Imazethapyr, a heterocyclic aromatic
amine, is a widely used crop
herbicide first registered for use in the United States in 1989. We evaluated
cancer incidence among
imazethapyr-exposed
pesticide applicators enrolled in the Agricultural Health Study (AHS). The AHS is a prospective cohort of 57,311 licensed
pesticide applicators in the U.S., enrolled from 1993-1997. Among the 49,398 licensed
pesticide applicators eligible for analysis, 20,646 applicators reported use of
imazethapyr and 2,907 incident
cancers developed through 2004.
Imazethapyr exposure was classified by intensity-weighted lifetime exposure days calculated as [years of use x days per year x intensity level]. Poisson regression analysis was used to evaluate the relationship between
imazethapyr exposure and
cancer incidence. We found significant trends in risk with increasing lifetime exposure for
bladder cancer (p for trend 0.01) and
colon cancer (p for trend 0.02). Rate ratios (RRs) were increased by 137% for
bladder cancer and 78% for
colon cancer when the highest exposed were compared to the nonexposed. The excess risk for
colon cancer was limited to proximal
cancers, (RR = 2.73, 95% confidence intervals 1.42, 5.25, p for trend 0.001). No association was observed for prostate, lung, rectum, kidney, oral, pancreas, lymphohematopoietic
cancers or
melanoma. These findings provide new evidence that exposure to aromatic
amine pesticides may be an overlooked exposure in the etiology of bladder and
colon cancer. The use of
imazethapyr and other imidazolinone compounds should continue to be evaluated for potential risk to humans.