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Bibliography Tag: neonicotinoids

Kasiotis and Machera, 2015

Kasiotis, K. M., & Machera, K.; “Neonicotinoids and their Metabolites in Human Biomonitoring: A Review;” Hellenic Plant Protection Journal, 2015, 8(2), 33-45; DOI: 10.1515/hppj-2015-0006.


Neonicotinoids (NNDs) constitute a major class of insecticides with a broad and versatile spectrum of applications in agriculture. Hence, their residues are found in several environmental compartments and can be transferred via several pathways to numerous organisms. Despite their profound impact on honeybees and wild bees (impairment of memory, impact on immune system), their presence in humans is far less reported, possibly due to the low to moderate toxicological eff ects that they elicit. The aim of the present review is to emphasize on developments in the biomonitoring of NNDs. It focuses mainly on chromatographic analysis of NNDs and their metabolites in human biological fl uids, discussing key features, such as sample preparation and analytical method validation. Nonetheless, case reports regarding intoxication incidents are presented, highlighting the signifi cance of such cases especially in the developing world. FULL TEXT

Han et al., 2018

Han, Wenchao, Tian, Ying, & Shen, Xiaoming; “Human exposure to neonicotinoid insecticides and the evaluation of their potential toxicity: An overview;” Chemosphere, 2018, 192, 59-65; DOI: 10.1016/j.chemosphere.2017.10.149.


Neonicotinoid insecticides have become the fastest growing class of insecticides over the past few decades. The insecticidal activity of neonicotinoids is attributed to their agonist action on nicotinic acetylcholine receptors (nAChRs). Because of the special selective action on nAChRs in central nervous system of insects, and versatility in application methods, neonicotinoids are used to protect crops and pets from insect attacks globally. Although neonicotinoids are considered low toxicity to mammals and humans in comparison with traditional insecticides, more and more studies show exposure to neonicotinoids pose potential risk to mammals and even humans. In recent years, neonicotinoids and their metabolites have been successfully detected in various human biological samples. Meanwhile, many studies have focused on the health effects of neonicotinoids on humans. Our aims here are to review studies on human neonicotinoid exposure levels, health effect, evaluation of potential toxicity and to suggest possible directions for future research.


Ichikawa et al., 2019

Ichikawa, G., Kuribayashi, R., Ikenaka, Y., Ichise, T., Nakayama, S. M. M., Ishizuka, M., Taira, K., Fujioka, K., Sairenchi, T., Kobashi, G., Bonmatin, J. M., & Yoshihara, S.; “LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth;” Plos One, 2019, 14(7), e0219208; DOI: 10.1371/journal.pone.0219208.



Neonicotinoid insecticides are widely used systemic pesticides with nicotinic acetylcholine receptor agonist activity that are a concern as environmental pollutants. Neonicotinoids in humans and the environment have been widely reported, but few studies have examined their presence in fetuses and newborns. The objective of this study is to determine exposure to neonicotinoids and metabolites in very low birth weight (VLBW) infants.


An analytical method for seven neonicotinoids and one neonicotinoid metabolite, N-desmethylacetamiprid (DMAP), in human urine using LC-ESI/MS/MS was developed. This method was used for analysis of 57 urine samples collected within 48 hours after birth from VLBW infants of gestational age 23-34 weeks (male/female = 36/21, small for gestational age (SGA)/appropriate gestational age (AGA) = 6/51) who were admitted to the neonatal intensive care unit of Dokkyo Hospital from January 2009 to December 2010. Sixty-five samples collected on postnatal day 14 (M/F = 37/22, SGA/AGA = 7/52) were also analyzed.


DMAP, a metabolite of acetamiprid, was detected in 14 urine samples collected at birth (24.6%, median level 0.048 ppb) and in 7 samples collected on postnatal day 14 (11.9%, median level 0.09 ppb). The urinary DMAP detection rate and level were higher in SGA than in AGA infants (both p<0.05). There were no correlations between the DMAP level and infant physique indexes (length, height, and head circumference SD scores).


These results provide the first evidence worldwide of neonicotinoid exposure in newborn babies in the early phase after birth. The findings suggest a need to examine potential neurodevelopmental toxicity of neonicotinoids and metabolites in human fetuses.


Crall et al., 2018

Crall, James D, Switzer, Callin M, Oppenheimer, Robert L, Ford Versypt, Ashlee N, Dey, Biswadip, Brown, Andrea, Eyster, Mackay, Guerin, Claire, Pierce, Naomi E, Combes, Stacey A, & de Bivort, Benjamin L, “Neonicotinoid exposure disrupts bumblebee nest behavior, social networks, and thermoregulation,” Science, 2018, 362(6415), 683-686. DOI: 10.1126/science.aat1598.


Neonicotinoid pesticides can negatively affect bee colonies, but the behavioral mechanisms by which these compounds impair colony growth remain unclear. Here, we investigate imidacloprid’s effects on bumblebee worker behavior within the nest, using an automated, robotic platform for continuous, multicolony monitoring of uniquely identified workers. We find that exposure to field-realistic levels of imidacloprid impairs nursing and alters social and spatial dynamics within nests, but that these effects vary substantially with time of day. In the field, imidacloprid impairs colony thermoregulation, including the construction of an insulating wax canopy. Our results show that neonicotinoids induce widespread disruption of within-nest worker behavior that may contribute to impaired growth, highlighting the potential of automated techniques for characterizing the multifaceted, dynamic impacts of stressors on behavior in bee colonies. FULL TEXT

Klarich et al., 2017

Klarich, Kathryn L., Pflug, Nicholas C., DeWald, Eden M., Hladik, Michelle L., Kolpin, Dana W., Cwiertny, David M., & LeFevre, Gregory H., “Occurrence of Neonicotinoid Insecticides in Finished Drinking Water and Fate during Drinking Water Treatment,” Environmental Science & Technology Letters, 2017, 4(5), 168-173. DOI: 10.1021/acs.estlett.7b00081.


Neonicotinoid insecticides are widespread in surface waters across the agriculturally intensive Midwestern United States. We report for the first time the presence of three neonicotinoids in finished drinking water and demonstrate their general persistence during conventional water treatment. Periodic tap water grab samples were collected at the University of Iowa over 7 weeks in 2016 (May−July) after maize/soy planting. Clothianidin, imidacloprid, and thiamethoxam were ubiquitously detected in finished water samples at concentrations ranging from 0.24 to 57.3 ng/L. Samples collected along the University of Iowa treatment train indicate no apparent removal of clothianidin or imidacloprid, with modest thiamethoxam removal (∼50%). In contrast, the concentrations of all neonicotinoids were substantially lower in the Iowa City treatment facility finished water using granular activated carbon (GAC) filtration. Batch experiments investigated potential losses. Thiamethoxam losses are due to base-catalyzed hydrolysis under high-pH conditions during lime softening. GAC rapidly and nearly completely removed all three neonicotinoids. Clothianidin is susceptible to reaction with free chlorine and may undergo at least partial transformation during chlorination. Our work provides new insights into the persistence of neonicotinoids and their potential for transformation during water treatment and distribution, while also identifying GAC as a potentially effective management tool for decreasing neonicotinoid concentrations in finished drinking water.

Klarich Wong et al., 2019

Klarich Wong, Kathryn L., Webb, Danielle T., Nagorzanski, Matthew R., Kolpin, Dana W., Hladik, Michelle L., Cwiertny, David M., & LeFevre, Gregory H., “Chlorinated Byproducts of Neonicotinoids and Their Metabolites: An Unrecognized Human Exposure Potential?,” Environmental Science & Technology Letters, 2019, 6(2), 98-105. DOI:10.1021/acs.estlett.8b00706.


We recently reported the initial discovery of neonicotinoid pesticides in drinking water and their potential for transformation through chlorination and alkaline hydrolysis during water treatment. The objectives of this research were: (1) to determine if neonicotinoid metabolites are relevant to drinking water exposure and (2) to identify the products formed from chlorination of neonicotinoids and their metabolites. Desnitro-imidacloprid and imidacloprid-urea, two known metabolites of imidacloprid, are documented for the first time in drinking water. Desnitro-imidacloprid was present above the lower level of detection (0.03 ng/L) in 67% of samples (six of nine) from drinking water systems but detectable in all samples (up to 0.6 ng/L). Although concentrations of desnitro-imidacloprid were lower than concentrations of the parent neonicotinoids, desnitro-imidacloprid exhibits significantly greater mammalian toxicity than imidacloprid. Using LC-HR-ToF-MS/MS analysis of results from laboratory experiments, we propose structures for novel transformation products resulting from the chlorination of clothianidin, imidacloprid, desnitro-imidacloprid, imidacloprid-urea, and hydrolysis products of thiamethoxam. Formation of chlorinated neonicotinoid byproducts occurs at time scales relevant to water treatment and/or distribution for the imidacloprid metabolites (t1/2 values from 2.4 min to 1.0 h) and thiamethoxam hydrolysis products (4.8 h). Neonicotinoid metabolites in finished drinking water and potential formation of novel disinfection byproducts during treatment and/or distribution are relevant to evaluating the exposure and potential impacts of neonicotinoids on human health.

Simon-Delso et al., 2015

N. Simon-Delso,corresponding author V. Amaral-Rogers, L. P. Belzunces, J. M. Bonmatin, M. Chagnon, C. Downs, L. Furlan, D. W. Gibbons, C. Giorio, V. Girolami, D. Goulson, D. P. Kreutzweiser, C. H. Krupke, M. Liess, E. Long, M. McField, P. Mineau, E. A. D. Mitchell, C. A. Morrissey, D. A. Noome, L. Pisa, J. Settele, J. D. Stark, A. Tapparo, H. Van Dyck, J. Van Praagh, J. P. Van der Sluijs, P. R. Whitehorn, and M. Wiemers, “Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites,” Environmental Science and Pollution Research International, 2015; 22, DOI: 10.1007/s11356-014-3470-y


Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time—depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts. FULL TEXT

Cimino et al., 2017

Andria M. Cimino, Abee L. Boyles, Kristina A. Thayer, and Melissa J. Perry, “Effects of Neonicotinoid Pesticide Exposure on Human Health: A Systematic Review,” Environmental Health Perspectives, 2017, 125:2, DOI: 10.1289/EHP515.


BACKGROUND: Numerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species, including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure.

OBJECTIVE: In this systematic review, we sought to identify human population studies on the health effects of neonics.

METHODS: Studies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the National Toxicology Program’s Office of Health Assessment and Translation.

RESULTS: Eight studies investigating the human health effects of exposure to neonics were identified. Four examined acute exposure: Three neonic poisoning studies reported two fatalities (n = 1,280 cases) and an occupational exposure study of 19 forestry workers reported no adverse effects. Four general population studies reported associations between chronic neonic exposure and adverse developmental or neurological outcomes, including tetralogy of Fallot (AOR 2.4, 95% CI: 1.1, 5.4), anencephaly (AOR 2.9, 95% CI: 1.0, 8.2), autism spectrum disorder [AOR 1.3, 95% credible interval (CrI): 0.78, 2.2], and a symptom cluster including memory loss and finger tremor (OR 14, 95% CI: 3.5, 57). Reported odds ratios were based on exposed compared to unexposed groups.

CONCLUSIONS: The studies conducted to date were limited in number with suggestive but methodologically weak findings related to chronic exposure. Given the wide-scale use of neonics, more studies are needed to fully understand their effects on human health.  FULL TEXT

Carmichael et al., 2016

Carmichael SL, Yang W, Roberts E, Kegley SE, Brown TJ, English PB, Lammer EJ, Shaw GM, “Residential agricultural pesticide exposures and risks of selected birth defects among offspring in the San Joaquin Valley of California,” Birth Defects Research Part A: Clinical and Molecular Teratology, 2016, 106:1, doi: 10.1002/bdra.23459.


BACKGROUND: We examined associations of birth defects with residential proximity to commercial agricultural pesticide applications in California. Subjects included 367 cases representing five types of birth defects and 785 nonmalformed controls born 1997 to 2006.

METHODS:Associations with any versus no exposure to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for covariates. Overall, 46% of cases and 38% of controls were classified as exposed to pesticides within a 500 m radius of mother’s address during a 3-month periconceptional window.

RESULTS:We estimated odds ratios (ORs) for 85 groups and 95 chemicals with five or more exposed cases and control mothers. Ninety-five percent confidence intervals (CI) excluded 1.0 for 11 ORs for groups and 22 ORs for chemicals, ranging from 1.9 to 3.1 for groups and 1.8 to 4.9 for chemicals except for two that were <1 (noted below).

CONCLUSION:For groups, these ORs were for anotia/microtia (n = 95 cases) and dichlorophenoxy acids/esters and neonicotinoids; anorectal atresia/stenosis (n = 77) and alcohol/ethers and organophosphates (these ORs were < 1.0); transverse limb deficiencies (n = 59) and dichlorophenoxy acids/esters, petroleum derivatives, and triazines; and craniosynostosis (n = 79) and alcohol/ethers, avermectins, neonicotinoids, and organophosphates. For chemicals, ORs were: anotia/microtia and five pesticides from the groups dichlorophenoxy acids/esters, copper-containing compounds, neonicotinoids, organophosphates, and triazines; transverse limb deficiency and six pesticides – oxyfluorfen and pesticides from the groups copper-containing compounds, 2,6-dinitroanilines, neonicotinoids, petroleum derivatives and polyalkyloxy compounds; craniosynostosis and 10 pesticides – oxyfluorfen and pesticides from the groups alcohol/ethers, avermectins, n-methyl-carbamates, neonicotinoids, ogranophosphates (two chemicals), polyalkyloxy compounds (two chemicals), and pyrethroids; and congenital diaphragmatic hernia (n = 62) and a copper-containing compound.  FULL TEXT

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