(Beyond Pesticides, June 21, 2024) A recent review of the scientific literature, published in Science of The Total Environment, analyzes multiple species of bees on a molecular level to better understand the poisoning mechanisms that could, as the authors see it, inform chemical risk assessments with more precision. The mechanisms “implicated in the tolerance of bees to specific pesticides, and thus as determinants of insecticide sensitivity, … include metabolic detoxification, insecticide target proteins, the insect cuticle and bee gut microbiota,” the authors write.
This review references more than 90 studies performed over the last 30+ years, with most being published in the last 5-10 years, as the understanding and importance of molecular determinants of bee sensitivity has emerged. Pollinators, such as bees, provide crucial ecosystem services by pollinating both wild plants and essential crops. The exposure these insects are subjected to threatens their existence, which occurs through pesticide contamination that can lead to impacts on growth and development or even colony collapse.
“While bees have only been exposed to human-made pesticides over the recent past (last 80 years) they have co-evolved with plants and fungi which produce a range of xenobiotics, including plant allelochemicals and mycotoxins,” the authors state. “This has led to the evolution of sophisticated systems that allow bees to detoxify or circumvent the natural xenobiotics they encounter in their environment.” These complex systems are widely different between various insects and within individual species of bees. This review finds that, “Bees can exhibit profound variation in their sensitivity to different insecticides – including to compounds belonging to the same class” in the 20,000+ species throughout the world.
Honeybees (Apis mellifera) are the most widely studied and are the species that the U.S. Environmental Protection Agency (EPA) uses in laboratory testing for pesticide risk assessments. This species has “>1000-fold less sensitive to the neonicotinoid thiacloprid than the neonicotinoid imidacloprid in acute contact bioassays,” while the leaf-cutting bee (Megachile rotundata) is extremely sensitive to many insecticides that are labeled as “moderately and practically non-toxic to honeybees, such as the cyano-substituted neonicotinoid insecticides acetamiprid and thiacloprid and the synthetic pyrethroid insecticide tau-fluvalinate.” This raises the question as to why some bees have greater tolerance to certain insecticides but not others, and what underlying mechanisms create the differences in sensitivity.
In studying the metabolic detoxification within various bee species, cytochrome P450 monooxygenase (P450), an enzyme system that is crucial for detoxification and oxidative metabolism, was found to have the largest role in pesticide sensitivity. The authors find that, “P450s play an important role in bee sensitivity to pyrethroid and neonicotinoid insecticides and may be especially important in the detoxification of chemotypes that exhibit low toxicity to bees.” After identifying P450s as determinants of insecticide sensitivity in bee pollinators, specific genes were studied. “This revealed that P450s belonging to the CYP9Q subfamily, most notably CYP9Q3, metabolise thiacloprid (and acetamiprid) with high efficiency but have limited activity against imidacloprid, providing a molecular explanation for the profound difference in honeybee sensitivity to N-nitroguanidine and N-cyanoamidine neonicotinoids,” the authors share.
In a study of leaf-cutting bees without CYP9Q-type genes, they were up to >2500-fold more sensitive to insecticides after acute contact than honeybees, bumblebees, and red mason bees. This highlights the role of specific genes in metabolic detoxification that not all bee species have, leaving them more vulnerable to certain pesticides. Additional studies on honeybees, specifically Apis cerana, identified five P450 genes (referred to as Acc301A1, Acc303A1, Acc306A1, Acc315A1, and AccCYP6k1) that are altered by several insecticides. When expression of those genes was lower, the mortality rate of the honeybees after pesticide treatment was significantly higher.
The authors postulate that, “P450 genes may have important endogenous functions. Thus, silencing such genes can reduce the overall fitness of… bees, which may, in turn, result in increased sensitivity.” They continue in saying, “The sensitivity of bees to different insecticides within the same mode of action class can also reside in differences in the affinity of these insecticides for their target sites. An excellent example of this is for pyrethroid insecticides, which act on insect voltage-gated sodium channels.” A study on amino acid sequences of sodium channels from 11 bee species and 47 non-bee insect species identified three residues that were specific to bee species but were not present in any other species. This contributes to the low tolerance of certain bees, such as bumblebees, to pyrethroids.
The authors speculate that the role of P450-mediated detoxification across bee diversity also affects target-sites and the alignment of amino acid sequences within various species. They may also play a role in the ability of certain compounds to penetrate the cuticle, which makes up the exoskeleton of a bee. In a study of radio-labeled neonicotinoids, imidacloprid was shown to penetrate the honeybee cuticle much more readily than thiacloprid and acetamiprid. “This variation in penetration speed and internal body concentrations of different neonicotinoids suggest that a pharmacokinetic component contributes to the different acute contact toxicity of these insecticides,” the authors state. “The pharmacokinetics of neonicotinoids may differ for different bee species, and further work on the role of the insect cuticle in influencing bee sensitivity to members of this insecticide class and others is required.”
The last important mechanism identified are bee microbiota. The authors share that, “Emerging research is providing evidence that the sensitivity of bees to insecticides can also be influenced by their microbiome” through direct or indirect detoxification. Previous studies “demonstrate that microbiota derived from honeybee guts have the capacity to detoxify insecticides,” while more recent studies give a potential explanation as to why that occurs. It was found that the presence of several P450 genes played a role. In bees where lower levels of CYP6AS1, CYP6AS3, CYP6AS4, CYP6AS10, CYP9Q2 and CYP9Q3 were found in the midgut of bees, there was a lower tolerance to pesticides such as thiacloprid and tau-fluvalinate.
These results offer more in-depth tools for identifying pesticide sensitivity in insect species, while also highlighting the inadequacies of the current pesticide review process utilized by EPA, as well as the flawed regulations in place, given the complexities of these systems. Certain neonicotinoids have been banned in Europe after a review of their risk to bee health by the European Food Safety Authority (EFSA) and yet are still allowed in the U.S. today. The current system in place for risk assessment for pesticides that impact bees includes a tiered process, with Tier I as a screening tool within the laboratory and Tiers II and II as field studies. According to EPA, Tier I uses “conservative assumptions regarding exposure (i.e., assumptions that are likely to overestimate exposure) and uses the most sensitive toxicity estimates from laboratory studies of individual bees to calculate risk estimates.” These studies, however, only focus on honeybees and do not take into account the varying sensitivity in other bee species.
U.S. regulatory agencies have a history of ignoring science, as demonstrated with the U.S. Department of Agriculture (USDA) whistleblower case previously covered by Beyond Pesticides in 2016. This case involved a pollinator researcher who says his firing by the agency was retaliation for his cutting-edge research linking neonicotinoid insecticides to declining monarch butterfly populations. A more recent whistleblower case regarding EPA’s risk assessment for both new and existing chemicals occurred in 2021. Four scientists maintain that these assessments were improperly changed by agency managers during the Trump administration. Corruption within EPA has been an ongoing topic for years, with regulatory and statutory failures inflicting harm on health and the environment. Many citizens have expressed intense criticism of EPA’s scientific integrity, and say that the agency has lost sight of its health and environmental mission. Additional examples of EPA’s failure can be seen here, here, here, and here.
This literature review offers the ability to inform with more specificity pesticide risk assessments, which are a regulatory requirement for pesticide registration. As the authors say, “Risk is defined as a function of hazard (intrinsic toxicity of a chemical) and exposure (expected concentration an organism is exposed to). The hazard assessment is currently largely based on experimental data collected from a handful of ‘model’ bee species such as honeybees and bumble bees. However, bees (Anthophila) are an exceptionally diverse clade of insects with broad differences in ecology and life history traits, and, as demonstrated by the studies reviewed here, can exhibit marked differences in sensitivity to pesticides.”
Leslie W. Touart, Ph.D., senior science and policy analyst for Beyond Pesticides, adds, “Although EPA has identified a full suite of pollinator data requirements, it’s not clear the agency has taken their pollinator protection policies seriously with appropriate data call-ins for existing registered products and ensuring these data are available before granting new or renewed registrations. Agency protective actions when toxicity data and exposure estimates indicate risk typically are limited to label statements such as ‘this product is highly toxic to bees’ or ‘foliar application of this product is prohibited to a crop from onset of flowering until flowering is complete’ as the only mitigation measures implemented.”
The current EPA review system does not factor in the growing body of scientific evidence regarding the negative impacts of pesticide exposure on a wide range of bee species, as well as other vital pollinators. This study summarizes research with emerging tools that offer the ability to obtain specified data and insight into varied bee species sensitivity. Bees are only one group of insects that are at risk, and the diversity of all detoxification systems for all insects should be considered. While pesticides claim to target only certain types of insects, the variation of genetic and molecular intra- and inter-species mechanisms need to be considered.
The authors conclude, “Finally, bees are exceptionally diverse in their ecology and life history. The expanding data available on the ability of these species to detoxify or circumvent natural and synthetic insecticides offers an excellent opportunity to understand the ecological factors influencing the evolution of xenobiotic detoxification genes in one of the most diverse and ecologically important group of insects on the planet.”
While the authors recapitulate a multitude of studies with data that identify important mechanisms to consider in risk assessments for bee species, they also framed their article with bias. Two of the five authors report that they are employees of Bayer AG, Crop Science Division. Instead of using this scientific evidence to solely inform risk assessment or to provide evidence that supports the need for alternatives to harmful pesticides, the authors say that this should “facilitate the future development of pest-selective bee-safe insecticides.” This research, however, shows that a “bee-safe insecticide” is not possible when each bee species has varying sensitivity. What is considered low toxicity for one species can be highly lethal for another. Widely used systemic pesticides move through the vascular system of plants and are expressed through pollen, nectar, and guttation droplets causing indiscriminate poisoning to bees and other insects who forage the landscape.
To help protect these vital organisms, as well as all wildlife and the environment, the path forward is organic. Everything starts in the soil—healthy, resilient soil reduces any need for pesticides and promotes biodiversity. Terrain free from pesticides benefits wildlife and promotes natural predators that provide natural controls. Organic systems also save wildlife from the dangerous impacts of pesticides, which encourages them to flourish, and they restore the natural balance that is unable to exist in a conventional agricultural system. See Beyond Pesticides’ resources for going and supporting organic here and here.
In further support of bees, Beyond Pesticides has a week’s worth of actions that you can perform at any time in honor of Pollinator Week to help spread the buzz by informing others and eliciting change. In view of EPA’s failure to protect pollinators from pesticides, the lives of those essential insects, birds, and mammals are increasingly dependent on state and local laws that under threat of U.S. Congressional action in the upcoming Farm Bill. The Farm Bill covers many areas—ranging from the supplemental nutritional assistance program (SNAP) to trade—and one provision that the pesticide industry would like to include is preemption of local authority to restrict pesticide use. This attack on local governance would undercut the local democratic process to protect public health and safety, especially important without adequate federal protection of the ecosystems that sustain life. You can tell your U.S. Representative and Senators to support a Farm Bill that promotes a sustainable future.
You can also order a Pesticide-Free Zone sign to showcase your organic yard or garden, share resources with your community, and share photos of pollinators on social media with the hashtags #PollinatorWeek or #ProtectPollinators—then submit them to our Art Page!
