title: Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays.
abstract: The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was evaluated in five in vitro screening assays to assess the potential for interaction with the androgen, estrogen and steroidogenesis pathways in the endocrine system. The assays were conducted to meet the requirements of the in vitro component of Tier 1 of the United States Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP), and included assays for estrogen receptor (ER) binding (rat uterine cytosol ER binding assay), ER-mediated transcriptional activation (HeLa-9903-ERα transactivation assay), androgen receptor (AR) binding (rat prostate cytosol AR binding assay), aromatase enzymatic activity inhibition (recombinant human CYP19 aromatase inhibition assay), and interference with steroidogenesis (H295R steroidogenesis assay). Results from these five assays demonstrated that 2,4-D does not have the potential to interact in vitro with the estrogen, androgen, or steroidogenesis pathways. These in vitro data are consistent with a corresponding lack of endocrine effects observed in apical in vivo animal studies, and thus provide important supporting data valuable in a comprehensive weight of evidence evaluation indicating a low potential of 2,4-D to interact with the endocrine system.
authors.affiliation: Toxicology & Environmental Research & Consulting, Dow Chemical Company, Midland, MI, USA. Electronic address: kcoady@dow.com.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Coady
authors.affiliation: Toxicology & Environmental Research & Consulting, Dow Chemical Company, Midland, MI, USA.
authors.forename: H Lynn
authors.initials: HL
authors.lastname: Kan
authors.affiliation: Toxicology & Environmental Research & Consulting, Dow Chemical Company, Midland, MI, USA.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Schisler
authors.affiliation: Toxicology & Environmental Research & Consulting, Dow Chemical Company, Midland, MI, USA; Exponent, Inc., Midland, MI, USA.
authors.forename: B Bhaskar
authors.initials: BB
authors.lastname: Gollapudi
authors.affiliation: Exponent, Inc., Alexandria, VA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Neal
authors.affiliation: Exponent, Inc., Alexandria, VA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Williams
authors.affiliation: Toxicology & Environmental Research & Consulting, Dow Chemical Company, Midland, MI, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: LeBaron
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001681:Biological Assay; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D006540:Herbicides; D011944:Receptors, Androgen; D015084:2,4-Dichlorophenoxyacetic Acid; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: 2,4-D; Androgen receptor; Aromatase; Endocrine Disruptor Screening Program; Estrogen receptor; Steroidogenesis