Anophthalmia in litters of female rats treated with the food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Anophthalmia in litters of pregnant rats treated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP), a food-derived carcinogen, was incidentally encountered in a risk-assessment study with 3-generation exposure to PhIP. Female Fischer 344 animals were given 200 ppm PhIP in the diet for 4 wk before mating with nontreated males and also during gestation and lactation periods. Mean numbers of newborn rats per litter in control and PhIP-treated groups were 7.9 +/- 2.9 and 7.1 +/- 1.6 in trial 1 and 8.3 +/- 1.9 and 6.1 +/- 2.4 in trial 2 Among 49 (trial 1) and 63 (trial 2) offspring from PhIP-treated dams, 9 (18.4%) and 32 (50.8%) demonstrated anophthalmia, and I (2.0%) and 8 (12.7%) demonstrated hydrocephaly. Five of 7 (71.4%) and 13 of 14 (92.9%) dams delivered pups with malformations in trials I and 2, respectively. Also, in a previous study that was carried our with the same protocol and that used the Sprague-Dawley strain of rats, anophthalmia and hydrocephaly were observed in 2 and 1 out of 175 pups, respectively, from 100 ppm PhIP-treated darns. No congenital malformations were found in control groups of the same size in either experiment. In addition to having been previously identified as a cause of carcinogenic activity, our findings suggest that PhIP is capable of causing anophthalmia in rats when administered during the gestational period.