immuno-therapy solutions, in antiseptics, disinfectants, and contraceptives; in
fungicides and herbicides; in dental fillings and thermometers; and many other products, makes it a
ubiquitous source of danger” (p. 150). He then went on to document the systemic failure to
remove this toxin from pharmaceutical products, “Despite calls for abandonment and a general
prohibition in 1967, mercury is still listed in many pharmacopoeias, including that of the United
States . . . Thus mercury is still much more frequently used than is generally believed. This seems
incomprehensible because side effects are not only potentially disastrous but also numerous and
well documented.” In describing the numerous and well-documented side effects of the use of
mercury in medicine, he stated that these included “Neurologic and psychiatric symptoms, renal
toxicity, erythroderma, and other signs of poisoning,” (p. 150) and furthermore, “Knowledge of all
these side effects has been available for some time” (p. 150). He concluded by arguing, “Recom-
mendations not to use mercury salts in children or only on prescription are insufficient. Removal
from textbooks seems overdue . . . However, calls for their abandonment (as early as 1960) or
restricted use have not sufficed. Only a general ban and their removal from the pharmacopoeias
will be effective in stopping the use of these dangerous, outmoded substances” (p. 150).
Brunner et al. (1991) evaluated the effects of Thimerosal in an in vitro porcine brain tubulin
assembly assay. These researchers examined the influence of Thimerosal on different parameters
[lag-phase, polymerization velocity, end absorption (steady-state level), reversibility, and influence
on disassembly at 4°C]. It was observed that low concentrations of Thimerosal led to a rapid inhibition
of tubulin assembly and disassembly of microtubules.
Additionally, Seal et al. (1991), in their article on the case against Thimerosal, concluded,
“Thimerosal is a weak antibacterial agent that is rapidly broken down to products, including ethylm-
ercury residues, which are neurotoxic. Its role as a preservative in vaccines has been questioned,
and the pharmaceutical industry considers its use as historical” (p. 315).
Hilleman (1991) from the Merck Vaccine Task Force expressed a newly initiated internal con-
cern over the mercury exposure infants were receiving through standard immunizations. It was
expressed:
PROBLEM: The regulatory control agencies in some countries, particularly Scandinavia (especially
Sweden), but also U.K., Japan, and Switzerland, have expressed concern for Thimerosal, a mercurial
preservative, in vaccines . . . PUTTING THIS INTO PERSPECTIVE: For Babies: The 25 μg of mercury in a
single 0.5 mL dose and extrapolated to a 6 lb. baby would be 25× the adjusted Swedish daily allowance
of 1.0 μg for a baby of that size. The total mercury burden in a baby is unknown but it has been stated
that the blood level of a newborn may exceed that of the mother. If 8 doses of Thimerosal-containing
vaccine were given in the first 6 months of life (3 DPT, 2 HIB, and 3 Hepatitis B) 200 μg of mercury
given, say to an average size of 12 lbs., would be about 87X the Swedish daily allowance of 2.3 μg of
mercury for a baby of that size. When viewed in this way, the mercury load appears rather large. (p. 1, 5)
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Lowe and Southern (1994) evaluated the antimicrobial action of various preservatives for vac-
cines. They described, “The preservative most commonly used is Thiomersal. Other preservatives
are being evaluated because: (i) this material has become difficult to obtain; (ii) the use of
mercury-containing compounds in medicinal products is considered potentially harmful; and
(iii) it has been found that some vaccine components are unstable in the presence of this material”
(p. 115). In light of these facts, the researchers undertook a series of experiments comparing the
antimicrobial activity of phenoxyethanol with Thimerosal in diphtheria, tetanus, and pertussis
(adsorbed) vaccine. It was observed, “Both chemicals were equally effective in inactivating chal-
lenge doses of Gram-negative and Gram-positive micro-organisms, as well as yeast” (p. 915). In
significant contrast to their concerns regarding the potentially harmful effect of mercury-containing
compounds, Lowe and Southern (1994) noted, “the low toxicity of phenoxyethanol in children
has been reported” (p. 915).
Lowell et al. (1996), from the Washington University School of Medicine, made overt the asso-
ciation between Thimerosal and mercury poisoning by evaluating the adverse effects resulting from
administration of Thimerosal-containing hepatitis B immunoglobulin (HBIG). They reported:
CONCLUSION
The high order of toxicity from Thimerosal and its ethylmercury breakdown product has been
known and published for decades. Nonetheless, Thimerosal remains in the drug supply, especially
in various vaccines manufactured both for the United States and globally. The ubiquitous and
largely unchecked place of Thimerosal in pharmaceutical products, therefore, represents a medical
crisis in the modern day. Reforms in the manufacture and the licensing of vaccines and other drugs,
which should have been accomplished proactively, had anyone properly assessed their mercury
content, must now be conducted, reactively, under significant systemic stress. With no warning,
recall, or ban of mercury in vaccines and other drugs as of yet, the victim of this mandated, unwar-
ranted, and massive mercury exposure is still an unsuspecting public, and most especially its unborn
and newborn children.
REFERENCES
Aberer, W. 1991. Topical mercury should be banned-dangerous, outmoded, but still popular. J. Am. Acad. Dermatol., 24:150–151.
Advisory Committee on Immunization Practices. 2006. Prevention and control of influenza: recommendations of the Advisory Commit-
tee on Immunization Practices (ACIP). Mortal. Morbid. Weekly Rev. 55:1–42.
Al-Kassab, S., and Saigh, N. 1962. Mercury and calcium excretion in chronic poisoning with organic mercury compounds. J. Fac. Med.
Baghdad 4:118–123.
Anonymous. 1943. Mercurials as ‘preservatives.’ J. Am. Med. Assoc. 122:1253.
Anonymous. 1983. Mercury poisoning in child treated with aqueous Merthiolate. MD State Med. J. 32:523.
THIMEROSAL AND ITS ETHYLMERCURY BREAKDOWN PRODUCT 595
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Anundi, I., Hogberg, J., and Stead A. H. 1979. Glutathione depletion in isolated hepatocytes: its relation to lipid peroxidation and
cellular damage. Acta Pharmacol. Toxicol. 49:45–51.
Ardatova, A. N., Poloz, D., and Yakusheva, O. V. 1969. Toxic effects of Granosan. Veterinariya (Moscow) 46:56–58.
Axton, J. H. M. 1972. Six cases of poisoning after a parenteral organic mercurial compound (Merthiolate). Postgrad. Med. J. 48:417–421.
Bakulina, A. V. (1968). The effect of subacute Granosan poisoning on the progeny. Soviet Med. 31:60–63.
Birbin, S. S., Alekseeva, A., and Bulatov, A. A. 1968. The poisoning of swine treated with Granosan. Veterinariya 8:60–61.
Blair, A. M. J. N., Clark, B., Clark, A. J., and Wood, P. 1975. Tissue concentrations of mercury after chronic dosing of squirrel monkeys
with Thiomersal. Toxicology 3:171–176.
Brunner, M., Albertini, S., and Wurgler, F. E. 1991. Effects of 10 known or suspected spindle poisons in the in vitro porcine brain tubulin
assembly assay. Mutagenesis 6:65–70.
Cinca, I., Dumitrescu, I., Onaca, P., Serbanescu, A., and Nestorescu, B. 1980. Accidental ethyl mercury poisoning with nervous system,
skeletal muscle, and myocardium injury. J. Neurol. Neurosurg. Psychiat. 43:143–149.
Cogswell, H. D., and Shown, A. 1948. Reaction following the use of tincture of Merthiolate. Ariz. Med. 5:42–43.
Cox, N. H., and Forsyth, A. 1988. Thiomersal allergy and vaccination reactions. Contact Dermatitis 18:229–233.
Cummins, S. L. (1937). Merthiolate in the treatment of tuberculosis. Lancet 230:962–963.
Dahhan, S. S., and Orfaly, H. 1962. Mercury poisoning and electorcardiographic changes. J. Fac. Med. Baghdad 4:104–111.
Damlugi, S. 1962. Mercurial poisoning with fungicide Granosan M. J. Fac. Med. Baghdad 4:83–103.
Davisson, E.O., Powell, H. M., MacFarlane, J. O., Hodgson, R., Stone, R. L., and Culbertson C. G. 1956. The preservation of poliomyelitis
vaccine with stabilized Merthiolate. J. Lab. Clin. Med. 47:8–19.
Derban, L. K. 1974. Outbreak of food poisoning due to alkyl-mercury fungicide on southern Ghana state farm. Arch. Environ. Health
28:49–52.
Digar, A., Sensharma, G. C., and Samal, S. N. 1987. Lethality and teratogenecity of organic mercury (Thimerosal) on the chick embryo. J.
Anat. Soc. India 36:153–159.
Ellis, F. A. 1943. Possible danger in use of Merthiolate ophthalmic ointment. Arch. Ophthalmol. 30:265–266.
Ellis, F. A. 1947. The sensitizing factor in Merthiolate. J. Allergy 18:212–213.
Engley, F .B. 1950. Evaluation of mercurial compounds as antiseptics. Ann. NY Acad. Sci. 53:197–206.
Engley, F. B. 1956. Mercurials as disinfectants: Evaluation of mercurial antimicrobic action and comparative toxicity for skin tissue cells.
Chicago: 42nd Mid-Year Meeting of the Chemical Specialties Manufacturer’s Association.
Fagan, D. G., Pritchard, J. S., Clarkson, T. W., and Greenwood, M. R. 1977. Organ mercury levels in infants with omphaloceles treated
with organic mercurial antiseptic. Arch. Dis. Child. 52:962–964.
Forstrom, L., Hannuksela, M., Kousa, M., and Lehymuskallio, E. 1980. Merthiolate hypersensitivity and vaccination. Contact Dermatitis
6:241–245.
Francois, G., Duclos, P., Margolis, H., Lavanchy, D., Siegrist, C. A., Meheus, A., Lambert, P. H., Emiroglu, N., Badur, S., and Van
Damme, P. 2005. Vaccine safety controversies and the future of vaccination programs. Pediatr. Infect. Dis. J. 24:953–961.
Gasset, A. R., Itoi, M., Ishii, Y., and Ramer, R. M. 1975. Teratogenicities of ophthalmic drugs. 2. Teratogenicities and tissue accumulation
of Thimerosal. Arch. Ophthalmol. 93:52–55.
Gibson, S. T. 1976. Memorandum from Assistant to the Director, Department of Biologics, Food and Drug Administration, “Use of
Thimerosal in Biologics Production.” Washington, DC.
Goncharuk, G. A. 1971. Experimental investigations of the effect of organomercury pesticides on generative functions and on progeny.
Hyg. Sanit. 36:40–43.
Heinonen, O. P., Slone, D., and Shapiro, S. 1977. Birth defects and drugs in pregnancy. Littleton, MA: Publishing Sciences Group.
Hekkens, F. E. A., Polak-Vogelzang, A. A., and Kreeftenberg, J. G. 1983. The antimicrobial effectiveness of some preservatives in inacti-
vated human vaccines. J. Biol. Stand. 9:277–285.
Heyworth, M. F. 1982. Clinical experience with antilymphocyte serum. Immunol. Rev. 65:79–97.
Heyworth, M. F., and Truelove, S. C. 1979. Problems associated with the use of Merthiolate as a preservative in anti-lymphocytic globulin.
Toxicology 12:325–333.
Hilleman, M. R. 1991. Merck Memorandum, “Vaccine Task Force Assignment: Thimerosal (Methiolate) Preservative—Problems, Analysis,
Suggestions for Resolution.” Whitehouse Station, NJ.
Itoi, M., Ishii, Y., and Kaneko, N. 1972. Teratogenicities of antiviral ophthalmics on experimental animals. Jpn. J. Clin. Ophthal. 26:631–640.
Jalili, M. A., and Abbasi, A. H. 1961. Poisoning by ethyl mercury toluene sulphonanilide. Br. J. Ind. Med. 18:303–308.
Jamieson, W. A., and Powell, H. M. 1931. Merthiolate as a preservative for biological products. Am. J. Hyg. 14:218–224.
Kendrick, D. B. 1989. Blood program in World War II. Washington, DC: Office of the Surgeon General, Department of the Army.
Kharasch, M. S. 1928. Alkyl merucric sulphur Compound and process for producing it. US Patent 1,672,615.
Kharasch, M. S. 1932. Stabilized bactericide and process of stabilizing it. U.S. Patent 1,862,896.
Kharasch, M. S. 1935. Stabilized organo-meruri-sulphur compounds. U.S. Patent 2,012,820.
Kinsella, R. A. 1941. Chemotherapy of bacterial endocarditis. Ann. Intern. Med. 15:982–986.
Kravchenko, A. T., Dzagurov, S. G., and Chervonskaia, G. P. 1983. Evaluation of the toxic action of prophylactic and therapeutic prepa-
rations on cell cultures. III. The detection of toxic properties in medical biological preparations by the degree of cell damage in the
L132 continuous cell line. Zh. Mikrobiol. Epidemiol. Immunobiol. 3:87–92.
Lowe, I., and Southern, J. 1994. The antimicrobial activity of phenoxyethanol in vaccines. Lett. Appl. Microbiol. 18:115–116.
Lowell, J. A., Burgess, S., and Shenoy, S. 1996. Mercury poisoning associated with hepatitis-B immunoglobulin. Lancet 347:480.
Mal’tsev, P. V. 1972. Granosan poisoning in children. Feldsher Akush. 37:14–16.
Marks, H. H., Powell, H. M., and Jamieson, W. A. 1932. Merthiolate as a skin disinfecting agent. J. Lab. Clin. Med. 18:443–449.
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Matheson, D. S., Clarkson, T. W., and Gelfand, E. W. 1980. Mercury toxicity (acrodynia) induced by long term injection of gammaglobulin.
J. Pediatr. 97:153–155.
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Hemolytic streptococci: In vivo and in vitro studies. J. Am. Med. Assoc. 136:37–41.
Mukai, N. 1972. An experimental study of alkylmercurial encephalopathy. Acta Neuropathol. 72:102–109.
Mukhtarova, N. D. 1977. Late sequelae of nervous system pathology caused by the action of low concentrations of ethyl mercury
chloride. Gig. Tr. Prof. Zabol. 3:4–7.
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Clin. Fac. Med. Sao Paulo 45:216–218.
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Microbiol. 15:590–593.
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Offit, P. A., and Jew, R. K. 2003. Addressing parents’ concerns: Do vaccines contain harmful preservatives, adjuvants, additives, or
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Oharazawa, H. 1968. Effect of ethylmercuric phosphate in the pregnant mouse on chromosome abnormalities and fetal malformation. J.
Jpn. Obstet. Gynecol. 20:1479–1487.
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Parry, J. M. 1977. The use of yeast cultures for the detection of environmental mutagens using a fluctuation test. Mutat. Res. 46:165–176.
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atriya Moscow 35:56–60.
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104:311–313.
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Salle, A. J., and Lazarus, A. S. 1935. A comparison of the resistance of bacteria and embryonic tissue to germicidal substances. Proc. Soc.
Exp. Biol. Med. 32:665–667.
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Seal, D., Ficker, L., Wright, P., and Andrews, V. 1991. The case against Thiomersal. Lancet 338:315–316.
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forty-four epidemic cases. J. Am. Med. Assoc. 95:776–780.
Spann, J. W., Heath, R. G., Kreitzer, J. F., and Locke, L. N. 1972. Ethyl-mercury-p-toluene-sulfonanilide: Lethal and reproductive effects
on pheasants Science 175:328–330.
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Material Safety Data Sheet
Chlortetracycline Hydrochloride, can be used as Secondary Standard
ACC# 62722
Section 1 - Chemical Product and Company Identification
MSDS Name: Chlortetracycline Hydrochloride, can be used as Secondary Standard
Catalog Numbers: AC268240000, AC268245000
Synonyms: CTC; 7-Chlorotetracycline . HCl
Company Identification:
Acros Organics N.V.
One Reagent Lane
Fair Lawn, NJ 07410
For information in North America, call: 800-ACROS-01
For emergencies in the US, call CHEMTREC: 800-424-9300
EMERGENCY OVERVIEW
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get
medical aid.
Skin: Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing
and shoes. Wash clothing before reuse.
Ingestion: Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If
conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation: Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If
breathing is difficult, give oxygen. Get medical aid.
Notes to Physician: Treat symptomatically and supportively.
General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH
(approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated
by thermal decomposition or combustion. Vapors may be heavier than air. They can spread along the ground and
collect in low or confined areas. Generated by www.PDFonFly.com at 12/9/2010 7:18:27 PM
Extinguishing Media: Use agent most appropriate to extinguish fire. Do NOTURL: get https://fscimage.fishersci.com/msds/62722.htm
water inside containers. Use water
spray, dry chemical, carbon dioxide, or appropriate foam.
Flash Point: 210 deg C ( 410.00 deg F)
Autoignition Temperature: Not available.
Explosion Limits, Lower:N/A
Upper: N/A
NFPA Rating: (estimated) Health: ; Flammability: ; Instability:
Handling: Wash thoroughly after handling. Use with adequate ventilation. Avoid breathing dust, mist, or vapor.
Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Store
protected from light. Use only in a chemical fume hood. Keep from contact with moist air and steam.
Storage: Do not store in direct sunlight. Store in a tightly closed container. Store in a cool, dry, well-ventilated
area away from incompatible substances. Keep refrigerated. (Store below 4°C/39°F.) Store protected from moisture.
OSHA Vacated PELs: Chlortetracycline Hydrochloride: No OSHA Vacated PELs are listed for this chemical.
Personal Protective Equipment
Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face
protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin: Wear appropriate protective gloves to prevent skin exposure.
Clothing: Wear appropriate protective clothing to prevent skin exposure.
Respirators: Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a
NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other
symptoms are experienced.
RTECS#:
CAS# 64-72-2: QI7800000
LD50/LC50:
CAS# 64-72-2:
Oral, mouse: LD50 = 2314 mg/kg;
.
Carcinogenicity:
CAS# 64-72-2: Not listed by ACGIH, IARC, NTP, or CA Prop 65.
No information available.
Chemical waste generators must determine whether a discarded chemical is classified as a hazardous waste. US EPA
guidelines for the classification determination are listed in 40 CFR Parts 261.3. Additionally, waste generators must
consult state and local hazardous waste regulations to ensure complete and accurate classification.
RCRA P-Series: None listed.
RCRA U-Series: None listed.
US FEDERAL
TSCA
CAS# 64-72-2 is not listed on the TSCA inventory. It is for research and development use only.
Health & Safety Reporting List
None of the chemicals are on the Health & Safety Reporting List.
Chemical Test Rules
None of the chemicals in this product are under a Chemical Test Rule.
Section 12b
None of the chemicals are listed under TSCA Section 12b. Generated by www.PDFonFly.com at 12/9/2010 7:18:27 PM
TSCA Significant New Use Rule URL: https://fscimage.fishersci.com/msds/62722.htm
None of the chemicals in this material have a SNUR under TSCA.
CERCLA Hazardous Substances and corresponding RQs
None of the chemicals in this material have an RQ.
SARA Section 302 Extremely Hazardous Substances
None of the chemicals in this product have a TPQ.
Section 313 No chemicals are reportable under Section 313.
Clean Air Act:
This material does not contain any hazardous air pollutants.
This material does not contain any Class 1 Ozone depletors.
This material does not contain any Class 2 Ozone depletors.
Clean Water Act:
None of the chemicals in this product are listed as Hazardous Substances under the CWA.
None of the chemicals in this product are listed as Priority Pollutants under the CWA.
None of the chemicals in this product are listed as Toxic Pollutants under the CWA.
OSHA:
None of the chemicals in this product are considered highly hazardous by OSHA.
STATE
CAS# 64-72-2 is not present on state lists from CA, PA, MN, MA, FL, or NJ.
California Prop 65
California No Significant Risk Level: None of the chemicals in this product are listed.
European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols:
XN
Risk Phrases:
R 63 Possible risk of harm to the unborn child.
Safety Phrases:
S 36/37 Wear suitable protective clothing and gloves.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek medical advice
immediately (show the label where possible).
S 28A After contact with skin, wash immediately with plenty of water
.
enter your search here
Welcome Guest
Ordering
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Collection NIA Aging Cell Culture Repository
Assurance Form Signatory
Subcollection Specially Characterized Fibroblasts
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Sample Description MRC-5 - NORMAL HUMAN FETAL LUNG FIBROBLAST
FAQs
Biopsy Source Lung
Lymphoblast Cultures
Cell Type Fibroblast
Fibroblast Cultures
Tissue Type Lung
Fetal Bovine Serum
Transformant Untransformed
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Species Homo sapiens
Cell Types
Common Name Human
Culture Medium
Age At Sampling 14 FW
ISCN Nomenclature
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Searching Mutations
Race Caucasian
Quick Search
Relation to Proband proband
Safety Guidelines
Clinically Affected No
Quality Control
Confirmation Clinical summary/Case history
Passage vs PDL
ISCN 46,XY
Miscellaneous
Remarks The MRC-5 cell line was developed in September 1966 from lung tissue taken from a 14 week fetus
aborted for psychiatric reason from a 27 year old physically healthy woman. The cell morphology is Feedback
fibroblast-like. The karyotype is 46,XY; normal diploid male. Cumulative population doublings to Links
senescence is 42-48. G6PD isoenzyme is type B. Contact Us
Cell Collections
Catalog ID AG05965-F
Product Cell Culture
Pricing Commercial Pricing: $180.00
Academic and not-for-profit pricing: $100.00
NIA Grantees: $40.00
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NOT fax form to Coriell Customer Service)
Characterizations
Sample Description MRC-5 - NORMAL HUMAN FETAL LUNG FIBROBLAST
PDL at Senescence 59
PDL at Freeze 17
IDENTIFICATION OF
Species of Origin Confirmed by Chromosome Analysis
SPECIES OF ORIGIN
Phenotypic Data
Remark The MRC-5 cell line was developed in September 1966 from lung tissue taken from a 14 week fetus aborted for
psychiatric reason from a 27 year old physically healthy woman. The cell morphology is fibroblast-like. The karyotype is
46,XY; normal diploid male. Cumulative population doublings to senescence is 42-48. G6PD isoenzyme is type B.
Publications
Guo WJ, Datta S, Band V, Dimri GP, Mel-18, a polycomb group protein, regulates cell proliferation and senescence via
transcriptional repression of Bmi-1 and c-Myc oncoproteins Molecular biology of the cell18:536-46 2006
PubMed ID: 17151361
Skandalis A, Uribe E, A survey of splice variants of the human hypoxanthine phosphoribosyl transferase and DNA polymerase
beta genes: products of alternative or aberrant splicing? Nucleic Acids Res32(22):6557-64 2004
PubMed ID: 15601998
Von Kobbe C, May A, Grandori C, Bohr VA, Werner syndrome cells escape hydrogen peroxide-induced cell proliferation arrest.
FASEB J18(15):1970-2 2004
PubMed ID: 15459124
Hande MP, Balajee AS, Tchirkov A, Wynshaw-Boris A, Lansdorp PM, Extra-chromosomal telomeric DNA in cells from Atm(-/-
) mice and patients with ataxia-telangiectasia. Hum Mol Genet10(5):519-28 2001
PubMed ID: 11181576
Gyulai Z, Endresz V, Burian K, Pincus S, Toldy J, Cox WI, Meric C, Plotkin S, Gonczol E, Berencsi K, Cytotoxic T
lymphocyte (CTL) responses to human cytomegalovirus pp65, IE1-Exon4, gB, pp150, and pp28 in healthy individuals: reevaluation
of prevalence of IE1-specific CTLs. J Infect Dis181(5):1537-46 2000
PubMed ID: 10823751
Piret B, Schoonbroodt S, Piette J, The ATM protein is required for sustained activation of NF-kappaB following DNA damage.
Oncogene18(13):2261-71 1999
PubMed ID: 10327072
Jongmans W, Vuillaume M, Chrzanowska K, Smeets D, Sperling K, Hall J, Nijmegen breakage syndrome cells fail to induce
the p53-mediated DNA damage response following exposure to ionizing radiation. Mol Cell Biol17(9):5016-22 1997
PubMed ID: 9271379
Duan C, Clemmons DR, Transcription factor AP-2 regulates human insulin-like growth factor binding protein-5 gene expression. J
Biol Chem270:24844-51 1995
PubMed ID: 7559606
Borsi L, Balza E, Gaggero B, Allemanni G, Zardi L, The alternative splicing pattern of the tenascin-C pre-mRNA is controlled by
the extracellular pH. J Biol Chem270:6243-5 1995
PubMed ID: 7534307
Futreal PA, Cochran C, Marks JR, Iglehart JD, Zimmerman W, Barrett JC, Wiseman RW, Mutation analysis of the THRA1
gene in breast cancer: deletion/fusion of the gene to a novel sequence on 17q in the BT474 cell line. Cancer Res54:1791-4 1994
PubMed ID: 7511052
Kilfeather SA, Collins D, McCormack P, Cotter T, O'Malley K, The effect of in vitro aging on human lung fibroblast beta-
adrenergic receptor density, coupling and response. Mech Ageing Dev63:247-56 1992
PubMed ID: 1319530
Jacobs, Characteristics of a human diploid cell designated MRC-5. Nature277:168 (1970):247-56 1970
PubMed ID: 1319530
External Links
dbSNP dbSNP ID: 15181
Images
Data are not available
Culture Protocols
PDL at Senescence 59
PDL at Freeze 16.99
Split Ratio 1:7
Temperature 37 C
Percent CO2 5%
Medium Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids
Serum 10% fetal bovine serum Not inactivated
Substrate None specified
enter your search here
Welcome Guest
Ordering
Online Ordering
Overview
Placing First Online Order
Collection NIA Aging Cell Culture Repository
Assurance Form Signatory
Subcollection Specially Characterized Fibroblasts
Frozen Shipments Policy
Sample Description WI-38 - NORMAL HUMAN FETAL LUNG FIBROBLAST
FAQs
Biopsy Source Lung
Lymphoblast Cultures
Cell Type Fibroblast
Fibroblast Cultures
Tissue Type Lung
Fetal Bovine Serum
Transformant Untransformed
Searching
Species Homo sapiens
Cell Types
Common Name Human
Culture Medium
Age At Sampling 12 FW
ISCN Nomenclature
Sex Female
Searching Mutations
Race Caucasian
Quick Search
Family 1053
Safety Guidelines
Family Member 2
Quality Control
Relation to Proband proband
Passage vs PDL
Clinically Affected No
Miscellaneous
Confirmation Clinical summary/Case history
Feedback
ISCN 46,XX
Links
Remarks The WI-38 cell line was developed in July 1962 from lung tissue taken from a therapeutically aborted
fetus of about 3 months gestational age. Cells released by trypsin digestion of the lung tissue were used Contact Us
for the primary culture. The cell morphology is fibroblast-like. The karyotype is 46,XX; normal diploid Cell Collections
female. A maximum lifespan of 50 population doublings for this culture was obtained at the Repository. A
thymidine labelling index of 86% was obtained after recovery. G6PD is isoenzyme type B. This culture of
WI-38 is an expansion from passage 9 frozen cells obtained from the submitter.
Catalog ID AG06814-J
Product Cell Culture
Pricing Commercial Pricing: $180.00
Academic and not-for-profit pricing: $100.00
NIA Grantees: $40.00
Catalog ID NA06814
Product DNA
Quantity 0.050mg
Source cell culture
Pricing Commercial Pricing: $55.00
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NIA Grantees: $55.00
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NOT fax form to Coriell Customer Service)
Characterizations
Sample Description WI-38 - NORMAL HUMAN FETAL LUNG FIBROBLAST
PDL at Senescence 50
PDL at Freeze 44
Passage Frozen 38
IDENTIFICATION OF Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and
SPECIES OF ORIGIN Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis
Phenotypic Data
Remark The WI-38 cell line was developed in July 1962 from lung tissue taken from a therapeutically aborted fetus of about 3
months gestational age. Cells released by trypsin digestion of the lung tissue were used for the primary culture. The cell
morphology is fibroblast-like. The karyotype is 46,XX; normal diploid female. A maximum lifespan of 50 population
doublings for this culture was obtained at the Repository. A thymidine labelling index of 86% was obtained after recovery.
G6PD is isoenzyme type B. This culture of WI-38 is an expansion from passage 9 frozen cells obtained from the submitter.
Publications
Li B, Jog SP, Reddy S, Comai L, WRN controls formation of extrachromosomal telomeric circles and is required for TRF2DeltaB-
mediated telomere shortening Molecular and cellular biology28:1892-904 2008
PubMed ID: 18212065
Tresini M, Lorenzini A, Torres C, Cristofalo VJ, Modulation of replicative senescence of diploid human cells by nuclear ERK
signaling J Biol Chem282(6):4136-51 2007
PubMed ID: 17145763
Dauth I, Krüger J, Hofmann TG, Homeodomain-interacting protein kinase 2 is the ionizing radiation-activated p53 serine 46 kinase
and is regulated by ATM Cancer research67:2274-9 2007
PubMed ID: 17332358
Singh NK, Singh NN, Androphy EJ, Singh RN, Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique
silencer element located in the last intron Molecular and cellular biology26:1333-46 2006
PubMed ID: 16449646
Wang W, Martindale JL, Yang X, Chrest FJ, Gorospe M., Increased stability of the p16 mRNA with replicative senescence.
EMBO Rep6(2):158-64 2005
PubMed ID: 15678155
Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I, Evolutionarily conserved and nonconserved cellular localizations
and functions of human SIRT proteins Molecular biology of the cell16:4623-35 2005
PubMed ID: 16079181
Gosslau A, Chen M, Ho CT, Chen KY, A methoxy derivative of resveratrol analogue selectively induced activation of the
mitochondrial apoptotic pathway in transformed fibroblasts Br J Cancer92(3):513-21 2005
PubMed ID: 15668717
Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC, Senescing human cells and ageing mice
accumulate DNA lesions with unrepairable double-strand breaks. Nat Cell Biol6(2):168-70 2004
PubMed ID: 14755273
Kahl CR, Means AR, Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent protein kinase I. J Biol Chem279
(15):15411-9 2004
PubMed ID: 14754892
Kahl CR, Means AR, Calcineurin regulates cyclin D1 accumulation in growth-stimulated fibroblasts. Mol Biol Cell15(4):1833-42 2004
PubMed ID: 14767060
Marchesini N, Osta W, Bielawski J, Luberto C, Obeid LM, Hannun YA, Role for mammalian neutral sphingomyelinase 2 in
confluence-induced growth arrest of MCF7 cells. J Biol Chem279(24):25101-11 2004
PubMed ID: 15051724
Silverman J, Takai H, Buonomo SB, Eisenhaber F, de Lange T, Human Rif1, ortholog of a yeast telomeric protein, is regulated
by ATM and 53BP1 and functions in the S-phase checkpoint. Genes Dev18(17):2108-19 2004
PubMed ID: 15342490
Xin H, Pereira-Smith OM, Choubey D, Role of IFI 16 in cellular senescence of human fibroblasts. Oncogene23(37):6209-17 2004
PubMed ID: 15208661
Von Kobbe C, May A, Grandori C, Bohr VA, Werner syndrome cells escape hydrogen peroxide-induced cell proliferation arrest.
FASEB J18(15):1970-2 2004
PubMed ID: 15459124
Schawalder J, Paric E, Neff NF, Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA
helicase. BMC Cell Biol4:15:1970-2 2003
PubMed ID: 14577841
Li GZ, Eller MS, Firoozabadi R, Gilchrest BA, Evidence that exposure of the telomere 3' overhang sequence induces
senescence Proceedings of the National Academy of Sciences of the United States of America100:527-31 2003
PubMed ID: 12515865
Baird DM, Rowson J, Wynford-Thomas D, Kipling D, Extensive allelic variation and ultrashort telomeres in senescent human
cells. Nat Genet33(2):203-7 2003
PubMed ID: 12539050
Hande MP, Balajee AS, Tchirkov A, Wynshaw-Boris A, Lansdorp PM, Extra-chromosomal telomeric DNA in cells from Atm(-/-
) mice and patients with ataxia-telangiectasia. Hum Mol Genet10(5):519-28 2001
PubMed ID: 11181576
Ding W, Gao S, Scott RE, Senescence represses the nuclear localization of the serum response factor and differentiation
regulates its nuclear localization with lineage specificity. J Cell Sci114(Pt 5):1011-8 2001
PubMed ID: 11181183
Lu J, Ho CT, Ghai G, Chen KY, Differential effects of theaflavin monogallates on cell growth, apoptosis, and Cox-2 gene
expression in cancerous versus normal cells. Cancer Res60(22):6465-71 2000
PubMed ID: 11103814
Luberto C, Hannun YA, Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during
SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipase C? J Biol
Chem273:14550-9 1998
PubMed ID: 9603970
Gamard CJ, Dbaibo GS, Liu B, Obeid LM, Hannun YA, Selective involvement of ceramide in cytokine-induced apoptosis.
Ceramide inhibits phorbol ester activation of nuclear factor kappaB. J Biol Chem272(26):16474-81 1997
PubMed ID: 9195956
Borsi L, Balza E, Gaggero B, Allemanni G, Zardi L, The alternative splicing pattern of the tenascin-C pre-mRNA is controlled by
the extracellular pH. J Biol Chem270:6243-5 1995
PubMed ID: 7534307
Venable ME, Lee JY, Smyth MJ, Bielawska A, Obeid LM, Role of ceramide in cellular senescence. J Biol Chem270:30701-8
1995
PubMed ID: 8530509
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, et al, A
biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A92:9363-7 1995
PubMed ID: 7568133
Venable ME, Blobe GC, Obeid LM, Identification of a defect in the phospholipase D/diacylglycerol pathway in cellular
senescence. J Biol Chem269:26040-4 1994
PubMed ID: 7929315
Dimri GP, Campisi J, Altered profile of transcription factor-binding activities in senescent human fibroblasts. Exp Cell Res212:132-
40 1994
PubMed ID: 8174635
Dimri GP, Hara E, Campisi J, Regulation of two E2F-related genes in presenescent and senescent human fibroblasts. J Biol
Chem269:16180-6 1994
PubMed ID: 8206919
Ganguly T, Duker NJ, Differential cell cycle modulation of human DNA glycosylases against oxidized pyrimidines. Mutat
Res235:137-46 1990
PubMed ID: 2308590
Pereira-Smith OM, Stein GH, Robetorye S, Meyer-Demarest S, Immortal phenotype of the HeLa variant D98 is recessive in
hybrids formed with normal human fibroblasts. J Cell Physiol143:222-5 1990
PubMed ID: 2332448
Kunisada T, Miller CD, Schneider EL, Ultraviolet light-induced DNA damage in transcribed sequences: no change in repair with
age. Mutat Res237:75-81 1990
PubMed ID: 2164149
McNearney T, Ballard L, Seya T, Atkinson JP, Membrane cofactor protein of complement is present on human fibroblast,
epithelial, and endothelial cells. J Clin Invest84:538-45 1989
PubMed ID: 2474570
Giordano T, Kleinsek D, Foster DN, Increase in abundance of a transcript hybridizing to elongation factor I alpha during cellular
senescence and quiescence. Exp Gerontol24:501-13 1989
PubMed ID: 2483690
Giordano T, Foster DN, Identification of a highly abundant cDNA isolated from senescent WI-38 cells. Exp Cell Res185:399-406
1989
PubMed ID: 2480908
Gibson JM, Milam SB, Klebe RJ, Late passage cells display an increase in contractile behavior. Mech Ageing Dev48:101-10
1989
PubMed ID: 2739467
Kondo H, Kasuga H, Noumura T, The heterogeneity of human fibroblasts as determined from the effects of hydrocortisone on
cell growth and specific dexamethasone binding. Exp Cell Res158:342-8 1985
PubMed ID: 4007059
Hayflick, The limited in vitro lifetime of human diploid cell strains. Exp Cell Res37:614 (1965):342-8 1965
PubMed ID: 4007059
Hayflick, The serial cultivation of human diploid cell strains. Exp Cell Res25:585 (1961):342-8 1961
PubMed ID: 4007059
External Links
dbSNP dbSNP ID: 10119
Images
View karyotype
Culture Protocols
PDL at Senescence 50
PDL at Freeze 44
Passage Frozen 38
Split Ratio 1:4
Temperature 37 C
Percent CO2 5%
Medium Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids
Serum 15% fetal bovine serum Not inactivated
Substrate None specified
Subcultivation Method trypsin-EDTA
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Mutant Polio Virus Spreads in Nigeria 1. Pat Robertson Haiti Comments Spark Uproar
124 Children Afflicted This Year By Paralyzing Disease, Believed To Be Caused By Same Vaccine Used 2. Poll: Obama Health Care Marks Hit New Low
To Fight It 3. Rush Limbaugh Slams Obama's Response to
Font size Print E-mail Share 24 Comments Haiti Earthquake
4. Rush Limbaugh Stands by Haiti Comments
(AP) Polio, the dreaded paralyzing disease stamped out in the
5. Heidi Montag's Plastic Surgery Obession
industrialized world, is spreading in Nigeria. And health officials
say in some cases, it's caused by the vaccine used to fight it.
DISCUSSED
In July, the World Health Organization issued a warning that this 1. Sarah Palin: Criticism is a "Bunch of B.S."
vaccine-spread virus might extend beyond Africa. So far, 124 (592 recent comments)
Nigerian children have been paralyzed this year - about twice
those afflicted in 2008.
The polio problem is just the latest challenge to global health LATEST NEWS
authorities trying to convince wary citizens that vaccines can save
them from dreaded disease. For years, myths have abounded Time Quickly Running
about vaccines - that they were the Western world's plan to out for Haiti Victims
sterilize Africans or give them AIDS. The sad polio reality fuels
In this Feb. 23, 2004 file photo, health workers Critical 72-Hour Window
misguided fears and underscores the challenges authorities face
vaccinates a child with drops of polio vaccines at Closing for People Trapped;
using a flawed vaccine.
Leeland primary school in Lagos, Nigeria. (AP) Relief Challenges Remain
Nigeria and most other poor nations use an oral polio vaccine Daunting
FAST FACTS because it's cheaper, easier, and protects entire communities.
Nigeria
Learn about the people, economy and But it is made from a live polio virus - albeit weakened - which Mullen: Up to 10K Troops
history. carries a small risk of causing polio for every million or so doses Heading to Haiti
given. In even rarer instances, the virus in the vaccine can mutate
U.S. Military Relief Efforts
into a deadlier version that ignites new outbreaks.
Underway with More Aid
STORIES
In Nigeria, Clinton Lambastes Corruption The vaccine used in the United States and other Western nations Coming; U.S. Death Toll
Obama: "Africa's Future Is Up to Africans" is given in shots, which use a killed virus that cannot cause polio. Climbs to 6
It is a worrying development for officials who hope to end polio epidemics in India and Africa by the end of this year, NEWS IN PICTURES
after missing several earlier deadlines. "It's very disturbing," said Dr. Bruce Aylward, who heads the polio
department at the World Health Organization.
This year, the number of polio cases caused by the vaccine has doubled: 124 children have so far been paralyzed,
compared to 62 in 2008, out of about 42 million children vaccinated. For every case of paralysis, there are hundreds
of other children who don't develop symptoms, but pass on the disease.
When Nigerian leaders suspended polio vaccination in 2003, believing the vaccine would sterilize their children and
infect them with HIV, Nigeria exported polio to nearly two dozen countries worldwide, making it as far away as
Indonesia.
Nigeria resumed vaccinations in 2004 after tests showed the vaccine was not contaminated with estrogen, anti-
fertility agents or HIV.
Experts have long believed epidemics unleashed by a vaccine's mutated virus wouldn't last since the vaccine only
contains a weakened virus strain - but that assumption is coming under pressure. Some experts now say that once Relief, Aid Enter Haiti
viruses from vaccines start circulating they can become just as dangerous as wild viruses. Relief Efforts Enter Haiti as Aftermath of
Earthquake Continues
"The only difference is that this virus was originally in a vaccine vial," said Olen Kew, a virologist at the U.S. Centers
for Disease Control and Prevention.
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The oral polio vaccine used in Nigeria and elsewhere contains a mild version of the live virus. Children who have
been vaccinated pass the virus into the water supply through urine or feces. Other children who then play in or drink
that water pick up the vaccine's virus, which gives them some protection against polio.
But in rare instances, as the virus passes through unimmunized children, it can mutate into a strain dangerous
enough to ignite new outbreaks, particularly if immunization rates in the rest of the population are low.
Kew said genetic analysis proves mutated viruses from the vaccine have caused at least seven separate outbreaks
in Nigeria.
Though Nigeria's coverage rates have improved, up to 15 percent of children in the north still haven't been
vaccinated against polio. To eradicate the disease, officials need to reach about 95 percent of the population.
Nigeria's vaccine-linked outbreak underlines the need to stop using the oral polio vaccine as soon as possible,
since it can create the very epidemics it was designed to stop, experts say. WHO is researching other vaccines that
might work better, but none is on the horizon.
Until a better vaccine is ready, WHO and U.S. CDC officials say the oral vaccine is the best available tool to
eradicate polio and that when inoculation rates are nearly 100 percent it works fine.
"Nigeria is almost a case study in what happens when you don't follow the recommendations," Kew said.
Since WHO and partners began their attempt to rid the world of polio in 1988, officials have slashed the disease's
incidence by more than 99 percent.
But numerous deadlines have been missed and the number of cases has been at a virtual standstill since 2000.
Critics have also wondered whether it is time to give up, and donors may be sick of continuing to fund a program
with no clear endgame.
"Eradication is a gamble," said Scott Barrett, an economist at Columbia University who has studied polio policies.
"It's all or nothing ... and there is a very real risk this whole thing may fall apart."
Aside from Nigeria, polio persists in a handful of other countries, including Afghanistan, Pakistan, India, Chad,
Angola and Sudan.
Aylward agreed the Nigeria situation was another unwelcome hurdle, but was confident eradication was possible.
"We still have a shot," he said. "We're throwing everything at it including the kitchen sink."
© MMIX The Associated Press. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed.
CBSNEWS.COM ON DIGG
Only an idiot (not an expert) would believe a weakened or attenuated strain would be less virulent than the wild
strain. A weakened strain has less of an MOI (multiplicity of infection) but it is only weakened as a vaccine, if it
causes the disease, when it is passed on, it is no longer weakened because the radiation or products used to
weaken the master seed is not used to weaken future generations. Because of this, why would anyone in their
right mind think that a weakened virus would stay weakened if it caused the disease. That is like taking a sip of
water and assuming due to that one sip, no water is ever needed to be drunk again. The idea of such idiocy
boggles the mind.
Take a broken health care system, combine it with an ever growing pool of Americans who have no access to
health care, and throw in single case of a vaccine-resistant disease...
We already have that--we presently have drug resistant syphillis, gonnorhea, staph, TB,
meningitis...etc. There is no such thing as a vaccine resistant disease. There may be drug resistant
diseases (bacteria or mycopathogens) but due to how vaccines work there is no such thing as a
vaccine resistant disease.
A vaccine is nothing more than material from the actual virus that is introduced to a person so their
body will recognize the real pathogen if it ever shows up and immediately deal with it. The stuff that the
body recognizes are called antigens. The stuff your body releases to combat foreign antigens are
called antibodies.
The viral antigens can be given by introducing a killed virus, a live but weakened virus or by introducing
bits of viral tissue to a healthy person. The body then takes note of the virus, catalogs it and attacks
immediately if it meets it again. The way virus kill is to go into the body and confuse it, and slow down
or not even cause the body to attack it--when this happens by the time the body becomes aware, the
person is too compromised to recover.
So vaccines give a body a heads up to a certain viral antigens. These are the identifying markers of any
foreign, living substance. So there is no such thing as a vaccine resistant disease as any part of a virus
can be used to make a vaccine, but there are virus that mutate enough to prevent an effective vaccine
from being made--because by the time the body recognizes the antigens, the virus changes it antigen
makeup.
they should stop being so cheap and give them the best vaccine
WHO/National Public Health-have many attributes in common. Operation by a board or Commission of "One
size fits all" mentality who do not want to be bothered by individual needs and the tradgic results of "Economized
Health Care". We now have unleashed a mutant polio strain that has dire consequences for Polio containment
world wide because those few who rule "WHO" refused to listen.
in my entire lifetime i have always heard of the plight of africa. its always one thing or another. however often
times they can do for themselves and dont. or destroy what has been given to them. such as farming
equipment, irrigation and such. HOWEVER at least NGO's should be allowed if desired to provide care to those
that cannot help themselves.
bonjour
c'est désolant et triste de voir d'un coté des sommes faramineuses sont dépensées dans des guerres inutiles,
et d'un autre coté les enfants en afrique et ailleurs continuent de mourir de faim et de maladies qui étaient
sencées etre disparues, eh bien elles continuent de tuer en afrique comme la polio, la tuberculose, les les mth
etc.faute de moyens..vaccins entre autres..au revoir
if your going to post on an english speaking board please respect the language and post in english or
else post on a french board.
The vast majority of Americans probably don't know how to read or speak French, so what is the point
of writing it? There is no one to read it. Or very few, anyways.
If you can read English, then you must know how to write it as well.
If you wrote in Spanish, you would have a better chance of someone understanding it.
But then there is a reason why you are doing it, isn't there? Attention, maybe?
I don't get why we're trying to rid Africa of diseases. It's so overpopulated as it is that preventing deaths there is
actually making life worse for everyone. Quality of life over quantity of life.
you can use education to help them learn how to have some birth control and abstinence, you don't
have to just let disease spread as you are suggesting.
TO rf35: And if it were YOUR death that we were trying to prevent "quality of life over quantity of life", how
would you feel about it then? Would you say, go ahead and take my life that others may live? So they
may have their quality of life as I pass out of Life? Somehow I think you would be pushing your way to
the front of the line to get an immunization shot if you thought it would save your life.
Tell you what!!! You go tell the African peoples that the vaccine is an American plot to "Rid the world of Black
peoples". While you are at it tell these people that "Any medicine or food from America is Bio-Designed to affect
the Negroid races only". This way they will reject our Aid shipments and the whole continent will die from Polio,
HIV, Malaria, Typhus, STDs, and we will end up in control of Africas wealth.
SSSSSHHHHHHEEEEEEEEEEEEESSSSSSSHHHHHHH!!!!!!!!!!
Hey, ToolMangler1, carefull with your sense of humor/sarcasm. The lefties will believe it and want to
apologize to all of Africa for the USA trying to eliminate them & steal their resources. The righties will
think it's a good idea and try to do it. :)
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to Illness
CDC reports case of woman who contracted vaccinia virus, main ingredient in the shot
By Steven ReinbergHealthDay Reporter
THURSDAY, July 1 (HealthDay News) -- After having sex with a soldier recently Infectious Disease Basics
vaccinated against smallpox, a young woman in Washington state developed an How They MRSA
illness caused by the vaccinia virus used in the shot, U.S. health officials report. Spread and How Lyme Disease
to Stop Them
Avian Influenza
This type of viral transmission, while rare, is not unheard of, according to the U.S. (Bird Flu)
Centers for Disease Control and Prevention. Cold & Flu
the form of a live vaccine, so there is always some risk of infection, McCollum said. "The vaccine is not
smallpox virus," she stressed, "but it's a closely related virus called vaccinia."
Although the woman told her doctor about her possible exposure to smallpox vaccine via sexual contact
with her recently vaccinated boyfriend, the doctor tested her for common STDs but did not test for
vaccinia, according to the report published in the July 1 issue of the CDC journal Morbidity and Mortality
The Next Big Virus: Monkey Business?
Weekly Report. A virus in search of a disease is lurking in monkeys in Asia.
Will it become the next HIV?
Despite taking the antibiotics and antiviral medications that the doctor had prescribed, the woman
continued having lesions and pain for the next three days, McCollum said.
A second doctor then sent her to an infectious disease specialist who confirmed that she had the vaccinia
Taming Ebola
virus. Researchers are getting close to defusing the threat of one
of the most dangerous diseases of all.
Vaccinia is relatively mild compared to smallpox, and the woman did not need any specific treatment. She
did suffer some pain, soreness and irritation, which eventually resolved, McCollum said.
However, "we were quite concerned that she might transmit it to her household contacts," McCollum said,
because one of her roommates had had a kidney transplant. The transplant patient was Drug-Resistant TB
Will virulent and hard-to-treat forms of TB lead to a
immunosuppressed and taking a lot of medication. "A vaccinia virus infection, particularly in an resurgence of this plague in the U.S.?
immunosuppressed individual, can be very serious and life-threatening," McCollum noted.
McCollum noted that there have been other cases of this infection transmitted from smallpox-vaccinated
individuals to others. "At CDC, we don't know about every case of vaccinia that occurs," she said.
Including this case, the CDC is aware of five similar cases occurring over the past year, she said. "All the
cases were women presenting with genital lesions that had had recent sexual contact exposure to military
vaccinees."
In addition to military personnel, others who are vaccinated include some health care workers and
laboratory personnel who work with the virus, McCollum said.
In terms of immunizations generally, McCollum said the danger of transmitting a virus via a recent
vaccination is present with vaccines that contain what's known as live virus. Most vaccines -- including
most childhood and flu vaccines -- are made from the killed virus, and therefore pose no such danger, she
said.
Infectious disease expert Dr. Marc Siegel, an associate professor of medicine at New York University in
New York City, said that "smallpox vaccine being a live virus, there is a two-to-three-week period when you
are still infectious from the vaccination site and you have to be very careful to cover it."
The oral polio vaccine is another live-attenuated vaccine, which has in very rare instances been associated
with causing polio, Siegel noted.
However, the vast majority of vaccines utilize killed virus so this is not a problem with them, he reiterated.
"One exception is the inhaled flu vaccine. You could transmit influenza in a very weakened form to an
immunocompromised person," he said. "But vaccinia is more infectious than that."
"This is a reminder that live virus vaccines, which are increasingly in disuse, carry their own risk of minor
infection and should not be used in immunocompromised people," Siegel said.
Live virus vaccines do have one advantage, in that they create a stronger immune response than do killed
virus vaccines, Siegel added.
More information
For more information on smallpox, visit the U.S. Centers for Disease Control and Prevention.
SOURCES: Andrea McCollum, Ph.D., Epidemic Intelligence Service officer, U.S. Centers for Disease Control and
Prevention; Marc Siegel, M.D., associate professor, medicine, New York University, New York City; July 1, 2010,
Morbidity and Mortality Weekly Report
About Health & Fitness MSN Health & Fitness does not provide medical or any other health care advice, diagnosis or treatment. See additional information.
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http://www.cogforlife.org/merckresponse.htm
Still Need More Proof That Aborted Fetal Cell Lines Are Used in These Vaccines?
Let Merck tell you in their own words...as convoluted as they may be! And if Merck says no further
fetal tissue will be needed now or in the future, why did they just buy the rights to a new aborted
fetal cell line PER C6? Read the press release!