Evaluation of alternative methods for establishing safe levels of occupational exposure to vinyl halides.
The facts that reduction of occupational vinyl chloride exposures to levels within or below the 0.5-5 ppm range has so far been successful in eliminating vinyl chloride-induced liver angiosarcoma and that humans appear to be less sensitive to the carcinogenic effect of vinyl chloride than rats offered an opportunity to verify or dispute risk assessment extrapolation models used, and proposed, by the U.S. EPA. Safe occupational vinyl chloride exposures were defined as levels associated with an incidence of one angiosarcoma in 100,000 exposed workers, determined from rat bioassay data using default no-threshold (linearized multistage model and benchmark dose approach with linear extrapolation) and threshold (NOEL/LOEL and benchmark dose uncertainty factor approaches) models, and then compared against the likely protective range of 0.5-5 ppm. Safe levels derived using either no-threshold model are equivalent and are two to three orders of magnitude below the 0.5-5 ppm range. Safe levels derived using either threshold model, when applying uncertainty factors which reflect equal or less sensitivity in humans compared to rats, fall within the 0.5-5 ppm range. Similar results were obtained for vinyl bromide and vinyl fluoride. These results undermine the U.S. EPA default assumption of no-threshold for vinyl halides as well as for other DNA-reactive carcinogens while simultaneously supporting the notion that a practical threshold exists. They further suggest that when threshold models are appropriate, the default assumption of greater sensitivity in humans compared to rats should be carefully evaluated.
Storm
J E
JE
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Rozman
K K
KK
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D006394:Hemangiosarcoma / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D008452:Maximum Allowable Concentration; D016273:Occupational Exposure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012307:Risk Factors; D014752:Vinyl Chloride / Q000633:toxicity; D014753:Vinyl Compounds / Q000633:toxicity*
D002273:Carcinogens; D014753:Vinyl Compounds; C016829:vinyl fluoride; C003763:vinyl bromide; D014752:Vinyl Chloride