A low dose chemical mixture modulates the effect of PFNA in male rats

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Purpose: When mathematical models are applied for assessment of chemical mixture effects, assumptions of lack of synergy or potentiation have to be made; Thus joint effects of chemicals are anticipated not to be unexpectedly high. The present investigation was designed to test whether a chemical mixture at human relevant doses interacts with perfluorononanoic acid (PFNA) by synergy or potentiation.

Methods: Male rats were given PFNA at 0.0125, 0.25 or 5 mg/kg bw/day for 14 days with or without a mixture containing 12 endocrine disrupters (total dose 2.5 mg/kg bw/day), bergamottin from grapefruit juice (0.2 mg/kg bw/day), and glabridin from liquorice (0.3 mg/kg bw/day). Rats were examined pathologically, plasma hormones and mRNA levels of several enzymes were measured, and metabolomic profiling of plasma was performed.

Results and conclusion: High dose PFNA exhibited liver steatosis and effects on testes enzyme mRNA levels. These effects were similar both with and without mixture. In contrast, co-treatment with mixture increased both relative and absolute liver weights of the 5 mg/kg/day PFNA, suggesting that liver toxicity was exacerbated by the mixture.

These data suggest that a chemical mixture at a human relevant dose potentiates the response of the rat to PFNA, but not at a human relevant dose of PFNA. Thus, with the parameters measured to date, this investigation supports the hypothesis that synergism or potentiation due to ADME interactions are absent at human relevant doses.
Original languageEnglish
JournalToxicology Letters
Issue numberSupplement
Pages (from-to)230-231
Publication statusPublished - 2013
Event49th Congress of the European Societies of Toxicology (EUROTOX) - Interlaken, Switzerland
Duration: 1 Sep 20134 Sep 2013
Conference number: 49


Conference49th Congress of the European Societies of Toxicology (EUROTOX)

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