Oral p-tert-octylphenol exposures induce minimal toxic or estrogenic effects in adult female Sprague-Dawley rats.
Contamination of the environment with endocrine-disrupting chemicals (EDC) has raised concerns about potential health hazards for humans and wildlife. Human and wildlife exposure to one such ubiquitous chemical, p-tert-octylphenol (OP), are likely, due to its persistence in the environment and its presence in food, water, and items of daily use. OP is reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Detrimental effects of OP exposures on the reproductive system have been observed in most, but not all, in vivo experiments. This study examined estrogenic effects of oral exposures of adult female rats to OP. In vitro, OP bound weakly to human ER and a co-activator protein, and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage daily for 35 d (25, 50, or 125 mg/kg/d). Body and organ weights and ovarian follicle populations were not significantly altered in OP-exposed adult rats, despite detectable levels of OP in reproductive organs. The estrous cycle of rats was slightly altered, but there were no significant estrogen-like changes in histomorphology or gene expression of the uterus. Prepubertal rats given 125 or 250 mg/kg OP by gavage for 3 d had reduced body weight compared to vehicle-exposed rats but failed to show any uterotrophic response, although 17alpha-ethinyl estradiol (EE, 10 microg/kg/d, ip) induced a threefold increase in uterine weight. Overall, results suggest that toxicity will occur before estrogenic effects with oral exposures to OP. Relevant environmental exposures likely pose little risk for estrogenic effects.
Sahambi
Sukhdeep K
SK
INRS-Institut Armand-Frappier, Institut national de la recherche scientifique, Laval, Québec, Canada.
Pelland
Amelie
A
Cooke
Gerard M
GM
Schrader
Timothy
T
Tardif
Robert
R
Charbonneau
Michel
M
Krishnan
Kannan
K
Haddad
Sami
S
Cyr
Daniel G
DG
Devine
Patrick J
PJ
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000378:metabolism / Q000633:toxicity*; D004958:Estradiol / Q000097:blood; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D013501:Surface-Active Agents / Q000378:metabolism / Q000633:toxicity*; D018675:Toxicity Tests; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011960:Receptors, Estrogen; D013501:Surface-Active Agents; D004958:Estradiol; C105260:4-tert-octylphenol