How Do You Assess if a Chemical Causes Cancer?

It’s been revealed that International Agency for Research on Cancer (IARC) scientists had removed findings from studies that concluded glyphosate to be noncarcinogenic before publishing their final report claiming that it is a likely carcinogen.  Years of testing glyphosate, the most widely used herbicide in the world, has shown us that the chemical is not carcinogenic. Why can’t the public believe it?

Can anyone make sense of the debate over glyphosate, the active molecule in the most widely used herbicide in the world? According to a study by University of California–San Diego researchers published last year, urine samples from a group of 100 southern California residents showed that levels of glyphosate and its metabolite, aminomethylphosphonic acid have increased fifteenfold between 1993 and 2016.

Unsurprisingly, the publication of this research added considerable fuel to the regulatory fire sweeping Brussels and Washington alike over the use of the chemical, even though the study is limited in scope and has no bearing on the weed killer’s health effects. On Nov. 27, the European Commission agreed to renew the molecule’s market reauthorization for five years, after serious opposition from member states. EU members still retain the right to ban the chemical domestically if they so wish. Meanwhile, on Capitol Hill, lawmakers from the House Committee on Science, Space, and Technology have opened an investigation into the International Agency for Research on Cancer, an arm of the World Health Organization that receives U.S. funding, because the agency stands accused of editing its findings to support a 2015 decision that glyphosate is probably carcinogenic.

Several things are going on here that are worth untangling. At the heart of the problem is the messy fact that when scientists and policymakers carelessly substitute risk for hazard, flawed conclusions are drawn.

We are generally bad at understanding risk. Determining the carcinogenicity of any foreign bodies that ends up in our ecosystems involves assessing degrees of uncertainty. Unlike with pharmaceutical trials, it is impossible to carry out a randomized clinical trial with glyphosate or any other weed killer.

It goes without saying that weed killers should be toxic to their intended target and benign to humans. Animal studies can be a tool for gauging a biocide’s carcinogenic potential, but they can only provide hazard signals, as multiple studies have shown that simply extrapolating research conducted on rodents to humans rarely produces accurate results. Animal testing therefore has limited value in determining carcinogenicity, because it does not necessarily allow researchers to draw conclusions of causation between a given substance and the occurrence of cancer in test animals, let alone in humans.

Differentiating between absolute risk in the lab and true risk for human health is essential.

This is an important factor to consider with regards to the glyphosate debate. When IARC announced in June 2015 that glyphosate was “probably carcinogenic” to humans, Kate Guyton, a toxicologist and lead author of the IARC monograph, stated that “because the evidence in laboratory animals was sufficient and the evidence in humans was limited, this places [glyphosate] in Group 2A [of probable carcinogens].” It was later revealed that IARC scientists had removed findings from studies that concluded glyphosate to be noncarcinogenic before publishing the final version. The edits were made in the monograph’s chapter on animal studies, which crucially informed IARC’s assessment that glyphosate causes cancer.

The debate sparked by IARC’s evaluation highlights why human studies are so essential. Indeed, one key study—whose initial findings were not included in IARC’s literature review due to their internal prohibition on considering unpublished data—is the Agricultural Health Study, a long-term observational analysis of the health effects of herbicides on 89,000 farmers and their families in Iowa and North Carolina. Running since 1993, the AHS has consistently failed to find that glyphosate use is linked with increased risk of cancer. Parts of the study, whose failure to find any evidence of glyphosate’s carcinogenicity was already well-known among IARC staff, were finally published earlier in November.

These findings have been backed up by other studies as well.
Last year, the U.N.’s Food and Agriculture Organization and the World Health Organization presented a joint review report on pesticide residue in indirectly exposed persons, including farming and production workers’ families, as well as consumers. The report did not find any evidence of increased risk of cancer from glyphosate exposure. Instead, after having examined the epidemiological evidence of occupational exposures, the report concluded, “Glyphosate is unlikely to pose a carcinogenic risk to humans by food intake.”