Epidemiological investigations address possible exposures (in this case, to pesticides such as 2,4-D) and their potential association with human disease. These studies consist of three types: ecologic, case-control and cohort. The cohort studies relying on a very likely exposed group are the most persuasive type, while the ecologic studies in which exposures were uncertain are the least persuasive.
Ecologic studies are usually based on reviews of public records and no personal interviews are conducted. Case-control studies are based on questionnaires completed by members of a certain population (usually consisting of a population of about 1,000 people) believed to have been exposed to the compound under study. Often no actual exposure measurements were made, and exposure is assumed based on the memory of the participants (farmers or, in many cases, the farmer’s next of kin or neighbors, are asked about the farmer's pesticide practices over the previous forty years or more).
Cohort studies are long-term studies (i.e., 20 years or more) of a given population, which include actual examination of medical records and, in some cases, actual exposure measurements or exposure assessments. The combination of long-term study and exposure measurement makes cohort studies the far more persuasive. In this regard, the 1997 International Agency for Research on Cancer review1 of 36 different cohorts involved in the manufacture of phenoxy herbicides found that there was no increase of cancer incidence in these workers.
The process of identifying causes of disease within pesticide exposed populations is complex, primarily because pesticides are merely one of many environmental exposures that people may encounter. Therefore, to say that a pesticide is associated with increased adverse health effects – cancer, respiratory problems, immune disorders, and birth defects – requires:
the determination of a positive association between pesticide exposure and a specific disease, and,
that other known causes be ruled out.
For instance, farmers are not exposed only to pesticides, but also to other potential risk factors such as fertilizers, nitrates, fuels and engine exhausts, solvents, organic and inorganic dusts, ultraviolet radiation, plant pathogens and animal pathogens. Behavioral, dietary, and genetic factors may impact their risk of disease, as well.
2,4-D Epidemiology Studies:
There are more than 140 epidemiological published studies pertinent to 2,4-D. The 2,4-D ecologic and case-control studies tend to be somewhat equivocal or ambiguous, with some studies suggesting a relationship between 2,4-D and non- Hodgkin's lymphoma (NHL), a form of cancer. Ambivalency is not uncommon in epidemiology when dealing with a non-carcinogen or a very weak carcinogen.
The studies most often quoted by NGOs are the National Cancer Institute's (NCI) Kansas (Hoar 1986)2 and Nebraska (Zahm 1990)3 farmworker studies, both of which received considerable media attention and are frequently cited by activist groups to support their position that 2,4-D is a possible carcinogen. These early studies that purported an association 2,4-D and NHL were not validated by later NCI studies, Iowa/Minnesota (Cantor 1992)4, which showed no association between 2,4-D and cancer. The case-control studies were critically weakened by differential exposure perceptions among respondents. And all the studies were critically weakened by undocumented exposure to a specific herbicide.
All three studies relied heavily on information provided by proxy respondents. That is, in many cases, the person chosen to participate in the study was not available, so next-of-kin or neighbors were asked about the unavailable person's pesticide use over a previous period of more than forty years. Subsequent studies have shown that information on pesticide use provided by proxies is often invalid. In the NCI Nebraska study, for example, when the information provided by the self-respondents (i.e. the farmers themselves) is analyzed separately from the information provided by the neighbors or next-of-kin, there is no association between 2,4-D and cancer (Olsen 1996)5.
A recent NCI published paper, (De Roos 2003)6, completed a re-analysis of the Kansas and Nebraska farm worker studies and reported, “This analysis of the pooled data found no association with having ever used 2,4-D.” The weight of evidence from these NCI studies is that 2,4-D is not a carcinogen. In the reanalysis study, NCI researchers also concluded: “Although epidemiological data on cancer risks from exposure to specific pesticides are scant, it also suggests that while some pesticides may present a cancer risk, many, maybe even most, pesticides do not.”
The latter two studies, Cantor and De Roos, are never cited by those opposed to the use of pesticides.
The extensive toxicology of 2,4-D (i.e., animal feeding studies done under controlled laboratory conditions in accordance with EPA GLP standards) does not support the hypothesis that 2,4-D is a carcinogen, and the cohort studies in epidemiology (most persuasive type) almost always agree with the toxicology.
For example, the review of the extensive toxicology and epidemiology of 2,4-D completed in 2001 by Garabrant and Philbert of the University of Michigan School of Public Health7 concluded:
“Despite several thorough in vitro and in vivo animal studies, no experimental evidence exists supporting the theory that 2,4-D or any of its salts or esters damages DNA under physiologic conditions. Studies in rodents demonstrate a lack of oncogenic or carcinogenic effects following lifetime dietary administration of 2,4-D. Epidemiologic studies provide scant evidence that exposure to 2,4-D is associated with soft tissue sarcoma, non-Hodgkin’s lymphoma, Hodgkin’s disease or any other cancer. Overall, the available evidence from epidemiologic studies is not adequate to conclude that any form of cancer is causally associated with 2,4-D exposure.”
An excellent reference guide for further information on epidemiology studies is the Purdue University July 1998 report entitled, “Pesticides and Epidemiology: Unraveling Disease Patterns” (Purdue University Pesticide Programs, Report No. PPP-43, July 1998, West Lafayette, Indiana 47907), available at: http://www.btny.purdue.edu/Pubs/PPP/PPP-43.pdf
About the Task Force
The Industry Task Force II on 2,4-D Research Data is organized to provide funding for some 300 Good Laboratory Practice (GLP) research studies required to respond to the EPA re-registration and PMRA pesticide re-evaluation programs. The 2,4-D Task Force is comprised of those companies owning the technical registrations on the active ingredient in 2,4-D herbicides. They are Dow AgroSciences (U.S.), Nufarm, Ltd. (Australia) and Agro-Gor Corp., a U.S. corporation jointly owned by Atanor, S.A. (Argentina) and PBI Gordon Corp. (U.S.).
1 Kogevinas M. et. al. 1997. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. American Journal of Epidemiology.
2 Hoar, SK. et. al. 1986. Agricultural Herbicide Use and Risk of Lymphoma and Soft-tissue Sarcoma, JAMA. 256:1141-7 see also correction, JAMA 256:3351
3 Zahm, SH. et.al. 1990. Case-Control Study of Non-Hodgkin’s Lymphoma and the Herbicide 2,4-Dichlorophenoxyacetic Acid (2,4-D) in Eastern Nebraska. Epidemiology, Vol 1, Number 5: 349-356.
4 Cantor, KP. et al. 1992. Pesticides and Other Agricultural Risk Factors for non-Hodgkin's Lymphoma Among Men in Iowa and Minnesota. Cancer Research, 52, 2447-2455.
5 Olsen, GW. Bodner, KM. 1996. The Effect of the Type of Respondent on Risk Estimates of Pesticide Exposure in a Non-Hodgkin’s Lymphoma Case-Control Study, J. of Agromedicine, Vol 3(1).
6 De Roos, A.J. Zahm, SH. Cantor, KP. Weisenburger, DD. Holmes, FF. Burmeister, LF. and Blair, A. 2003. Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among
men. Occup Environ Med. 60(9): 1-9. National Cancer Institute.
7 Garabrant DH. Philbert MA. Review of 2,4-Dichlorophenoxyacetic Acid (2,4-D) Epidemiology and Toxicology. CRC Critical Reviews in Toxicology, 32(4):233-257.