Human poisonings with neonicotinoid pesticides – frequency and severity show public health risks, regulatory failures

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Sass, Daniel Raichel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5054262/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Nov, 2024 Read the published version in Environmental Health → Version 1 posted 14 You are reading this latest preprint version Abstract Background - Neonicotinoid pesticides (‘neonics’) – imidacloprid, thiamethoxam, clothianidin, acetamiprid, dinotefuran - are the most widely used class of insecticides in the world. They have a neurotoxic mechanism of action, similar to nicotine. They are detected in food, waterways, tap water, and breast milk. In addition to environmental pollution, neonics are the pesticides most frequently reported as associated with human poisonings. Methods - We make use of the non-occupational human pesticide poisoning reports in the U.S. Environmental Protection Agency (EPA) online Incident Data System (IDS). Note that IDS reports are predominantly self-reported information of varying and often low level of detail and are not routinely validated or verified by EPA. Results - We reviewed 842 non-occupational human poisoning incidents associated with neonics in the IDS from 2018 through 2022. There are four human fatality reports, two associated with clothianidin and two with acetamiprid. Major illnesses such as seizures were reported in several cases, including with dinotefuran cockroach bait product, and an imidacloprid lawn product. Moderate poisonings make up 88% of the total poisonings (740 of 842), with most of those associated with imidacloprid (547 incidents) or dinotefuran (102 incidents). Common reported symptoms classified as moderate often included two or more of the following: headaches; dizziness; lethargy; eye or throat irritation; skin itching and rash; chemical burns and skin peeling; face swelling; muscle weakness or tremors; vomiting; diarrhea; pain and tightness in chest; open sores; and general pain. These incidents stem mainly from residential uses, such as lawn and garden insect repellents, home pest treatments for bed bugs or roaches, and products used to treat pets for fleas and ticks. Conclusion - Given the evidence of neurotoxicity, EPA should use its legal authority to cancel unsafe products and unnecessary uses – including from seed treatments, and residential pet and lawncare products - to prevent further human suffering. Neonicotinoid neurotoxic pesticide poisoning human seizure death Figures Figure 1 Background Neonicotinoid pesticides, or “neonics,” are the most widely used insecticides in the world, in large part because they were initially characterized as posing little to no risk to vertebrates, including humans 1 – with the first neonic manufacturer, Bayer, stating “[t]he toxicity of neonicotinoids to mammals and humans is very low”. 2 The chemicals are similar to nicotine and are toxic by a similar mechanism, acting as an agonist on the nicotinic acetylcholine receptor (nAChR), to overstimulate affective nerve cells and systems. 3 The concerns with neonics have predominantly been reported related to their devastating effects on bees, aquatic invertebrates, and beneficial insects. In fact, the U.S. Environmental Protection Agency (EPA) predicts that the three most common neonics (imidacloprid, thiamethoxam, clothianidin) put at risk over 200 threatened and endangered species, about 11% of the entire endangered species list, including beneficial pollinating insects like bees and butterflies. 4 Here we review of the extensive human poisoning incident data for neonics, to show that current uses of neonic pesticide products can – and do – harm people. The class of neonics includes: imidacloprid; thiamethoxam; clothianidin; acetamiprid; dinotefuran. They are registered in over 120 countries, on more than 140 fruit, vegetable, and field crops to target sucking and chewing insects such as aphids or emerald ash borers. 5 The EPA has approved over 1,000 products containing neonics, including for agricultural crops, urban landscaping, and indoor bed bug and flea and tick treatments for pets. Since neonics persist in soil and are highly water soluble, both the agricultural and consumer uses of neonic products contaminate soil and water. A national stream sample report by the U.S. Geological Survey found that clothianidin and thiamethoxam detections in surface water were related to uses on crops, whereas imidacloprid was the most frequently detected neonic in urban stream samples (37% of samples), with concentrations related to lawns, gardens, parks, and playgrounds. 6 A study in Minnesota reported a similar pattern, with the highest neonic detections associated with agricultural use, mainly clothianidin, followed by neonics use in urban areas, mainly imidacloprid, suggesting that both agriculture and urban uses contribute to chronic exposure.<sup7 In addition to environmental pollution, neonics are the pesticides most frequently reported as associated with human poisonings. In 2021, the Midwest Center for Investigative Reporting reported in USA Today on poisonings from pesticides leaching from flea and tick collars, particularly one brand that contains 10% imidacloprid (a neonic) and 4.5% flumethrin (a pyrethroid insecticide). The reports included around 1,700 pet deaths and just under 1,000 people being poisoned. The EPA launched an investigation, ultimately concluding that the pet collars were not the cause of any pet deaths. EPA re-confirmed its approval of the collars without any formulation changes, but did require additional label warnings to help consumers recognize and report potential poisoning incidents. 8 A follow up investigation by the EPA’s independent Office of Inspector General reported on emails from 2017 to 2022 that show EPA staff concerns were repeatedly ignored by both EPA management and the pesticide product manufacturer. 9 Here we provide an updated and deeper analysis into the available data on non-occupational human poisoning incidents reported to be associated with neonicotinoid pesticides. Methods As of July 2023, EPA made 10 years of pesticide incident data available on its online Incident Data System (IDS). 10 The IDS is a national database, populated with human health information from several sources, largely from pesticide manufacturers, which are required to notify EPA of “information regarding unreasonable adverse effects on the environment of the pesticides” they register, including occupational, residential and ecological incidents. 11 Additional submissions to EPA may come from private individuals, poison control centers, states, National Pesticide Information Centers (NPIC), and government or non-government agencies. 12 IDS reports are predominantly self-reported information of varying and often low level of detail around exposure circumstances, symptoms, and/or medical outcome. The information is not routinely validated or verified by EPA, though reports from poison control centers and some states may be confirmed. 13 See EPA’s website for details including data limitations. 14 While ecological incidents are also included in IDS, we did not analyze these data. Our data analysis excludes any other databases or data sources, so as to avoid potential for double counting the same cases reported to multiple entities. For example, the NPIC shares some incident reports with IDS, roughly five-to-ten reports each month. While IDS contains some occupational incidents, most occupational poisonings are reported to two other databases. The California Pesticide Illness Surveillance Program (PISP) includes physician-reported pesticide worker poisonings for the state of California. The Sentinel Event Notification System for Occupational Risk (SENSOR) is a national database that aggregates reports from states, physicians, emergency room records, workers’ compensation claims, and Poison Control Centers. Neither PISP nor SENSOR are incorporated into the IDS. Since most of the occupational incidents that EPA uses come from PISP or SENSOR, with many fewer coming through IDS, by limiting the source of poisoning incidents to just the EPA’s IDS, occupational incidents are largely excluded from this analysis. For those readers interested in occupational exposures, we direct them to the National Institute for Occupational Safety and Health (NIOSH) which compiles data from the SENSOR-Pesticides Program and the National Poison Data System and reports the findings in its Pesticide Illness and Injury Surveillance Program. 15 To prevent double-counting within the IDS data, we scrutinized each line-entry individually, excluding duplicate poisoning cases reported on multiple line-entries. We also excluded any reports not reasonably attributable to pesticide exposure, such as one report of an injury from a ‘plane crash,’ presumably during crop dusting activities. Intentional pesticide ingestion cases were also excluded since they do not represent the intended use of the product. However, we included poisoning reports where the product was used as intended, but possibly not as per label directions, for example: poisonings from a splash or spill while using the product; exposure due to improper ventilation; or premature re-entry into a pesticide-treated area in conflict with label instructions. We included these reports because they represent the real-world use and injury patterns associated with these products. Results Over a five-year period from 2018 through 2022, U.S. EPA received reports of just over 840 people poisoned with neonics; these values should be considered estimates given the lack of individual details in the data reports. Incidents included symptoms ranging from human fatalities (H-A) to major (H-B), moderate (H-C), or minor (H-D) injuries. Imidacloprid was implicated in roughly 70% of the total individual poisonings, most with moderate symptoms of poisoning. See Table 1 for the tabulations of the number of human poisoning incidents by severity and by individual neonic pesticide. The EPA incident reports include four human fatality reports, two associated with clothianidin and two with acetamiprid. For the two clothianidin associated fatalities, EPA states only that in 2019, “2 people died involving Crossfire Bed Bug treatment.” The two acetamiprid fatalities were from 2018: an entry for “Ortho Flower, Fruit and Vegetable Insect Killer Ready-To-Use” with a hand wand applicator reported that “[s]ymptoms include sudden death;” another for “transport termicide [sic] insecticide” reported that, “a man in poor health died after a pesticide application in Section 8 apartments.” Although we submitted a request under the Freedom of Information Act (FOIA) request to EPA on July 11, 2023, for the full reports for these four fatalities, we have not received any response to date, and the full reports are not otherwise publicly available. For nonfatal exposures, the overwhelming majority of them are classified as “moderate” severity (H-C). Moderate poisonings make up 88% of the total poisonings (740 of 842), with most of those associated with imidacloprid (547 incidents) or dinotefuran (102 incidents). Common reported symptoms classified as moderate often included two or more of the following: headaches; dizziness; lethargy; eye or throat irritation; skin itching and rash; chemical burns and skin peeling; face swelling; muscle weakness or tremors; vomiting; diarrhea; pain and tightness in chest; open sores; and general pain. The nonfatal reported incidents stem mainly from residential uses, such as lawn and garden insect repellents, home pest treatments for bed bugs or roaches, and products used to treat pets for fleas and ticks. In many cases, the person who was poisoned was the person applying the pesticide product. In others, the poisoned individuals were exposed after the product was applied by someone else. For example, in 2018 a family of five (two adults and three children) reported symptoms that included skin rashes, vomiting and dizziness (classified as minor symptoms, H-D) upon returning to their apartment after it was treated with a dinotefuran product. The family did not seek medical attention, according to incident reported. In some cases, agricultural uses resulted in exposures to non-occupational bystanders. For example, in 2019, a school bus with open windows carrying twenty-nine students was “allegedly drifted on by an air blast sprayer making an application” of an acetamiprid product to a citrus orchard. The bus driver and nine students reported having irritated eyes and skin, nausea and headaches (classified as minor symptoms, H-D). Other reported symptoms included dizziness, irregular heartbeat, chemical burns, diarrhea, nausea and vomiting, and seizures. It is unclear how each of these are classified – whether as major (H-B), moderate (H-C), or minor (H-D) – since a single line report usually consisted of an aggregate of the number of individuals in each category, sometimes followed by a list of symptoms, but without clarifying which symptoms are associated with which category. For example, a report from 2018 simply states, “Bayer: Includes 21 H-C and 5 H-B. Symptoms include paraesthesia, oedema, skin change, etc.,” without any indication of how many people and from which category had suffered which symptoms. In another example, a report from 2020 simply says, “United Industries: Includes 2 H-B (-004&-006), 19 H-C…. Symptoms include laceration, bleed, numbness, etc.” For this reason, we provide a summary of the numbers of individuals in each category, but are unable to include their respective symptoms. We changed the classification in only three cases. In each of these, seizures were reported, which we re-classified from moderate (H-C) to major symptoms (H-B). One, a 2018 entry for a dinotefuran cockroach bait product, reported, “BASF: Includes 1 H-C. Symptoms include seizure.” Another 2021 entry from an imidacloprid pet product reported, “Elanco: Includes 19 H-C. Symptoms include convulsion, seizure, hemorrhage, etc.” It is unknown what additional symptoms the “etc.” may refer to, or how many of the nineteen individuals had which of the symptoms listed. In this case, we re-classified the report as one H-B individual since there was at least one seizure, and eighteen H-C individuals. The third case was in 2022 by FMC Corporation associated with an imidacloprid lawn product that reported, “FMC: Includes 1 H-C. Symptoms include blotchy & red face, seizure, pass out.” All other reports we reviewed in the database of convulsions or seizures were already classified the symptoms as major (H-B). Discussion While the severity and frequency of the acute pesticide poisoning reports associated with the neonic insecticides are surprisingly high, they are likely to be underreported for many reasons, including not knowing how to report an incident, not going to the hospital or health care facility, many treating physicians are not trained to recognize the signs and symptoms of pesticide poisoning, and, that the person poisoned may not know why they are feeling ill or what product they may have been exposed to. 27 Additionally, while acute illness is more likely to be reported because of the rapid onset of symptoms, it may be that low level chronic exposures to neonics during early life neurodevelopment may be even more problematic. 28 A systematic review of epidemiologic studies of neonic exposure in the general population identified a small but statistically significant association with neonic exposure during pregnancy and adverse developmental or neurological impairments including teratology of Fallot, 29 anencephaly, 30 autism spectrum disorder, 31 and a cluster of nervous system problems including memory loss and finger tremors. 32 33 The same review also reported that occupational exposure studies of adult forestry workers did not report adverse effects, suggesting that early life development is a period of heightened vulnerability at levels lower than those triggering poisoning in healthy adults. 34 Biomonitoring by the Centers for Disease Control and Prevention (CDC) finds that chronic neonic exposure is widespread in the U.S. population, 35 with more recent testing of 171 pregnant women from across the country and Puerto Rico finding neonics in the bodies of over 95% of participants, with levels rising over the course of the four-year study (2017-2020). 36 Because the human brain has only a very limited ability to repair or recover from neurotoxic assault, even transient or low levels of exposure to environmental pollutants such as lead, mercury, air pollution and neurotoxic pesticides like chlorpyrifos can have lasting adverse effects. 37 38 A study we recently published reviews the evidence of developmental neurotoxicity associated with neonics. We report on rodent laboratory toxicology studies sponsored by the manufacturer (the ‘registrant’) exposed to neonics during prenatal and early postnatal development that resulted in statistically significant shrinkage of brain tissue in high-dose offspring for five neonicotinoids: acetamiprid, clothianidin, imidacloprid, thiacloprid, and thiamethoxam. 39 Given that workers are largely people of reproductive age, and may also include individuals that are pregnant or breastfeeding, occupational exposures to neonics may pose a risk not only for the exposed adult, but also for the next generation. EPA found that most occupational risks for imidacloprid could only meet the regulatory approval standard if workers wear a long-sleeved shirt, long pants, shoes and socks, or with personal protective equipment (PPE) and gloves, and in some cases would need to wear double layer clothing and gloves. 40 For clothianidin and thiamethoxam, EPA’s PPE requirements are similar except that some occupational tasks also require use of a respirator. 41 Fundamentally, PPE is an attempt to provide a barrier between the person and the hazard, but the hazard remains. For all these reasons, PPE is considered one of the least effective and desirable ways to protect workers, including farmworkers and those working with pesticides. 42 43 44 45 46 47 These protections are the least effective line of defense, as described by the Hierarchy of Controls that ranks safeguards from most to least effective, with the most effective being elimination of the hazard, followed by reducing it through substitution. 48 For neonics, these two top-tier prevention strategies – elimination and substitution - can be readily employed since the vast majority of neonic uses are applied in the absence of an actual pest problem. 49 50 While most of the reported acute poisoning incidents discussed in this paper are from non-agricultural uses of the pesticides, three neonics - imidacloprid, clothianidin and thiamethoxam - are also approved for over 100 different products used to coat or “treat” crop seeds. Pesticide seed treatments take advantage of the systemic nature of the chemicals. The coatings are designed to be absorbed through a plant’s roots as it grows, making all of the plant’s tissues poisonous to insects, including both target pests and beneficial insects such as bees, butterflies, and other pollinators. 51 52 53 Though the use of seed treatments is not tracked, one can estimate it by examining U.S. Geological Survey (USGS) Pesticide Use annual reports, which beginning in 2015 discontinued reporting on the seed treatment applications. 54 The precipitous drop in reported use from 2014 to 2015 can be presumed to be roughly the amount used as seed treatments that are no longer reported. USGS reports indicate that agricultural uses of thiamethoxam are almost all from seed treatments (1.2 million pounds per year, lbs/year, on corn and soy seeds, and about 0.2 million lbs/year for non-seed uses), and the case is similar for clothianidin (3.5 million lbs/year on corn seed treatments, and about 0.1 million lbs/year for non-seed uses). Imidacloprid agricultural use is split about half and half (with about 1 million lbs/year for soybean and cotton seed treatments, and about 1 million lbs/year on non-seed uses). In 2024, EPA updated its occupational risks for neonics to include health risks to workers treating seeds with pesticides and handling treated seeds; EPA identified several activities that posed elevated risks to workers, including cleaning seed treatment equipment, even when maximum personal protective equipment (PPE) is used (double-layered clothing and a respirator rated with a protection factor of 10, PF-10). 55 Of concern, PPE for worker protection is often uncomfortable, poorly fitted, difficult to wear while doing work tasks, and can be less effective in higher temperatures such as during outdoor farmwork. 56 57 A small study that conducted biomonitoring (urine samples) and tap water testing of Iowa farm families found that for people that worked directly with pesticides including treated seeds, occupational exposures and house dust was their greatest source of exposure. 58 In its 2020 imidacloprid evaluation, EPA noted that, “[t]he total number of imidacloprid incidents reported to IDS, from 2013 to 2018, appeared to be increasing over time. The agency will continue to monitor the incident data and if a concern is triggered, additional analysis will be conducted.” 59 The U.S. Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) authorizes EPA to cancel a pesticide registration when existing risks related to its use are unacceptable and registrants have not made changes to the registration to address the unacceptable risks. 60 EPA should use its legal authority to cancel unsafe products and unnecessary uses – including from seed treatments, and residential pet and lawncare products - to ensure that farmworkers, pesticide applicators, home gardeners, and children playing on lawns or cuddling with family pets are not needlessly poisoned in the first place. Conclusion Here we have presented an analysis of non-occupational human poisoning incidents associated with neonicotinoid pesticides, as reported in EPA’s Incident Database System. While the data have recently become available to the public, they are not in a form that can be aggregated for analysis. Here we have done the work of aggregating and then individually evaluating each of the data summary reports (EPA does not make the full reports publicly available). This information is particularly important as local, state, and federal agencies grapple with how to address the impacts to workers, families, communities and ecosystems from the widespread use of this class of neurotoxic and developmentally neurotoxic insecticides. Abbreviations EPA U.S. Environmental Protection Agency FIFRA U.S. Federal Insecticide, Fungicide and Rodenticide Act FOIA U.S. Freedom of Information Act FQPA U.S. Food Quality Protection Act H A–human fatality H B–human major injuries H C–human moderate injuries H D–human minor injuries IDS EPA's Incident Data System nAChR nicotinic acetylcholine receptor Neonics neonicotinoid pesticides NIOSH U.S. National Institute for Occupational Safety and Health NPIC National Pesticide Information Centers PF 10–respirator with a protection factor of 10 PISP California Pesticide Illness Surveillance Program PPE Personal Protective Equipment SENSOR Sentinel Event Notification System for Occupational Risk Declarations Ethics approval and consent to participate – N/A Consent for publication – N/A Availability of data and materials - The datasets analyzed for this study can be found in the NRDC repository at the following link https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342 Competing interests - The authors declare that they have no competing interests. Funding - Natural Resources Defense Council (NRDC) general funds. Authors' contributions - JBS conducted all data analyses. JBS and DR both conducted literature reviews and developed policy recommendations. Acknowledgements – We thank the reviewers of this article for suggestions to improve it. References Tomizawa, M. & Casida, J. E. 2005. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu. Rev. Pharmacol. Toxicol., 45, 247–268. doi: 10.1146/annurev.pharmtox.45.120403.095930 Bayer CropScience. 2016. The bee safety of neonicotinoid insecticides. Bayer Bee Care Center. BeeInformed, 3, 1–16. Available at: https://www.bayer.com/sites/default/files/BEEINFOrmed_issue3_The_Bee_Safety_of_Neonicotinoids-1iusc0izc_0.pdf Tomizawa, M. & Casida, J. E. 2005. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu. Rev. Pharmacol. Toxicol., 45, 247–268. doi: 10.1146/annurev.pharmtox.45.120403.095930 EPA 2023. 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Exposure to contemporary and emerging chemicals in commerce among pregnant women in the United States: the Environmental Influences on Child Health Outcome (ECHO) Program. Environmental science & technology, 56, 6560–6573. doi: 10.1021/acs.est.1c08942 Landrigan P, Grandjean P. Pollution and the developing brain. Lancet. 2021 Nov 27;398(10315):1961. doi: 10.1016/S0140-6736(21)02393-X . PMID: 34838170. Grandjean P, Landrigan PJ. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014 Mar;13(3):330-8. doi: 10.1016/S1474-4422(13)70278-3 . Epub 2014 Feb 17. PMID: 24556010; PMCID: PMC4418502. Sass JB, Donley N, Freese B. 2024 Neonicotinoid pesticides: evidence of developmental neurotoxicity from regulatory rodent studies. Front. Toxicol., Accepted September, 2024. doi: 10.3389/ftox.2024.1438890 EPA 2020. Imidacloprid. Proposed Interim Registration Review Decision, Occupational Risks, p. 17. U.S. Environmental Protection Agency. January, 2020. Docket ID EPA-HQ-OPP-2008-0844. Available at: https://www.epa.gov/sites/default/files/2020-01/documents/imidacloprid_pid_signed_1.22.2020.pdf EPA 2020. Clothianidin and Thiamethoxam. Proposed Interim Registration Review Decision Case Numbers 7620 and 7614 U.S. Environmental Protection Agency. January, 2020. Available at:. January 2020. https://www.epa.gov/sites/default/files/2020-01/documents/clothianidin_and_thiamethoxam_pid_final_1.pdf Barrón Cuenca, J., Dreij, K. & Tirado, N. 2024. Human pesticide exposure in Bolivia: a scoping review of current knowledge, future challenges and research needs. International journal of environmental research and public health, 21, 305. doi: 10.3390/ijerph21030305 . Liang, Y., Tong, F., Zhang, L., Li, W., Huang, W. & Zhou, Y. 2018. Fatal poisoning by terbufos following occupational exposure. Clinical toxicology, 56, 140–142. doi: 10.1080/15563650.2017.1340647 . Khode, D., Hepat, A., Mudey, A. & Joshi, A. 2024. Health-related challenges and programs among agriculture workers: a narrative review. Cureus, 16. doi: 10.7759/cureus.57222 . Perry, M. J., Marbella, A. & Layde, P. M. 2002. Compliance with required pesticide‐specific protective equipment use. American journal of industrial medicine, 41, 70–73. doi: 10.1002/ajim.10026 . Pedersen, D. H., Wilkins Iii, J., Bean, T. L., Mitchell, G. L., Crawford, J. M. & Jones, L. A. 1999. Agricultural hazard data from a population-based survey of cash grain farms: Ohio observations. Applied occupational and environmental hygiene, 14, 299–305. doi: 10.1080/104732299302882 Mandel, J. H., Carr, W. P., Hillmer, T., Leonard, P. R., Halberg, J. U., Sanderson, W. T. & Mandel, J. S. 1996. Factors associated with safe use of agricultural pesticides in Minnesota. The Journal of Rural Health, 12, 301–310. doi: 10.1111/j.1748-0361.1996.tb00819.x . NIOSH 2024a. Hierarchy of Controls. National Institute for Occupational Safety and Health. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/niosh/hierarchy-of-controls/about/?CDC_AAref_Val=https://www.cdc.gov/niosh/topics/hierarchy/default.html Grout, T. A., Koenig, P. A., Kapuvari, J. K. & Mcart, S. H. 2021. Neonicotinoid insecticides in New York state: economic benefits and risk to pollinators. Available at: https://cornell.app.box.com/v/2020-neonicotinoid-report CornellCALS. 2024. Neonicotinoid Insecticide Alternatives [Online]. Cornell College of Agriculture and Life Sciences (CALS). New York State Integrated Pest Management. Available: https://cals.cornell.edu/new-york-state-integrated-pest-management/research-initiatives/current-projects/alternatives-neonic-insecticides Lin, C. H., Sponsler, D. B., Richardson, R. T., Watters, H. D., Glinski, D. A., Henderson, W. M., Minucci, J. M., Lee, E. H., Purucker, S. T. & Johnson, R. M. 2021. Honey bees and neonicotinoid‐treated corn seed: contamination, exposure, and effects. Environmental Toxicology and Chemistry, 40, 1212–1221. doi: 10.1002/etc.4957 . E Van Deynze, B., Swinton, S. M., Hennessy, D. A., Haddad, N. M. & Ries, L. 2024. Insecticides, more than herbicides, land use, and climate, are associated with declines in butterfly species richness and abundance in the American Midwest. PLOS ONE, 19, e0304319. doi: 10.1371/journal.pone.0304319 Woodcock, B. A., Bullock, J. M., Shore, R. F., Heard, M. S., Pereira, M. G., Redhead, J., Ridding, L., Dean, H., Sleep, D. & Henrys, P. 2017. Country-specific effects of neonicotinoid pesticides on honey bees and wild bees. Science, 356, 1393–1395. doi: 10.1126/science.aaa1190 USGS. 2024. Estimated Annual Agricultural Pesticide Use [Online]. U.S. Geological Survey. Available: https://water.usgs.gov/nawqa/pnsp/usage/maps/compound_listing.php EPA 2024. EPA Releases Updated Occupational Exposure Assessments for Seed Treatment Uses for Three Neonicotinoids. U.S. Environmental Protection Agency, July 26, 2024. Available at: https://www.epa.gov/pesticides/epa-releases-updated-occupational-exposure-assessments-seed-treatment-uses-three#:~:text=Today%2C%20the%20U.S.%20Environmental%20Protection,systemic%20insecticides%20that%20work%20by Ismail, I., Gaskin, S., Pisaniello, D. & Edwards, J. W. 2018. Organophosphorus pesticide exposure in agriculture: effects of temperature, ultraviolet light and abrasion on PVC gloves. Industrial health, 56, 166–170. doi: 10.2486/indhealth.2017-0157 Thredgold, L., Gaskin, S., Quy, C. & Pisaniello, D. 2019. Exposure of agriculture workers to pesticides: the effect of heat on protective glove performance and skin exposure to dichlorvos. International Journal of Environmental Research and Public Health, 16, 4798. doi: 10.3390/ijerph16234798 Thompson, D. A., Kolpin, D. W., Hladik, M. L., Lehmler, H.-J., Meppelink, S. M., Poch, M. C., Vargo, J. D., Soupene, V. A., Irfan, N. M. & Robinson, M. 2023. Prevalence of neonicotinoid insecticides in paired private-well tap water and human urine samples in a region of intense agriculture overlying vulnerable aquifers in eastern Iowa. Chemosphere, 319, 137904. doi: 10.1016/j.chemosphere.2023.137904 EPA 2020. Imidacloprid. Proposed Interim Registration Review Decision, Occupational Risks, p. 17. U.S. Environmental Protection Agency. January, 2020. Docket ID EPA-HQ-OPP-2008-0844. Available at: https://www.epa.gov/sites/default/files/2020-01/documents/imidacloprid_pid_signed_1.22.2020.pdf EPA 2023. Pesticide Cancellation Under EPA's Own Initiative. Last updated November 15, 2023. https://www.epa.gov/pesticide-tolerances/pesticide-cancellation-under-epas-own-initiative#:~:text=Section%206(b)%20of%20the,changes%20to%20the%20terms%20and Additional Declarations Competing interest reported. JBS, DR have no financial competing interests. As part of our job with a public interest non-profit group, we make public statements on the science, policy, and regulatory actions, including litigation to enforce environmental laws, relevant to the subject matter of this manuscript. Supplementary Files CopyofSpecifiedIngredientIncidentsforDinotefuranClothianidinImidaclopridAcetamipridandThiamethoxam.xlsx Cite Share Download PDF Status: Published Journal Publication published 20 Nov, 2024 Read the published version in Environmental Health → Version 1 posted Editorial decision: Revision requested 30 Sep, 2024 Reviews received at journal 30 Sep, 2024 Reviews received at journal 24 Sep, 2024 Reviews received at journal 18 Sep, 2024 Reviews received at journal 14 Sep, 2024 Reviewers agreed at journal 14 Sep, 2024 Reviewers agreed at journal 12 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviewers agreed at journal 10 Sep, 2024 Reviewers invited by journal 09 Sep, 2024 Editor assigned by journal 09 Sep, 2024 Submission checks completed at journal 09 Sep, 2024 First submitted to journal 08 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5054262","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":360527353,"identity":"234c17f6-d56f-4997-a8e2-eb4b035b5ea9","order_by":0,"name":"Jennifer B. Sass","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqUlEQVRIiWNgGAWjYBACxgYQWQHEB0jTcoYULRB9baRoYe4//Pjjz3l38vmOH2B8XPGLGAtmpJlJ8257ZjnzTAKz4dk+orQwmDEzbjtsYHCDgU2ysYcYLf3HP3/8OYckLQ05BhK8DVAtDT+IclhOmTTPscMGkmcSmw0bG4jQYth/fPPHHzWHDfiOHz74sOEPMVoQ5gJjFRxBhIA8KpcYW0bBKBgFo2DEAQBi5zr3TpzwuAAAAABJRU5ErkJggg==","orcid":"","institution":"Natural Resources Defense Council","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"B.","lastName":"Sass","suffix":""},{"id":360527354,"identity":"22bf39b1-2295-48e7-8599-2bdf75527bf8","order_by":1,"name":"Daniel Raichel","email":"","orcid":"","institution":"Natural Resources Defense Council","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Raichel","suffix":""}],"badges":[],"createdAt":"2024-09-08 22:31:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5054262/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5054262/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12940-024-01139-2","type":"published","date":"2024-11-20T15:58:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67192926,"identity":"e7ac34bc-958e-425e-8147-c2c734911fe9","added_by":"auto","created_at":"2024-10-22 08:44:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25139,"visible":true,"origin":"","legend":"\u003cp\u003eTabulation of Entries in the U.S. EPA Incident Data System of human pesticide poisoning incidents associated with neonicotinoid insecticides over a 60-month period from 2018 through 2022.\u003c/p\u003e\n\u003cp\u003eLegend: Each incident represents an individual person; these values should be considered estimates given the lack of individual details in the data reports. The severity of the injury is reported as it was reported in the EPA database except in 3 cases for which a seizure was reported, but the incident was classified as H-C (moderate) and which here is classified as H-B (major) consistent with EPA ratings.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5054262/v1/d6a61c459c6ce339c6261d8a.png"},{"id":69835535,"identity":"273e3c2a-ed15-4807-892c-43a534c260b7","added_by":"auto","created_at":"2024-11-25 16:13:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":365575,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5054262/v1/1e527737-44f7-45fb-831f-6a46d55e95bc.pdf"},{"id":67192927,"identity":"88efee59-fc91-42f4-9d7d-4216a54624c9","added_by":"auto","created_at":"2024-10-22 08:44:11","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":611995,"visible":true,"origin":"","legend":"","description":"","filename":"CopyofSpecifiedIngredientIncidentsforDinotefuranClothianidinImidaclopridAcetamipridandThiamethoxam.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5054262/v1/4fa76f37f4e95c35ca0b5bb4.xlsx"}],"financialInterests":"Competing interest reported. JBS, DR have no financial competing interests. As part of our job with a public interest non-profit group, we make public statements on the science, policy, and regulatory actions, including litigation to enforce environmental laws, relevant to the subject matter of this manuscript.","formattedTitle":"Human poisonings with neonicotinoid pesticides – frequency and severity show public health risks, regulatory failures","fulltext":[{"header":"Background","content":"\u003cp\u003eNeonicotinoid pesticides, or \u0026ldquo;neonics,\u0026rdquo; are the most widely used insecticides in the world, in large part because they were initially characterized as posing little to no risk to vertebrates, including humans\u003csup\u003e1\u003c/sup\u003e \u0026ndash; with the first neonic manufacturer, Bayer, stating \u0026ldquo;[t]he toxicity of neonicotinoids to mammals and humans is very low\u0026rdquo;.\u003csup\u003e2\u003c/sup\u003e The chemicals are similar to nicotine and are toxic by a similar mechanism, acting as an agonist on the nicotinic acetylcholine receptor (nAChR), to overstimulate affective nerve cells and systems. \u003csup\u003e3\u003c/sup\u003e\u003c/a\u003e The concerns with neonics have predominantly been reported related to their devastating effects on bees, aquatic invertebrates, and beneficial insects. In fact, the U.S. Environmental Protection Agency (EPA) predicts that the three most common neonics (imidacloprid, thiamethoxam, clothianidin) put at risk over 200 threatened and endangered species, about 11% of the entire endangered species list, including beneficial pollinating insects like bees and butterflies.\u003csup\u003e4\u003c/sup\u003e \u003cp\u003eHere we review of the extensive human poisoning incident data for neonics, to show that current uses of neonic pesticide products can \u0026ndash; and do \u0026ndash; harm people.\u003c/p\u003e \u003cp\u003eThe class of neonics includes: imidacloprid; thiamethoxam; clothianidin; acetamiprid; dinotefuran. They are registered in over 120 countries, on more than 140 fruit, vegetable, and field crops to target sucking and chewing insects such as aphids or emerald ash borers.\u003csup\u003e5\u003c/sup\u003e The EPA has approved over 1,000 products containing neonics, including for agricultural crops, urban landscaping, and indoor bed bug and flea and tick treatments for pets. Since neonics persist in soil and are highly water soluble, both the agricultural and consumer uses of neonic products contaminate soil and water. A national stream sample report by the U.S. Geological Survey found that clothianidin and thiamethoxam detections in surface water were related to uses on crops, whereas imidacloprid was the most frequently detected neonic in urban stream samples (37% of samples), with concentrations related to lawns, gardens, parks, and playgrounds.\u003csup\u003e6\u003c/sup\u003e A study in Minnesota reported a similar pattern, with the highest neonic detections associated with agricultural use, mainly clothianidin, followed by neonics use in urban areas, mainly imidacloprid, suggesting that both agriculture and urban uses contribute to chronic exposure.\u003csup7\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn addition to environmental pollution, neonics are the pesticides most frequently reported as associated with human poisonings. In 2021, the Midwest Center for Investigative Reporting reported in USA Today on poisonings from pesticides leaching from flea and tick collars, particularly one brand that contains 10% imidacloprid (a neonic) and 4.5% flumethrin (a pyrethroid insecticide). The reports included around 1,700 pet deaths and just under 1,000 people being poisoned. The EPA launched an investigation, ultimately concluding that the pet collars were not the cause of any pet deaths. EPA re-confirmed its approval of the collars without any formulation changes, but did require additional label warnings to help consumers recognize and report potential poisoning incidents.\u003csup\u003e8\u003c/sup\u003e A follow up investigation by the EPA\u0026rsquo;s independent Office of Inspector General reported on emails from 2017 to 2022 that show EPA staff concerns were repeatedly ignored by both EPA management and the pesticide product manufacturer.\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHere we provide an updated and deeper analysis into the available data on non-occupational human poisoning incidents reported to be associated with neonicotinoid pesticides.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAs of July 2023, EPA made 10 years of pesticide incident data available on its online Incident Data System (IDS).\u003csup\u003e10\u003c/sup\u003e The IDS is a national database, populated with human health information from several sources, largely from pesticide manufacturers, which are required to notify EPA of \u0026ldquo;information regarding unreasonable adverse effects on the environment of the pesticides\u0026rdquo; they register, including occupational, residential and ecological incidents.\u003csup\u003e11\u003c/sup\u003e Additional submissions to EPA may come from private individuals, poison control centers, states, National Pesticide Information Centers (NPIC), and government or non-government agencies.\u003csup\u003e12\u003c/sup\u003e IDS reports are predominantly self-reported information of varying and often low level of detail around exposure circumstances, symptoms, and/or medical outcome. The information is not routinely validated or verified by EPA, though reports from poison control centers and some states may be confirmed.\u003csup\u003e13\u003c/sup\u003e See EPA\u0026rsquo;s website for details including data limitations.\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWhile ecological incidents are also included in IDS, we did not analyze these data. Our data analysis excludes any other databases or data sources, so as to avoid potential for double counting the same cases reported to multiple entities. For example, the NPIC shares some incident reports with IDS, roughly five-to-ten reports each month. While IDS contains some occupational incidents, most occupational poisonings are reported to two other databases. The California Pesticide Illness Surveillance Program (PISP) includes physician-reported pesticide worker poisonings for the state of California. The Sentinel Event Notification System for Occupational Risk (SENSOR) is a national database that aggregates reports from states, physicians, emergency room records, workers\u0026rsquo; compensation claims, and Poison Control Centers. Neither PISP nor SENSOR are incorporated into the IDS. Since most of the occupational incidents that EPA uses come from PISP or SENSOR, with many fewer coming through IDS, by limiting the source of poisoning incidents to just the EPA\u0026rsquo;s IDS, occupational incidents are largely excluded from this analysis. For those readers interested in occupational exposures, we direct them to the National Institute for Occupational Safety and Health (NIOSH) which compiles data from the SENSOR-Pesticides Program and the National Poison Data System and reports the findings in its Pesticide Illness and Injury Surveillance Program.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTo prevent double-counting within the IDS data, we scrutinized each line-entry individually, excluding duplicate poisoning cases reported on multiple line-entries. We also excluded any reports not reasonably attributable to pesticide exposure, such as one report of an injury from a \u0026lsquo;plane crash,\u0026rsquo; presumably during crop dusting activities. Intentional pesticide ingestion cases were also excluded since they do not represent the intended use of the product. However, we included poisoning reports where the product was used as intended, but possibly not as per label directions, for example: poisonings from a splash or spill while using the product; exposure due to improper ventilation; or premature re-entry into a pesticide-treated area in conflict with label instructions. We included these reports because they represent the real-world use and injury patterns associated with these products.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOver a five-year period from 2018 through 2022, U.S. EPA received reports of just over 840 people poisoned with neonics; these values should be considered estimates given the lack of individual details in the data reports.\u003ca class=\"FNLink\" href=\"#Fn16\" id=\"#FNLinkFn16\"\u003e\u003c/a\u003e Incidents included symptoms ranging from human fatalities (H-A) to major (H-B), moderate (H-C), or minor (H-D) injuries.\u003ca class=\"FNLink\" href=\"#Fn17\" id=\"#FNLinkFn17\"\u003e\u003c/a\u003e Imidacloprid was implicated in roughly 70% of the total individual poisonings, most with moderate symptoms of poisoning.\u003c/p\u003e \u003cp\u003eSee Table\u0026nbsp;1 for the tabulations of the number of human poisoning incidents by severity and by individual neonic pesticide.\u003c/p\u003e \u003cp\u003eThe EPA incident reports include four human fatality reports, two associated with clothianidin and two with acetamiprid. For the two clothianidin associated fatalities, EPA states only that in 2019, \u0026ldquo;2 people died involving Crossfire Bed Bug treatment.\u0026rdquo; \u003ca class=\"FNLink\" href=\"#Fn18\" id=\"#FNLinkFn18\"\u003e\u003c/a\u003e The two acetamiprid fatalities were from 2018: an entry for \u0026ldquo;Ortho Flower, Fruit and Vegetable Insect Killer Ready-To-Use\u0026rdquo; with a hand wand applicator reported that \u0026ldquo;[s]ymptoms include sudden death;\u0026rdquo; another for \u0026ldquo;transport termicide [sic] insecticide\u0026rdquo; reported that, \u0026ldquo;a man in poor health died after a pesticide application in Section 8 apartments.\u0026rdquo; \u003ca class=\"FNLink\" href=\"#Fn19\" id=\"#FNLinkFn19\"\u003e\u003c/a\u003e Although we submitted a request under the Freedom of Information Act (FOIA) request to EPA on July 11, 2023, for the full reports for these four fatalities, we have not received any response to date, and the full reports are not otherwise publicly available.\u003c/p\u003e \u003cp\u003eFor nonfatal exposures, the overwhelming majority of them are classified as \u0026ldquo;moderate\u0026rdquo; severity (H-C). Moderate poisonings make up 88% of the total poisonings (740 of 842), with most of those associated with imidacloprid (547 incidents) or dinotefuran (102 incidents). Common reported symptoms classified as moderate often included two or more of the following: headaches; dizziness; lethargy; eye or throat irritation; skin itching and rash; chemical burns and skin peeling; face swelling; muscle weakness or tremors; vomiting; diarrhea; pain and tightness in chest; open sores; and general pain.\u003c/p\u003e \u003cp\u003eThe nonfatal reported incidents stem mainly from residential uses, such as lawn and garden insect repellents, home pest treatments for bed bugs or roaches, and products used to treat pets for fleas and ticks. In many cases, the person who was poisoned was the person applying the pesticide product. In others, the poisoned individuals were exposed after the product was applied by someone else. For example, in 2018 a family of five (two adults and three children) reported symptoms that included skin rashes, vomiting and dizziness (classified as minor symptoms, H-D) upon returning to their apartment after it was treated with a dinotefuran product. The family did not seek medical attention, according to incident reported.\u003ca class=\"FNLink\" href=\"#Fn20\" id=\"#FNLinkFn20\"\u003e\u003c/a\u003e\u003c/p\u003e \u003cp\u003eIn some cases, agricultural uses resulted in exposures to non-occupational bystanders. For example, in 2019, a school bus with open windows carrying twenty-nine students was \u0026ldquo;allegedly drifted on by an air blast sprayer making an application\u0026rdquo; of an acetamiprid product to a citrus orchard.\u003ca class=\"FNLink\" href=\"#Fn21\" id=\"#FNLinkFn21\"\u003e\u003c/a\u003e The bus driver and nine students reported having irritated eyes and skin, nausea and headaches (classified as minor symptoms, H-D).\u003c/p\u003e \u003cp\u003eOther reported symptoms included dizziness, irregular heartbeat, chemical burns, diarrhea, nausea and vomiting, and seizures. It is unclear how each of these are classified \u0026ndash; whether as major (H-B), moderate (H-C), or minor (H-D) \u0026ndash; since a single line report usually consisted of an aggregate of the number of individuals in each category, sometimes followed by a list of symptoms, but without clarifying which symptoms are associated with which category. For example, a report from 2018 simply states, \u0026ldquo;Bayer: Includes 21 H-C and 5 H-B. Symptoms include paraesthesia, oedema, skin change, etc.,\u0026rdquo; without any indication of how many people and from which category had suffered which symptoms.\u003ca class=\"FNLink\" href=\"#Fn22\" id=\"#FNLinkFn22\"\u003e\u003c/a\u003e In another example, a report from 2020 simply says, \u0026ldquo;United Industries: Includes 2 H-B (-004\u0026amp;-006), 19 H-C\u0026hellip;. Symptoms include laceration, bleed, numbness, etc.\u0026rdquo;\u003ca class=\"FNLink\" href=\"#Fn23\" id=\"#FNLinkFn23\"\u003e\u003c/a\u003e For this reason, we provide a summary of the numbers of individuals in each category, but are unable to include their respective symptoms.\u003c/p\u003e \u003cp\u003eWe changed the classification in only three cases. In each of these, seizures were reported, which we re-classified from moderate (H-C) to major symptoms (H-B). One, a 2018 entry for a dinotefuran cockroach bait product, reported, \u0026ldquo;BASF: Includes 1 H-C. Symptoms include seizure.\u0026rdquo;\u003ca class=\"FNLink\" href=\"#Fn24\" id=\"#FNLinkFn24\"\u003e\u003c/a\u003e Another 2021 entry from an imidacloprid pet product reported, \u0026ldquo;Elanco: Includes 19 H-C. Symptoms include convulsion, seizure, hemorrhage, etc.\u0026rdquo; It is unknown what additional symptoms the \u0026ldquo;etc.\u0026rdquo; may refer to, or how many of the nineteen individuals had which of the symptoms listed.\u003ca class=\"FNLink\" href=\"#Fn25\" id=\"#FNLinkFn25\"\u003e\u003c/a\u003e In this case, we re-classified the report as one H-B individual since there was at least one seizure, and eighteen H-C individuals. The third case was in 2022 by FMC Corporation associated with an imidacloprid lawn product that reported, \u0026ldquo;FMC: Includes 1 H-C. Symptoms include blotchy \u0026amp; red face, seizure, pass out.\u0026rdquo;\u003ca class=\"FNLink\" href=\"#Fn26\" id=\"#FNLinkFn26\"\u003e\u003c/a\u003e All other reports we reviewed in the database of convulsions or seizures were already classified the symptoms as major (H-B).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWhile the severity and frequency of the acute pesticide poisoning reports associated with the neonic insecticides are surprisingly high, they are likely to be underreported for many reasons, including not knowing how to report an incident, not going to the hospital or health care facility, many treating physicians are not trained to recognize the signs and symptoms of pesticide poisoning, and, that the person poisoned may not know why they are feeling ill or what product they may have been exposed to.\u003csup\u003e27\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdditionally, while acute illness is more likely to be reported because of the rapid onset of symptoms, it may be that low level chronic exposures to neonics during early life neurodevelopment may be even more problematic.\u003csup\u003e28\u003c/sup\u003e A systematic review of epidemiologic studies of neonic exposure in the general population identified a small but statistically significant association with neonic exposure during pregnancy and adverse developmental or neurological impairments including teratology of Fallot,\u003csup\u003e29\u003c/sup\u003e anencephaly,\u003csup\u003e30\u003c/sup\u003e autism spectrum disorder,\u003csup\u003e31\u003c/sup\u003e and a cluster of nervous system problems including memory loss and finger tremors.\u003csup\u003e32\u003c/sup\u003e \u003csup\u003e33\u003c/sup\u003e The same review also reported that occupational exposure studies of adult forestry workers did not report adverse effects, suggesting that early life development is a period of heightened vulnerability at levels lower than those triggering poisoning in healthy adults. \u003csup\u003e34\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBiomonitoring by the Centers for Disease Control and Prevention (CDC) finds that chronic neonic exposure is widespread in the U.S. population,\u003csup\u003e35\u003c/sup\u003e with more recent testing of 171 pregnant women from across the country and Puerto Rico finding neonics in the bodies of over 95% of participants, with levels rising over the course of the four-year study (2017-2020).\u003csup\u003e36\u003c/sup\u003e Because the human brain has only a very limited ability to repair or recover from neurotoxic assault, even transient or low levels of exposure to environmental pollutants such as lead, mercury, air pollution and neurotoxic pesticides like chlorpyrifos can have lasting adverse effects.\u003csup\u003e37\u003c/sup\u003e \u003csup\u003e38\u003c/sup\u003e A study we recently published reviews the evidence of developmental neurotoxicity associated with neonics. We report on rodent laboratory toxicology studies sponsored by the manufacturer (the \u0026lsquo;registrant\u0026rsquo;) exposed to neonics during prenatal and early postnatal development that resulted in statistically significant shrinkage of brain tissue in high-dose offspring for five neonicotinoids: acetamiprid, clothianidin, imidacloprid, thiacloprid, and thiamethoxam.\u003csup\u003e39\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eGiven that workers are largely people of reproductive age, and may also include individuals that are pregnant or breastfeeding, occupational exposures to neonics may pose a risk not only for the exposed adult, but also for the next generation. EPA found that most occupational risks for imidacloprid could only meet the regulatory approval standard if workers wear a long-sleeved shirt, long pants, shoes and socks, or with personal protective equipment (PPE) and gloves, and in some cases would need to wear double layer clothing and gloves.\u003csup\u003e40\u003c/sup\u003e For clothianidin and thiamethoxam, EPA\u0026rsquo;s PPE requirements are similar except that some occupational tasks also require use of a respirator.\u003csup\u003e41\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFundamentally, PPE is an attempt to provide a barrier between the person and the hazard, but the hazard remains. For all these reasons, PPE is considered one of the least effective and desirable ways to protect workers, including farmworkers and those working with pesticides.\u003csup\u003e42\u003c/sup\u003e \u003csup\u003e43\u003c/sup\u003e \u003csup\u003e44\u003c/sup\u003e \u003csup\u003e45\u003c/sup\u003e \u003csup\u003e46\u003c/sup\u003e \u003csup\u003e47\u003c/sup\u003e These protections are the least effective line of defense, as described by the Hierarchy of Controls that ranks safeguards from most to least effective, with the most effective being elimination of the hazard, followed by reducing it through substitution.\u003csup\u003e48\u003c/sup\u003e\u0026nbsp; For neonics, these two top-tier prevention strategies \u0026ndash; elimination and substitution - can be readily employed since the vast majority of neonic uses are applied in the absence of an actual pest problem.\u003csup\u003e49\u003c/sup\u003e \u003csup\u003e50\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eWhile most of the reported acute poisoning incidents discussed in this paper are from non-agricultural uses of the pesticides, three neonics - imidacloprid, clothianidin and thiamethoxam - are also approved for over 100 different products used to coat or \u0026ldquo;treat\u0026rdquo; crop seeds. Pesticide seed treatments take advantage of the systemic nature of the chemicals. The coatings are designed to be absorbed through a plant\u0026rsquo;s roots as it grows, making all of the plant\u0026rsquo;s tissues poisonous to insects, including both target pests and beneficial insects such as bees, butterflies, and other pollinators.\u003csup\u003e51\u003c/sup\u003e \u003csup\u003e52\u003c/sup\u003e \u003csup\u003e53\u003c/sup\u003e Though the use of seed treatments is not tracked, one can estimate it by examining U.S. Geological Survey (USGS) Pesticide Use annual reports, which beginning in 2015 discontinued reporting on the seed treatment applications.\u003csup\u003e54\u003c/sup\u003e\u0026nbsp; The precipitous drop in reported use from 2014 to 2015 can be presumed to be roughly the amount used as seed treatments that are no longer reported. USGS reports indicate that agricultural uses of thiamethoxam are almost all from seed treatments (1.2 million pounds per year, lbs/year, on corn and soy seeds, and about 0.2 million lbs/year for non-seed uses), and the case is similar for clothianidin (3.5 million lbs/year on corn seed treatments, and about 0.1 million lbs/year for non-seed uses). Imidacloprid agricultural use is split about half and half (with about 1 million lbs/year for soybean and cotton seed treatments, and about 1 million lbs/year on non-seed uses).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn 2024, EPA updated its occupational risks for neonics to include health risks to workers treating seeds with pesticides and handling treated seeds; EPA identified several activities that posed elevated risks to workers, including cleaning seed treatment equipment, even when maximum personal protective equipment (PPE) is used (double-layered clothing and a respirator rated with a protection factor of 10, PF-10).\u003csup\u003e55\u003c/sup\u003e Of concern, PPE for worker protection is often uncomfortable, poorly fitted, difficult to wear while doing work tasks, and can be less effective \u0026nbsp;in higher temperatures such as during outdoor farmwork.\u003csup\u003e56\u003c/sup\u003e \u003csup\u003e57\u003c/sup\u003e A small study that conducted biomonitoring (urine samples) and tap water testing of Iowa farm families found that for people that worked directly with pesticides including treated seeds, occupational exposures and house dust was their greatest source of exposure.\u003csup\u003e58\u003c/sup\u003e\u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn its 2020 imidacloprid evaluation, EPA noted that, \u0026ldquo;[t]he total number of imidacloprid incidents reported to IDS, from 2013 to 2018, appeared to be increasing over time. The agency will continue to monitor the incident data and if a concern is triggered, additional analysis will be conducted.\u0026rdquo;\u003csup\u003e59\u003c/sup\u003e The \u0026nbsp;U.S. Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) authorizes EPA to cancel a pesticide registration when existing risks related to its use are unacceptable and registrants have not made changes to the registration to address the unacceptable risks.\u003csup\u003e60\u003c/sup\u003e EPA should use its legal authority to cancel unsafe products and unnecessary uses \u0026ndash; including from seed treatments, and residential pet and lawncare products - \u0026nbsp;to ensure that farmworkers, pesticide applicators, home gardeners, and children playing on lawns or cuddling with family pets are not needlessly poisoned in the first place.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eHere we have presented an analysis of non-occupational human poisoning incidents associated with neonicotinoid pesticides, as reported in EPA\u0026rsquo;s Incident Database System. While the data have recently become available to the public, they are not in a form that can be aggregated for analysis. Here we have done the work of aggregating and then individually evaluating each of the data summary reports (EPA does not make the full reports publicly available). This information is particularly important as local, state, and federal agencies grapple with how to address the impacts to workers, families, communities and ecosystems from the widespread use of this class of neurotoxic and developmentally neurotoxic insecticides.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEPA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eU.S. Environmental Protection Agency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFIFRA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eU.S. Federal Insecticide, Fungicide and Rodenticide Act\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFOIA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eU.S. Freedom of Information Act\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFQPA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eU.S. Food Quality Protection Act\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eA\u0026ndash;human fatality\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eB\u0026ndash;human major injuries\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC\u0026ndash;human moderate injuries\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eD\u0026ndash;human minor injuries\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEPA's Incident Data System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003enAChR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enicotinic acetylcholine receptor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNeonics\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eneonicotinoid pesticides\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNIOSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eU.S. National Institute for Occupational Safety and Health\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNPIC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Pesticide Information Centers\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e10\u0026ndash;respirator with a protection factor of 10\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePISP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCalifornia Pesticide Illness Surveillance Program\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePPE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePersonal Protective Equipment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSENSOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSentinel Event Notification System for Occupational Risk\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u0026ndash; N/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u003c/strong\u003e\u0026ndash; N/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials \u003c/strong\u003e- The datasets analyzed for this study can be found in the NRDC repository at the following link https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e - The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e -\u0026nbsp;Natural Resources Defense Council (NRDC) general funds.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e-\u0026nbsp;JBS conducted all data analyses. JBS and DR both conducted literature reviews and developed policy recommendations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e \u0026ndash; We thank the reviewers of this article for suggestions to improve it. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Tomizawa, M. \u0026amp; Casida, J. E. 2005. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu. Rev. Pharmacol. Toxicol., 45, 247\u0026ndash;268. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1146/annurev.pharmtox.45.120403.095930\u003c/span\u003e\u003cspan address=\"10.1146/annurev.pharmtox.45.120403.095930\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Bayer CropScience. 2016. The bee safety of neonicotinoid insecticides. Bayer Bee Care Center. BeeInformed, 3, 1\u0026ndash;16. 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Toxicol., 45, 247\u0026ndash;268. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1146/annurev.pharmtox.45.120403.095930\u003c/span\u003e\u003cspan address=\"10.1146/annurev.pharmtox.45.120403.095930\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Imidacloprid, Thiamethoxam and Clothianidin: Draft Predictions of Likelihood of Jeopardy and Adverse Modification for Federally Listed Endangered and Threatened Species and Designated Critical Habitats. May 1, 2023. 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Neonicotinoid insecticides in surface water, groundwater, and wastewater across land‐use gradients and potential effects. Environmental toxicology and chemistry, 40, 1017\u0026ndash;1033. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/etc.4959\u003c/span\u003e\u003cspan address=\"10.1002/etc.4959\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Seresto Pet Collar Review. U.S. Environmental Protection Agency. Updated July 13, 2023. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epa.gov/pets/seresto-pet-collar-review\u003c/span\u003e\u003cspan address=\"https://www.epa.gov/pets/seresto-pet-collar-review\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e OIG. 2024. The EPA Needs to Determine Whether Seresto Pet Collars Pose an Unreasonable Risk to Pet Health. U.S. Environmental Protection Agency, Office of the Inspector General (EPA OIG). Report No. 24-E-0023. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epaoig.gov/reports/evaluation/epa-needs-determine-whether-seresto-pet-collars-pose-unreasonable-risk-pet\u003c/span\u003e\u003cspan address=\"https://www.epaoig.gov/reports/evaluation/epa-needs-determine-whether-seresto-pet-collars-pose-unreasonable-risk-pet\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. EPA Posts Pesticide Incident Data Publicly. Release on July 27, 2023. U.S. Environmental Protection Agency. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epa.gov/pesticides/epa-posts-pesticide-incident-data-publicly#:~:text=Released%20on%20July%2027%2C%202023,incident%20data%20on%20its%20website\u003c/span\u003e\u003cspan address=\"https://www.epa.gov/pesticides/epa-posts-pesticide-incident-data-publicly#:~:text=Released%20on%20July%2027%2C%202023,incident%20data%20on%20its%20website\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2024. Incident Reporting by Pesticide Manufacturers/ Registrants. U.S. Environmental Protection Agency. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epa.gov/pesticide-incidents/incident-reporting-pesticide-manufacturers-registrants\u003c/span\u003e\u003cspan address=\"https://www.epa.gov/pesticide-incidents/incident-reporting-pesticide-manufacturers-registrants\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2024. Reporting Unintended Exposure and Harm from Pesticides (Incidents). U.S. Environmental Protection Agency. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epa.gov/pesticide-incidents\u003c/span\u003e\u003cspan address=\"https://www.epa.gov/pesticide-incidents\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2015. OPP Report on Incident Information: The Baseline. U.S. Environmental Protection Agency. Office of Pesticide Programs (OPP). Document ID EPA-HQ-OPP-2011-0183-0026. Posted by EPA August 24, 2015. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.regulations.gov/document/EPA-HQ-OPP-2011-0183-0026\u003c/span\u003e\u003cspan address=\"https://www.regulations.gov/document/EPA-HQ-OPP-2011-0183-0026\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2024. About the Incident Data System (IDS), last updated July 24, 2024. \"EPA has limited confidence in the accuracy and validity of the data because the data entries are reports of one individual\u0026rsquo;s perspective of what happened. These perspectives vary widely, which is why EPA evaluates the legitimacy of the reports before using them for regulatory decisions. The public should use caution when analyzing these data as EPA does not guarantee the completeness or adequacy of the contents of the IDS. Any rigorous analysis of these data would be expected to reveal errors in the content of the data sets.\" Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epa.gov/pesticide-incidents/about-incident-data-system-ids\u003c/span\u003e\u003cspan address=\"https://www.epa.gov/pesticide-incidents/about-incident-data-system-ids\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e NIOSH 2024. Worker Health and Safety Surveillance: Pesticide Illness and Injury Surveillance. National Institute for Occupational Safety and Health (NIOSH). Last updated January 17, 2024. Available at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/niosh/surveillance/pesticide/index.html\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/niosh/surveillance/pesticide/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. EPA response to LJ Rhoads, Natural Resources Defense Council (NRDC) Freedom of Information Act request EPA-2023-002283. U.S. Environmental Protection Agency\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports for five pesticide active ingredients for the years 2009 through present, with special priority given to those from 2019 through present, provided in Excel Workbook format. Request Number EPA-2023-002283. Received March 8, 2023. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports for five pesticide active ingredients for the years 2009 through present, with special priority given to those from 2019 through present, provided in Excel Workbook format. Request Number EPA-2023-002283. Received March 8, 2023. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports for five pesticide active ingredients for the years 2009 through present, with special priority given to those from 2019 through present, provided in Excel Workbook format. Request Number EPA-2023-002283. Received March 8, 2023. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports for five pesticide active ingredients for the years 2009 through present, with special priority given to those from 2019 through present, provided in Excel Workbook format. Request Number EPA-2023-002283. Received March 8, 2023. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Report 032589-00001. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Report 031139-00026. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Report# 033477-00006. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Report# 031035-00001. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Report# 034040-00001. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Report# 034921-00001. U.S. Environmental Protection Agency. Pesticide Poisoning Incident Reports. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\u003c/span\u003e\u003cspan address=\"https://docs.google.com/spreadsheets/d/1f0qEXVxZ_V49waD-t54aOKdTS06lfzeh/edit#gid=736068342\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Boedeker, W., Watts, M., Clausing, P. \u0026amp; Marquez, E. 2020. The global distribution of acute unintentional pesticide poisoning: estimations based on a systematic review. BMC public health, 20, 1\u0026ndash;19. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12889-020-09939-0\u003c/span\u003e\u003cspan address=\"10.1186/s12889-020-09939-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Bennett, D., Bellinger, D. C., Birnbaum, L. S., Bradman, A., Chen, A., Cory-Slechta, D. A., et al. (2016). Project TENDR: targeting environmental neuro-developmental risks the TENDR consensus statement. Environ. Health Perspect. 124 (7), A118\u0026ndash;A122. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1289/EHP358\u003c/span\u003e\u003cspan address=\"10.1289/EHP358\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Carmichael, S. L., Yang, W., Roberts, E., Kegley, S. E., Padula, A. M., English, P. B., Lammer, E. J. \u0026amp; Shaw, G. M. 2014. Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California. Environmental research, 135, 133\u0026ndash;138. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.envres.2014.08.030\u003c/span\u003e\u003cspan address=\"10.1016/j.envres.2014.08.030\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Yang, W., Carmichael, S. L., Roberts, E. M., Kegley, S. E., Padula, A. M., English, P. B. \u0026amp; Shaw, G. M. 2014. Residential agricultural pesticide exposures and risk of neural tube defects and orofacial clefts among offspring in the San Joaquin Valley of California. American journal of epidemiology, 179, 740\u0026ndash;748. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/aje/kwt324\u003c/span\u003e\u003cspan address=\"10.1093/aje/kwt324\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Keil AP, Daniels JL, Hertz-Picciotto I. Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Environ Health. 2014 Jan 23;13(1):3. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1476-069X-13-3\u003c/span\u003e\u003cspan address=\"10.1186/1476-069X-13-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 24456651; PMCID: PMC3922790.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Cimino, A. M., Boyles, A. L., Thayer, K. A. \u0026amp; Perry, M. J. 2017. Effects of neonicotinoid pesticide exposure on human health: a systematic review. Environmental health perspectives, 125, 155\u0026ndash;162. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1289/EHP515\u003c/span\u003e\u003cspan address=\"10.1289/EHP515\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e \u003c/li\u003e\u003cli\u003e\u003cspan\u003e Marfo, J. T., Fujioka, K., Ikenaka, Y., Nakayama, S. M., Mizukawa, H., Aoyama, Y., Ishizuka, M. \u0026amp; Taira, K. 2015. Relationship between urinary N-desmethyl-acetamiprid and typical symptoms including neurological findings: a prevalence case-control study. PloS one, 10, e0142172. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0142172\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0142172\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u0026nbsp;\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Cimino, A. M., Boyles, A. L., Thayer, K. A. \u0026amp; Perry, M. J. 2017. Effects of neonicotinoid pesticide exposure on human health: a systematic review. Environmental health perspectives, 125, 155\u0026ndash;162. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1289/EHP515\u003c/span\u003e\u003cspan address=\"10.1289/EHP515\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e \u003c/li\u003e\u003cli\u003e\u003cspan\u003e Ospina, M., Wong, L.-Y., Baker, S. E., Serafim, A. B., Morales-Agudelo, P. \u0026amp; Calafat, A. M. 2019. 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L., Lehmler, H.-J., Meppelink, S. M., Poch, M. C., Vargo, J. D., Soupene, V. A., Irfan, N. M. \u0026amp; Robinson, M. 2023. Prevalence of neonicotinoid insecticides in paired private-well tap water and human urine samples in a region of intense agriculture overlying vulnerable aquifers in eastern Iowa. Chemosphere, 319, 137904. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.chemosphere.2023.137904\u003c/span\u003e\u003cspan address=\"10.1016/j.chemosphere.2023.137904\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2020. Imidacloprid. Proposed Interim Registration Review Decision, Occupational Risks, p. 17. U.S. Environmental Protection Agency. January, 2020. Docket ID EPA-HQ-OPP-2008-0844. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epa.gov/sites/default/files/2020-01/documents/imidacloprid_pid_signed_1.22.2020.pdf\u003c/span\u003e\u003cspan address=\"https://www.epa.gov/sites/default/files/2020-01/documents/imidacloprid_pid_signed_1.22.2020.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e EPA 2023. Pesticide Cancellation Under EPA's Own Initiative. Last updated November 15, 2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.epa.gov/pesticide-tolerances/pesticide-cancellation-under-epas-own-initiative#:~:text=Section%206(b)%20of%20the,changes%20to%20the%20terms%20and\u003c/span\u003e\u003cspan address=\"https://www.epa.gov/pesticide-tolerances/pesticide-cancellation-under-epas-own-initiative#:~:text=Section%206(b)%20of%20the,changes%20to%20the%20terms%20and\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"environmental-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"enhe","sideBox":"Learn more about [Environmental Health](http://ehjournal.biomedcentral.com)","snPcode":"12940","submissionUrl":"https://submission.nature.com/new-submission/12940/3","title":"Environmental Health","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neonicotinoid, neurotoxic, pesticide, poisoning, human, seizure, death","lastPublishedDoi":"10.21203/rs.3.rs-5054262/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5054262/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground - Neonicotinoid pesticides (\u0026lsquo;neonics\u0026rsquo;) \u0026ndash; imidacloprid, thiamethoxam, clothianidin, acetamiprid, dinotefuran - are the most widely used class of insecticides in the world. They have a neurotoxic mechanism of action, similar to nicotine. They are detected in food, waterways, tap water, and breast milk. In addition to environmental pollution, neonics are the pesticides most frequently reported as associated with human poisonings.\u003c/p\u003e \u003cp\u003eMethods - We make use of the non-occupational human pesticide poisoning reports in the U.S. Environmental Protection Agency (EPA) online Incident Data System (IDS). Note that IDS reports are predominantly self-reported information of varying and often low level of detail and are not routinely validated or verified by EPA.\u003c/p\u003e \u003cp\u003eResults - We reviewed 842 non-occupational human poisoning incidents associated with neonics in the IDS from 2018 through 2022. There are four human fatality reports, two associated with clothianidin and two with acetamiprid. Major illnesses such as seizures were reported in several cases, including with dinotefuran cockroach bait product, and an imidacloprid lawn product. Moderate poisonings make up 88% of the total poisonings (740 of 842), with most of those associated with imidacloprid (547 incidents) or dinotefuran (102 incidents). Common reported symptoms classified as moderate often included two or more of the following: headaches; dizziness; lethargy; eye or throat irritation; skin itching and rash; chemical burns and skin peeling; face swelling; muscle weakness or tremors; vomiting; diarrhea; pain and tightness in chest; open sores; and general pain. These incidents stem mainly from residential uses, such as lawn and garden insect repellents, home pest treatments for bed bugs or roaches, and products used to treat pets for fleas and ticks.\u003c/p\u003e \u003cp\u003eConclusion - Given the evidence of neurotoxicity, EPA should use its legal authority to cancel unsafe products and unnecessary uses \u0026ndash; including from seed treatments, and residential pet and lawncare products - to prevent further human suffering.\u003c/p\u003e","manuscriptTitle":"Human poisonings with neonicotinoid pesticides – frequency and severity show public health risks, regulatory failures","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-22 08:44:06","doi":"10.21203/rs.3.rs-5054262/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-30T08:52:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-30T08:23:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-24T10:24:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-18T12:15:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-14T14:39:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"199827992089784561782005948036923929396","date":"2024-09-14T13:19:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256867265955152630891477213302971585467","date":"2024-09-12T06:50:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"231176341728542344245213862463741601829","date":"2024-09-11T22:30:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109037674094383618762410624442134361785","date":"2024-09-11T19:15:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"201213153975532465166178195503973421423","date":"2024-09-10T10:46:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-09T10:12:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-09T07:16:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-09T07:13:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Environmental Health","date":"2024-09-08T22:30:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"environmental-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"enhe","sideBox":"Learn more about [Environmental Health](http://ehjournal.biomedcentral.com)","snPcode":"12940","submissionUrl":"https://submission.nature.com/new-submission/12940/3","title":"Environmental Health","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a0980ff-bc10-4778-8e31-ae45160c7ec3","owner":[],"postedDate":"October 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-25T16:08:14+00:00","versionOfRecord":{"articleIdentity":"rs-5054262","link":"https://doi.org/10.1186/s12940-024-01139-2","journal":{"identity":"environmental-health","isVorOnly":false,"title":"Environmental Health"},"publishedOn":"2024-11-20 15:58:10","publishedOnDateReadable":"November 20th, 2024"},"versionCreatedAt":"2024-10-22 08:44:06","video":"","vorDoi":"10.1186/s12940-024-01139-2","vorDoiUrl":"https://doi.org/10.1186/s12940-024-01139-2","workflowStages":[]},"version":"v1","identity":"rs-5054262","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5054262","identity":"rs-5054262","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}