Normal sexual development of rats exposed to butyl benzyl phthalate from conception to weaning.
Butyl benzyl phthalate (BBP) has been administered in drinking water (1000 micrograms/liter) to pregnant AP rats during gestation and lactation. The sexual development of the pups was then monitored until their termination at postnatal day 90 (pnd 90). Pups derived from animals exposed to diethylstilbestrol (DES) in drinking water (50 micrograms/liter) acted as a positive control group. Glass drinking bottles were employed following demonstration of absorption of BBP into plastic drinking bottles. Drinking water intake was monitored and the estimated average exposures of the dams was 182.6 micrograms/kg/day BBP and 8.6 micrograms/kg/ day DES. A total of 240 control pups, 204 BBP pups, and 64 DES pups were obtained for study. The sexual development of both genders of pups was monitored. The body weights of the DES pups were significantly reduced at birth, an effect that persisted until pnd 90. The body weights of the BBP pups were marginally increased at birth, but this difference resolved by pnd 90. DES affected the sexual development of the pups for all endopoints monitored-anogenital (AG) distance on pnd 2; average day of vaginal opening and prepuce separation; uterus, testes, and accessory sex gland weight; and cauda epididymis sperm count and homogenization resistant testicular sperm count at pnd 90. BBP failed to affect any of these parameters, with the exception of a 1.1-day advance in the average day of vaginal opening and a small increase in male AG distance on pnd 2. These last two effects are related to the increased weight of the BBP pups. The incidence of FSH-containing cells in the pituitary gland of animals from each group was unaffected at pnd 90. The effects observed for the DES pups are consistent with the results of earlier studies by Sharpe et al. (Environ. Health Perspect. 103, 1136-1143, 1995). However, the absence of an effect of BBP administration on pup testis weight and testicular sperm count at pnd 90 is in contrast to reductions in these measurements reported earlier by Sharpe et al. (Environ. Health Perspect. 103, 1136-1143, 1995) for similarly derived BBP pups.
Ashby
J
J
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
Tinwell
H
H
Lefevre
P A
PA
Odum
J
J
Paton
D
D
Millward
S W
SW
Tittensor
S
S
Brooks
A N
AN
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004054:Diethylstilbestrol / Q000633:toxicity; D004326:Drinking / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010795:Phthalic Acids / Q000633:toxicity*; D010902:Pituitary Gland / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D012733:Sex Differentiation / Q000187:drug effects*; D012741:Sexual Maturation / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D010795:Phthalic Acids; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; C027561:butylbenzyl phthalate