A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult female offspring rats.
Di(2-ethylhexyl) phthalate (DEHP) is used in numerous consumer products, mainly imparting flexibility and durability to polyvinyl chloride (PVC) based plastics. It is a known reproductive and developmental toxicant in male rodents. However, data regarding effects of DEHP on female reproductive health are particularly sparse. We performed an extensive dose-response study following developmental exposure to DEHP and evaluated the effects on adult female reproductive function. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low doses were: 0.015, 0.045, 0.135, 0.405 and 1.215mgDEHP/kg/bw/day and the high doses were: 5, 15, 45, 135 and 405mg DEHP/kg/bw/day. At the doses tested, no effects on organ (liver, kidney, spleen, thymus, thyroid, ovary and uterus) or body weights were detected. Female offspring presented a normal pattern of estrous cyclicity with no hormonal alterations (serum estradiol and progesterone). A statistically significant increase in tertiary atretic follicles was observed at the highest dose (405mgDEHP/kg/day). Morphometric analysis indicated that uterus and vagina luminal epithelial cell height were unaffected by treatment. An increase in the number of ovarian atretic tertiary follicles was the only effect observed in adult female offspring exposed in utero and during lactation to DEHP.
Grande
Simone W
SW
Charité University Medical School Berlin, Campus Benjamin Franklin, Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Garystrasse 5, 14195 Berlin, Germany.
Andrade
Anderson J M
AJ
Talsness
Chris E
CE
Grote
Konstanze
K
Golombiewski
Andrea
A
Sterner-Kock
Anja
A
Chahoud
Ibrahim
I
D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004031:Diestrus / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004971:Estrus / Q000187:drug effects; D005260:Female; D007441:Intubation, Gastrointestinal; D007774:Lactation / Q000502:physiology*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000254:growth & development; D014621:Vagina / Q000187:drug effects / Q000254:growth & development
D010968:Plasticizers; D004051:Diethylhexyl Phthalate