Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects.
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.
Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Søborg DK-2400, Denmark.
Niels
http://orcid.org/0000-0002-1188-445X
N
Hadrup
Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Søborg DK-2400, Denmark.
Terje
T
Svingen
Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Søborg DK-2400, Denmark.
Karen
K
Mandrup
Division of Food Chemistry, National Food Institute, Technical University of Denmark, Søborg DK-2400, Denmark.
Kasper
K
Skov
Division of Food Chemistry, National Food Institute, Technical University of Denmark, Søborg DK-2400, Denmark.
Mikael
M
Pedersen
Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen DK-2100, Denmark.
Hanne
H
Frederiksen
Division of Food Chemistry, National Food Institute, Technical University of Denmark, Søborg DK-2400, Denmark.
Henrik Lauritz
HL
Frandsen
Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Søborg DK-2400, Denmark.
Anne Marie
AM
Vinggaard
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004147:Dioxins / Q000097:blood / Q000633:toxicity* / Q000652:urine; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity* / Q000652:urine; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006571:Heterocyclic Compounds / Q000097:blood / Q000633:toxicity* / Q000652:urine; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D055442:Metabolome; D008670:Metals / Q000097:blood / Q000633:toxicity* / Q000652:urine; D010575:Pesticides / Q000097:blood / Q000633:toxicity* / Q000652:urine; D010743:Phospholipids / Q000097:blood / Q000652:urine; D010795:Phthalic Acids / Q000097:blood / Q000633:toxicity* / Q000652:urine; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity* / Q000652:urine; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D004147:Dioxins; D004785:Environmental Pollutants; D006571:Heterocyclic Compounds; D008670:Metals; D010575:Pesticides; D010743:Phospholipids; D010795:Phthalic Acids; C032279:phthalic acid; D011078:Polychlorinated Biphenyls