ToxSci Advance Access originally published online on February 3, 2009
Toxicological Sciences 2009 108(2):437-444; doi:10.1093/toxsci/kfp023
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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
National Food Institute, Technical University of Denmark, Department of Toxicology and Risk Assessment, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark
1 To whom correspondence should be addressed. E-mail: Ulha{at}food.dtu.dk.
Received November 21, 2008; accepted January 28, 2009
| Abstract |
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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.
Key Words: nitrate; nitrite; endocrine disruption; H295R assay; T-Screen; steroidogenesis; developmental toxicity; rat.