Pa. Valberg et Ay. Watson, LUNG-CANCER RATES IN CARBON-BLACK WORKERS ARE DISCORDANT WITH PREDICTIONS FROM RAT BIOASSAY DATA, Regulatory toxicology and pharmacology, 24(2), 1996, pp. 155-170
The recent demonstration of lung tumors in rats chronically exposed to
airborne carbon-black particles has prompted reevaluation of the carc
inogenicity of carbon black. However, accumulating evidence suggests t
hat rat responses to inhaled particles are unique and are mediated by
the sequelae to lung overload conditions. To test the predictive value
of the rat inhalation bioassay for human lung cancer risk, we examine
d epidemiologic studies of workers exposed to carbon black during its
manufacture or use. industries in which significant airborne carbon-bl
ack exposure has occurred were not associated with increased lung canc
er risk. We also predicted the number of occupational lung cancer case
s that one would expect in exposed workers, based on the cancer potenc
y of carbon black derived from rat studies. Our quantitative compariso
n of the tumorigenicity of carbon black predicted from rat studies to
the lung cancer rate in carbon-black workers showed a marked discrepan
cy between the lung cancers predicted and those actually observed. We
found that far more lung cancers are predicted from the rat bioassay t
han can be demonstrated in workers, We determined that it is highly un
likely that this discrepancy is due to chance. We conclude that extrap
olating the incidence of lung tumors in rats inhaling inert, insoluble
particles, such as carbon black, to humans must be seriously question
ed. Using rat inhalation bioassay data for carbon black to estimate lu
ng tumor risk in humans must be seriously questioned unless the mechan
isms of the rat's unique response are shown to be relevant to humans.
(C) 1996 Academic Press, Inc.