OECD validation of phase 3 Hershberger assay in Korea using surgically castrated male rats with coded chemicals.
As a participating laboratory for the OECD Hershberger validation program, we conducted a phase 3 trial to test the reliability of the Hershberger assay using coded substances. Male Sprague-Dawley rats were castrated at 6 weeks of age and allowed to recover for 8 days. All the coded substances were administered orally once daily for 10 consecutive days. In the antagonist version of the assay, 0.4 mg kg(-1) of testosterone propionate (TP), a reference androgen, was co-administered with the coded compounds C, D, H, I or K, by a subcutaneous injection. As anticipated, TP alone produced statistically significant increases in the five mandatory accessory sex organ weights. The coded substance L (trenbolone 40 mg kg(-1)), the test agonist, caused significant increases in the weights of the androgen-dependent tissues. The five coded compounds, p,p'-DDE at two doses (codes C and I), linuron at two doses (codes D and K) and flutamide (code H), all significantly decreased the weights of the TP-stimulated sex organs. These results suggest the OECD Hershberger assay to be a reliable screening method for detecting androgen agonists and antagonists.
Moon
Hyun-Ju
HJ
National Institute of Toxicological Research, Korea Food and Drug Administration, 194 Tongil-ro, Eunpyung-gu, Seoul 122-704, Korea.
Kang
Tae Seok
TS
Kim
Tae Sung
TS
Kang
Il Hyun
IH
Ki
Ho Youn
HY
Kim
Seung Hee
SH
Han
Soon Young
SY
D045930:Anabolic Agents / Q000633:toxicity; D000726:Androgen Antagonists / Q000633:toxicity; D000728:Androgens / Q000819:agonists; D000818:Animals; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005485:Flutamide / Q000633:toxicity; D005500:Follow-Up Studies; D007306:Insecticides / Q000633:toxicity; D007723:Korea; D008044:Linuron / Q000633:toxicity; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013739:Testosterone / Q000633:toxicity; D014204:Trenbolone Acetate / Q000633:toxicity
D045930:Anabolic Agents; D000726:Androgen Antagonists; D000728:Androgens; D052244:Endocrine Disruptors; D007306:Insecticides; D008044:Linuron; D013739:Testosterone; D003633:Dichlorodiphenyl Dichloroethylene; D005485:Flutamide; D014204:Trenbolone Acetate