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ToxSci Advance Access published online on February 3, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp023
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

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

Pernille Reimer Hansen*, Camilla Taxvig*, Sofie Christiansen*, Marta Axelstad*, Julie Boberg*, Maria Kristina Kiersgaard*, Christine Nellemann* and Ulla Hass*

* National Food Institute, Technical University of Denmark, Dept. of Toxicology and Risk Assessment, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark, Tel.:+4572347544

Correspondence to: Ulla Hass: Ulha{at}food.dtu.dk

Received November 21, 2008; revision received January 8, 2009; accepted January 28, 2009


  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 foetuses. Pregnant dams were dosed with nitrate in the drinking water from gestational day (GD) 7 to GD 21 at the following dose levels 17.5, 50, 150, 450 and 900 mg/l. At GD21, foetuses 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 foetuses 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.

Key Words: nitrate; nitrite; Endocrine disruption; H295R assay; T-Screen; Steroidogenesis; Developmental toxicity; rat.


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