Cancer risks in Swedish pesticide applicators in agriculture, forestry and gardening : a toxicological and epidemiological approach

Abstract: The aims of this thesis were (1) to study the cancer risks in Swedish pesticide applicators, which is one of the occupational groups that is most exposed to pesticides in Sweden. This could be done by utilizing a complete register kept by the Swedish Board of Agriculture which include 20,245 subjects with licenses issued between 1965 and 1976, for epidemiological studies. This was possible by linkage between different registers and identifying cancer cases in the Swedish Cancer Register; (2) to compare cancer risk in farmers- an occupational group with a similar life style, but with less use of pesticides; (3) to study the effect of use of protective equipment as regards cancer risk when handling pesticides; (4) to update and perform a critical analysis of the overall risk of cancer after occupational use of pesticides; (5) to study the use and composition of phenoxy acid herbicides in Sweden. This is of significant value because phenoxy acid herbicides have been used to a great extent for several decades, and are thought to be risk factors of malignant lymphoma (Hodgkin's disease, non-Hodgkin's lymphoma), and soft tissue sarcoma; (6) test the hypothesis that exposure to phenoxy acid herbicides and chlorophenols is a risk factor of malignant lymphoma and soft tissue sarcoma. Studies on the risk of cancer after exposure to pesticides were reviewed concerning epidemiological and experimental animal studies. It was found that further epidemiological studies with detailed exposure assessment for individual pesticides were needed, taking into consideration work practices, use of protective equipment, and other measures to reduce risk (Paper I). Calculations of the total composition of commercial phenoxy acid herbicides purchased Sweden from the late 1940s and onwards have been performed. It was found that the estimated sales increased until the early 1980s and Swedish studies had previously found that old formulations mainly of 2,4,5-trichlorophenoxy acetic acid contained toxic dioxins such as 2,3,7,8-tetra- chlorodibenzo-p-dioxin, as well as chlorophenols, chlorocresols and dimethylnitrosamines in some products (Paper II). Register studies using the pesticide applicator cohort with a random sample of the cohort and then regarding inquires on the use of pesticides and protective equipment, tobacco habits, and occupations during the 1950s, 1960s, and 1970s were analyzed for risk of malignant lymphoma and soft tissue sarcoma. Although there was rather poor use of protective equipment during pesticide application during the 1950s and 1960s these studies with a mean observation time of 13.9 and 12.2 years, respectively, and corresponding person- years 282,000 and 248,000 of follow-up could not find any increased risk of soft tissue sarcoma or non- Hodgkin's lymphoma. and found only a non-significant increased risk of Hodgkin's disease (Papers III and IV). The overall risk of cancer was analyzed on the same cohort and a statistically significant decreased risk was found. Significantly decreased risks were also found for liver, pancreas, lung, and kidney cancers. No significant increase in risk was found. Higher risks for pesticide applicators than for agricultural workers were found for testicular cancer, tumors of the nervous system and endocrine glands, and for Hodgkin's disease (Paper V). The unclear etiology of the increasing incidence of prostate cancer worldwide has provoked much attention and several incidence and mortality studies have found an association between farming and prostate cancer. This study, a follow-up study of Swedish pesticide applicators until 1991, found a statistically significant increase in risk of prostate cancer compared with the general population (Paper VI). The aim of the case-control study was to test the hypothesis that occupational exposure to phenoxy acid herbicides is a risk factor for malignant lymphoma and soft tissue sarcoma and that the use of protective equipment would reduce the risk of cancer. The case- control study was performed nested within the cohort of Swedish pesticide applicators. No increased risk due to the use of phenoxy acid herbicides was found, but a striking finding was that cases wore protective equipment considerably less often than controls and that poor protection increased the risk of malignant lymphoma and soft tissue sarcoma compared to nonusers of phenoxy acid herbicides. CONCLUSION. This thesis concludes that no evidence of association between the use of any pesticide and increased risk for malignant lymphoma or soft tissue sarcoma, or other cancers was found, but supports the recommendation that protective equipment should be worn in order to minimize the uptake of potentially dangerous pesticides.