title: Evaluation of endocrine disrupting effects of nitrate after in utero exposure in rats and of nitrate and nitrite in the H295R and T-screen assay.
abstract: Animal studies have shown that nitrate acts as an endocrine disrupter affecting the androgen production in adult males. This raises a concern for more severe endocrine disrupting effects after exposure during the sensitive period of prenatal male sexual development. As there are no existing studies of effects of nitrate on male sexual development, the aim of the study was to examine how in utero exposure to nitrate would affect male rat fetuses. Pregnant dams were dosed with nitrate in the drinking water from gestational day (GD) 7 to GD21 at the following dose levels 17.5, 50, 150, 450, and 900 mg/l. At GD21, fetuses were examined for anogenital distance, plasma thyroxine levels, testicular and plasma levels of testosterone and progesterone, and testicular testosterone production and histopathology. In addition, endocrine disrupting activity of nitrate and nitrite were studied in two in vitro assays, the H295R assay and T-screen. There were no consistent indications that nitrate induces anti-androgenic effects in male fetuses or that prenatal nitrate exposure affected the thyroid axis. However, a more comprehensive study with long-term exposure before and during pre- and postnatal development would be relevant to sufficiently address the concerns based on the indications for endocrine disrupting effects in adult animals.
authors.affiliation: Department of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Søborg, Denmark.
authors.forename: Pernille Reimer
authors.initials: PR
authors.lastname: Hansen
authors.forename: Camilla
authors.initials: C
authors.lastname: Taxvig
authors.forename: Sofie
authors.initials: S
authors.lastname: Christiansen
authors.forename: Marta
authors.initials: M
authors.lastname: Axelstad
authors.forename: Julie
authors.initials: J
authors.lastname: Boberg
authors.forename: Maria Kristina
authors.initials: MK
authors.lastname: Kiersgaard
authors.forename: Christine
authors.initials: C
authors.lastname: Nellemann
authors.forename: Ulla
authors.initials: U
authors.lastname: Hass
mesh_terms: D000311:Adrenal Glands / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D052244:Endocrine Disruptors; D005260:Female; D006854:Hydrocortisone / Q000096:biosynthesis; D007150:Immunohistochemistry; D008297:Male; D009566:Nitrates / Q000633:toxicity*; D009573:Nitrites / Q000633:toxicity*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012741:Sexual Maturation / Q000187:drug effects; D013256:Steroids / Q000096:biosynthesis; D013737:Testis / Q000254:growth & development / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013974:Thyroxine / Q000097:blood
chemical_list: D052244:Endocrine Disruptors; D009566:Nitrates; D009573:Nitrites; D011988:Receptors, Thyroid Hormone; D013256:Steroids; D013739:Testosterone; D011374:Progesterone; D013974:Thyroxine; D006854:Hydrocortisone