Teratogenic responses

The developmental effects of 1,4-dichlorobenzene have been evaluated in New Zealand White rabbits (Hayes et al. 1985). Pregnant rabbits were exposed to 1,4-dichlorobenzene by inhalation at 800 ppm for 6 hours per day on Gd 6-18. At 300 ppm, there was a significant increase in the number of litters with resorptions and the percentages of resorbed implantations per litter however, this effect was not seen at 800 ppm and was thus probably not treatment-related. An increased incidence of retroesophageal right subclavian artery present in the offspring was noted it was not considered to constitute a teratogenic response to exposure to 1,4-dichlorobenzene, but was considered only a minor variation. Based on the NOAEL of 300 ppm, an acute-duration MRL of 0.8 ppm was calculated as described in the footnote to Table 2-1 and Appendix A (Hayes et al. 1985). 

Johannsen FR, Levinskas GJ, Schardein JL Teratogenic response of dimethylacetamide in rats. Fundam Appl Toxicol 9 550-556, 1987... 

Robinson JF et al (2012) A comparison of gene expression responses in rat whole embryo culture and in vivo time-dependent retinoic acid-induced teratogenic response. Toxicol Sci 126(l) 242-254... 

Beagles fed Carbaryl in the diet at five dose levels (3.125 to 50 tg/kg/day) throughout gestation, exhibited teratogenic responses at all levels except at the lowest doses. Smalley et al. (1968) reported abdominal-thoracic fissures, brachygnathia, ecaudate pups, failed skeletal formation and extra phalanges. 

A similar inference has been made for caffeine teratogenicity (Sullivan et al. 1987) A large single dose induced a teratogenic response, but the same amount given as four equal doses caused no malformations. 

The criticism often presented about the FETAX is that it is a poor representation of native species of amphibians or of other vertebrates. Xenopus is of course not native to the Americas, but it is a typical amphibian and its comparability in teratogenic response to mammalian species has already been documented. Xenopus is also widely available, and the basic methodology can also be transferred to other frogs and toads. 

Mimura, J., K. Yamashita, K. Nakamura, M. Morita, T.N. Takagi, K. Nakao, M. Ema, K. Sogawa, M. Yasuda, M. Katsuki and Y. Fujii-Kuriyama. Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor. Genes Cells 2 645-654, 1997. 

Studies of developmental toxicity have been undertaken both in the rat and the rabbit (Hackett et al., 1992). In the former exposure was from gestation day 6-15 and doses used were 0, 0.5, 1.0 and 1.5 mg kg 1 bw day 1 and in the latter exposure was from gestation day 6-19 and doses used were 0, 0.05 and 0.07 mg kg 1 bw day-1. Maternal toxicity was seen but there no evidence of a teratogenic response. 

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

The committee considered several key pieces of evidence derived from animal studies in its deliberations. Those studies identified effects on hormone function, gonad structure, and developmental (teratogenic) responses that have been incompletely examined in human epidemiologic investigations and provided additional weight of evidence that supports the committee s conclusions. 

The identity of the gene loci influencing the teratogenic response to cadmium has yet to be determined. At the present time any simple relationship between teratogenicity and a lo-... 

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