Perfluorohexanoic acid toxicity, part I: Development of a chronic human health toxicity value for use in risk assessment
| Autor: | Judi Durda, Janet K. Anderson, Philip E. Goodrum, Anthony L. Luz |
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| Rok vydání: | 2019 |
| Předmět: |
Reference dose
business.industry Physiology General Medicine 010501 environmental sciences Toxicology 030226 pharmacology & pharmacy 01 natural sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Toxicity Medicine Perfluorooctanoic acid business Fluorotelomer Risk assessment Chronic toxicity Carcinogen 0105 earth and related environmental sciences Toxicant |
| Zdroj: | Regulatory Toxicology and Pharmacology. 103:41-55 |
| ISSN: | 0273-2300 |
| DOI: | 10.1016/j.yrtph.2019.01.019 |
| Popis: | Perfluorohexanoic acid (PFHxA) is a short-chain, six-carbon perfluoroalkyl acid (PFAA) and is a primary impurity, degradant, and metabolite associated with the short-chain fluorotelomer-based chemistry used globally today. The transition to short-chain fluorotelomer-based products as a cornerstone in replacement fluorochemistry has raised questions regarding potential human health risks associated with exposure to fluorotelomer-based substances and therefore, PFHxA. Here, we present a critical review of data relevant to such a risk assessment, including epidemiological studies and in vivo and in vitro toxicity studies that examined PFHxA acute, subchronic, and chronic toxicity. Key findings from toxicokinetic and mode-of-action studies are also evaluated. Sufficient data exist to conclude that PFHxA is not carcinogenic, is not a selective reproductive or developmental toxicant, and does not disrupt endocrine activity. Collectively, effects caused by PFHxA exposure are largely limited to potential kidney effects, are mild and/or reversible, and occur at much higher doses than observed for perfluorooctanoic acid (PFOA). A chronic human-health-based oral reference dose (RfD) for PFHxA of 0.25 mg/kg-day was calculated using benchmark dose modeling of renal papillary necrosis from a chronic rat bioassay. This RfD is four orders of magnitude greater than the chronic oral RfD calculated by the U.S. Environmental Protection Agency for PFOA. The PFHxA RfD can be used to inform public health decisions related to PFHxA and fluorotelomer precursors for which PFHxA is a terminal degradant. These findings clearly demonstrate that PFHxA is less hazardous to human health than PFOA. The analyses presented support site-specific risk assessments as well as product stewardship initiatives for current and future short-chain fluorotelomer-based products. |
| Databáze: | OpenAIRE |
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