title: Toxicological response of Sprague Dawley rats from inhalation exposure to perfluorooctane sulfonyl fluoride (POSF).
abstract: Perfluorooctane sulfonyl fluoride (POSF) was a volatile starting material in the production of perfluorooctane sulfonate (PFOS), a stable surfactant that has been extensively studied due to its ubiquitous environmental distribution and slow clearance in humans. Because the inhalation toxicity of POSF on repeated exposure has not been previously reported, the current study evaluated the inhalation toxicity of POSF at 30, 100, and 300ppm (v/v) in rats for up to 13 weeks with a four-week recovery period. The extent of PFOS formation was also measured because POSF hydrolyzed to form PFOS. In addition, detailed urinalysis and examination of the urinary bladder were included to determine if factors associated with the development of bladder cancer were present. Exposure to POSF at 300ppm was associated with reduction in body weight-gain, necrosis of laryngeal cartilage, increased lung and bronchi weight with septal thickening, and changes in alveolar macrophages. The microscopic observations in larynx and lung are consistent with likely hydrolysis of POSF to form hydrogen fluoride (HF). Exposure to POSF at 100 and 300ppm was associated with increased relative liver weight, hepatocellular hypertrophy (except for females exposed to 100ppm POSF), and lowering of serum cholesterol (male only). After 13 weeks of exposure to 30, 100, or 300ppm POSF, serum PFOS concentration approximated 7, 35, or 100μg/mL, respectively. Approximately 0.1% of inhaled POSF was converted to PFOS. No changes indicative of bladder effects were observed in these rats exposed to POSF at any dose.
authors.affiliation: 3M Company, Medical Department,Building 220-6W-08, St. Paul, MN 55144, USA. Electronic address: salutox@gmail.com.
authors.forename: John L
authors.initials: JL
authors.lastname: Butenhoff
authors.affiliation: 3M Company, Medical Department,Building 220-6W-08, St. Paul, MN 55144, USA. Electronic address: gwolsen@mmm.com.
authors.forename: Geary W
authors.initials: GW
authors.lastname: Olsen
authors.affiliation: 3M Company, Medical Department,Building 220-6W-08, St. Paul, MN 55144, USA. Electronic address: s.chang@mmm.com.
authors.forename: Sue
authors.initials: S
authors.lastname: Chang
mesh_terms: D017738:Alkanesulfonic Acids / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004435:Eating / Q000187:drug effects; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D006858:Hydrofluoric Acid / Q000378:metabolism / Q000633:toxicity; D006868:Hydrolysis; D006984:Hypertrophy; D019570:Inhalation Exposure; D007817:Laryngeal Cartilages / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D008297:Male; D009336:Necrosis; D009929:Organ Size; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D013997:Time Factors; D018675:Toxicity Tests; D015430:Weight Gain / Q000187:drug effects
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; D002784:Cholesterol; C076994:perfluorooctane sulfonic acid; D006858:Hydrofluoric Acid
keywords: Inhalation; PFOS; POSF; Perfluorooctane sulfonyl fluoride