One of the complicated parts of assessing the hazards and risks of glyphosate is that the product that everyone uses (for example, Round-Up) is not just glyphosate. The active ingredient is glyphosate, but the final formulation sold in stores is a combination of glyphosate and other “inert” ingredients.
[Note: I’m going to stubbornly use quotation marks around the words “inert” throughout this article, to emphasize my point that this is not an accurate characterization. “Inert” implies inactive, which is not true. Read on for more.]
These “inert” ingredients are subject to essentially no testing, disclosure, and regulatory requirements, even though they almost always make up a larger percentage of the final product than active ingredients. And, evidence indicates that combinations of the “inert” and active ingredients can actually be more toxic than the pure active compound (for example, see here, here, and here).
A new publication by Mesnage et al. in Food and Chemical Toxicology reviews the problems with the status quo and the implications for health effects research. Given the relevance of this topic to my previous blog posts on glyphosate (see here and here) and pesticides in general, I’ll summarize some of the authors’ key points below.
But first, some terminology: what is the difference between active and “inert” pesticide ingredients?
Under the U.S. Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), an active ingredient is one that is intended to be toxic to the target species. For example, glyphosate, the active ingredient used in glyphosate-based herbicides (GBHs), blocks an essential enzyme pathway in plants. All other ingredients in a pesticide product, often added to improve effectiveness, are classified as “inert.”
Abounding uncertainty about “inerts”
Contrary to what their name suggests, however, “inert” ingredients may not actually be inert. In fact, the U.S. Environmental Protection Agency (EPA) explicitly states that this designation “does not mean non-toxic.”
But, it’s challenging to get extensive and accurate information about these chemicals because:
- Neither the “inert” ingredients nor the final formulations (the combination of active + “inert” ingredients) are subject to most standard regulatory toxicity tests, such as evaluation of cancer and reproductive effects. As a result, pesticide approvals are based on the unrealistic scenario of exposure to the active ingredient alone.
- Companies can routinely claim the identity and concentration of these “inert” ingredients as confidential business information (CBI). That is why you’ll often see labels like the extremely vague one below. As a result, it’s difficult – actually, essentially impossible – for scientists to independently evaluate possible toxicity. We are kept blind to these final products.
- Because we don’t know the identity of these “inert” ingredients, there are essentially no monitoring data on environmental or human exposure.
So, in summary, we don’t know how toxic the “inert” ingredients or final formulations are; the identity of these “inert” ingredients is kept secret from the public; and we aren’t monitoring any of these chemicals for their presence in our bodies or the environment.
All of this makes it challenging for the EPA to conduct accurate pesticide risk assessments, which require information on both hazard (ie: toxicity) and exposure.
An added barrier is that companies often change their formulations over time and across regions. Apparently, there are usually between 100-150 different formulations of GBHs on the market at any given time, and over 2000 different varieties have been registered in Europe since 2012.
How are we supposed to evaluate the health effects of such a moving target? Robust epidemiological studies require precise definitions of exposure (referred to as the “consistency” principle) to prove causality. In essence, the exposure under investigation should be defined very specifically, such that it is not possible for variations in versions of the exposure to have different effects, which could muddy the overall conclusion of the study.
(As a concrete example, think about investigating the impact of “exercise” on health. Exercise is very broad, so it wouldn’t be helpful or informative to evaluate the effect of general “exercise,” which could span everything from a 30-minute walk once per month to a 2-hour run each day. The effects of these different types of exercise could have very different impacts on health. So, a better study question would be focused on a more specific type of exercise.)
For pesticide epidemiology, all of these changing formulations make it very challenging to draw conclusions on health effects across time and space. It’s quite likely that one study based in multiple locations could be evaluating the effects of different products at the same time. A study looking at one region over a period of several years also faces the same problem. As the authors of the recent publication stated, “formulated GBHs with the same product name from different countries may not be the same mixture of chemicals, nor the same as the brand-name product bought previously, or in the future.”
This is one possible reason for differing conclusions about hazard, and it makes reproducibility nearly impossible.
The authors put forth a few suggestions to improve this murky situation. Some can be acted on by researchers now, such as including detailed product information (ex: trade name, dates of manufacture, product ID number) in the methods sections of their papers, to facilitate reproducibility and comparison across studies.
Other proposals will need to wait until there is political will for policy change. Most important is the need for full public disclosure of pesticide product composition. (By the way, back in 1997, the American Medical Association urged Congress to “support all efforts to list both active and inert ingredients on pesticide container labels.”) The authors also suggest monitoring of food and feed for concentrations of the “inert” ingredients (that is, if we can get access to information about their identities!), so we can understand patterns of exposure.
Additionally, it is essential to revise the pesticide approval processes to include full testing of “inert” ingredients as well as the final formulated products. We urgently need a regulatory system that accounts for these real-world exposures.
It’s high time for transparency on these formulations and their effects on human health and the environment.