Reproductive and developmental toxicity in F1 Sprague-Dawley male rats exposed to di-n-butyl phthalate in utero and during lactation and determination of its NOAEL

Abstract

Di-n-butyl phthalate (DBP) is one of the commonly used plasticizers in China. DBP can enter the environment and organisms through various routes and then affect reproductive and developmental processes of the organism and its descendants (mainly affecting male offspring). It is known that animals are sensitive to exposure of DBP in utero and during lactation. In the present study, pregnant rats were treated with different doses of DBP (0, 50, 250, and 500 mg/kg body weight/day) by daily gavage from GD1 to PND21. The developmental condition of F1 rats and the reproductive system of mature F1 male rats were monitored. DBP had no obvious effect on pregnant rats; however, it reduced several parameters including birth weight, number of live pups per litter, body weight gain and male anogenital distance. Severe damage to the reproductive system of mature F1 male rats included testicular atrophy, underdeveloped or absent epididymis, undescended testes, obvious decline of epididymal sperm parameters, total sperm heads per g testis, decrease of organ/body weight ratio of epididymis and prostate, and was observed in the group treated with 250 mg/kg BW/day and higher. These results showed that the male reproductive system was the main target organ of DBP exposure. The NOAEL (no observable adverse effect level) for developmental toxicity of DBP was established based on pup body weight and male reproductive lesions at 50 mg/kg BW/day. Accordingly, the RfD for human exposure to DBP through oral intake was recommended as 500 mg/kg BW/day.