3-GENERATION REPRODUCTION STUDY OF RATS GIVEN 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) IN THE DIET

A 3-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 continuously maintained on diets providing dose levels of 0, 0.001, 0.01 or 0.1 .mu.g TCDD/kg per day. No significant toxicity was noted in the F0 [father] 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 .mu.g TCDD/kg per day; these effects precluded continuation of this high dose level in subsequent generations. At 0.01 .mu.g TCDD/kg per day, fertility was significantly decreased in the F1 and F2 but not F0 generations. Other indications of toxicity seen at 0.01 .mu.g TCDD/kg per 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 .mu.g TCDD/kg per 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 .mu.g TCDD/kg per day. The reproductive capacity of rats ingesting TCDD was clearly affected at dose levels of 0.01 and 0.1 .mu.g TCDD/kg per day, but not at 0.001 .mu.g TCDD/kg per day, through 3 successive generations.