Cancer Incidence among Pesticide Applicators Exposed to Dicamba in the Agricultural Health Study
Samanic, Claudine, Rusiecki, Jennifer, Dosemeci, Mustafa, Hou, Lifang, Hoppin, Jane A., Sandler, Dale P., Lubin, Jay, Blair, Aaron, Alavanja, Michael C. R., Environmental Health Perspectives
BACKGROUND: Dicamba is an herbicide commonly applied to crops in the United States and abroad. We evaluated cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in North Carolina and Iowa.
METHODS: Detailed pesticide exposure information was obtained through a self-administered questionnaire completed from 1993 to 1997. Cancer incidence was followed through 31 December 2002 by linkage to state cancer registries. We used Poisson regression to estimate rate ratios and 95% confidence intervals for cancer subtypes by tertiles of dicamba exposure. Two dicamba exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days (lifetime days x intensity score).
RESULTS: A total of 41,969 applicators were included in the analysis, and 22,036 (52.5%) reported ever using dicamba. Exposure was not associated with overall cancer incidence nor were there strong associations with any specific type of cancer. When the reference group comprised low-exposed applicators, we observed a positive trend in risk between lifetime exposure days and lung cancer (p = 0.02), but none of the individual point estimates was significantly elevated. We also observed significant trends of increasing risk for colon cancer for both lifetime exposure days and intensity-weighted lifetime days, although these results are largely due to elevated risk at the highest exposure level. There was no apparent risk for non-Hodgkin lymphoma.
CONCLUSIONS: Although associations between exposure and lung and colon cancer were observed, we did not find clear evidence for an association between dicamba exposure and cancer risk.
KEY WORDS: cancer incidence, farming, neoplasms, pesticides, United States. Environ Health Perspect 114:1521-1526 (2006). doi:10.1289/ehp.9204 available via http://dx.doi.org/ [Online 13 July 2006]
Dicamba (3,6-dichloro-2-methoxybenzoic acid) is a benzoic acid herbicide used to control annual and perennial broadleaf weeds in grain crops, grasslands, and non-crop areas such as fence rows and roadways. Dicamba may be used in combination with other herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D) or atrazine. In 2001 Dicamba ranked 24th of the 25 most commonly used agricultural pesticides with 7-10 million pounds applied, and 7th of the 10 most commonly used home and garden pesticides (Kiely et al. 2004).
Dicamba was first registered for use in 1967 (National Pesticide Information Center 2005). The U.S. Environmental Protection Agency (EPA) has classified this general use pesticide as toxicity class III--slightly toxic (Extension Toxicology Network 1996), and as a Group D carcinogen: "not classifiable as to human carcinogenicity" (U.S. EPA 2004). There is no experimental evidence that dicamba is mutagenic or carcinogenic (Extension Toxicology Network 1996; U.S. EPA 2005), although rats fed dicamba at high levels over long periods experienced liver changes and decreased body weight (Edson and Sanderson 1965). Limited animal evidence suggests that dicamba could induce tumors through epigenetic mechanisms (Espandiari et al. 1998, 1999).
In epidemiologic studies, occupational use of dicamba has been associated with non-Hodgkin lymphoma (NHL; McDuffie et al. 2001) and multiple myeloma (Burmeister 1990). More recently, in the Agricultural Health Study (AHS) cohort, dicamba was associated with an increased risk of lung cancer in a nested case-control analysis (Alavanja et al. 2004). Dicamba has been found in carpet dust samples, with higher levels from states with higher prevalence of lawn and garden use (Colt et al. 2005), and in 1.4% of urine samples collected between 1976 and 1980 from 6,990 participants in the Second National Health and Nutrition Examination Survey (Kutz et al. 1992).
Despite its common use and some epidemiologic evidence that suggests increased cancer risk, existing evaluations of dicamba-related health effects are inadequate. …