Non-acute exposure of neonicotinoids, health risk assessment, and evidence integration: a systematic review

Abstract

Neonicotinoid pesticides are utilized against an extensive range of insects. A growing body of evidence supports that these neuro-active insecticides are classified as toxicants in invertebrates. However, there is limited published data regarding their toxicity in vertebrates and mammals. the current systematic review is focused on the up-to-date knowledge available for several neonicotinoid pesticides and their non-acute toxicity on rodents and human physiology. Oral lethal dose 50 (LD₅₀) of seven neonicotinoids (i.e. imidacloprid, acetamiprid, clothianidin, dinotefuran, thiamethoxam, thiacloprid, and nitenpyram) was initially identified. Subsequently, a screening of the literature was conducted to collect information about non-acute exposure to these insecticides. 99 studies were included and assessed for their risk of bias and level of evidence according to the Office of Health and Translation (OHAT) framework. All the 99 included papers indicate evidence of reproductive toxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, immunotoxicity, and oxidative stress induction with a high level of evidence in the health effect of rodents and a moderate level of evidence for human health. The most studied type of these insecticides among 99 papers was imidacloprid (55 papers), followed by acetamiprid (22 papers), clothianidin (21 papers), and thiacloprid (11 papers). While 10 of 99 papers assessed the relationship between clothianidin, thiamethoxam, dinotefuran, and nitenpyram, showing evidence of liver injury, dysfunctions of oxidative stress markers in the reproductive system, and intestinal toxicity. This systematic review provides a comprehensive overview of the potential risks caused by neonicotinoid insecticides to humans and rodents with salient health effects. However, further research is needed to better emphasize and understand the patho-physiological mechanisms of these insecticides, taking into account various factors that can influence their toxicity.

Keywords:

• Neonicotinoids
• sub-lethal toxicity
• animal studies
• humans
• insecticides
• systematic review

Acknowledgments

We would like to thank Pr. Basil Aboul-Enein (Johnson & Wales University, College of Health & Wellness, Department of Health Science, 8 Abbott Park Place Providence, RI 02903 USA. London School of Hygiene & Tropical Medicine, Faculty of Public Health and Policy, 15–17 Tavistock Place, London, WC1H 9SH, United Kingdom) for his guidance during the screening process in Embase. We would like also to thank Dr. Lucy Semerjian (University of Sharjah, college of health sciences, department of environmental health, UAE) and Dr. Khaled Megahed Abass (University of Sharjah, college of health sciences, department of environmental health, UAE) for thoughtful critical reviews of the manuscript. We gratefully acknowledge Dr. Roger O. McClellan and Dr. Jesse Denson Hesch for their time and effort in reviewing this work as well as all the anonymous reviewers who were selected by the Editor for their comprehensive and useful comments which served to highly improve this manuscript.

Author contributions

All authors participated in writing the protocol, designed the search strategy, performed data extraction, and assessed the risk of bias and confidence in the level and body of evidence. IB performed the screening and wrote the first draft of the manuscript. KZ, GA, and KB reviewed the final manuscript and approved it for submission.

Declaration of interest

The authors declare no conflicts of interest. The authors’ affiliations are listed on the cover page. The authors have not participated in or anticipated participation in any legal, regulatory, or advocacy proceedings related to the contents of the paper.

Supplemental Material

Supplemental data for this article can be found on the https://doi.org/10.1080/10408444.2024.2310593.