Prenatal developmental toxicity studies of l,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor) in rats and rabbits

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  • Prenatal developmental toxicity studies of 1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor) in rats and rabbits
  • Prenatal developmental toxicity studies of 1,1,1‐trichloro‐2,2‐bis(4‐methoxyphenyl)ethane (methoxychlor) in rats and rabbits

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ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of methoxychlor in general accordance with the improved Japanese MAFF guidelines (12-Nousan-No. 8147, 2–1–18, 2000). Methoxychlor dissolved in corn oil was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,1,50, or 150 mg/kg/day and to pregnant Kbl:JW rabbits on GD 6–27 at a dose of 0,1, 15, or 45 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs. Adverse effects on maternal animals were found at 2 higher doses in both species; i.e. vaginal red discharge (rat only), abortion or premature delivery (rabbit only), and significantly decreased body weight gains and food consumption. While the numbers of corpora lutea and implants were comparable between the control and treated groups in both species, slight increase in the percent resorptions and fetal deaths in rats and a reduction of fetal weights in both species were observed at the highest dose. Anogenital distance and testicular histology were not affected in rats. Although fetal examination revealed significant increase in the incidences of 27 presacral vertebrae at 2 higher doses in rabbits, there was no treatment-related increase in the incidence of malformations in rats and rabbits. Based on these results, it is concluded that methoxychlor causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in decreased fetal weights and an increased incidence of fetal resorptions or skeletal variations at maternally toxic doses.

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