We describe the androgen receptor (AR) agonistic/antagonistic effects of 140 veterinary drugs regulated in Republic of Korea, by setting maximum residue limits. It was conducted using two in vitro test guidelines of the Organization for Economic Cooperation and Development (OECD)—the AR-EcoScreen AR transactivation (TA) assay and the 22Rv1/MMTV_GR-KO AR TA assay. These were performed alongside the AR binding affinity assay to confirm whether their AR agonistic/antagonistic effects are based on the binding affinity to AR. Prior to conducting the AR TA assay, the proficiency test was passed the proficiency performance criterion for the AR agonist and AR antagonist assays. Among the veterinary drugs tested, four veterinary drugs (dexamethasone, trenbolone, altrenogest, and nandrolone) and six veterinary drugs (cymiazole, dexamethasone, zeranol, phenothiazine, bromopropylate, and isoeugenol) were determined as AR agonist and AR antagonist, respectively in both in vitro AR TA assays. Zeranol exhibited weak AR agonistic effects with a PC₁₀ value only in the 22Rv1/MMTV_GR-KO AR TA assay. Regarding changing the AR agonistic/antagonistic effects through metabolism, the AR antagonistic activities of zeranol, phenothiazine, and isoeugenol decreased significantly in the presence of phase I + II enzymes.These data indicate that various veterinary drugs could have the potential to disrupt AR-mediated human endocrine system. Furthermore, this is the first report providing information on AR agonistic/antagonistic effects of veterinary drugs using in vitro OECD AR TA assays.

Various chemicals containing pesticides can induce adipogenesis and cause obesity. Organophosphorus pesticides have been used for pest control. Here, we investigated the estrogen receptor (ER)-dependent adipogenesis-inducing effect of representative organophosphorus pesticides (OPs), diazinon, phoxim, terbufos and tolclofos-methyl in 3T3-L1 adipocytes. Four OPs exhibited ER agonistic effect, determined using the OECD Performance Based Test Guideline No. 455; in vitro ER stably transfected transactivation assay using ERα-HeLa-9903 cell line, through binding affinity to ERα. Additionally, they increased lipid droplet accumulation in a dose-dependent manner, which was suppressed by ICI182,780, a well-known ER antagonist. Four OPs treatment induced peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and perilipin expression. Furthermore, PPARγ, C/EBPα and perilipin expression was inhibited by co-treatment with ICI182,780. The increased mRNA expression of lipoprotein lipase and fatty acid synthase by four OPs was suppressed by co-treatment with ICI182,780. These results indicated that diazinon, phoxim, terbufos, and tolclofos-methyl might have adipogenesis-inducing effect mediated by interacting with ER.