Letter addressed to The Ontario College of Family Physicians (Dr. Hook)

Dear Dr. Hook:

Re: Pesticides and Human Health Newsletter (undated)

I am writing to you with regard to the above-noted document that has been published and distributed by the Ontario College of Family Physicians.

May I begin by observing that I am somewhat perplexed that a professional, science-based medical organization such as the College would publish a policy statement of this nature. The publication contains an extraordinary number of factual errors and does not accurately portray the regulation of pesticides in Canada under the Pest Control Products Act or the ongoing work of other regulatory agencies such as the United States Environmental Protection Agency (EPA), the European Commission Health and Consumer Protection Directorate or the World Health Organization (WHO).

That stated, there are a number of allegations in this publication that associate 2,4-dichlorophenoxyacetic acid (2,4-D) with cancer, which are of direct and significant concern to the Task Force. The most blatant errors appear on page 3, under the heading “Chlorphenoxy Herbicides: Lawn & Weed Killers such as 2,4-D or Killex, Par 3”; for example:

“There are many studies linking exposure to these herbicides with cancer. Studies from Sweden have suggested that workers exposed are at an increased risk of developing soft-tissue sarcoma, Hodgkin’s disease and non-Hodgkin’s lymphoma. Hoar et al found that exposure to herbicides on greater than 20 days per year resulted in a 6 fold increase in non-Hodgkin’s lymphoma.”

Industry Task Force II on 2,4-D Research Data is gravely concerned about statements that associate 2,4-D with certain human health effects, specifically cancer.

The Task Force is organized under U.S. pesticide law to provide funding for some 270 new research studies required to respond to both the Canadian and U.S. pesticide re-registration programs. These studies, which in accordance with both U.S. and Canadian law, must be done by either Pest Management Regulatory Agency or U.S. EPA Good Laboratory Practice (GLP) qualified laboratories. To-date more than thirty such laboratories have been used in Canada and the U.S. All 270 studies have been completed, at a cost of $ 30 million (US), and submitted to the appropriate regulatory authorities.

As the proprietor of state-of-the-art research data that has been submitted to pesticide regulatory agencies around the world, the Task Force is quite well versed in the human health effects of 2,4-D.

The Pesticides newsletter references the National Cancer Institute’s (NCI) Kansas farm worker study (Hoar. JAMA 1986;256:1141-1147) as evidence that the herbicide 2,4-D causes non-Hodgkins lymphoma (NHL). The Kansas study, a case-control study, was actually three studies in one. It dealt with NHL, soft tissue sarcoma (STS) and Hodgkins Disease. The authors found no associations between herbicide use and STS or Hodgkins Disease.

However, the authors presented a table (Table 3, “Odds ratios (OR) for NHL in relation to frequency of 2,4-dichlorophenoxyacetic acid (2,4-D) use“) which showed that the odds ratios (OR) increased with increasing days of 2,4-D use per year. The table was based on just 23 cases and 61 controls. The highest risk estimate of 7.6 was based on 5 cases and 6 controls who reported using herbicides 21 days a year or more.

The study was based on data obtained using a questionnaire via the telephone. When others examined the questionnaire used, they noted that it did not ask questions specific to 2,4-D use but the general use of herbicides. When asked about the data on which Table was based, the authors published a correction, dropping the direct link between 2,4-D and NHL (see Correction JAMA 1986;256:3351).

The author of the College’s newsletter failed to cite this important correction.

The Hoar study is the first of three NCI herbicide/NHL case-control studies. The second is the NCI Nebraska study (Zahm, maiden name Hoar. Epidemiology 1990;1;349-356). Unlike the Kansas study, the authors did ask specific questions about 2,4-D use in the Nebraska study. The highest OR of 3.3 was based on three cases and four controls, and no individual risk was determined to be statistically significant. In other words, none of the findings was outside the realm of chance. Additionally, risk estimates obtained from proxy interviews were much greater than those obtained from direct informants. When data from direct informants was analyzed separately, there were no associations with NHL, significant or otherwise (Olsen. Agromedicine, 1996;3:37-49).

The NCI Iowa/Minnesota study (Cantor. Cancer Research, 1992; 52:2447-2455) was the largest of the three NCI studies, with more cases and controls than the two other studies combined. As with the Kansas study, it did not ask questions specific to 2,4-D use. However, the authors decided to re-interview a portion of the subjects to strengthen the study. The study showed no significant risk between herbicide use and NHL and the supplemental interview showed no increased risk for 2,4-D use.

The findings of the Kansas study (an association between herbicide use and NHL) and the older Swedish studies (which date back to the 1970s) have not been supported by later, more powerful cohort studies. Recent examples are the fifty year study of chemical workers who manufactured or formulated 2,4-D products (Burns. JOEM, 2001;58:24-30) and the twenty year study of 34,000 pesticide applicators (Fleming. JOEM,1999;4:279-288).

The author of the College’s newsletter failed to cite NCI’s Nebraska or Iowa/Minnesota epidemiological studies or the Burns or the Flemming epidemiological studies.

In January 1997, after the NCI studies were published, the EPA classified 2,4-D as a “Class D” compound. Under EPA’s classification of carcinogenicity, “Class A” compounds are “known carcinogens”, “Class B” compounds are “probable carcinogens” and “Class C” compounds are “possible carcinogens”. The “D” classification means that there is insufficient evidence of carcinogenicity in the data package to place the compound in any of the three higher classifications (http://www.24d.org/Rev4.pdf).

Furthermore, the U.S. Environmental Protection Agency toxicology profile for 2,4-D identifies the herbicide as non-carcinogenic, non-teratagenic and non-mutagenic (http://www.24d.org/epa_memo.pdf). In addition, the World Health Organization reviewed the full 2,4-D toxicological study package and concluded in their publication, Pesticide Residues in Food – 1996, “there was no evidence of carcinogenicity”.

The author of the College’s newsletter failed to cite the current position of the EPA and the WHO.

As you may know, the International Agency for Research on Cancer (IARC) will consider only peer-reviewed, published studies, and unlike both U.S. EPA and WHO, IARC does not consider the numerous proprietary studies conducted by EPA/GLP qualified laboratories or the EPA reviews (e.g., Data Evaluation Reports) of those studies.

Given this modus operandi, the 2,4-D Task Force has taken the extraordinary step of allowing more than a dozen reviews of its proprietary data to be published in peer-reviewed journals. A number of key epidemiologic cohort studies pertinent to 2,4-D have also recently been published (as referenced above). The University of Michigan School of Public Health has completed a review of the recent epidemiology and toxicology of 2,4-D and has submitted their review for publication. Once published, IARC will update its evaluation of 2,4-D and we fully expect their conclusions to be in line with those of U.S. EPA and WHO.

In light of the above-referenced scientific evidence, I respectfully ask that the Ontario College of Family Physicians immediately issue a statement that accurately reflects the current position of the United States Environmental Protection Agency and the World Health Organization regarding the carcinogenicity of 2,4-D. Failure to do so will further impugn the integrity of the manufacturers and the product without the prerequisite scientific evidence to support the allegations published in the Pesticides and Human Health Newsletter.

I thank you for your interest in this matter and look forward to speaking with you should you have any questions regarding same.

Sincerely