PRINCIPLES OF TOXICOLOGY

toxicity. However, methylmercury accumulation was sufficient to cause CNS abnormalities in
developing fetuses, with cerebral palsy being the most common problem. It was later discovered
that mercury levels increased in the placenta and fetal membranes of pregnant women that were
exposed to metallic mercury during work. However, these exposures were apparently not sufficient
to cause developmental toxicity since there was no increase in spontaneous abortion rates
and no defects found in the offspring.
Developmental Toxicity Summary
Developmental toxicity can be separated into two categories. Early in pregnancy, the predominant
effect of chemical and other stresses is spontaneous abortion. Later, when the specific differentiation
of the various organs and structures is taking place, the response to some toxicants is congenital defects
of structure or function. Determining whether spontaneous abortions have been caused by a particular
chemical exposure is extremely difficult, primarily because there is such a high background rate and
so many non-toxicological causes. Detecting a difference in the spontaneous abortion rate within a
population is difficult for similar reasons.
Most congenital defects are due to inherited or developmental genetic factors rather than teratogenic
chemicals. Though in many cases there is a desire to establish whether a defect is the result of external
factors, clearly identifying relevant factors and isolating the definitive cause is frequently impossible.
From a population perspective, finding a relevant, common factor to ascribe to a certain set of defects
is difficult and establishing a causal role for such a factor is even more challenging. It is relevant to
consider that the best examples of chemical-induced teratogenesis relate to therapeutic doses of
chemicals given with the knowledge and documentation of a health professional.
Experimental results have clearly established mechanisms by which both early and later development
can be affected by exogenous chemicals. This information is useful in prioritizing investigations
of potential human health effects and judging whether reported effects could reasonably be expected
TABLE 11.3 Suspected Human Developmental Toxicants and Teratogens
Industrial/Environmental Pharmaceutical Agents and Drugs
Anesthetic gases (e.g., Halothane) Aminopterin
Benzene Busulfan
Cadmium Coumarin anticoagulants
Carbon disulfide Cyclophosphamide
Chloroprene Diethylstilbestrol (DES)
Chlorobiphenyls Dimethylformamide
Diethylhexyl phthalate Ethanol
Dioxins Isotretinoin and other retinoids
Ethylene oxide Lithium
Lead Phenytoin
Methylmercury Opiates
Toluene Tetracyclines
Thalidomide
Valproic acid
Miscellaneous Nonchemical Agents
Cytomegalovirus Rubella
Diabetes Syphilis
Ionizing radiation Toxoplasmosis
Phenylketonuria
11.3 DEVELOPMENTAL TOXICOLOGY 231