What Every Chemist Should Know About ~eratogens-chemicals that Cause Birth Defects

Roger E. Beyler and Vera Kolb Meyers Department of Chemistry and Biochemistry, Southern Illinois University, Carbondale, IL 62901 Between 2% and 3% of all babies horn in this country (and in other countries where data are available) have serious malformations requiring medical attention ( I ) . Society in general and chemists in particular are becoming aware that chemicals cause some of these malformations in the newborn human. About one third of these conditions are life threatening. More than twice as manv defects are detected with increasing age of the child as arbrecognized at hirth. The result is that prenatal mnlformations account for nearly half of the patients in pediatric wards in our hospital* (2). Thus, there is need ior impnwement uf the initial health of our uffspring. I t is a major problem and deserves a high priority in any program to improve the nation's health. Only a small proportion of these hirth defects can he traced to known and certain causes. About 5%and 10%respectively, of the defects are known to he due to chromosomal aberrations and gene mutations. However, since recognition of gene mutations and minor chromosome aberrations in humans is exceedingly difficult, it is possible that a far greater proportion of hirth defects are due to genetic causes. Less than 3% of malformations are known to he caused by chemicals suhstances (3).That leaves a large percentage of defects unaccounted for a t present.' Some of the unaccounted for defects are undouhtedlv due to so-called environmental (and mostly chemical) hazards. Thev prohahlv include things found so commonly in our environment that we overlook them: ethyl alcohol, carbon monoxide from cigarettes, or caffeine from excessively used stimulant drinks. Or for some they could h e d m toa parent's chemical exposure on the job. A few hirth (lefects are probably Data on birth defects are not very reliable. Percentages cited above are conservatively low. A very recent publication gives reproductive abnormality and impairment data that are substantially greater than in references 1, 2, and 3: "Chemical Hazards to Human Reproduction," 1 1 5 and 111-24 to Council on Environmental Quality,January 1981. pp. 1 26. This book (284 pp.. including referencesand appendix) is for sale from the Superintendent o f Documents, U.S. Government Printing Office, Washington, DC 20402. due to over-the-counter and prescription drugs. I t is ohvious in the latter example that a large percentage of pregnant women take one or more drugs early in pregnancy, even if it is onlv for a minor health orohlem. Some of these d r w s mav . not yet he recognized as hazardous to the embryo, as was true for DES thirtv . vears ago. The general class of chemical suhstanccs considered here is called teratogens, and knowledgeahle chemists should lrrcome informed on this subject.
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What I s a Teratoaen? The field known as terarology may be defined as the scientific studv of hiolwical monstrosities and malfunctions. The word "teraiogen2' i i derived from the Greek word teratos meaning monster and the Latin word cenus meaning hirth. A teratogen, then, is an agent which a& during pregnancy to oroduce a ~hvsical or functional defect in the embryo, fetus, or iffspring i4 j . Physical defects, such as those found in Siamese twins, douhie-headed humans, dwarfs, etc., are overt and have been observed and recorded on stone and wood since time immemorial. The history of ancient (5) and of more recent (6) teratology is rather interesting. Maternal impressions in early times (for examnle. a mother friehtened hv a rabbit had a child ~ - - ~ .- ~ with a harelip) br the not-so-ancient use bf x-ray therapy for pregnant women are historical facts that put our present state of knowledge into perspective. Functional defects, such as the impaired mental ability that is a risk in offspring of women who use excessive amounts of drugs or alcohol during pregnancy, are more covert than are physical defects. Establishing cause for various functional defects will continue to challenge teratologists for years to come. An impaired function, in contrast to an ohvious structural malformation, is often not detected at hirth. Eventually, parental recognition of the defect occurs with the child's increasing age.
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Teratogens versus Other Reproductive Hazards in the Workplace Much of our recent teratogen concern has been devoted to

Volume 59

Number 9

September 1982


The focus of attention is most often on the reproductive hazards for women of child-bearing aee workine in the chemical industry. bearing National Research Council sponsorship and review. we have looked for biological activity classes (or groupings) and for structural classes that are multiplicated in the teratogen list. etc. (24). carcinogens.nractices .22) from an RTECS computer search had in common. One health hazard briefly covered is that of emhryotoxins. industrial hvgienists. Even a small exposure of short duration to a potent (new and untested) teratogen might present a great risk. More recent coverage. Greater Eare must he exercised when one is working with new compounds. Most (like aspirin. Teratogen precautions are also included in the ACS safety publication for use in academic lahoratories (13). Teratogens in the Academic Laboratory What ahout smaller amountsofa terntogen than what one might he exposed to in manufncturing. one might expect the list of teratogens and that of mutagens to have many identical entries. as evidenced by use of the Ames (mutagen) test for screening potential carcinogens. since they may be teratogenic. teratogens. some overlap between teratogens and mutagens has already been reported (11). this paper isdesigned toadd to the hooklet bv inforniine chemists in teaching lahoratories about a few basic facts and where to turn for more complete information on the suhject of teratogens. I t is a chapter titled "Drugs in Pregnancy" found in a paperback hook published by Consumers Union (19). particularly one that is among our "common" reagents and solvents. the embryo. Academic teaching laboratories are also specifically considered in this useful book. others are found in our environment in low concentration. As described below. Information on human teratogens. two-volume publication on the handling of teratogens. In a recent listing there a substantial duplication of chemicals cited as teratogenic and those cited as carcinogenic (156 out of 527 teratogens are carcinogenic) (9). ~ e .h & elooked f i r chemical features and biological activities that 527 teratogens (4. Functional group considerations for teratogenicity. as we endeavored to oreanize the data. requests for copies came from chemists and their spuuses. the same safety procedures must be used for teratogens that are used for any very toxic material. I t is of interest to examine chemicals that are teratogens and those that are mutagens.000 different substances (20). found in the literature prior to our search (4. and mutagens underlines the fact that safety methods are essentially the same for all three of them (12). Its files of information are very com. prehensive. or pnckaging processes? A resrarch chemist must take extra precnutiuns.ailnhle. I t may he primarily a question of whether the agent has its effect on ova. protection of both male and female employees to identical levels of air contamination may be justified. the phar~acolog&al procedures and animal species used to test these are given. hormones. toxicologists. a compendium of toxicity data abstracted from the scientific literature. I t also covers environmental teratogenic compounds. Therefore.rmativnsmd malfunctions ubserved. A very recent book on hazardous laboratory chemicals. 'I'he Kn\.so-called "reproductive hazards in the workplace.ironmenrd Trrntolwy Information Center (ETICJ was established a t Oak Ridge National Laboratory in 1975 to "collect. Journal of Chemical Education . primarily from the viewpoint of drugs used in the mid-sixties. The National Institute for Occupational Safety and Health (NIOSH) has published annually a Registry of ToxicEffects of Chemical Substances (RTECS). as svell as a concise description of'the type uimalfi. (3). etc. notahly the types of drugs. and several others. spermatazoa. of the hazards: carcinogens. Xlutivated by that response. An average of about 1500 new toxic compounds are added every quarter. biological. Obviously. polvhaloaenated biphenyls. Most would a g r e e i h s an extra iegree of nrotection is needed for these women because of increased susceptibility of the embryo/fetus to chemicals as compared to adults in general. T h r list of over five hundred teratogens the lxx~klet contained seemed to fill a minor void on the subjwr. route of exposure or administration.) for nearly 34. Standards that are set bv safetv . organize. Most people 760 have heard about the effects of thalidomide. some of the chemicals on the list we obtained are very common in everyday life. and disseminate information on the evaluation of chemical. 85 new teratogen listings were added during approximately 9 months in 1979 (21). and management personnel in industry. I t is a generally accepted view that mutagens and carcinogens have substantial overlap as well (lo). rather than teratogens. but what other compounds are in that category? When the booklet of Meyers a n d ~ e y e r 14) s brcame a\. deals with health hazards in the laboratory as distinct from those in pilot plant or manufacturing operations (14). It was not our desire to use a descriptor approach (23) for a few functional groups we might choose. species exposed. formulating.221 are limited to a few classes: sulfonamides. because safe levels of exposure have not t m n estahlished for most teratogens. However. government scientists. ~ e r a t o l o ~and k s epidemiologistsare becoming increasingly convinced that birth defects can result from occupational exposure of males to chemicals that cause sperm damage. . This mav be more ef" fective a t a later stage of structure-activity analysis. A recent. one should not underestimate the risk from prolonged exposure to a weakly teratogenic compound. These "birth defect via sperm damage chemicals" may best be classified as mutagens. I t is the place to ao for information on teratogenicitv of chemicals and other t&atogenic agents. with some emphasis on environmental teratogens and how to deal with the problem. Good safetv will include nrotection from aU three . ~ h o m & ~ shepard . The most comprehensive treatment of teratogenic drugs from the clinical perspective is a book by Nishimura and Tanimura (18). from pharmacologists. 'i'he most recentlv updnted rdition of this mtalog (1980) has w r r one thousand &irs. The 1978 edition of RTECS includes toxicity data (type of toxicity. any academic lab may have some teratogenic risk.8). Literature on Teratogens Information about what compounds are teratogens has not been readily available to the average chemist. is covered by Smithells (16). The motivation for our search of the literature for a list of teratogens was an inquiry from a pregnant student who was concerned about working in our undergraduate teaching lab. description of exposure. and physical agents for teratogenic activity" (15). phthalimides. will become more frequent." the subject of several recent articles in Chemical and Engineering News (7. There is also one very down-to-earth reference on teratogens that is worthy of mention. Therefore. toxic dose levels. I t is written for the publicat-large and would be suitable reading for students in nonmajors chemistry courses or for high school students. is provided by Miller (17). Others have also been looking for biological classes of teratogens. or the fetus. Probably the most concise source of data on chemicals which are teratoeenic is a reference book (neriodicallv updated) by the w h k n o w n teratologist. and mutagens. as more information about teratogenic hazaards becomes available. - - Precautions for Interpretation of the Teratogen Llst from RTECS The obligation of chemists and especially of chemical educators to inform people about the hazards from teratogen exposure is obvious.and toxicologists need to pay attentionto such considerations in the immediate future. When use of teratogens in lahoratories cannot be avoided.eneineers. Such inquiries by our students.

several polypeptides (angiotensin. genetic susceptibility (26).reas. nutritional factors (251. alkvlmercurv comnounds. hydantoins (which could also be considered to be imides). like imides. believing that vitamins are harmless. the h o s t notorious teratogen). nervous. ganglion blocking. Classliication of Teraioaens bv Chemical Structures all chemical agents at a high enough dose can result in embryo or fetal lethality. and rabbits. alkaloidal toxic. e c t . artivities knwm t#. The data obtained are not evaluated and represent in such instances no more than a preliminary screening test. caused a congenital palsy which sometimes was not noticed until children reached grammar school age.fetotoxic" or. Cnrcinogens. responsible ..ntf~ct wII growth and reU division are widen( in Tahle 2. Japan. However. Then too. alcohol) nrobablv .fetopathogmir" agents in the teratogen classification (291. Mice. including amines. . benzanthracene. Concentration of chemicals in an animal embryo after intravenous or intraperitoneal injection. the dose levels for m a w of the animal tests are huge in comparison with what a women might receive. whoho not include '. and polynuclear hydrocarbons. hydrazines. The chlorinated hydrocarbons (including 2. of Teratogenic Compounds It hecame obvious during the writing of structural formulas from the RTECS computer-produced names that two useful groupings of the compounds were possible: a chemical structure or functional group classification and a biological activity classification. others. Tahle 1 illustrates the clas&fication of teratogens by chemical structure. include dozens of teratoeenic comnounds. Previous literature sources (particularly 1. reauire . excessive dosaee in adults. and nitrosamines are generally carcinogens. which are the most commonly used laboratory animals.. CCla. One must hear in mind that manv of the com~ounds on the teratogen list have been so identiffed on the basis of a single study performed on just one animal species. Also.. Other N-containing groupings. carbamates.18) have identified a number of teratogenic classes. etc.) and the polynuclear hydrocarhons (methylcholanthrene. such as CO. nicotine. thiocarbamates. galactose. antineoplastic agents).32). Primates. ~er&ogenic effect ofthese is of concern. and heaw metals. A few teratogens on the list are unexpected. CHC18. . first identified in Minamata Bay. and hexachlorohenzene. since many women take self-prescribed massive doses of all kinds of vitamins. henzvnvrene) have carcinogenic vroverties. and suifonamides. none has produced such a comprehensive listing as we are giving in the tables that follow. vinyl chloride. rats. claiming that u hile r. not all chemicals are capable of causing a specific teratogenic defect.. azo dyes. Sulfur-containing teratogens usually have phosphorus (thiophosphates) or nitrogen also present: thiadiazoles. quaternary ammonium salts. pesticides. Possibly their teratogenicity is due to their hormonal. eastrointestinal. and phenothiazines (chlorpromazine. the animal data in this areaunfortunately donot transfer well to the human. etc. chlorinated hydrocarhons. which are similar to humans in that r e s. purines. Azo compounds. immunogenic factors (27. Thtu vmved ro he rhe case.ltor. sex hormones. lead compounds. ~ l ' s z it . as for volatile materials in the envirohment). are not used routinelvdue to their high cost. is so important and why chemists share with physicians. have only three or four specific teratogen examples.). are usually rather special structures.. Many specific examples of these functions." or similar categories. Radiation. compounds that affect or control the growth of particular organs or components of the hodv (sex hormones. so their teratois not unexpected (oide & & a ) . Nitrogen heterocycles such as piperazines.) of the develonine emhrvo. There are teratoloeists. for example. toxicologists.) teratogens are not classified into "proven" and "suspected" (as with carcinogens). That is why interpretation of the data . larger doses than are usually taken by the average person in oraer to become hazardous. vud Tahle 2 gives the-most obvious biological activities we found on examination of the list of teratogens. like the indandiones. some mentioned before. however. 'I\)begin with. the method of administration of compounds to animals is often different from those that are most frequent in human exposure (oral.irt~lally Table 1. have a different. and pyrimidines may each have their teratogenicity explained for a variety of biological reasons (uide infra). expected to give abnormal cell division (and thus teratogenic) effects. Further work is obviouslv needed tolearn whv the two milk-related sugars are on the iist. They are generally quite toxic to animals and humans. However. imides ~includinrrhalidurnide. . Some. The mercury compounds certainly are lethal in animal tests a t sufficientlv high dosaee hut clearlv give functional abnormalities (teratogenicity) in humans a t the appropriate dose (30). etc. The distinction is not so simple. with N bonded to C=O or S=O. may he considerably higher than from other routes of administration. more primitive placenta than humans. include the full complement: nit~osamines. It is norrworthy that a numl)er 1)1nitrogen classes of rornoounds anuenr: . A good correlation in animallhuman teratogenicity data is by no means routine. nmides. are on the list. or "strong. is reasonable topredict that general celipoisons. penta-. In addition. and antidiabetic aeents): and cheki'cals which could affect'major systems (circ. triazenes. Minamata disease from methylmercury poisoning. One mieht hone that there would be relativelv few surnrises when the teratogens were examined from the standptint of their hiolwical acti\itv." "medium.281.erse effect on an ~mbryoffetus is exwsed at sublethal doses.4-D. and viral infection should also be identified as causing birth defects." "weak. The alkaloids in the list are most often those that are known to have antineoplastic activity. effects. Teratogenic antineoplastics include: nitrogen mustards and alkylating agents of all varieties. sulfonamides. etc. .. hradykinin.caffeine. etc. insulin. the extrapolation of animal data to humans seems reasonable for many chemicals such as: chemicals which affect cell division or cell growth (antibiotics. With few exceptions to the known human teratogens (such as thalidomide. insulin) and a few amino acids. or inhaled. such as lactose. and others the task of giving cautious and well-considered information to the public. will wheh the mdther have an ad. tiiazines. purine and Classes Acrylater and Methacrylater Alkaloids Amldes and Sullonamldes Amlnes and Ammonium Salts A m Comwunds and Hvdradnes Cmbamates and Thiocarbamaiw Chlorinated and Polynuclear Hydrocarbons Heavy Metals Indandiones Imldes Nitroso Compounds Phenethylamlner Piperazlnes Polypeptides Purines and Pyrimidines Salicylates Steroids Sulfur Heterocycles (wch as Thladlaroles and Phenolhlarlnes) Thiophosphates Triazenes and Trlazlneo Ureas Volume 59 Number 9 September 1982 761 . The latter two vitamins are also known to cause hypervitaminosis s v m ~ t o m s after vroloneed. and fat soluble vitamins such as A and D (31. not enough data are available to permit such classification.

I t indicates how one may use good judgement about teratogenicity for any new chemical that fits into either (or both) of the categories found in Table 1or 2. A number of aeents that affect the circulatorv in. They shoild be used with ereat care.762 of chemicals? A partial answer is presented in our publication (22).aipl&ation. A number of barbiturates are listed. for examole) and a t least one plant growthregulator (indoleacetic acid) are included.pr. or rubber gloves. In our academic research laboratories we must inform all personnel of teratogen hazards and enforce safety procedures. bmdvkinir~. Lack of knowledge is one of the main reasons for fears about chemicals. . are noticeablv on the list and merit caution in thei.Table 2. Anticoaau~ant~exhib hemorrhagic it hazards for the fetus or embryo: coumarins are quite dangerous.4. Hvmotlw. Some of these are presented in Tahle 3. Some Common Chemicals which are Teratogenlc ( 4 ) Glyclnonltrlle Herachlorobenrene lodoacetic Acid Lead Anllblotlu Anticoagulants Antlepileptlw Antihistamines (and the reldsd antl-nau~aa drw) AntineOplastlCs Antlpsychotlw Blood Pramre Rsgulatm (VaMeonnrlctorsand Vasodilators) Cardnogerm CNS D e ~ r e ~ a niAnaNthdlcL ls . and some of the tetracvcline varieties. . Funglcldss. A few predicted "positives" that prove to he "false" as teratogens are better than having a family live through many years with a child having a birth defect. are on the list. Responsibility of those in the teaching profession also extends to informing the public-at-large. eroun. including thiadiazoles and xanthines (caffeine and theophyline) are on the list.un(s Dlruetics Gangllon Blocking Agents Hormones. and thiophospbates are on thelist. Chemical companies are increasingly showing concern that candidates for emnlovment are well informed about safe handling of chemic&"(34. heparin would be safer. safety measures equivalent to those for handling carcinogens (33) should be followed. Often we have taught more about environmental chemical hazards in our non-majors courses than in the standard courses for majors. Only a few faculty members will be involved in research that has maior t e r a h e n risk: however. However. Several diuretics. or with chemicals which are listed in RTECS as teratogens. Classification o l Teratogens by Biological Actlvltles Table 3. solvents (benzene and DMF are on the list). The maior insecticide classes of carhamates. such as solvents and simple reagents. . One finds the complete gamut of pesticides: herbicides (2. ~ " n i i rides. The antiepileptics one finds include hydantoins. and alkaloids used for cancer treatment (like vincristine and vinblastine). Often. Those of us in the education orofession orobablv have a greater obligation than chemistsin general to deal with teratoeen data. Narcotics. many are likely to teach a class that deals with some aspect of the suhject. and reser~ine) are found in'l'sble 2.35). thouah nor as broadlv svrawd.chLas adinomycin D and kitom$cin C). which are generally considered to be general CNS depressants or hypnotic-sedatives.. chemists are not even aware of a teratogenic hazard! Unfortunately. Many teratogens in the list are lethal to plants or lower animal forms.. We cannot ban salicylates.5-T and 2. superficialiy it may appear that these inconveniences are not justified since most of the teratogens from the list are of a "suspected"or "vaguely suspectedk type as far as humans are concerned. we must delete reaeents. In many cases. antifolic acid aeents (methotrexate). Hallucinogenic agents like LSD and mescaline are listed. As with carcinogens in the teaching laboratory. because our students are novices in the field. and preparations that involve teratogens. barbiturates. A very large group of activities in Table 2 relate to an effect on the nervous system. Many people worry about anything that has a chemical name. succinimides. not sprayed in large auantities in PODulated areis hecause of thiir possihle t&atoyenicity. nant women. Diuretics are frequently taken by women and may be prescribed during pregnancy to counteract fluid retention. Both cannabis and tetrahydrocannabinol appear on our list. When one works with such chemicals. A few antibiotics not used for cancer. Anti-depressants and ganglionic blocking agents (like tetraethylammonium chloride) have representatives among the teratogens.rs) CNS Stimulants and Antid. cluding w ~ n e that affect blood pressure (such as angiotensin. . Antlhormones (and hnlratlvea) Pestlsldes (Herbicides.. svstem. ranging from applied bio-medicinal research to pure mechanistic studies. " . and oxazolidines. That ought to change. Inrectlcldes) Pshychotmimetlcs (or Haltuclnog-) Vltaminr lfat sotublab - AcryIIc Acid Anlllne Benzene 2-Butanone Cadmium Carbon Monoxide Carbon Tetrachloride Chlorolorm Diphenylamine DMF OMSO Ethanol Formaldehyde Mercury Nltrobenzene Nltrous Oxide Phenol Polychlorbatedand Polybromlnated biphenyls (PCB and PBB) Salicyclb Acid Toluene pyrimidine antagonists (such as 5-fluorouracil and 6-mercaotoourine). as are representatives of two other major drug abuse categories: narcotics and CNS stimulants. . more often than not. Compounds having general chemical structures presented in Table 1andlor having general biological activities presented in Tahle 2 are very often synthesized in the laboratory for a variety of reasons. Our microbiologist associates have long dealt with similar problems in working with viruses and more recently in carrying out recombinant DNA research. Tranquilizers and antipsychotics include meprobamate and chlorpromazine. Research with teratogens and potential teratogens deserves similar consideration. The application of these safety measures means that minor inconveniences (like a hood or glove box for volatiles. . This is an area in which we can set an example of good practice for both our students and the chemical profession in general. Debate continues in some quarters about the hazard of marijuana use by ~-preg. - Conclusion: How t o Use Teratogen D a t a How should chemists use the RTECS data on teratogenicity . are on the list. the benefit from diminishing the risk in cases where the teratogen hazard is real more than compensates for any minor inconvenience in instances where the teratogen hazard is small or does not exist.4-D. and care in disposal) will he introduced. . such as several from the strentomvces . many very common chemicals. antibiotics (s. The obligation to judge the risks and establish needed procedures obviously lies with the faculty member directing the research. which deals with makine " an educated euess about the teratogenicity of chemical compounds. chemists work with the same type of compound for years. caffeine. Our obligation in the classroom to inform students about teratogens is perhaps even greater. Sedatives. or etha- Journal of Chemical Education . and Tranqdllz. whether they are listed on food labels or on a prescription drug from the doctor. Analasslcs. chlorinated hvdroc&ons.

.A7 .p. and on-line mmputerdata base (updated quarterly). (181.W1. 1973...nol. L.B. Wilson. "Registry of Toxic Effect. 113-130. American Elsicvier Pub1 Co. Printed edition: Superinfendent of Document*. ..2. LippinmUCo. 68. H..453 pp. I... C ~ M Keufman. (8) Rawls. Chicaeo. S. F. Nsws. New York. R. "Prudent Practices for Handling Hslsrdovn Chemicals in Labonrtories. ~13. E n g Newa. Ref. pp. L..(8) 28(19801. (Editors]. J.. Ine." NIOSH GPO Stack 017-033. evailabla from the suthore a t cost ($3. 1963. (Editor). R.p~.. "Methods for Detection of Environmental Agent* that Produce Congenital Defeds. J. 1976. V. and Warkany. DC.. Press. miaofiehe issue (updated quarterly). pp. L. (6). A337 (1976) Volume 59 Number 9 September 1982 763 ." 5th Ed. R.snd Pryae-Davies. PlenumPr~ae. M. Rsbenstein. and Cevender. Mutagem. 5. H. ~ ~ Ref. (9) Ref.. (5) Wsrkany. (25). 21&250 Ref (251. J.W352~1. 101-108. (12) Walters.Vol." Ann Arbor Science Publ. 3.NY..AeademicPrpas.K. R E. J. Miller. (1) Rswls. "Clinical Aspem of the Teratogenieity olDrue. E n 8 Nems. W. pp. Ref. U. "Catalog of TerafgenieAgent*. and Mamis. Thomas. but we can warn people about the possible danger from excessive use of these during pregnancy. in "Birth Defectp: Fishbein. pp.New York. D.. . ?.printededition (updated ennudly). Ann Arbor.. .C. D.in "Chemical Mutagens.6-16. 197I. or when taking any drug.. 3rd Ed.1979 (microfiche). and Beyler. of Chemical Subtanees. ReL (11. "Safety in Academic Chemistry Laboratories: A Puhlieafian of the ACS Committee on ChemicalSafety. Chicago.H.." National Academu Pres. J. Washington.. technicians.(Editor).in ''Advances in Tcratolagy. 21-56. S. 25. Meyerr. J.pp.. D. Consumer Unin. Available a. 1972. R.Vol. It is our responsibility to set the example of protecting future offspring by teaching and enforcing good safety practices for any and all individuals (students.. T.Acadcmic Pres. T. Mieh. Teratgenic. Springfield. (3) Shepard.. or others) working in our academic laboratories. EouC. Philadelphia.9 (1980). 1980. (1979). Ref (121 pp." Sameni.pp. (6) Miller. IEdifor1.. J. J. CHEM. 55. A. "The Medicine Show: Consumers Union'sPraetieal Guideto Some Everyday Health Problemsand Health Ploducts...Vol. no.pp. (7) 35 (1980).1978. (Editor).58. 1965. M.. (41. ...381pp.."paperback prinVd at Southern nlinok Uniwsity. J..~. l a 2 4 See also Warkany. . Carbondale. CHBM.Y. w .385-652... (4) Meyors. EDUC.Voi. G.NewYork. V. Teratagens and Highly Toxic Substances.Vol.rr~.Inc.... 1981. DC. I. in "Envimnmental Toxicology. Shaman."Wmllam.D. Ref."The Johns Hopklm U n i v ~ i t y Bdtimare. "Tmorigenie. ~ ~ ~ . (101 Dagsni. Government Printing Offire.p." ~ i ~ h H.... (18). R.and Mpyen. W. M. I966. C.58. and Mutasenic Citations: Subfilea of the Registry ofToxic Effects of Chemical Substances. 101-108 and 119-126. Chom.. (11) Ref. 1960. 9.292 (1978). J." Wwllam.277 no. Ret (21. 251-'278.. (61. Hollaender. . I. 303.S.. and do Serres. i p ..Chrm. 8." by National Institute for Oeeupafionsl Safety and Health (NIOSH). pp. H. 10. M.. XI. (Editoral. Fischbeck. IL." Ameriean Elsevier PuhL Co. . Charlea C. 1 9 7 5 . pp. . M. R. 37 pp. 113-160. p. . A . Washineton. K. 1. 129-152. Literature Cited (1) Smith&. 1979. "Safe Handling ofChemiea1 Csreinogena. Chem.N~w York.254.EDUC.. (Editors).56."Congenital Malfomstions. F. (2) Shepard. E w . L. 119. ReL (13). 21-37. J. Uniwrsiry ."Chemi& Which Caus~BirthDefecta-T~atogtapntap.. 251-253. Gal.. "T~atolagy Principlesand T&igue~:'The of Chieseo P r e .ip. Principles and Methods lor Their DFtection: New York.Mount Vsmon.. . 99-270.." Year Book Medical Publishers.. M. T. 1980. A BriefGuide. 55. 241-263.Principles aod Policies. and i ~Tanimura. We should teach people to follow instructions carefully when using any pesticide.. in "Advances inTeratolom. . .

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