title: Uptake and disposition of 1,1-difluoroethane (HFC-152a) in humans.
abstract: The aim of this study was to determine the toxicokinetics of inhaled 1,1-difluoroethane (HFC-152a) in humans. Healthy volunteers were exposed to 0, 200 or 1000 ppm 1,1-difluoroethane for 2h at light exercise in an exposure chamber. Capillary blood, urine and exhaled air were sampled up to 22 h post-exposure and analyzed for 1,1-difluoroethane. Fluoride and other potential metabolites were analyzed in urine. Symptoms of irritation and central nervous system effects were rated and inflammatory markers were analyzed in blood. Within a few minutes of exposure to 200 and 1000 ppm, 1,1-difluoroethane increased rapidly in blood and reached average levels of 7.4 and 34.3 μM, respectively. The post-exposure decreases in blood were fast and parallel to those in exhaled air. The observed time courses in blood and breath agreed well with those obtained with the PBPK model. The PBPK simulations indicate a net uptake during exposure to 1000 ppm of 6.6 mmol (6.7%) which corresponds to the amount exhaled post-exposure. About 20 μmol excess fluoride (0.013% of inhaled 1,1-difluoroethane on a molar basis) was excreted in urine after exposure to 1000 ppm, compared to control. No fluorine-containing metabolites were detected in urine. Symptom ratings and changes in inflammatory markers revealed no exposure-related effects.
authors.affiliation: Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Lena.Ernstgard@ki.se
authors.forename: Lena
authors.initials: L
authors.lastname: Ernstgård
authors.forename: Bengt
authors.initials: B
authors.lastname: Sjögren
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dekant
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmidt
authors.forename: Gunnar
authors.initials: G
authors.lastname: Johanson
mesh_terms: D000328:Adult; D001273:Atmosphere Exposure Chambers; D001711:Biotransformation; D001823:Body Composition / Q000502:physiology; D001944:Breath Tests; D016207:Cytokines / Q000097:blood; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics* / Q000633:toxicity*; D007249:Inflammation / Q000097:blood / Q000139:chemically induced; D019570:Inhalation Exposure; D008297:Male; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D016207:Cytokines; D006845:Hydrocarbons, Fluorinated; C059268:1,1-difluoroethane