Coumaphos Exposure and Incident Cancer among Male Participants in the Agricultural Health Study (AHS)
Christensen, Carol H., Platz, Elizabeth A., Andreotti, Gabriella, Blair, Aaron, Hoppin, Jane A., Koutros, Stella, Lynch, Charles F., Sandler, Dale P., Alavanja, Michael C. R., Environmental Health Perspectives
BACKGROUND: Coumaphos is an organophosphate livestock insecticide. Previous research in the Agricultural Health Study (AHS) cohort observed a positive association between coumaphos and prostate cancer in men with a family history of prostate cancer.
OBJECTIVES: This study was performed to determine the association between coumaphos and other major cancer sites and to explore the consistency of the association with prostate cancer early (1993-1999) and later (2000-2005) in AHS follow-up.
METHODS: This study included 47,822 male licensed pesticide applicators. Incident cases were ascertained by linkage to state cancer registries, and exposure data were collected by enrollment questionnaire. Poisson regression was used to estimate rate ratio (RR) and 95% confidence interval (CI) of cancer for coumaphos exposure controlling for potentially confounding variables.
RESULTS: Approximately 8% of applicators reported use of coumaphos; 8.5% reported a family history of prostate cancer. Cumulative exposure to coumaphos was not associated with cancer risk overall or with any major cancer site including prostate. In men with a family history of prostate cancer, we observed a positive association between ever use of coumaphos and prostate cancer in both early (RR = 2.07; 95% CI, 1.19-3.62, p-interaction = 0.005) and later (RR = 1.46; 95% CI, 0.89-2.40; p-interaction = 0.11) periods of follow-up. Across all years, this association was statistically significant (RR = 1.65; 95% CI, 1.13-2.38; p-interaction = 0.004).
CONCLUSION: Coumaphos was not associated with any cancer evaluated here. In men with a family history of disease, there was evidence of an association between coumaphos and prostate cancer, possibly due to genetic susceptibility; however, other explanations, including chance, are plausible.
KEY WORDS: agriculture, cancer, coumaphos, insecticide, livestock, neoplasms, occupational exposure, organophosphate, pesticide, prostate. Environ Health Perspect 118:92-96 (2010). doi:10.1289/ehp.0800446 available via http://dx.doi.org/[Online 11 September 2009]
Coumaphos [O,O-diethyl O-(3-chloro-4-methyl-2 oxo-2H-l-benzopyran-7-yl) phosphorothioate], an organophosphate (OP) insecticide first registered in 1958, is used to control pests on beef cattle, dairy cows, goats, horses, sheep, and swine [U.S. Environmental Protection Agency (EPA) 1996]. Approximately 83% of the total chemical usage is on beef and dairy cattle. From 1990 to 1999, approximately 71,000 pounds of coumaphos were used on 6 million livestock annually (Smearman 2000). Coumaphos is applied primarily as a liquid (animal immersed in an insecticide-containing dip) but is also applied through a hand-held sprayer or dust formulation (U.S. EPA 1996). In addition to direct exposure to coumaphos among agricultural workers, family members of agricultural workers may be secondarily exposed in the home through contact with contaminated clothing or equipment (Arcury et al. 2007). The general population may be exposed through consumption of coumaphos-treated food products--for example, milk from coumaphos-treated dairy cattle (Cardeal Zde and Dias Paes 2006). However, commercial pesticide products containing the active ingredient coumaphos cannot be purchased by the general public.
In vitro studies indicate coumaphos is not mutagenic using either Salmonella typhimu-rium or Escherichia coli assays with and without metabolic activation (U.S. EPA 1996). There was no evidence of carcinogenicity or increased tumor formation in two 2-year feeding studies in different strains of rat (dose range: 1-25 ppm and 10 and 20 ppm, respectively), in one strain of mouse (dose range: 10 and 20 ppm), or in one 1-year feeding study in beagle dogs (dose range: 1-90 ppm) (U.S. EPA 1996). Dosing regimens in the four animal feeding studies were adequate to detect cancer based on range-finding studies. In 1994, the U.S. EPA classified coumaphos as a group E carcinogen: no evidence of carcinogenicity based on studies of at least two animal species. …