Evidence for embryotoxicity of gossypol in mice and chicks with no evidence of mutagenic activity in the Ames test.

Effects of gossypol treatment were studied in pregnant mice and chick embryos. Pregnant Balb C mice were treated orally with 60 or 120 mg/kg of gossypol acetic acid on days 6-13 of pregnancy and killed on day 18. The uteri were removed, the number of resorptions and late fetal deaths were recorded, and the fetuses were weighed and assessed for malformations. Fertilized hen eggs were injected with 0.25 mg gossypol/egg at 24, 48, 72, or 96 h of incubation. The embryos were examined at day 9 of incubation. The mutagenic potential of gossypol was determined by the Ames test. Treatment of mice with gossypol produced significant adverse effects on the dam and offspring including decreased pregnancy weight gain of the dam and growth retardation of the offspring. There were increased resorptions and late fetal deaths in mice and high mortality in chick embryos. Exencephalic fetuses were observed in one of four litters exposed to the higher dose of gossypol, micromelia was observed in one of 26 chick embryos treated at 24 h, and gastroschisis was observed in one of 21 chick embryos treated at 72 h. No malformations were observed in the controls. The number of revertants per plate in the gossypol treatment group (100 or 500 mg gossypol/plate) did not differ significantly from that of control. This study provides evidence that gossypol has embryotoxic and possibly teratogenic activity in mouse and chick embryos but no mutagenic activity according to the Ames assay.