Teratogenicity susceptibility

Hoshino K, Hyashi Y, Takehira Y, et al. 1981. Influences of genetic factors on the teratogenicity of environmental pollutants Teratogenic susceptibility to benzo[a]pyrene and Ah locus in mice. Congenital Anomalies 97-103. 

Determinants of Teratogenic Susceptibility. Factors which influence the teratogenic response are listed in Table III. 

Ema M, Itami T, Kawasaki H (1992) Susceptible period for the teratogenicity of di-normal-butyltin dichloride in rats. Toxicology, 73(1) 81-92. 

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. 

Some variations exist between the susceptibility of mammalian species to the teratogenic action of nickel salts. No detrimental reproductive and developmental effects have been documented in humans [422], Yet exposure to nickel salts must be assumed to constitute a teratogenic risk. 

An additional assessment factor, of up to 10, has been apphed in some cases where the NOAEL has been derived for a critical effect, which is considered as a severe and irreversible effect, such as teratogenicity or non-genotoxic carcinogenicity, especially if associated with a shallow dose-response relationship. The principal rationale for an additional factor for nature of toxicity has been to provide a greater margin between the exposure of any particularly susceptible humans and the dose-response curve for such toxicity in experimental animals. 

Eujinaga M, Baden JM, Mazze RI Susceptible periods of nitrous oxide teratogenicity in Sprague-Dawley rats. Teratology 40 439-444,1989... 

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. 

The susceptibility of both an embryo and a fetus to a teratogen is variable, depending on the stage of development when exposure occurs. For gross anatomical abnormalities, the critical periods of organogenesis are the most susceptible to exposure, whereas other types of abnormality may have other critical periods for exposure. 

The sensitive period for induction of malformations is the 5- to 14-day period in the rat and mouse and the third week to the third month in humans. This is illustrated in Figure 6.22 for the teratogen actinomycin D. The later period of fetal development, like the initial proliferative stage, is less susceptible to specific effects and an "all-or-none" type of response is usually seen, such as either death or no gross effect. 

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