[Reproductive and developmental toxicity of F1 male rats treated with DBP in utero and during lactation].
OBJECTIVE
To observe the effects of Di-n-butyl phthalate (DBP) on the developmental condition of F1 rats and on the reproductive system of mature F1 male rats and to establish the NOAEL of DBP.


METHODS
In this study, pregnant rats were treated with different dose of DBP (0, 50, 250 and 500 mg per kg per day) by gavage in utero and during lactation (from GD1 to PND21). The effects of DBP on F1 rats were observed.


RESULTS
DBP had no obvious effect on pregnant rats but could decline pups' born weight, live pups per litter, body weight gain and male pups' anogenital distance obviously. Severe damages on the reproductive system of mature F1 male rats (testicular atrophy, underdevelopmental epididymis, absent of epididymis, undescended testes, obvious decline of epididymal sperm parameters, total sperm heads per g testis, decrease of organ/body weight ratio of epididymis, liver, kidney and prostate, etc.) were observed in the group of 250 mg per kg per day and higher.


CONCLUSIONS
These results showed that male reproductive system was the target organ of DBP and the damages on pups were partly irreversible. According to these results, the NOAEL of DBP, which was not available in the current database, was established based on the outcomes of this study, i.e., 50 mg per kg per day. Accordingly, the RfD for human exposure to DBP through oral intake was recommended as 500 micrograms per kg per day.
Zhang
Yunhui
Y
School of Public Health, Fudan University, Shanghai 200032, China.
Chen
Bingheng
B
Ding
Xuncheng
X
Jiang
Xuezhi
X
D000014:Abnormalities, Drug-Induced; D000818:Animals; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004781:Environmental Exposure; D005260:Female; D007774:Lactation; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000002:abnormalities / Q000187:drug effects* / Q000473:pathology
D003993:Dibutyl Phthalate