Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects

Niels Hadrup, Terje Svingen, Karen Mandrup Egebjerg, Kasper Skov, Mikael Pedersen, Hanne Frederiksen, Henrik Lauritz Frandsen, Anne Marie Vinggaard

Research output: Contribution to journalJournal articleResearchpeer-review

231 Downloads (Pure)

Abstract

Humans are exposed to a large number of environmental chemicals in their daily life, many of which are readily detectable in blood or urine. It remains uncertain if these chemicals can cause adverse health effects when present together at low doses. In this study we have tested whether a mixture of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid dose) or 1.6 (High dose) mg/kg bw/day. The lowest dose was designed with the aim of obtaining plasma or urine concentrations in rats at levels approaching those observed in humans. Some single congeners were administered at doses representative of combined doses for chemical groups. With this baseline, we found effects on weight, histology and gene expression in the liver, as well as changes to the blood plasma metabolome in all exposure groups, including low-dose. Additional adverse effects were observed in the higher dosed groups, including enlarged kidneys and alterations to the metabolome. No significant effects on reproductive parameters were observed.
Original languageEnglish
Article numbere0162027
JournalP L o S One
Volume11
Issue number9
Number of pages22
ISSN1932-6203
DOIs
Publication statusPublished - 2016

Cite this

@article{02503244979d49879ddd9e2ed6ce24ed,
title = "Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects",
abstract = "Humans are exposed to a large number of environmental chemicals in their daily life, many of which are readily detectable in blood or urine. It remains uncertain if these chemicals can cause adverse health effects when present together at low doses. In this study we have tested whether a mixture of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid dose) or 1.6 (High dose) mg/kg bw/day. The lowest dose was designed with the aim of obtaining plasma or urine concentrations in rats at levels approaching those observed in humans. Some single congeners were administered at doses representative of combined doses for chemical groups. With this baseline, we found effects on weight, histology and gene expression in the liver, as well as changes to the blood plasma metabolome in all exposure groups, including low-dose. Additional adverse effects were observed in the higher dosed groups, including enlarged kidneys and alterations to the metabolome. No significant effects on reproductive parameters were observed.",
author = "Niels Hadrup and Terje Svingen and Egebjerg, {Karen Mandrup} and Kasper Skov and Mikael Pedersen and Hanne Frederiksen and Frandsen, {Henrik Lauritz} and Vinggaard, {Anne Marie}",
year = "2016",
doi = "10.1371/journal.pone.0162027",
language = "English",
volume = "11",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects. / Hadrup, Niels; Svingen, Terje; Egebjerg, Karen Mandrup; Skov, Kasper; Pedersen, Mikael; Frederiksen, Hanne; Frandsen, Henrik Lauritz; Vinggaard, Anne Marie.

In: P L o S One, Vol. 11, No. 9, e0162027, 2016.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects

AU - Hadrup, Niels

AU - Svingen, Terje

AU - Egebjerg, Karen Mandrup

AU - Skov, Kasper

AU - Pedersen, Mikael

AU - Frederiksen, Hanne

AU - Frandsen, Henrik Lauritz

AU - Vinggaard, Anne Marie

PY - 2016

Y1 - 2016

N2 - Humans are exposed to a large number of environmental chemicals in their daily life, many of which are readily detectable in blood or urine. It remains uncertain if these chemicals can cause adverse health effects when present together at low doses. In this study we have tested whether a mixture of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid dose) or 1.6 (High dose) mg/kg bw/day. The lowest dose was designed with the aim of obtaining plasma or urine concentrations in rats at levels approaching those observed in humans. Some single congeners were administered at doses representative of combined doses for chemical groups. With this baseline, we found effects on weight, histology and gene expression in the liver, as well as changes to the blood plasma metabolome in all exposure groups, including low-dose. Additional adverse effects were observed in the higher dosed groups, including enlarged kidneys and alterations to the metabolome. No significant effects on reproductive parameters were observed.

AB - Humans are exposed to a large number of environmental chemicals in their daily life, many of which are readily detectable in blood or urine. It remains uncertain if these chemicals can cause adverse health effects when present together at low doses. In this study we have tested whether a mixture of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid dose) or 1.6 (High dose) mg/kg bw/day. The lowest dose was designed with the aim of obtaining plasma or urine concentrations in rats at levels approaching those observed in humans. Some single congeners were administered at doses representative of combined doses for chemical groups. With this baseline, we found effects on weight, histology and gene expression in the liver, as well as changes to the blood plasma metabolome in all exposure groups, including low-dose. Additional adverse effects were observed in the higher dosed groups, including enlarged kidneys and alterations to the metabolome. No significant effects on reproductive parameters were observed.

U2 - 10.1371/journal.pone.0162027

DO - 10.1371/journal.pone.0162027

M3 - Journal article

VL - 11

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 9

M1 - e0162027

ER -