International Agency for Research on Cancer (IARC) - Summaries & Evaluations


VOL.: 41 (1986) (p. 357)

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Chlorophenoxy herbicides have been produced extensively since the 1950s for use in agriculture and as defoliants, although production and use are now decreasing in many countries. Widespread occupational exposure to chlorophenoxy herbicides and their chlorinated dibenzodioxin impurities is known to have occurred during their production, formulation, application and disposal. Increased urinary levels of chlorophenoxy compounds and increased concentrations of some chlorinated dibenzodioxins in adipose tissue have been measured in highly exposed persons. The presence of dibenzodioxins and dibenzofurans has been demonstrated in the adipose tissue of nonoccupationally exposed people in many countries.

During occupational exposure, such as ground spraying and other manual application of these herbicides, dermal absorption is a major route of entry into the body.

In manufacturing plants, exposures occur during the handling of raw materials, intermediates, finished products and process wastes. High-level short-term occupational exposures have also been caused by industrial accidents.

5.2 Experimental data

Previous IARC evaluations of the carcinogenicity to experimental animals of several individual chlorophenoxy herbicides and of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), an impurity found in some of these herbicides, are summarized in section 3.1, in this volume.

5.3 Human data

Studies comparing the occurrence of congenital malformations in areas and periods characterized by different usage of chlorophenoxy herbicides were uninformative with regard to the teratogenicity of these agents. Two case-control studies on birth anomalies among the children of Australian and US veterans and of New Zealand pesticide sprayers showed no excess risk associated with paternal exposure to herbicides.

No study was available of pregnancy outcomes of women exposed occupationally to chlorophenoxy herbicides.

In one study of persons exposed to chlorophenoxy herbicides during military operations in Viet Nam, conducted ten years after exposure, no increase in the incidence of chromosomal aberrations or sister chromatid exchanges was observed.

Cytogenetic studies have been carried out on workers occupationally exposed to chlorophenoxy herbicides during spraying. In three of the studies, there was also exposure to other herbicides and the effect of chlorophenoxy herbicides could not be assessed. Studies in which occupational exposure was only to chlorophenoxy herbicides showed no increased incidence of chromosomal aberrations or sister chromatid exchanges.

In a large Danish cohort study of chemical workers exposed to chlorophenoxy herbicides [particularly (4-chloro-2-methylphenoxy)acetic acid (MCPA), 2-(4-chloro-2-methylphenoxy)propanoic acid (mecoprop), 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-(2,4-dichlorophenoxy)propanoic acid (dichlorprop)], as well as other chemicals, no overall increase in cancer incidence rate was observed, but there were significantly increased risks of soft-tissue sarcoma and lung cancer in different subcohorts, which were not necessarily those with the highest exposures to chlorophenoxy herbicide preparations. A Finnish cohort study of brush control workers with short follow-up time showed no increased risk. A small Swedish cohort study of railroad workers who sprayed herbicides showed an increased risk of cancers at all sites combined for those exposed to both chlorophenoxy harbicide preparations and other herbicides. An excess incidence of all cancers was also reported from a very small cohort of Swedish forestry foremen exposed to chlorophenoxy herbicide preparations and other herbicides. A study of long-term pesticide applicators in the German Democratic Republic, heavily exposed to a number of chemicals, including 2,4-D and MCPA, demonstrated an increased risk of bronchial carcinoma.

A population-based case-control study conducted in northern Sweden showed a statistically significant association between exposure to chlorophenoxy herbicides, especially in forestry, and the occurrence of soft-tissue sarcomas. A second study on this type of tumour was conducted in southern Sweden, where a significant increase in the risk of developing soft-tissue sarcomas was associated with previous exposures to chlorophenoxy herbicides, mainly in agriculture. An increased risk of soft-tissue sarcoma was described among highly exposed Italian rice weeders in a population-based case-control study. A case-control study from New Zealand did not demonstrate an increased risk of soft-tissue sarcoma in people exposed to chlorophenoxy herbicides.

A statistically significant association between malignant lymphoma and exposure to chlorophenoxy herbicides was found in a Swedish case-control study; however, no such association was seen in a case-control study of these tumours from New Zealand. In a Danish cohort of chemical workers exposed to chlorophenoxy herbicides, there was also no increased risk of malignant lymphoma.

Three Swedish case-control studies of colon, liver and nasal cancer, respectively, which used the same study design and methods as in the studies on soft-tissue sarcoma and malignant lymphoma, did not demonstrate significantly increased risks. Exposure recall bias of cancer patients thus does not seem to explain the differences between the results of the Swedish and the New Zealand case-control studies of soft-tissue tumours and lymphomas.

In summary, well-conducted case-control studies have provided the most information on the association between cancer and occupational exposure to chlorophenoxy herbicides. Statistically significant elevated odds ratios have been observed for cancers at some sites, but not consistently, independent studies. The results of one cohort study on the incidence of soft-tissue sarcoma support the finding in case-control studies of an increased relative risk for these tumours. Other cohort studies have added little information. No consistent exposure-response relationship emerged from the different studies, and, in the studies that found an association, exposures were shorter than those usually associated with occupation-related cancers.

5.4 Evaluation

There is limited evidence that occupational exposures to chlorophenoxy herbicides are carcinogenic to humans.

For definition of the italicized terms, see Preamble Evaluation.

Subsequent evaluation: Suppl. 7 (1987)

Last updated: 23 April 1998

    See Also:
       Toxicological Abbreviations