When Americans buy products, they make a few reasonable assumptions:

• The product is what it says it is.
• The product does what it says it does.
• The product is safe for use as directed.

The third point sits at the center of several legal battles surrounding the safety of glyphosate, along with worry that glyphosate exposure may be linked with non-Hodgkin’s lymphoma.

Glyphosate is best known as the active ingredient in the weedkiller Roundup, and is one of the most popular herbicides in commercial and personal use. Worries over its safety can be traced back to 2015 when the World Health Organization’s (WHO) International Agency for Research on Cancer classified the chemical as “probably carcinogenic.”

Another expert WHO group, the Joint Meeting of Pesticide Residues disagrees. So does the U.S. Environmental Protection Agency. In fact, glyphosate is one of the most researched herbicides in the world. More than 800 studies have been conducted over the past 40 years to determine the safety of glyphosate products, and several meta-analyses have examined the quality of the data.

Despite all of these efforts, little clarity surrounding the issue has been achieved. And so, the worry persists. When knowledge is missing, worry fills the void.

To help fill this knowledge gap and bring clarity to the debate on glyphosate safety, the Center funded an independent critical review of eight existing meta-analyses of observational studies examining the relationship between glyphosate and non-Hodgkin’s lymphoma.

The findings were published in the peer-reviewed Journal of Toxicology and Risk Assessment on March 31, 2022, and the conclusions should put consumers at ease, especially while cleaning up the yard and garden for springtime. A comprehensive analysis of the findings from the Center is available here.

An international panel of six senior scientists expressed low confidence that any of the studies demonstrated a causal link between glyphosate exposure and non-Hodgkin’s lymphoma.

The findings support the most recent actions taken by the EPA to allow for the continued use of glyphosate without a warning label. Further, the results raise some big questions on the validity of thousands of pending lawsuits claiming that glyphosate exposure causes cancer.

SciPinion, a top scientific consulting firm with a focus on toxicology and chemistry, assembled a panel of six senior experts in epidemiology and meta-analysis to methodically review the eight meta-analyses. The panel included senior scientists with expertise in the fields of epidemiology, biostatistics, toxicology. The critical review was double blind, which means the experts were anonymous to each other and the study funder.

SciPinion implemented an advanced methodology that required the experts to complete three rounds of scoring. The experts were asked to provide confidence ratings on a scale of 1 (lowest) to 10 (highest) in each of four areas:

• Study methods
• Study results
• Study conclusions/discussion
• Application of the study to risk assessment decision making

These have been accepted by the field as areas that must be considered when conducting meta-analyses on observational studies. The confidence scores for each of these are illustrated in the graph below, which is taken from the journal.

Only a moderate degree of variation was noted in scores among the experts. Importantly, there was a consistent score of low confidence—an average score of three with no score above five (on a scale of 1-10).

What this means for consumers

These findings indicate that consumers can be confident there is no evidence of a relationship between glyphosate and non-Hodgkin’s lymphoma. Farmers can also rest assured, as many of them support the use of glyphosate pesticides on a large scale due to its efficacy and how it eliminates the need for tilling.

What this means for regulators, judges, policymakers

Regulators with oversight over the use of glyphosate, along with attorneys and judges involved in glyphosate litigation, should consider these findings to ensure future decisions are based on strong science. It provides especially relevant context for those presented with conflicting causal results from individual studies or meta-analyses.

Top review takeaways

The most important takeaways from the review are summarized here:

• Available data for non-Hodgkin’s lymphoma and glyphosate from case-control and cohort studies is limited.
• The meta-analyses published on these limited data have had differing results and conclusions. Some of the eight papers reported statistically significant increases in occurrence of NHL after exposure to glyphosate, while others did not. The goal of the review was to understand the reasons for these differences.
• Evidence of weak potential increase in non-Hodgkin’s lymphoma after glyphosate exposure in some case control studies do not appear to be confirmed by other case control studies.
• Available cohort studies show lack of an association between glyphosate and non-Hodgkin’s lymphoma.
• Additional meta-analyses are not needed at this time.
• Future efforts to evaluate risks of glyphosate exposure should concentrate efforts on supplementing existing databases by conducting new, high-quality cohort and case control studies to provide more definitive answers.
• With respect to conclusions on a causal relationship between glyphosate and non-Hodgkin’s lymphoma, the panel was consistent in concluding low confidence. This low confidence score is consistent with the vast majority of regulatory agencies on the carcinogenicity of glyphosate.

Beyond the findings, the review highlighted the importance of transparency when conducting meta-analyses, and the need for improved methods for qualifying evidence from case control and cohort studies into a single quantitative framework.

Meta-analyses of epidemiological/observational studies gather data from individual studies to synthesize what has been learned, often to determine the strength of any observed effects.

However, confidence in the findings of meta-analyses hinges on the quality of the individual studies that are included. The Center agrees with the review experts that there is a need for well-designed case control and cohort studies that would reduce uncertainties raised by the conflicting findings of these eight meta-analyses.

By their very nature, observational studies are unable to reach the highest possible level of evidence that meta analyses of randomized controlled trials do for clinical decision making. Even so, they provide important information for risk analysis.

The bottom line

The Environmental Protection Agency, European Food Safety Authority, United Nations’ Food and Agriculture Organization/World Health Organization, among others, have concluded that glyphosate, when used correctly, is unlikely to cause adverse health effects including cancer. These positions are supported by the findings of this critical review.

This published review is part of the Center’s ongoing effort to provide research grants to the brightest minds in toxicology and risk analysis to determine the validity of the research most commonly used in the making of regulatory, policy, and judicial decisions on four key issues: ethylene oxide, glyphosate, PFAS, and talc.

A comprehensive analysis of the findings from the Center is available here.