Review of risk assessments on 1,3-butadiene (1985-1991).
During the past decade, several assessments have estimated the carcinogenic risk of inhaled 1,3-butadiene (BD) to the general population as well as for occupational exposures. Although most of the risk assessments have been based on inhalation bioassays in mice, some of the assessments have included the 2-year inhalation bioassay in rats. Because of the marked species differences in the carcinogenic response to butadiene, estimates of risk vary over nine orders of magnitude going from the most sensitive target organ in female mice to less sensitive male rats. An important tool in determining which estimate is most relevant for extrapolation to humans is to ascertain consistency with human experience. Estimated workplace cancer risks which are based on the assumption that humans are as responsive as the mouse suggest added risks of 200 or more out of 1000 workers (1 in 5) exposed to 2 ppm butadiene (assume 40 years of exposure). This estimate is clearly inconsistent with what has been seen and this would not have been missed in epidemiology studies. Risk assessments based on the growing understanding of the mechanisms of toxicity and the importance of various tissues ability to produce and maintain reactive epoxide metabolites demonstrate why rats are much less susceptible than the mouse. By developing a mechanistic understanding of humans, it is possible to refine the traditional approach to risk assessment, whereby better risk assessments can be made. This paper presents a summary of eight risk assessments that have been developed to date for butadiene.
Cagen
S Z
SZ
Shell Oil Company, Houston, TX 77210, USA.
MacDonald
R L
RL
Van Gelder
G
G
D000818:Animals; D002070:Butadienes / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D018570:Risk Assessment
D002070:Butadienes; D002273:Carcinogens; D009153:Mutagens; C031763:1,3-butadiene