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International Journal of Toxicology
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Birthweight Depression in Male Rats Contiguous to Male Siblings in Utero Exposed to High Doses of 1,3-Butanediol during Organogenesis

R. F. Mankes

Associate Professor Department of Pharmacology and Toxicology Albany Medical College 47 New Scotland Ave. Albany, NY 12208

V. Renak

Associate Professor Department of Pharmacology and Toxicology Albany Medical College 47 New Scotland Ave. Albany, NY 12208

J. Fieseher

Associate Professor Department of Pharmacology and Toxicology Albany Medical College 47 New Scotland Ave. Albany, NY 12208

R. Lefevre

Associate Professor Department of Pharmacology and Toxicology Albany Medical College 47 New Scotland Ave. Albany, NY 12208

The embryotoxic effects of high doses of the narcotizing ethanol dimer 1,3-butanediol were evaluated in pregnant Long-Evans rats during the "critical period" of organogenesis. Butanediol was given by gavage at levels of 0,7060,4236, or 706 mg/kg per day (24,14.4, or 2.4% of the acute oral LD50 value for rats). Maternal sedation was observed at 7060 and 4236 mg/kg, but feed consumptions and maternal body weights were unaffected. Butanediol caused a significant, dose-dependent decrease in offspring birthweights. At the highest butanediol dose, birthweights were preferentially and significantly decreased in male pups not contiguous in utero to female siblings. Other group I1 offspring were not affected and did not differ significantly from controls. As butanediol was given prior to the period of greatest fetal growth and fetal sex steroidogenests, it is concluded that intra-uterine levels of female sex steroids (estradiol) enhance fetal repair of cellular damage (restitution ad integrum), whereas testosterone inhibits fetal repair or exacerbates previous embryonic damage by some unknown mechanism. Such interaction furthers the concept that intrauterine position affects the endpoints of developmental toxicity, as expressed at partuition.

International Journal of Toxicology, Vol. 5, No. 4, 189-196 (1986)
DOI: 10.3109/10915818609140743
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