Observations on the dose-response curve for arsenic exposure and lung cancer

Occupational studies in three countries have related quantitative estimates of arsenic exposure to lung cancer risks. Mine exposures in China appear to incur a higher relative risk than arsenic exposures elsewhere. All of the studies with quantitative data are consistent with a supralinear dose-response relationship. Two studies are also consistent with a linear relationship over an elevated background risk of lung cancer among arsenic-exposed workers. Neither toxicokinetic mechanisms nor confounding from age, smoking, or other workplace carcinogens that differ by exposure level appear likely to explain this curvilinearity. Plausible explanations include (i) synergism (with smoking) which varies in magnitude according to the level of arsenic exposure, (ii) long-term survivorship in higher exposure jobs among the healthier, less susceptible individuals, (iii) exposure estimate errors that were more prominent at higher exposure levels as a result of past industrial hygiene sampling or worker protection practices.