Neonicotinoid pesticides are commonly used in the United States to control insects on domestic animals and as seed coatings on agricultural crops, such as corn and soybeans. In areas of widespread use, neonicotinoids have been observed in surface waters, produce, and prepared foods. Because these pesticides are neurotoxic to insects through insect nicotinic acetylcholine receptors (nAChRs), concerns have been raised as to whether neonicotinoids may bind to receptors in off-target species, including humans, and result in adverse health effects. The associations between exposures to neonicotinoid pesticides and potential human health effects were nominated by private individuals to the National Toxicology Program (NTP) as a potential candidate for systematic review in 2014. NTP later learned that the U.S. EPA Office of Pesticide Programs (OPP) was also evaluating currently registered neonicotinoid pesticides as part of registration review activities. Thus, NTP consulted with EPA and solicited public comments during problem formulation activities to maximize the utility of this report.
The objective of the scoping activities was to identify and summarize scientific literature indexed in PubMed reporting exposure to one or more neonicotinoid pesticides registered for use in the United States and any reported outcome relevant to human health effects.
A scoping review was conducted following the Office of Health Assessment and Translation (OHAT) method for systematic review through an abbreviated data extraction step. A comprehensive search strategy was used to retrieve original research records from PubMed that contained reports of exposure to any of seven neonicotinoid pesticides (acetamiprid, clothianidin, imidacloprid, nitenpyram, thiacloprid, thiamethoxam, and dinotefuran) and all reported outcomes relevant to human health effects, including epidemiological, experimental animal, and in vitro model systems. Records were screened at the title-and-abstract level for relevance according to pre-specified inclusion/exclusion criteria. Included records were then screened at the full-text level to verify relevance and manually categorize studies by exposure, outcome, study type, species, and cell type, where appropriate.
A total of 191 studies were included as relevant to human health effects associated with exposure to neonicotinoid pesticides, including six epidemiological studies; 19 human case reports; and 113 experimental animal studies that included rodents, fish, Caenorhabditis elegans, and Drosophila. An interactive evidence map was prepared to allow exploration of the literature by pesticide, broad health effect categories, and evidence stream (e.g., human, animal, or in vitro). Most of the research focused on imidacloprid (n = 127 records). The most commonly reported outcome category across all evidence streams was neurological effects (n = 86), whereas congenital and developmental effects were investigated in four of the six epidemiological studies. For these health categories with the most records, the study designs including measured endpoints were captured to assess the consistency of measures for potential human health hazard evaluation.
In this scoping review, NTP compiled publicly available scientific literature on neonicotinoid exposure and health effects and summarized the state of the science and limitations of the evidence base of these data to support further health hazard and risk assessments. Various health effects have been reported in these data to be associated with exposure to neonicotinoids. However, a limited body of evidence was identified for use in health hazard assessment, primarily due to the heterogeneity of investigated health outcomes and measured endpoints. This scoping review by design summarizes publicly available scientific literature indexed in PubMed only and does not include any proprietary studies available to EPA, which likely contain relevant toxicological data that would complement these data and allow for more comprehensive health hazard assessment.
Boyd WA, Boyles AL, Blain RB, Skuce CR, Engstrom AK, Walker VR, Thayer KA, Rooney AA. 2020. NTP research report on the scoping review of potential human health effects associated with exposures to neonicotinoid pesticides. Research Triangle Park, NC: National Toxicology Program. Research Report 15. https://doi.org/10.22427/NTP-RR-15