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

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.

Reassessment of ecotoxicities of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane in Japanese quail under the OECD draft new avian one-generation reproduction test guideline

“…Tremors, convulsions, and subsequent deaths were observed as DDT's characteristic toxicity (Bryan et al, 1989;Dale et al, 1962;Takahashi et al, 2001) in all three studies conducted. The subchronic and one-generation reproduction studies demonstrated a clear sex diVerence in the occurrence of those Wndings in Japanese quail, males being more susceptible than females.…”

“…DDT is listed as one of the 12 persistent organic pollutants (POPs) to which an international cooperative strategy is required for prevention of environmental contamination (The Stockholm convention, 2001). We have studied in rats and rabbits to elucidate the potential developmental toxicity of p,pЈ-DDT, a major component of DDT, in general accordance with the improved Japanese MAFF guidelines (JMAFF, 2000) and reported no induction of congenital malformations in either species (Takahashi et al, 2001). Regarding reproductive toxicity against avian species, it has been reported that exposure of Japanese quail to p,pЈ-DDT resulted in decreases in egg production, fertility, and hatchability (Carnio and McQueen, 1973;Smith et al, 1969).…”

Two‐generation reproduction toxicity study in rats with 1,1,1‐trichloro‐2,2‐bis(4‐chlorophenyl)ethane (p,p′‐DDT)

“…Neurological responses are common in rats and birds when they were treated with p,p′ ‐DDT (Hudson et al . 1985; Takahashi et al . 2001; Ueda et al .…”

“…However, whether p,p′ ‐DDT does manifest such endocrine disruption in intact mammalian species has not yet fully been understood since only a limited number of data sets are available in terms of the reproductive and/or developmental toxicities (Ottoboni 1969; Rhouma et al . 2001; Takahashi et al . 2001).…”

“…In addition, p,p′-DDE, a major metabolite of p,p′-DDT, has been shown to © 2006 The Authors Journal compilation © 2006 Japanese Teratology Society have antiandrogenic activity (Wilson et al 2002;Yamasaki et al 2003;Yamada et al 2004) and to exert developmental toxicities in male rats (Kelce et al 1995;You et al 1998;Gray et al 2001), suggesting a serious potential risk of p,p′-DDT for human reproduction through endocrine dysfunction. However, whether p,p′-DDT does manifest such endocrine disruption in intact mammalian species has not yet fully been understood since only a limited number of data sets are available in terms of the reproductive and/ or developmental toxicities (Ottoboni 1969;Rhouma et al 2001;Takahashi et al 2001).…”