Animal teratogenicity data

The teratogenicity of OPPS in avian species and fish is well documented. Mammalian data indicate more fetotoxicity than teratogenicity. Still, 10 of the 20 animal teratogens listed in Table 20 are OPPa. 

CONSENSUS REPORTS lARC Cancer Review Animal Limited Evidence IMEMDT 21,327,79 Human Limited Evidence IMEMDT 21,327,79 Animal Inadequate Evidence IMEMDT 6,117,74. SAFETY PROFILE Suspected carcinogen with experimental carcinogenic, neoplastigenic, tumorigenic, and teratogenic data. Other experimental reproductive effects. Mutation data reported. A steroid drug for the treatment of menopause. When heated to decomposition it emits acrid smoke and irritating fumes. 

CONSENSUS REPORTS lARC Cancer Review Group 3 IMEMDT 7,56,87 Animal Sufficient Evidence IMEMDT 12,209,76. Reported in EPA TSCA Inventor). EPA Extremely Hazardous Substances List. SAFETY PROFILE Poison by ingestion and intraperitoneal routes. Experimental reproductive effects. Questionable carcinogen with experimental neoplastigenic and teratogenic data. Mutation data reported. When heated to decomposition it emits ver) toxic fumes of NOx and HCl. 

The data from the only available animal study (Prigge and Greve 1977) indicate that inhaled lead is not teratogenic. However, it impaired heme synthesis in both rat dams and fetuses. In this study, dams were exposed to 1, 3, or 10 mg lead/m3 (chemical species not provided) throughout gestation (days 1-21). Maternal and fetal ALAD were inhibited at all exposure levels in a dose-related manner, and fetal (but not maternal) hematocrit and body weight were decreased at the 10-mg/m3 lead level. These results suggest that the fetuses were more sensitive to lead-induced toxicity than were the dams. 

Developmental Effects. There are no data available on developmental effects of acrylonitrile in humans however, two well-conducted studies in rats have shown that acrylonitrile is teratogenic in animals by both inhalation and oral exposure (Murray et al. 1978). Fetal malformations occurred in a dose-related manner. When administered orally, malformations were present even at doses in which no maternal or fetal toxicity was apparent. 

Studies in animals indicate that acrylonitrile can produce teratogenic effects at doses that have little maternal toxicity, suggesting that pregnant women may also be susceptible. It also seems likely that individuals in poor health or with respiratory problems might be particularly susceptible to acrylonitrile, but there are no data on this point. 

Grossly elevated concentrations of dissolved copper produce teratogenicity in fish embryos. A significant number of malformed fish larvae came from eggs treated with 500 pg Cu/L (Birge and Black 1979). In studies with laboratory animals and elevated concentrations of copper salts, copper penetrates the placental barrier into the fetus intramuscular injection of 4 mg Cu/kg BW early in pregnancy adversely affects fetal central nervous system development (Aaseth and Norseth 1986). In humans, no definitive data are available on whether copper can cause birth defects however, incubation of human spermatozoa with metallic copper results in loss of sperm motility (Aaseth and Norseth 1986). 

Developmental Toxicity. There is no information on developmental effects in humans exposed to bromomethane, but two inhalation exposure studies in animals (rats and rabbits) indicate that developmental or teratogenic effects do not occur even at doses that are toxic to the dam (Hardin et al. 1981 Sikov et al. 1980). No information is available on developmental effects after oral exposure of animals to bromomethane, but the inhalation data suggest that is not likely to be of concern. 

Developmental Toxicity. Limited data suggest that carbon tetrachloride has a low potential for developmental toxicity in animals. Fetal size was reduced and viability and lactation indices were decreased following high-level inhalation exposure (Gilman 1971 Schwetz et al. 1974). Fetotoxicity and teratogenicity were not seen in offspring coming to term, but total resorption of fetuses occurred... 

The practical consequence from this is that in the study type under consideration, always the dam/litter rather than the individual fetus is the basic statistical unit (see Chapters 23, 33, 34 and 35). Six malformed fetuses from six different litters in a treated group of dams is much more likely to constitute a teratogenic effect of the test substance than ten malformed fetuses all from the same litter. It is, therefore, important to report all fetal observations in this context and to select appropriate statistical tests (e.g., Fisher s exact test with Bonferroni correction) based on litter frequency. For continuous data, a procedure to calculate the mean value over the litter means (e.g., ANOVA followed by Dunnet s test) is preferred. An increase in variance (e.g., standard deviation), even without a change in the mean, may indicate that some animals were more susceptible than others, and may indicate the onset of a critical effect. 

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