Teratogenic effects of chemicals

D.F. Swaab and M. Mirmiran, Functional teratogenic effects of chemicals on the developing brain, Monogr. Neural Sci., 12 (1986) 45-57. 

The fundamentals of testing for reproductive and teratogenic effects of chemical agents were described by Dr. R. Tyl. She laid emphasis on teratogenic phenomena in man, one-fifth of which were attributable to germinal mutations. Developmental criteria and landmarks in rodents were tabulated to illustrate the important applications of such data in safety testing. 

The bacteria-reversed mutation test is another method to investigate the mutagenic and teratogenic effect of chemicals. This uses numerous amino acid-dependent strains of Salmonella enterica (formerly S. typhimurium). The histidine-dependent strain of S. enterica has artificially induced point mutations. The test is carried out in a histidine-deficient bacterial medium. The histidine-independent bacterial... 

Health and Safety Factors. MSA is a strong toxic acid and is corrosive to skin. The acute oral toxicity of the sodium salt in mice LD q is 6.2 g/kg. The 1976 edition of the NIOSH Registry of Toxic Effects of Chemical Substances Hsts certain reaction products of MSA as having suspected mutagenic, teratogenic, and carcinogenic activity (410). 

Episodic pollution events can adequately be addressed by acute toxicity bioassays, however these are not sufficient to investigate the water quality for delayed toxicity effects of chemicals present. Chronic effects of pesticides can include carcinogenicity, teratogenicity, mutagenicity, neurotoxicity, and reproductive effects (endocrine disruption). 

Kalter, K. (1977). Correlation between teratogenic and mutagenic effects of chemicals in mammals. In Chemical Mutagens Principles and Methods for Their Detection (Hollanender, A., Ed.). Vol. 6, Plenum Press, New York, pp. 57-82. 

Walton B, Buchanan M. 1980. Teratogenic effects of fuel oils on insects developing in contaminated substrates. Second Chemical Congress of the North American Continent San Francisco, California. 

The rabbit is generally the non-rodent species or second species after the rat recommended by the regulatory authorities and is part of the package of regulatory reproductive studies for the detection of potential embryotoxic and/ or teratogenic effects of pharmaceuticals, chemicals, food additives, and other compoimds, including vaccines (see Chapters 1-7). 

In 1982 we drew attention to this problem in the article "What every chemist should know about teratogens—-chemicals that cause birth defects" (ref. 1). One year later we addressed the teratogen problem from the point of view of research chemists (ref. 2). Earlier, we have accumulated a list of over 500 teratogenic chemicals, proven or suspected, from the Registry of Toxic Effects of Chemical Substances (ref. 3, 4),... 

Since the concern of this monograph is teratogens, the effects of chemicals on sperm and male reproduction are not dealt with. However, for readers interested in the latter a recent review article by Schrag and Dixon, "Occupational Exposures Associated with Male Reproductive Dysfunction" (ref. 20)is recommended. Chapters on various aspects of male reproductive toxicology and on sperm production of men working under heavy-metal or organic-solvent exposure are presented by Hemminki et al. (ref. 19). 

REGISTRY OF TOXIC EFFECTS OF CHEMICAL SUBSTANCES AS A SOURCE FOR COMPILING A LIST OF TERATOGENS... 

Since the discovery of the fetal alcohol syndrome (FAS), extensive research has been carried out on the teratogenic effects of alcohol The consequences of early exposure to this substance can serve to illustrate the multiplicity of effects that a chemical can cause. Chronic exposure of the fetus to high levels of alcohol has been found to result in many cases in a large spectrum... 

It must also be realized that much information might already be present in the human population. Epidemiological studies of behavioral teratogenic effects of various substances to which developing humans have already been exposed, can yield much valuable information about the eventual dangers of many old chemicals. In addition, such studies can help to find a reliable way to extrapolate findings in animal studies to risks for human development. 

The results of the last study point out the difficulties in associating specific pesticide exposures to end results. As discussed in Chapter 14, pesticides are almost always applied admixed with solvents, surfactants, and other chemicals that aid in their solution, distribution, and adsorption. More times than not, mixtures of different pesticides are applied to achieve multiple effects. Such pesticide mixtures contain multiple lipophiles and hydro-philes and the mixtures produce effects that are greater than those anticipated from the individual components. Accordingly, it should not be surprising that the teratogenic effects of pesticide mixtures should exceed those of the single species and produce enhanced detrimental outcomes in offspring. 

Teratogenic effects of substances on test animals are evaluated from resorption (death of the conceptus), fetal toxicity (reduced body weight), aberrations (malformations), and minor anomalies. Statistical analysis is performed by surveying the four most important parameters namely, the number of litters with malformed fetuses, increase in the average number of fetuses with defects per litter, the number of resorptions, and dead fetuses. Finally, the incidence of malformation (response) is plotted against doses administered. Any dose-response relationship should indicate the teratogenicity of the chemical under experimental conditions. 

The Administrator shall coordinate, with the Assistant Secretary for Health of the Department of Health and Human Services, research undertaken by the Administrator and directed toward the development of rapid, reliable, and economical screening techniques for carcinogenic, mutagenic, teratogenic, and ecological effects of chemical substances and mixtures. 

CERLINE, and BIOSIS. In addition, the Registry of Toxic Effects of Chemical Substances, the Environmental Mutagen Information Center, and the Environmental Teratogen Information Center contain some data as well as bibliographic references. 

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