Toxicological profile of hydrofluoropolyethers

• Published in: Regulatory toxicology and pharmacology Vol. 41; no. 3; pp. 228 - 239
• Main Authors: Malinverno, G., Colombo, I., Visca, M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.04.2005
• Subjects: Animals; Embryonic Development; Ethers; Female; Fluorides - urine; Fluorinated fluids; Fluorine Compounds - toxicity; Hydrofluoropolyethers; Inhalation Exposure; Lethal Dose 50; Liver - pathology; Male; No-Observed-Adverse-Effect Level; Polymers - toxicity; Rats; Rats, Sprague-Dawley; Risk Assessment; Toxicology; Toxicology; Hydrofluoropolyethers; Fluorinated fluids; Risk assessment
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2004.12.003

Hydrofluoropolyethers (HFPE) are a family of linear oligomeric fluorinated fluids comprising a chain of difluoromethoxy and tetrafluoroethoxy repeating units with terminal OCF 2H end groups, each of which contains an isolated hydrogen atom. These fluids have been designed as low environmental impact substitutes for perfluorinated organic substances in a number of applications including heat transfer and fire suppression agents, and as a solvent. The toxicological profile of these new fluids has been evaluated and is presented in this paper. Acute toxicity tests have been performed on Sprague–Dawley Crl: CD (SD) BR rats using oral, dermal, and inhalation routes. No deaths were recorded even at the highest tested concentrations, and the resultant LD 50/LC 50 values were >5000 mg/kg (oral), >2000 mg/kg (dermal), and >26,411 ppm (inhalation: reversible anaesthetic effects, e.g., lethargy, seen at this exposure concentration). Other short-term tests (skin and eye irritation, skin sensitisation, genotoxicity tests in vitro and in vivo, cardiac sensitisation) were also performed, and no hazardous properties were identified. Effects of repeated exposure by inhalation were examined in rats over test periods of 5, 14, 28, and 90 days. Effects on embryo–foetal development in the rat have also been studied. The 28-day, 90-day and developmental studies were performed using nominal HFPE concentrations of 1000, 3300, and 10,000 ppm (6 h/day: actual exposures confirmed by test atmosphere analysis), and the highest tested concentration proved to be an NOAEL in each study. Major observed effects were elevated urinary (inorganic) fluoride levels and increased liver weights with centrilobular hepatocyte hypertrophy (considered an adaptive response, linked to hepatic metabolism of absorbed material).