title: OECD validation of the rodent Hershberger assay using three reference chemicals; 17alpha-methyltestosterone, procymidone, and p,p'-DDE.
abstract: The rodent Hershberger assay is being validated as an in vivo test method for detecting androgenic or antiandrogenic compounds by the Organization for Economic Cooperation and Development (OECD). As part of the international validation work, we studied 17alpha-methyltestosterone for evaluating androgenic activity, and procymidone and p,p'-DDE for evaluating antiandrogenic activity. Male Sprague-Dawley rats were castrated at postnatal day 42, and only the rats that showed preputial separation were used in this study. Seven days after castration, chemicals were administered daily by gavages to groups of rats for 10 days, as recommended by OECD phase-2 protocol. Administration of 17alpha-methyltestosterone induced increases of weights of accessory sex tissues and glands in a dose-dependent manner. Administration of procymidone and p,p'-DDE produced a dose-dependent decrease of weights of accessory sex tissues and glands in the rats co-treated with testosterone propionate (0.4 mg/kg/day) subcutaneously. Our data strongly suggested that the current protocol of OECD Hershberger assay (phase-2) should be used as a reliable method for the detection of endocrine related toxicity of other chemicals.
authors.affiliation: Endocrine Toxicology Team, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, South Korea. jaehoshin@hanmir.com
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Moon
authors.forename: Il Hyun
authors.initials: IH
authors.lastname: Kang
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Ji Youn
authors.initials: JY
authors.lastname: Ahn
authors.forename: Hoon
authors.initials: H
authors.lastname: Bae
authors.forename: Eui Bae
authors.initials: EB
authors.lastname: Jeung
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Han
mesh_terms: D000284:Administration, Oral; D045930:Anabolic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D003633:Dichlorodiphenyl Dichloroethylene / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D005837:Genitalia, Male / Q000187:drug effects / Q000473:pathology; D017408:Guidelines as Topic / Q000592:standards; D007279:Injections, Subcutaneous; D007306:Insecticides / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D007390:International Agencies; D007723:Korea; D008297:Male; D008777:Methyltestosterone / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D045930:Anabolic Agents; D001643:Bridged Bicyclo Compounds; D005659:Fungicides, Industrial; D007306:Insecticides; D003633:Dichlorodiphenyl Dichloroethylene; C035988:procymidone; D008777:Methyltestosterone