Program to prevent pregnancy while on medication.

Most of the attention currently focused on endocrine-active chemicals is directed to their effects on the development of offspring exposed to them in utero or during the neonatal period. Pregnant Crj:CD(SD)IGS rats were given ethinyl estradiol (EE) orally in doses of 0.5-50 microg/kg/day from gestational day 7 to postnatal day 18, and their offspring were examined for its effects. Our previous study according to a similar protocol demonstrated the occurrence of cleft phallus in the female offspring exposed to 50 microg/kg of EE in utero and during the lactation period. The present study was designed to assess (1) the reproducibility of the induction of cleft phallus, (2) the fertility of female rats with cleft phallus, and (3) whether any delayed effects, possibly delayed anovulation, were induced. At 50 microg/kg cleft phallus was observed in almost all of the female offspring, and slight retardation of body weight gain was detected in both sexes. At 15-17 weeks of age the animals with cleft phallus could copulate and had fertility comparable to the control group. At 6 months of age, on the other hand, 6/8 of the female offspring at 50 microg/kg exhibited abnormal cyclicity, including persistent estrus, and histological examination revealed follicular cysts and absence of corpora lutea in the ovaries of the rats with persistent estrus. These findings are consistent with delayed anovulation syndrome. The results suggest that observation of cyclicity at 6 months old is able to detect possible delayed ovarian dysfunction induced by perinatal exposure to chemicals.

Abnormalities, Drug-Induced↗

PubMed2003

Developmental toxicity and genotoxicity studies of 1,1,1,3,3,3-hexachloropropane (HCC-230fa) in rats.

The potential developmental toxicity and the in vitro and in vivo genotoxicity of HCC-230fa were assessed. In the developmental toxicity study, groups of 25 mated Crl:CD(R)(SD)BR rats were exposed (whole body) by inhalation to HCC-230fa over days 7-21 of gestation; the day of confirmed mating was designated as gestation day 1 (GD1). Exposures were 6 h per day at concentrations of 0, 0.5, 2.5, or 25 ppm. Body weight, food consumption, and clinical observation data were collected during the study. On day 22 of gestation, the dams were euthanized and examined grossly. The fetuses were removed and subsequently weighed, sexed, and examined for external, visceral, head, and skeletal alterations. Evidence of maternal and developmental toxicity was observed at 25 ppm and was noted as significant, compound-related reductions in mean maternal body weight, weight change, and food consumption. Significant fetal effects also were observed at 25 ppm as compound-related reductions in mean fetal weight and increased fetal malformations (filamentous tail, situs inversus, absent vertebrae) and variations (rudimentary cervical ribs, delayed sternebral ossification). There was no evidence of either maternal or developmental toxicity at 0.5 or 2.5 ppm. The genotoxicity of HCC-230fa was examined in a bacterial reversion assay and in erythrocyte micronucleus studies in two species by different routes of administration. No increases in the number of revertants were observed in the bacterial reversion assay. In one micronucleus study, HCC-230fa was administered by inhalation to rats as part of a 90-day study at doses indicated above. For the second study, ICR mice were given a single ip dose at 0, 166, 330, or 660 mg/kg. In both micronucleus studies, a significant increase in micronucleated erythrocytes was observed. The results of these studies suggest that HCC-230fa affects rapidly dividing cells and may have long-term consequences for occupational exposures.

Abnormalities, Drug-Induced↗