Lack of antiandrogenic effects in adult male rats following acute exposure to 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE).
Although the insecticide dichlorodiphenyltrichloroethane (DDT) was banned in the US in 1972, DDT and its major metabolite 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE) are still persistent in the environment. DDE at high doses is antiandrogenic in fetal and adult rats and, therefore, is of concern in humans exposed environmentally. The objective of this work was to determine the dose-response relationship between DDE and its antiandrogenic effect in adult, male rats and to quantitate the concentration of DDE in tissues following oral exposures. Adult, male, Long-Evans rats (11-13 weeks) were castrated, implanted with testosterone capsules, and dosed by oral gavage with 0, 5, 12.5, 25, 50, or 100 mg DDE per kg body weight (BW) per day in corn oil for 4 days. On day 5 the rats were euthanized and liver, adrenals, ventral prostate, and seminal vesicles were weighed as a measure of response to DDE exposure. Blood, adrenals, brain, fat, kidney, lung, liver, muscle, ventral prostate, seminal vesicles, and skin were analyzed for DDE concentrations. Testosterone and dihydrotestosterone were measured in serum. There was a decrease in prostate weight that was not dose dependent; only the prostate weights in rats treated with 12.5 mg DDE per kg BW per day were reduced significantly compared to controls. The liver displayed a dose-dependent increase in weight that was significantly greater than control at DDE doses of 25, 50, and 100 mg/kg BW per day. Blood concentrations of DDE ranged from 0.32 to 11.3 ppm, while tissue concentrations ranged from 0.72 to 2620 ppm with the highest concentration in fat. Although DDE concentrations in the androgen-responsive tissues were higher than concentrations previously shown in vitro to inhibit androgen-receptor transcriptional activity, these concentrations did not appear to be antiandrogenic in vivo. The doses administered to the rats in this study are at least 10(5)-fold greater than the daily, average of human dietary intake of DDE.
Leavens
Teresa L
TL
Curriculum in Toxicology, University of North Carolina, Chapel Hill, USA. leavens.teresa@epa.gov
Sparrow
Barney R
BR
Devito
Michael J
MJ
D000726:Androgen Antagonists / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D003633:Dichlorodiphenyl Dichloroethylene / Q000493:pharmacokinetics / Q000633:toxicity*; D013196:Dihydrotestosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D012669:Seminal Vesicles / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D014018:Tissue Distribution
D000726:Androgen Antagonists; D007306:Insecticides; D013196:Dihydrotestosterone; D013739:Testosterone; D003633:Dichlorodiphenyl Dichloroethylene