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Occupational &

Environmental
Toxicology
Erwin P. Carabeo, M.D., FPCP
Department of Pharmacology
San Beda College of Medicine

Occupational Toxicolgy

Chemicals found in the workplace

Major emphasis of occupational toxicolgy:
1. identify agents of concern
2. identify the diseases they cause (acute & chronic)
3. define conditions under which they could be used
safely
4. prevent absorption of harmful amounts of these
chemicals

Workplace Regulations

PELS
- permissible exposure limits
- have the power of law
- OSHA

TLV
- threshold limit values
- reference points in the evaluation of potential
workplace exposures

Environmental Toxicology  deals with the potentially deleterious impact of chemicals (pollutants) on living organisms  environment: air. soil and water .

ADI  acceptable daily intake  daily intake of chemical from food that during an entire lifetime appears to be without an appreciable risk  FAO/WHO .

Ecotoxicology  toxic effects of chemical and physical agents on populations and communities of living organisms  includes the transfer pathways of agents and interactions with the environment  traditional toxicology: toxic effects on individual organism .

Toxicologic Terms  Hazard – ability of the chemical to cause injury in a given situation or setting. assessment is based inherent toxicity of the substance and the amounts to which individuals are liable to be exposed  Risk – the expected frequency of the occurrence of an undesirable effect arising from exposure to chemical or physical agent .

atmospheric pollutants: inhalation and transdermal routes .industrial setting: inhalational is the major route of entry .Toxicologic Terms  Routes of Exposure – route of entry of chemicals into the body .water and soil pollutants: inhalation. ingestion and dermal contact .

Toxicologic Terms  Duration of Exposure – length of exposure to chemicals .acute exposure: single or multiple exposures lasting from seconds to 1 or 2 days .chronic exposure: multiple exposures continuing over a longer period of time .

its mobility through air. whether or not bioaccumulation occurs 4. degradability of the substance 2. water and soil 3.Chemical and Physical Characteristics that Determine Environmental Impact of Toxicants: 1. transport and biomagnification through food chains .

water and soil … exhibit bioaccumulation … exhibit biomagnification .!!! The pollutants that have the widest environmental impact … are poorly degradable … are relatively mobile in air.

 Bioaccumulation – accumulation of chemical within the tissues of an organism that occurs when the intake of a long-lasting contaminant exceeds the organism’s ability to metabolize or excrete the substance  Biomagnification – exponential increase in the concentration of a contaminant as it passes up the food chain .

Air Pollutants .

5 Major Air Pollutants  carbon monoxide (CO) – 52%  sulfur oxides – 14%  hydrocarbons – 14%  nitrogen oxides – 14%  particulate matter – 4% .

Sources of Air Pollutants  transportation  industry  generation of electricity  space heating  refuse disposal .

tasteless and non-irritating gas  by product of incomplete combustion  average concentration in atmosphere: 0.Carbon Monoxide  colorless.1 ppm  in heavy traffic: > 100 ppm . odorless.

Carbon Monoxide Mechanism of Action  combines reversibly with O2 binding sites of hemoglobin carboxyhemoglobin  failure of oxygen transport and transfer of oxygen to tissues  affinity for hemoglobin is 220X that of O2  brain and heart are the most affected .

convulsions.Carbon Monoxide Principal Signs of CO Intoxication: psychomotor impairment  headache  confusion and loss of visual acuity  tachycardia. tachypnea syncope and coma  deep coma. shock and respiratory failure  .

hyperbaric oxygen (2-3 atm): 20 minutes  .100% oxygen: 80 minutes .Carbon Monoxide Treatment for acute intoxication: removal from exposure source and maintenance of respiration  oxygen administration: .room air: elimination half time of CO – 320 min .

Sulfur Dioxide  SO2  colorless irritant gas  generated by the combustion of sulfur-containing fossil fuels .

Sulfur Dioxide Mechanism of Action  on contact with moist membranes sulfurous acid severe irritant effects on eyes. mucus membranes and skin  inhalation of SO2: bronchoconstriction .

Sulfur Dioxide
Clinical Effect and Treatment
irritation of the eyes, nose and throat
 reflex bronchoconstriction
 in asthmatics: acute asthmatic attack
 no specific treatment for SO2; treatment of the
irritation of respiratory tract and asthma

Nitrogen Oxides

nitrogen dioxide (NO2)

brownish irritant gas associated with fires

Nitrogen Oxides
Mechanism of Action
insoluble deep lung irritant capable of producing
pulmonary edema
 50 ppm: moderately irritating to the eyes and
nose
 50 ppm for 1 hour: pulmonary edema or chronic
pulmonary lesions
 100 ppm: pulmonary edema and death

cough.Nitrogen Oxides Clinical Effects acute exposure: irritation of the eyes and nose. chest pain  clinical signs may subside in about 2 weeks  second stage: abruptly increasing severity. mucoid or frothy sputum. dyspnea. recurring pulmonary edema and fibrotic destruction of terminal bronchioles  .

sedatives and antibiotics  .Nitrogen Oxides Treatment no specific treatment for acute intoxication  management of deep lung irritation and pulmonary edema: adequate oxygenation and alveolar ventilation  drugs: bronchodilators.

Ozone O3  bluish irritant gas normally occurring in the atmosphere  absorbent of UV light  workplace: ozone producing devices for air and water purification. high voltage electrical equipment  also found in polluted urban air  .

Ozone Clinical Effects effects resemble that of radiation  0.8 ppm: impairment of pulmonary function  . substernal pain and dyspnea  >0.1 ppm: changes in visual acuity.1 ppm for 10-30 min: irritation and dryness of the throat  >0.

Ozone  Treatment  similar to treatment of Nitrogen Oxide exposure .

Solvents .

cleaning agents  carbon tetrachloride. tetrachloroethylene. trichloroethylene. degreasing agents.Halogenated Aliphatic Hydrocarbons used as: industrial solvents. chloroform. methyl chloroform  CCl4 and trichloroethylene have been removed from the workplace  .

Halogenated Aliphatic Hydrocarbons Mechanism of Action & Clinical Effects CNS depression. CCl4 – most potent  nephrotoxicity  carcinogenicity  . chloroform – most potent  chronic exposure: impaired memory and peripheral neuropathy  hepatotoxicity.

Halogenated Aliphatic Hydrocarbons Treatment  no specific treatment for acute intoxication  management depends on the organ system involved .

nausea. coma . locomotor problems. headache .chronic exposure: bone marrow toxicity  aplastic anemia. leukemia.acute toxic effect: CNS depression . drowsiness.7500 ppm for 30 min: fatal .>3000 ppm: euphoria.Aromatic Hydrocarbons BENZENE . lymphoma.component of premium gasoline .250-500 ppm: vertigo. myeloma .

at 800 ppm: severe fatigue and ataxia . skin and eye irritant.Aromatic Hydrocarbons TOLUENE (Methylbenzene) .000 ppm: rapid loss of consciousness .at 10.fetotoxic .CNS depressant. .

CNS depressant and skin irritant .Aromatic Hydrocarbons XYLENE (Dimethylbenzene) .substitute for benzene in degreasing operations .no myelotoxic properties of benzene .

Pesticides .

Organochlorine Pesticides  DDT (chlorophenotane)  benzene hexachlorides  cyclodienes  toxaphenes .

testicular cancer (DDE).Organochlorine Pesticides Human Toxicology  interfere with activation of sodium channels and inhibition of Calcium ion transport  enhanced excitability of neurons  CNS stimulation  DDT: tremors  convulsions  no specific treatment of acute intoxication  increased cancer risk exposed to halogenated hydrocarbon pesticides: brain cancer (DDE). non-Hodgkin’s lymphoma .

Organochlorine Pesticides Environmental Toxicology considered as persistent chemicals because of slow degradation  bioaccumulation in aquatic ecosystems  induce significant abnormalities in the endocrine balance of sensitive animal and bird species  .

sarin and tabun)  absorbed by the skin.Organophosphorus Pesticides  used to combat a wide variety of pets  based on compounds which were developed for use as war gases (soman. respiratory and GI tracts  undergoes rapid biotransformation .

Organophosphorus Pesticides Human Toxicology  mechanism of action: inhibition of acetylcholinesterase  accumulation of acetyl choline. some may have direct cholinergic activity  altered cognitive and neurologic functions  inhibition of neuropathy target esterase  progressive demyelination of neurons  paralysis .

Organophosphorus Pesticides Environmental Toxicology not considered as persistent pesticides  relatively unstable and breakdown in the environment as a result of hydrolysis and photolysis  small impact on the environment  .

Carbamate Pesticides mechanism of action: inhibition of acetylcholinesterase  possess the toxic properties associated with organophosphorus pesticides  clinical effects are of shorter duration than those of organophosphorus pesticides  considered to be nonpersistent pesticides  .

pyrethrum . rotenone.Botanical Pesticides  pesticides derived from natural sources  nicotene.

Botanical Pesticides Nicotene  obtained from the dried leaves of Nicotiana tabacum and Nicotiana rustica  rapidly absorbed from mucosal surfaces  reacts with the acetylcholine receptor of the postsynaptic membrane  depolarization of the membrane  treatment directed at maintenance of vital signs and suppression of convulsions .

Botanical Pesticides Rotenone  obtained from Derris elliptica. dermatitis. L urucu  oral ingestion: GI irritation  conjunctivitis. Lonchorpus utilis. D mallaccensis. pharyngitis and rhinitis can also occur  treatment is symptomatic .

tetanic paralysis  treatment directed at management of symptoms. convulsions. mephenesin . pentobarbital.Botanical Pesticides Pyrethrum  may be absorbed after ingestion or inhalation. ivermectin. absorption from skin is not significant  not highly toxic to mammals  CNS effects: excitation.

Herbicides .

2.Chlorophenoxy Herbicides 2.4.5-T)  used for the destruction of weeds  toxicity ratings:  4 – human lethal dose 50 – 500 mg/kg  3 – human lethal dose 500 – 5000 mg/kg  large doses: coma and generalized hypotonia  confirmed link with non Hodgkin’s lymphoma  .4 Dichlorophenoxyacetic acid (2.4.5trichlorophenoxyacetic acid (2.4-D).

Glyphosate most widely used herbicide in the world  contact herbicide: absorbed through the leaves and roots  significant eye and skin irritant  have little persistence and lower toxicity than other herbicides  no specific treatment for glyphosate toxicity is available  .

alveolitis and progressive fibrosis  .Bipyridil Herbicides Paraquat – most important agent in this class  mechanism of action: reduction to free radical species  toxicity rating of 4 (human lethal dose of 50-500 mg/kg)  after oral exposure: hematemesis and bloody stools  delayed toxicity: lung edema.

use of adsorbents  after absorption.Bipyridyl Herbicides  hepatic. renal or myocardial involvement  interval between ingestion and death may be several weeks  treatment: gastric lavage. use of cathartics. treatment is successful in less than 50% of cases .

Environmental Pollutants .

Polychlorinated Biphenyls PCB’s. bioaccumulation in food chains  foods: major source of PCB residues in humans  . poorly metabolized. wax extenders and flame retardants  industrial use and manufacture was terminated in the US in 1977  persist in the environment: highly stable. plasticizers. coplanar biphenyls  uses: heat transfer fluids. lubricating oils. highly lipohilic. very resistant to degradation.

pancreas and thyroid  deficits in childhood intellectual function was seen in children born to mothers who had eaten large quantities of fish contaminated with PCBs  . breast.Polychlorinated Biphenyls occupational exposure to PCBs: dermatologic problems. hepatic involvement and elevated plasma triglycerides  increase in various cancers: melanoma.

Asbestos has been used widely for over 100 years  has been shown to cause progressive lung disease characterized by fibrotic process  higher levels of exposure: asbestosis  cigarette smoking increases the incidence of asbestos caused lung cancer  other cancers: mesothelioma. colon cancer. laryngeal cancer. stomach cancer. lymphomas  .

Metals .

cadmium and uranium . manganese. lead and mercury  new occupational exposure and poisoning: beryllium. occupational and environmental poisoning with metals is a major health problem  classic metal poisons: arsenic.

nuclear weapons. non sparking quality  uses: dental appliances. computer components  highly toxic by inhalation  inhalation of beryllium particles progressive pulmonary fibrosis (chronic beryllium disease) and cancer  prognosis is poor  .Beryllium light alkaline metal.

fever and malaise  chronic exposure: pulmonary fibrosis. shaking chills. television. severe kidney damage  .Cadmium uses: batteries. solder. pigments. cough. plastics  toxic by inhalation and ingestion  cadmium fume fever: acute respiratory disorder common in welders. plating operations. semiconductors.

Thank you! .