Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet

A three-generation reproduction study was conducted to evaluate the effects of chronic, low-level ingestion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Sprague-Dawley rats were maintained continuously on diets providing dose levels of 0, 0.001, 0.01, or 0.1 μg TCDD/kg/day. No significant toxicity was noted in the f₀ rats of either sex during the 90 days of TCDD ingestion prior to mating. Significant decreases in fertility and neonatal survival were observed in the f₀ generation rats receiving 0.1 μg TCDD/kg/day; these effects precluded continuation of this high dose level in subsequent generations. At 0.01 μg TCDD/kg/day, fertility was significantly decreased in the f₁ and f₂ but not f₀ generations. Other indications of toxicity seen at 0.01 μg TCDD/kg/day included decreases in litter size at birth, gestation survival (proportion of pups born alive), and neonatal survival and growth. Among the rats receiving 0.001 μg TCDD/kg/day, no effect on fertility, litter size at birth, or postnatal body weight was observed in any generation. No consistent effect on neonatal survival was observed at 0.001 μg TCDD/kg/day. In summary, the reproductive capacity of rats ingesting TCDD was clearly affected at dose levels of 0.01 and 0.1 μg TCDD/kg/day, but not at 0.001 μg TCDD/kg/day, through three successive generations.