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Objectives 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. Methods 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. Results 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). Conclusion 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

Growing evidence for global pollinator decline is causing concern for biodiversity conservation and ecosystem services maintenance. Neonicotinoid pesticides have been identified or suspected as a key factor responsible for this decline. We assessed the global exposure of pollinators to neonicotinoids by analyzing 198 honey samples from across the world. We found at least one of five tested compounds (acetamiprid, clothianidin, imidacloprid, thiacloprid, and thiamethoxam) in 75% of all samples, 45% of samples contained two or more of these compounds, and 10% contained four or five. Our results confirm the exposure of bees to neonicotinoids in their food throughout the world. The coexistence of neonicotinoids and other pesticides may increase harm to pollinators. However, the concentrations detected are below the maximum residue level authorized for human consumption (average ± standard error for positive samples: 1.8 ± 0.56 nanograms per gram).

Invertebrate declines are widespread in terrestrial ecosystems, and pesticide use is often cited as a causal factor. Here, we report that aquatic systems are threatened by the high toxicity and persistence of neonicotinoid insecticides. These effects cascade to higher trophic levels by altering food web structure and dynamics, affecting higher-level consumers. Using data on zooplankton, water quality, and annual fishery yields of eel and smelt, we show that neonicotinoid application to watersheds since 1993 coincided with an 83% decrease in average zooplankton biomass in spring, causing the smelt harvest to collapse from 240 to 22 tons in Lake Shinji, Shimane Prefecture, Japan. This disruption likely also occurs elsewhere, as neonicotinoids are currently the most widely used class of insecticides globally.

Neonicotinoid pesticides were first introduced in the mid-1990s, and since then, their use has grown rapidly. They are now the most widely used class of insecticides in the world, with the majority of applications coming from seed dressings. Neonicotinoids are water-soluble, and so can be taken up by a developing plant and can be found inside vascular tissues and foliage, providing protection against herbivorous insects. However, only approximately 5% of the neonicotinoid active ingredient is taken up by crop plants and most instead disperses into the wider environment. Since the mid-2000s, several studies raised concerns that neonicotinoids may be having a negative effect on non-target organisms, in particular on honeybees and bumblebees. In response to these studies, the European Food Safety Authority (EFSA) was commissioned to produce risk assessments for the use of clothianidin, imidacloprid and thiamethoxam and their impact on bees. These risk assessments concluded that the use of these compounds on certain flowering crops poses a high risk to bees. On the basis of these findings, the European Union adopted a partial ban on these substances in May 2013. The purpose of the present paper is to collate and summarise scientific evidence published since 2013 that investigates the impact of neonicotinoids on non-target organisms. Whilst much of the recent work has focused on the impact of neonicotinoids on bees, a growing body of evidence demonstrates that persistent, low levels of neonicotinoids can have negative impacts on a wide range of free-living organisms.

Background Neonicotinoids are a class of systemic insecticides widely used on food crops globally. These pesticides may be found in “off-target” food items and persist in the environment. Despite the potential for extensive human exposure, there are limited studies regarding the prevalence of neonicotinoid residues in foods sold and consumed in the United States. Methods Residue data for seven neonicotinoid pesticides collected between 1999 and 2015 by the US Department of Agriculture’s Pesticide Data Program (PDP) were collated and summarized by year across various food commodities, including fruit, vegetable, meat, dairy, grain, honey, and baby food, as well as water to qualitatively describe and examine trends in contamination frequency and residue concentrations. Results The highest detection frequencies (DFs) for neonicotinoids by year on all commodities were generally below 20%. Average DFs over the entire study period, 1999–2015, for domestic and imported commodities were similar at 4.5%. For all the samples (both domestic and imported) imidacloprid was the neonicotinoid with the highest overall detection frequency at 12.0%. However, higher DFs were observed for specific food commodity-neonicotinoid combinations such as: cherries (45.9%), apples (29.5%), pears (24.1%) and strawberries (21.3%) for acetamiprid; and cauliflower (57.5%), celery (20.9%), cherries (26.3%), cilantro (30.6%), grapes (28.9%), collard greens (24.9%), kale (31.4%), lettuce (45.6%), potatoes (31.2%) and spinach (38.7%) for imidacloprid. Neonicotinoids were also detected in organic commodities, (DF < 6%). Individual commodities with at least 5% of samples testing positive for two or more neonicotinoids included apples, celery, and cherries. Generally, neonicotinoid residues on food commodities did not exceed US Environmental Protection Agency tolerance levels. Increases in detection trends for both finished and untreated water samples for imidacloprid were observed from 2004 to 2011. Conclusions Analysis of PDP data indicates that low levels of neonicotinoids are present in commonly-consumed fruits and vegetables sold in the US. Trends in detection frequencies suggest an increase in use of acetamiprid, clothianidin and thiamethoxam as replacements for imidacloprid. Given these findings, more extensive surveillance of the food and water supply is warranted, as well as biomonitoring studies and assessment of cumulative daily intake in high risk groups, including pregnant women and infants.

The evolution of insect resistance to pesticides poses a continuing threat to agriculture and human health. While much is known about the proximate molecular and biochemical mechanisms that confer resistance, far less is known about the regulation of the specific genes/gene families involved, particularly by trans-acting factors such as signal-regulated transcription factors. Here we resolve in fine detail the trans-regulation of CYP6CM1, a cytochrome P450 that confers resistance to neonicotinoid insecticides in the whitefly Bemisia tabaci, by the mitogen-activated protein kinase (MAPK)-directed activation of the transcription factor cAMP-response element binding protein (CREB). Reporter gene assays were used to identify the putative promoter of CYP6CM1, but no consistent polymorphisms were observed in the promoter of a resistant strain of B. tabaci (imidacloprid-resistant, IMR), which overexpresses this gene, compared to a susceptible strain (imidaclopridsusceptible, IMS). Investigation of potential trans-acting factors using in vitro and in vivo assays demonstrated that the bZIP transcription factor CREB directly regulates CYP6CM1 expression by binding to a cAMP-response element (CRE)-like site in the promoter of this gene. CREB is overexpressed in the IMR strain, and inhibitor, luciferase, and RNA interference assays revealed that a signaling pathway of MAPKs mediates the activation of CREB, and thus the increased expression of CYP6CM1, by phosphorylation-mediated signal transduction. Collectively, these results provide mechanistic insights into the regulation of xenobiotic responses in insects and implicate both the MAPK-signaling pathway and a transcription factor in the development of pesticide resistance.

In this paper, we review the effects of large-scale neonicotinoid contaminations in the aquatic environment on non-target aquatic invertebrate and vertebrate species. These aquatic species are the fauna widely exposed to environmental changes and chemical accumulation in bodies of water. Neonicotinoids are insecticides that target the nicotinic type acetylcholine receptors (nAChRs) in the central nervous systems (CNS) and are considered selective neurotoxins for insects. However, studies on their physiologic impacts and interactions with non-target species are limited. In researches dedicated to exploring physiologic and toxic outcomes of neonicotinoids, studies relating to the effects on vertebrate species represent a minority case compared to invertebrate species. For aquatic species, the known effects of neonicotinoids are described in the level of organismal, behavioral, genetic and physiologic toxicities. Toxicological studies were reported based on the environment of bodies of water, temperature, salinity and several other factors. There exists a knowledge gap on the relationship between toxicity outcomes to regulatory risk valuation. It has been a general observation among studies that neonicotinoid insecticides demonstrate significant toxicity to an extensive variety of invertebrates. Comprehensive analysis of data points to a generalization that field-realistic and laboratory exposures could result in different or non-comparable results in some cases. Aquatic invertebrates perform important roles in balancing a healthy ecosystem, thus rapid screening strategies are necessary to verify physiologic and toxicological impacts. So far, much of the studies describing field tests on non-target species are inadequate and in many cases, obsolete. Considering the current literature, this review addresses important information gaps relating to the impacts of neonicotinoids on the environment and spring forward policies, avoiding adverse biological and ecological effects on a range of non-target aquatic species which might further impair the whole of the aquatic ecological web.

There is an ongoing unprecedented loss in insects, both in terms of richness and biomass. The usage of pesticides, especially neonicotinoid insecticides, has been widely suggested to be a contributor to this decline. However, the risks of neonicotinoids to natural insect populations have remained largely unknown due to a lack of field-realistic experiments. Here, we used an outdoor experiment to determine effects of field-realistic concentrations of the commonly applied neonicotinoid thiacloprid on the emergence of naturally assembled aquatic insect populations. Following application, all major orders of emerging aquatic insects (Coleoptera, Diptera, Ephemeroptera, Odonata, and Trichoptera) declined strongly in both abundance and biomass. At the highest concentration (10 μg/L), emergence of most orders was nearly absent. Diversity of the most species-rich family, Chironomidae, decreased by 50% at more commonly observed concentrations (1 μg/L) and was generally reduced to a single species at the highest concentration. Our experimental findings thereby showcase a causal link of neonicotinoids and the ongoing insect decline. Given the urgency of the insect decline, our results highlight the need to reconsider the mass usage of neonicotinoids to preserve freshwater insects as well as the life and services depending on them.

Bumblebees are essential pollinators of crops and wild plants, but are in decline across the globe. Neonicotinoid pesticides have been implicated as a potential driver of these declines, but most of our evidence base comes from studies of a single species. There is an urgent need to understand whether such results can be generalized across a range of species. Here, we present results of a laboratory experiment testing the impacts of field-relevant doses (1.87–5.32 ppb) of the neonicotinoid thiamethoxam on spring-caught wild queens of four bumblebee species: Bombus terrestris, B. lucorum, B. pratorum and B. pascuorum. Two weeks of exposure to the higher concentration of thiamethoxam caused a reduction in feeding in two out of four species, suggesting species-specific anti-feedant, repellency or toxicity effects. The higher level of thiamethoxam exposure resulted in a reduction in the average length of terminal oocytes in queens of all four species. In addition to providing the first evidence for general effects of neonicotinoids on ovary development in multiple species of wild bumblebee queens, the discovery of species-specific effects on feeding has significant implications for current practices and policy for pesticide risk assessment and use.