Glyphosate usage has increased considerably in the years since these studies collected their exposure data, so studies done now could include higher exposures and more exposed individuals, possibly leading to stronger conclusions. “This result doesn’t necessarily convince me there’s an association between glyphosate and NHL,” says epidemiologist Anneclaire De Roos, PhD, of Drexel University in Philadelphia, who authored one of the case-control studies as well as the 2005 AHS analysis. “I think what this tells us more than anything is we need to do more studies that look at high exposure levels to get more data.”

Level of exposure is certainly an important parameter — but it’s not the only component of cancer risk assessment that is worth mentioning, according to authors (some of whom are from IARC) of a new study published in the International Journal of Epidemiology on March 18, 2019.7

In a pooled analysis of agricultural worker cohorts from France, Norway, and the US, researchers examined the association between NHL and the “ever” use of 14 pesticide chemical groups and 33 individual active chemical ingredients in 316,270 farmers.7 The study found that the type of pesticide used influenced cancer risk, and the researchers also suggested that the active ingredients in the pesticides, too, could influence the development of cancer — and that the type of pesticide or chemical components used may also be associated with specific cancer subtypes.

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The investigators determined that after adjusting for exposure to other pesticides, the risk of NHL was actually inversely related to the use of organochlorine insecticides (meta-hazard ratio [meta-HR], 0.86; confidence interval [CI], 0.74–0.99) and phenoxy herbicides (meta-HR, 0.81; CI, 0.67-0.98), but this association was not seen with NHL and the active ingredients in these pesticides.


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In fact, the only elevated hazard ratio seen for NHL overall was in relation to the chemical terbufos. This chemical is currently not approved for use in the European Union or in Norway — but it is still in use in the US, and was the eighth most common organophosphate-based active ingredient in the US in 2012.8

There were also slightly higher hazard ratios (when comparing “ever” vs “never” use) for chronic lymphocytic leukemia/small lymphocytic lymphoma and deltamethrin; as well as for diffuse large B-cell lymphoma (DLBCL) and glyphosate.

The most frequently used organophosphate insecticide active ingredient in 2012 was DowDuPont’s chlorpyrifos, which a Court ruled in 2018 should be banned by EPA. Recently, EPA appealed that decision, and the ruling is being reconsidered. The most commonly used conventional pesticide active ingredient overall from 2001 to 2012 was glyphosate (eg, Roundup), which IARC classified as “probably carcinogenic to humans” in 2015.9

On March 18, 2019, a federal jury concluded in the case of Hardeman v Monsanto that there was persuasive evidence of an association between the use of Roundup and the plaintiff’s NHL.10

All said, it may be difficult to definitively link a single ingredient to the risk of developing cancer — even the authors of the most recent AGRICOH study pointed out that study subjects likely had exposure to multiple pesticide active ingredients. “Improvements in the specificity of the exposure assignments, by incorporating probability of use and adding parameters reflecting duration, frequency, and intensity of use, are required and planned for future in-depth analysis of the associations” observed between the risk of certain malignancies and pesticide exposure, wrote the authors.

References

  1. Zhang L, Rana I, Shaffer R, Taioli E, Sheppard L. Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: a meta-analysis and supporting evidence [published online February 10, 2019]. Mutat Res Rev Mutat Res. doi: 10.1016/j.mrrev.2019.02.001
  2. United States Environmental Protection Agency. Draft human health and ecological risk assessments for glyphosate. Updated August 2, 2018. Accessed March 16, 2019.
  3. Shaffer, R. Concerning glyphosate [blog].Rachel talks tox. Published February 14, 2019. Accessed March 11, 2019.
  4. Andreotti G, Koutros S, Hofmann JN, et al. Glyphosate use and cancer incidence in the Agricultural Health Study. J Natl Cancer Inst. 2017;110(5):509-516.
  5. Schinasi L, Leon ME. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Int. J Environ Res Public Health. 2014;11(4):4449-4527.
  6. Chang ET, Delzell E. Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers. J Environ Sci Health B. 2016;51(6):402-434.
  7. Leon ME, Schinasi LH, Lebailly P, et al. Pesticide use and risk of non-Hodgkin lymphoid malignancies in agricultural cohorts from France, Norway and the USA: a pooled analysis from the AGRICOH consortium [published online March 18, 2019]. doi: 10.1093/ije/dyz017
  8. Atwood D, Paisley-Jones C.United States Environmental Protection Agency. Pesticides industry: sales and usage 2008–2012. Washington, D.C.:2017. Accessed March 20, 2019.
  9. International Agency for Research on Cancer. IARC Monographs Volume 112: evaluation of five organophosphate insecticides and herbicides. Published March 20, 2015. Accessed March 21, 2019.
  10. Bayer AG. Bayer statement on jury’s decision in phase one of California glyphosate trial [press release]. Published March 19, 2019. Accessed March 20, 2019.