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

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@article{4e92b449897641a6b9eb634c7dccd073,
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.",
keywords = "developmental toxicity, endocrine disruption, H295R assay, steroidogenesis, T-Screen, nitrite, nitrate, rat",
author = "Hansen, {Pernille Reimer} and Camilla Taxvig and Sofie Christiansen and Petersen, {Marta Axelstad} and Julie Boberg and Kiersgaard, {Maria Kristina} and Nellemann, {Christine Lydia} and Ulla Hass",
year = "2009",
doi = "10.1093/toxsci/kfp023",
language = "English",
volume = "108",
pages = "437--444",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - 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

AU - Hansen, Pernille Reimer

AU - Taxvig, Camilla

AU - Christiansen, Sofie

AU - Petersen, Marta Axelstad

AU - Boberg, Julie

AU - Kiersgaard, Maria Kristina

AU - Nellemann, Christine Lydia

AU - Hass, Ulla

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - developmental toxicity

KW - endocrine disruption

KW - H295R assay

KW - steroidogenesis

KW - T-Screen

KW - nitrite

KW - nitrate

KW - rat

U2 - 10.1093/toxsci/kfp023

DO - 10.1093/toxsci/kfp023

M3 - Journal article

VL - 108

SP - 437

EP - 444

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -