2001Congenital AnomaliesRequires access

Prenatal developmental toxicity studies of 1,1,1‐trichloro‐2,2‐bis(4‐chlorophenyl)ethane (p, p‘‐DDT) in rats and rabbits

Ken L. Takahashi, Hiroaki Aoyama, Hitoshi Hojo, N Shimizu, Masayuki Kikuta, Hiromi Kushida, Hisao Kawakatsu, Koichi Y. Ebino, S. Teramoto

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Abstract

ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p'‐DDT in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147,2–1–18, 2000). p, p'‐DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6–27 at a dose of 0,5,20, or 80 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 only at the highest dose in both species; i.e., clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment‐related increase in the incidence of malformations in any of the species. Based on these results, it is concluded that p, p'‐DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose.

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ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p'‐DDT in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147,2–1–18, 2000). p, p'‐DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6–27 at a dose of 0,5,20, or 80 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 only at the highest dose in both species; i.e., clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment‐related increase in the incidence of malformations in any of the species. Based on these results, it is concluded that p, p'‐DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose.

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Available abstract

ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p'‐DDT in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147,2–1–18, 2000). p, p'‐DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6–27 at a dose of 0,5,20, or 80 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 only at the highest dose in both species; i.e., clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment‐related increase in the incidence of malformations in any of the species. Based on these results, it is concluded that p, p'‐DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose.

Key concepts: Fetus, Toxicity, Medicine, Teratology, Pregnancy, Body weight, Physiology, Incidence (geometry)

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Prenatal developmental toxicity studies of 1,1,1‐trichloro‐2,2‐bis(4‐chlorophenyl)ethane (p, p‘‐DDT) in rats and rabbits — Research Paper | ScholarLens