Pyrethroids are a class of widely used insecticides. Our recent epidemiological study of Chinese women reported that pyrethroid exposure was positively associated with the risk of primary ovarian insufficiency (POI). In this study, we utilized cypermethrin (CP), the most frequently detected pyrethroid in the environment, to recognize how lifelong and low-dose exposure to pyrethroids affects ovarian functions and the underlying mechanism(s). Female mice were exposed to CP at doses of human dietary intake of 6.7 μg/kg/day, an acceptable daily intake (ADI) of 20 μg/kg/day, or the chronic reference dose (RfD) of 60 μg/kg/day, starting from gestational day 0.5 until 44-week-old. We assessed effects on fertility, serum hormone levels, ovarian follicular development and ovarian transcriptomic profiles. Chronic exposure to CP at doses of ADI and RfD caused a significant reduction in the size of the primordial follicle pool on postnatal day (PND) 5 and the number of all types of follicles in 44-week-old mice, lower estrogen and higher gonadotropin levels, as well as decreased fertility. Significant increase in apoptosis and decrease in cell proliferation were observed in CP-exposed ovarian follicles from PND 5 and 44-week-old mice. Ovarian transcriptomic data showed that the pro-apoptotic protein BMF and the cell cycle inhibitor p27 were significantly up-regulated in CP-exposed ovaries. Cyp17a1, Cyp19a1 and Hsd17b1 genes involved in the key steps of steroidogenesis were down-regulated in the ovaries of female mice exposed to CP. This study first reported that lifelong exposure to CP at doses of ADI or RfD caused an ovarian phenotype similar to human POI in female mice and provided a mechanistic explanation. Our findings suggest that lifelong exposure to pyrethroids of low doses, which are recommended as ‘safe’ dosages, may have a significant impact on the ovarian health of female mammals and humans.

The scale of variation in species sensitivity to toxicants has been theoretically linked to mode of action. Specifically, it has been proposed there will be greater variations for chemicals with a putative specific biological target than for toxicants with a non-specific narcotic mechanism. Here we test the hypothesis that mode of action is related to variation in sensitivity in a specifically designed experiment for species from a single ecologically important terrestrial taxa, namely earthworms. Earthworm toxicity tests were conducted with five species for four chemicals, providing a series of increasingly complex modes of action: a putative narcotic polycyclic aromatic hydrocarbon (fluoranthene), and three insecticides (chlorpyrifos, cypermethrin, imidacloprid) with known neuronal receptor targets. Across all the chemicals, the standard epigeic test species Eisenia fetida and Lumbricus rubellus, were generally among the two least sensitive, while the endogenic Aporrectodea caliginosa and Megascolecidae Amynthas gracilis were generally more sensitive (never being among the two least sensitive species). This indicates a potential for bias in the earthworm ecotoxicology literature, which is dominated by studies in epigeic Lumbricidae, but contains few endogeic or Megascolecidae data. Results confirmed the lowest range of variation in sensitivities for effects on reproduction was for fluoranthene (2.5 fold). All insecticides showed greater variation for species sensitivity (cypermethrin: 7.5 fold, chlorpyrifos: 10.3 fold, imidacloprid: 31.5 fold) consistent with the specific mechanisms of the pesticides. Difference in toxicodynamics, based on mode of action specificity and receptor complexity was reflected in the magnitude of sensitivity variation. However, measurements of tissue concentrations also indicated the potential importance of toxicokinetics in explaining species sensitivity variations for chlorpyrifos and cypermethrin.

Novel stressors introduced by human activities increasingly threaten freshwater ecosystems. The annual application of more than 2.3 billion kg of pesticide active ingredient and 22 billion kg of road salt has led to the contamination of temperate waterways. While pesticides and road salt are known to cause direct and indirect effects in aquatic communities, their possible interactive effects remain widely unknown. Using outdoor mesocosms, we created wetland communities consisting of zooplankton, phytoplankton, periphyton, and leopard frog (Rana pipiens) tadpoles. We evaluated the toxic effects of six broad-spectrum insecticides from three families (neonicotinoids: thiamethoxam, imidacloprid; organophosphates: chlorpyrifos, malathion; pyrethroids: cypermethrin, permethrin), as well as the potentially interactive effects of four of these insecticides with three concentrations of road salt (NaCl; 44, 160, 1600 Cl⁻ mg/L). Organophosphate exposure decreased zooplankton abundance, elevated phytoplankton biomass, and reduced tadpole mass whereas exposure to neonicotinoids and pyrethroids decreased zooplankton abundance but had no significant effect on phytoplankton abundance or tadpole mass. While organophosphates decreased zooplankton abundance at all salt concentrations, effects on phytoplankton abundance and tadpole mass were dependent upon salt concentration. In contrast, while pyrethroids had no effects in the absence of salt, they decreased zooplankton and phytoplankton density under increased salt concentrations. Our results highlight the importance of multiple-stressor research under natural conditions. As human activities continue to imperil freshwater systems, it is vital to move beyond single-stressor experiments that exclude potentially interactive effects of chemical contaminants.

The aquatic ecosystem is seriously damaged because of the heavy use of pesticides and antibiotics. Fish is the indispensable link between environmental pollution and human health. However, the toxic effects of environment-related concentrations of pesticides and antibiotics in fish have not been thoroughly studied. In this study, grass carps exposed to cypermethrin (CMN, 0.651 μg/L) or/and sulfamethoxazole (SMZ, 0.3 μg/L) for 42 days caused oxidative stress, apoptosis and immunodeficiency in the spleen of grass carps. CMN or/and SMZ exposure led to oxidative damage (consumption of antioxidant enzymes (superoxide dismutase and catalase)) and lipid peroxidation (accumulation of malondialdehyde), induced apoptosis (increases in TUNEL index, Bax/bcl-2, p53, puma and Caspase family expression). In addition, the levels of immunoglobulin M (IgM), complement 3 (C3) were significantly decreased in all treatment groups, which trend was also found in C-reactive protein in CMN and MIX group, and lysozyme in MIX group. Transcription of almost all genes involved in the Toll-like receptors (TLR) signaling pathway was up-regulated under CMN or/and SMZ exposure. However, when subsequently attacked by Aeromonas hydrophila for 2 days, the TLR pathway was inhibited in spleens of all treatment groups accompanied by higher mortality. Overall, the environmentally relevant concentration of CMN and SMZ damages the immune system, triggering oxidative stress and apoptosis in carps. And by affecting the conduction of TLR signaling pathway, CMN or/and SMZ exposure inhibits the innate immune response of fish and reducing their disease resistance. This study highlights the importance of rational and regulated use of these pesticides and antibiotics.

The worldwide use of pesticides has led to increases in agricultural yields by reducing crop losses. However, increased pesticide use has resulted in pesticide-resistant pest species and recent studies have discovered pesticide-resistance in non-target species living close to farms. Such increased tolerance not only affects the species, but can alter the entire food web. Given that some species can evolve not only resistance to a single pesticide, but also cross-resistance to other pesticides that share the same mode of action, one would predict that cross-resistance to pesticides would also have effects on the entire community and affect community stability. To address this hypothesis, we conducted an outdoor mesocosm experiment comprised of 200 identical aquatic communities with phytoplankton, periphyton, and leopard frog (Lithobates pipiens) tadpoles. To these communities, we added one of four Daphnia pulex populations that we previously discovered were either resistant or sensitive to the insecticide of chlorpyrifos as a result of living close to or far from agriculture, respectively. We then exposed the communities to either no insecticide or three different concentrations of AChE-inhibiting insecticides (chlorpyrifos, malathion or carbaryl) or sodium channel-inhibiting insecticides (permethrin or cypermethrin). We discovered that communities containing sensitive Daphnia pulex experienced phytoplankton blooms and subsequent cascades through all trophic groups including amphibians at moderate to high concentrations of all five insecticides. However, communities containing resistant D. pulex were buffered from these effects at low to moderate concentrations of all AChE-inhibiting insecticides, but were not buffered against the pyrethroid insecticides. These data suggest that a simple change in the population-level resistance of zooplankton to a single insecticide can have widespread consequences for community stability and that the effects can be extrapolated to a wide variety of pesticides that share the same mode of action.

The dynamic flux of an organophosphate and four pyrethroid pesticides was determined in an air-(soil)-water-sediment system based on monitoring data from Guangzhou, China. The total air–water flux, including air–water gaseous exchange and atmospheric deposition, showed deposition from air to water for chlorpyrifos, bifenthrin and cypermethrin, but volatilization for lambda-cyhalothrin and permethrin. The transport of the pesticides from overlying water to sediment suggested that sediment acted as a sink for the pesticides. Additionally, distinct annual atmospheric depositional fluxes between legacy and current-use pesticides suggested the role of consumer usage in their transport throughout the system. Finally, pesticide toxicity was estimated from annual air–water-sediment flux within an urban stream in Guangzhou. A dynamic flux-based risk assessment indicated that inter-compartmental transport of chlorpyrifos decreased its atmospheric exposure, but had little influence on its aquatic toxicity. Instead, water-to-sediment transport of pyrethroids increased their sediment toxicity, which was supported by previously reported toxicity data.

Current-use insecticides including organophosphate (OPs) and synthetic pyrethroid (SPs) insecticides were analyzed in 35 sediment samples collected from Chaohu Lake in China, where a transition from a traditional agricultural to a modern urbanized society is ongoing. Total concentrations of five OPs and eight SPs ranged from 0.029 to 0.681 ng/g dry weight and 0.016–301 ng/g dry weight, respectively. Toxic unit analysis showed that 13% of the sediment samples likely produced over 50% of the mortality for benthic invertebrates. Analysis also showed that cypermethrin was the principal contributor to the toxicity. Spatial distribution evaluation implied that OPs were mainly from non-point sources associated with agricultural activities. Conversely, SPs may have been derived from runoff of inflowing rivers through urban regions, as their concentrations were well-correlated with concentrations of other urban-oriented contaminants.

Soils and agricultural products from the Red River basin in Northern Vietnam were reported to be contaminated by agrichemicals. To assess potential exposure of local farmers and consumers to these contaminants, pesticide use and management practices of local farmers were surveyed and residue concentrations were determined for recently used as well as for banned pesticides in water, soil, vegetables, and fish samples in two communes of Northern Vietnam. DDTs, HCHs, and Drin compounds still persist at relatively high concentrations in soil and occur in vegetable and fish samples. Recently used pesticides, such as fenobucarb, trichlorfon, cyfluthrin, and cypermethrin were detected in vegetable and fish samples. Thresholds for acceptable daily intake levels (ADI) were frequently reached in the analyzed food products pointing to the fact that current pesticide management practices do not only result in a pollution of the environment but also pose threats to human health.

The imprudent agricultural practices are leading to an increasing load of pesticides in agricultural fields. Thus, there is a need to minimize the harmful effect of pesticides by adopting sustainable strategies. In the recent past decade, kinetin, a plant synthetic hormone, has been reported as a pesticide toxicity alleviator in higher plants. But its role in mitigating pesticide toxicity in cyanobacteria is still limited. Thus, in current study an attempt has been made to investigate the potential of kinetin in regulating cypermethrin, an insecticide, induced toxicity in Anabaena PCC 7120 and Nostoc muscorum ATCC 27893. Cypermethrin (Cyp₁; 2 μg ml⁻¹ and Cyp₂; 4 μg ml⁻¹) showed negative impact on growth, photosynthetic pigments, photosynthetic O₂-evolution and primary photochemistry of PS II (Phi_P₀, Psi_₀, Phi_E₀) resulting in decrease in performance index (PIABS). However, under similar conditions, increases in energy flux parameters (ABS/RC, TR₀/RC, ET₀/RC and DI₀/RC) were noticed. Cypermethrin at both the doses enhanced the level of oxidative stress biomarkers (SOR, H₂O₂, and MDA equivalent contents) despite of increased antioxidant enzymatic activity (SOD, POD, CAT and GST).Under similar condition, cypermethrin at tested doses caused substantial decrease in non-enzymatic antioxidant contents (proline, cysteine and NP-SH). Nevertheless, kinetin treatment attenuated cypermethrin induced oxidative stress by further up-regulating the activity of enzymatic antioxidants and by enhancing the contents of non-enzymatic antioxidants. Thus, with the application of kinetin improved photochemistry of PS II and growth yield of both the cyanobacteria were observed even in the presence of cypermethrin. Current results establish that cypermethrin induces toxicity on photosynthesis, photosynthetic pigments and growth, and this effect was more pronounced in Anabaena PCC 7120 than Nostoc muscorum ATCC 27893. Furthermore, the potential role of kinetin in mitigating the toxicity of cypermethrin in both the cyanobacteria provides an insight to be used in paddy fields for sustainable agricultural practices.

Cypermethrin is a frequently used insecticide in agriculture and households but its chronic and molecular effects are poorly known are . Here we describe effects of sublethal cypermethrin exposure on the global transcriptome in the brain of honey bees determined by RNA-sequencing. Exposure for 48 h to 0.3 ng/bee cypermethrin (3 ng/mL sucrose solution) causes 38 differentially expressed genes (DEGs), of which 29 are up-regulated and 9 down-regulated. Exposure to 3 ng/bee causes differential expression of 265 DEGs (209 up-, 56 down-regulated). Among the 24 DEGs shared by both concentrations are genes encoding muscular structure, muscular processes and esterase B1. Functional analysis (GO term analysis) confirms the enrichment of muscular development, structure and function among the 89 and 35 significantly altered GO terms at the low and high concentration, respectively. Up-regulation of nine DEGs determined by RT-qPCR showed a good correlation with RNA-sequence data. Among them are genes including esterase B1, titin, twitchin, mucin-19, insulin like growth factor binding protein, golgin like protein and helix loop protein. Our study demonstrates for the first time molecular effects of cypermethrin at environmental concentrations, which include expressional induction of genes encoding muscular and cellular processes and metabolism enzymes. Further studies should demonstrate the physiological consequences in bees.