Nicotinamide deficiency promotes imidacloprid resistance via activation of ROS/CncC signaling pathway-mediated UGT detoxification in Nilaparvata lugens.

Metabolic alternation is a typical characteristic of insecticide resistance in insects. However, mechanisms underlying metabolic alternation and how altered metabolism in turn affects insecticide resistance are largely unknown. Here, we report that nicotinamide levels are decreased in the imidacloprid-resistant strain of Nilaparvata lugens, may due to reduced abundance of the symbiotic bacteria Arsenophonus. Importantly, the low levels of nicotinamide promote imidacloprid resistance via metabolic detoxification alternation, including elevations in UDP-glycosyltransferase enzymatic activity and enhancements in UGT386B2-mediated metabolism capability. Mechanistically, nicotinamide suppresses transcriptional regulatory activities of cap 'n' collar isoform C (CncC) and its partner small muscle aponeurosis fibromatosis isoform K (MafK) by scavenging the reactive oxygen species (ROS) and blocking the DNA binding domain of MafK. In imidacloprid-resistant N. lugens, nicotinamide deficiency re-activates the ROS/CncC signaling pathway to provoke UGT386B2 overexpression, thereby promoting imidacloprid detoxification. Thus, nicotinamide metabolism represents a promising target to counteract imidacloprid resistance in N. lugens.

Fipronil Affects Craniofacial and Heart Development in Zebrafish Embryos (Danio rerio).

Fipronil is a broad-spectrum insecticide that has off-target effects in developing vertebrate embryos. In this study, we investigate treatment of zebrafish embryos with fipronil over the course of 5 days and examine the effects on body length, the cardiovascular system, and craniofacial morphology. We found the insecticide caused shorter body length and a decrease in eye size. By examining specific heart chamber morphology, as well as jaw angle and length, we quantified defects including enlargement of the heart and increases in jaw length and width. Further studies are needed to assess the mechanisms of fipronil's effect on vertebrate development for both environmental and human health concerns.

Comparative evaluation of neonicotinoids and their metabolites-induced oxidative stress in carp primary leukocytes and CLC cells.

Neonicotinoids (NEOs) have been designed to act selectively on insect nicotinic acetylcholine receptors (nAChRs). However, nAChRs are also expressed in vertebrate immune cells, so NEOs may interfere with the immune system in exposed non-target animals. The present study shows that NEOs: imidacloprid and thiacloprid, and their main metabolites: desnitro-imidacloprid and thiacloprid amide, at sub-micromolar concentrations ranging from 2.25 to 20 µM, affect the immune cells of fish. This was found both in primary cultures of leukocytes isolated from the carp head kidney and in the continuous adherent carp monocyte/macrophage cell line. Moreover, the results revealed that the studied pesticides and metabolites generate oxidative stress in carp immune cells and that this is one of the most important mechanisms of neonicotinoid immunotoxicity. Significant increases were observed in the formation of ROS and malondialdehyde (MDA). The antioxidant status alteration was linked with decrease in antioxidant enzyme activity: superoxide dismutase (SOD), catalase (CAT), and non-enzymatic antioxidant glutathione (GSH). Importantly, the metabolites: desnitro-imidacloprid and thiacloprid amide showed significantly higher cytotoxicity towards fish leukocytes than their parent compounds, imidacloprid and thiacloprid, which emphasizes the importance of including intermediate metabolites in toxicology studies.

Comparative biotoxicity study for identifying better alternative insecticide especially green nano-emulsion which used as mosquitocides.

This research work was planned to test biosafety of different nanomaterials on the different animals models. These nanoparticles were previously used as potential insecticides of mosquito larvae. The biosafety of these nanoproducts were evaluated on certain organs of non target animals that associated with mosquito breeding sites in Egypt. Animal organs such as the kidneys of rats, toads, and the fish's spleen were used as models to study the biological toxicity of these nanomaterials. After 30 days of the animals receiving the nanomaterials in their water supply, different cell mediated immune cells were assessed in these tissues. Both TNF-α and BAX immuno-expression were also used as immunohistochemical markers. Histopathology was conducted to detect the effect of the tested nanoproducts at the tissue level of the liver and kidneys of both the rats and toads. Green nanoemulsion of the lavender essential oil was relatively more effective, safe, and biodegradable to be used as insecticides against mosquito larvae than the metal-based nanomaterials.

Seeds of nonhost species as sources of toxic compounds for the cowpea weevil Callosobruchus maculatus (F.).

Cowpea weevil, Callosobruchus maculatus, is the primary pest of stored cowpea seeds. The management of this infestation currently relies on insecticides, resulting in environmental pollution and selection of insecticide-resistant pests. Consequently, research efforts are being devoted to identify natural insecticides as sustainable and environment friendly alternatives for the control of C. maculatus. In this study, we explore the toxic effects of the nonhost seeds Parkia multijuga, Copaifera langsdorffii, Ormosia arborea, Amburana cearensis, Lonchocarpus guilleminianus, Sapindus saponaria, and Myroxylon peruiferum, on the cowpea weevil C. maculatus. Notably, all nonhost seeds led to reductions between 60 and 100% in oviposition by C. maculatus females. Additionally, the larvae were unable to penetrate the nonhost seeds. Artificial seeds containing 0.05% to 10% of cotyledon flour were toxic to C. maculatus larvae. Approximately 40% of larvae that consumed seeds containing 0.05% of O. arborea failed to develop, in contrast to control larvae. Proteomic analysis of A. cearensis and O. arborea seeds identify revealed a total of 371 proteins. From those, 237 are present in both seeds, 91 were exclusive to O. arborea seeds, and 43 were specific to A. cearensis seeds. Some of these proteins are related to defense, such as proteins containing the cupin domain and 11S seed storage protein. The in silico docking of cupin domain-containing proteins and 11S storage protein with N-acetylglucosamine (NAG)4 showed negative values of affinity energy, indicating spontaneous binding. These results showed that nonhost seeds have natural insecticide compounds with potential to control C. maculatus infestation.

Transcriptome analyses in juvenile yellow perch (Perca flavescens) exposed in vivo to clothianidin and chlorantraniliprole: Possible sampling bias.

The St. Lawrence River is an important North American waterway that is subject to anthropogenic pressures including intensive urbanization, and agricultural development. Pesticides are widely used for agricultural activities in fields surrounding the yellow perch (Perca flavescens) habitat in Lake St. Pierre (Quebec, Canada), a fluvial lake of the river where the perch population has collapsed. Clothianidin and chlorantraniliprole were two of the most detected insecticides in surface waters near perch spawning areas. The objectives of the present study were to evaluate the transcriptional and biochemical effects of these two pesticides on juvenile yellow perch exposed for 28d to environmental doses of each compound alone and in a mixture under laboratory/aquaria conditions. Hepatic mRNA-sequencing revealed an effect of chlorantraniliprole alone (37 genes) and combined with clothianidin (251 genes), but no effects of clothianidin alone were observed in perch. Dysregulated genes were mostly related to circadian rhythms and to Ca2+ signaling, the latter effect has been previously associated with chlorantraniliprole mode of action in insects. Moreover, chronic exposure to clothianidin increased the activity of acetylcholinesterase in the brain of exposed fish, suggesting a potential non-target effect of this insecticide. Further analyses of three clock genes by qRT-PCR suggested that part of the observed effects of chlorantraniliprole on the circadian gene regulation of juvenile perch could be the result of time-of-day of sacrifice. These results provide insight into biological effects of insecticides in juvenile perch and highlight the importance of considering the circadian rhythm in experimental design and results analyses.

Low concentrations of cyantraniliprole negatively affects the development of Spodoptera frugiperda by disruption of ecdysteroid biosynthesis and carbohydrate and lipid metabolism.

In addition to the acute lethal toxicity, insecticides might affect population dynamics of insect pests by inducing life history trait changes under low concentrations, however, the underlying mechanisms remain not well understood. Here we examined systemic impacts on development and reproduction caused by low concentration exposures to cyantraniliprole in the fall armyworm (FAW), Spodoptera frugiperda, and the putative underlying mechanisms were investigated. The results showed that exposure of third-instar larvae to LC10 and LC30 of cyantraniliprole significantly extended larvae duration by 1.46 and 5.41 days, respectively. Treatment with LC30 of cyantraniliprole significantly decreased the pupae weight and pupation rate as well as the longevity, fecundity and egg hatchability of female adults. Consistently, we found that exposure of FAW to LC30 cyantraniliprole downregulated the mRNA expression of four ecdysteroid biosynthesis genes including SfNobo, SfShd, SfSpo and SfDib and one ecdysone response gene SfE75 in the larvae as well as the gene encoding vitellogenin (SfVg) in the female adults. We also found that treatment with LC30 of cyantraniliprole significantly decreased the whole body levels of glucose, trehalose, glycogen and triglyceride in the larvae. Our results indicate that low concentration of cyantraniliprole inhibited FAW development by disruption of ecdysteroid biosynthesis as well as carbohydrate and lipid metabolism, which have applied implications for the control of FAW.

Aberrant splicing of a nicotinic acetylcholine receptor alpha 6 subunit is associated with spinosad tolerance in the thrips predator Orius laevigatus.

Susceptibility to insecticides is one of the limiting factors preventing wider adoption of natural enemies to control insect pest populations. Identification and selective breeding of insecticide tolerant strains of commercially used biological control agents (BCAs) is one of the approaches to overcome this constraint. Although a number of beneficial insects have been selected for increased tolerance to insecticides the molecular mechanisms underpinning these shifts in tolerance are not well characterised. Here we investigated the molecular mechanisms of enhanced tolerance of a lab selected strain of Orius laevigatus (Fieber) to the commonly used biopesticide spinosad. Transcriptomic analysis showed that spinosad tolerance is not a result of overexpressed detoxification genes. Molecular analysis of the target site for spinosyns, the nicotinic acetylcholine receptor (nAChR), revealed increased expression of truncated transcripts of the nAChR α6 subunit in the spinosad selected strain, a mechanism of resistance which was described previously in insect pest species. Collectively, our results demonstrate the mechanisms by which some beneficial biological control agents can evolve insecticide tolerance and will inform the development and deployment of insecticide-tolerant natural enemies in integrated pest management strategies.

Discovery of new N-Phenylamide Isoxazoline derivatives with high insecticidal activity and reduced honeybee toxicity.

Isoxazoline is a novel structure with strong potential for controlling agricultural insect pests, but its high toxicity to honeybees limits its development in agriculture. Herein, a series of N-phenylamide isoxazoline derivatives with low honeybee toxicity were designed and synthesized using the intermediate derivatization method. Bioassay results showed that these compounds exhibited good insecticidal activity. Compounds 3b and 3f showed significant insecticidal effects against Plutella xylostella (P. xylostella) with median lethal concentrations (LC50) of 0.06 and 0.07 mg/L, respectively, comparable to that of fluralaner (LC50 = 0.02 mg/L) and exceeding that of commercial insecticide fluxametamide (LC50 = 0.52 mg/L). It is noteworthy that the acute honeybee toxicities of compounds 3b and 3f (LD50 = 1.43 and 1.63 µg/adult, respectively) were significantly reduced to 1/10 of that of fluralaner (LD50 = 0.14 µg/adult), and were adequate or lower than that of fluxametamide (LD50 = 1.14 µg/adult). Theoretical simulation using molecular docking indicates that compound 3b has similar binding modes with fluralaner and a similar optimal docking pose with fluxametamide when binding to the GABA receptor, which may contribute to its potent insecticidal activity and relatively low toxicity to honey bees. This study provides compounds 3b and 3f as potential new insecticide candidates and provides insights into the development of new isoxazoline insecticides exhibiting both high efficacy and environmental safety.

Oral administration of phytochemicals protects honey bees against cognitive and motor impairments induced by the insecticide fipronil.

Pollution produced by exposure to pesticides is a major concern for food security because the negative impacts on pollinators. Fipronil, an insecticide broadly used around the globe has been associated with the ongoing decline of bees. With a characteristic neuroactive toxicodynamic, fipronil leads to cognitive and motor impairments at sublethal dosages. Despite of regional bans, multilevel strategies are necessary for the protection of pollinators. Recent evidence suggests that specific nutrients in the diets of bees may induce protection against insecticides. Here, we evaluated whether the administration of three phytochemicals, namely rutin, kaempferol and p-coumaric acid provide protection to the Africanized honey bee Apis mellifera against oral administration of realistic dosages of fipronil. We tested the potential impairment produced by fipronil and the protection induced by the phytochemicals in learning, 24h memory, sucrose sensitivity and motor control. We found that the administration of fipronil induced a concentration-dependent impairment in learning and motor control, but not 24h memory or sucrose sensitivity across a 24h window. We also found that the administration of rutin, p-coumaric acid, kaempferol and the mixture was innocuous and generally offered protection against the impairments induced by fipronil. Overall, our results indicate that bees can be prophylactically protected against insecticides via nutrition, providing an alternative to the ongoing conflict between the use of insecticides and the decline of pollinators. As the studied phytochemicals are broadly present in nectar and pollen, our results suggest that the nutritional composition, and not only its production, should be considered when implementing strategies of conservation via gardens and co-cropping.

Knockout of ecdysis triggering hormone receptor (ETHr) gene adversely affects the nymphal molting and adult reproduction in Bemisia tabaci.

Bemisia tabaci (Gennadius) is one of the most dangerous polyphagous pests in the world causing damage to various crops by sucking sap during the nymphal and adult stages. Chemical management of whiteflies is challenging because of the emergence of pesticide resistance. RNA interference has been well established in whitefly to study the functions of various genes. G-protein coupled receptors (GPCRs) are important targets for development of new generation insecticides. In this study, Ecdysis triggering hormone receptor (ETHr) gene expression was recorded in different stages of whitefly and its function has been studied through RNAi. The expression of ETHr is highest in third-instar nymphs followed by other nymphal instars, pupae and newly emerged adults. Silencing of ETHr resulted in significantly higher adult mortality (68.88%), reduced fecundity (4.46 eggs /female), reduced longevity of male and female (1.05 and 1.40 days, respectively) when adults were fed with dsETHr @ 1.0 µg/µl. Silencing of ETHr in nymphs lead to significantly higher mortality (81.35%) as compared to control. This study confirms that ETHr gene is essential for growth and development of whitefly nymphs and adults. Hence, it can be future target for developing dsRNA based insecticides for management of whitefly.

Identification of insect cuticular protein genes LCP17 and SgAbd5 from Helicoverpa armigera and evaluation their roles in fenvalerate resistance.

Insect cuticular protein (ICP) plays an important role in insect growth and development. However, research on the role of ICP in insecticide resistance is very limited. In this study, insect cuticular protein genes LCP17 and SgAbd5 were cloned and characterized in Helicoverpa armigera based on previous transcriptome data. The functions of LCP17 and SgAbd5 genes in fenvalerate resistance were assessed by RNA interference (RNAi), and their response to fenvalerate was further detected. The results showed that LCP17 and SgAbd5 were overexpressed in the fenvalerate-resistant strain comparing with a susceptible strain. The open reading frames of LCP17 and SgAbd5 genes were 423 bp and 369 bp, encoding 141 and 123 amino acids, respectively. LCP17 and SgAbd5 genes were highly expressed in the larval stage, but less expressed in the adult and pupal stages. The expression level of LCP17 and SgAbd5 genes increased significantly after fenvalerate treatment at 24 h. When the cotton bollworms larvae were exposed to fenvalerate at LD50 level, RNAi-mediated silencing of LCP17 and SgAbd5 genes increased the mortality from 50.68% to 68.67% and 63.89%, respectively; the mortality increased to even higher level, which was 73.61%, when these two genes were co-silenced. Moreover, silencing of these two genes caused the cuticle lamellar structure to become loose, which led to increased penetration of fenvalerate into the larvae. The results suggested that LCP17 and SgAbd5 may be involved in the resistance of cotton bollworm to fenvalerate, and LCP17 and SgAbd5 could serve as potential targets for H. armigera control.

Response of the terrestrial isopod Porcellio scaber to lipopolysaccharide challenge after microplastic and insecticide exposure.

The exposure of organisms to microplastics could compromise their ability to cope with other environmental stressors, such as infections. In this context, we investigated the effects of a 14-day exposure of the terrestrial isopod Porcellio scaber to tire particles in soil (1.5 % w w-1 dry weight) on the organisms' response to a secondary exposure, i.e., injection of the bacterial endotoxin lipopolysaccharide. In addition, the insecticide chlorpyrifos (2 mg kg-1 dry weight) was tested as a positive control. The survival and immune response of P. scaber was assessed at the end of the 7- and 14-day primary exposure and two days after the secondary exposure, by analyzing selected haemolymph immune parameters (total haemocyte count, differential haemocyte count, and haemocyte viability). No change in survival was observed after primary exposure of P. scaber to tire particles or chlorpyrifos. However, primary exposure to chlorpyrifos triggered a strong activation of the immune response, which was not the case following exposure to the tire particles. Further injection of lipopolysaccharide into the body did not affect the survival of animals exposed to tire particles or chlorpyrifos, while a strong immunomodulatory change was observed, particularly with chlorpyrifos, and to some extent, tire particles. Based on these results, we conclude that exposure of P. scaber to tire particles or chlorpyrifos has no significant effect on the susceptibility of the organism to lipopolysaccharide in terms of their mortality, but primary exposure to an insecticide significantly modulates the immune response of the organisms to a second stressor. We discuss the "stress on stress" approach for testing low-toxic substances, such as microplastics, where an environmentally realistic exposure is followed by a secondary exposure.

Deciphering the impact of greenhouse pesticides on hepatic metabolism profile: Toxicity experiments on HepG2 cells using chlorpyrifos and emamectin benzoate.

Epidemiological evidence on the health effects of pesticide exposure among greenhouse workers is limited, and the mechanisms are lacking. Building upon our team's previous population study, we selected two pesticides, CPF and EB, with high detection rates, based on the theoretical foundation that the liver serves as a detoxifying organ, we constructed a toxicity model using HepG2 cells to investigate the impact of individual or combined pesticide exposure on the hepatic metabolism profile, attempting to identify targeted biomarkers. Our results showed that CPF and EB could significantly affect the survival rate of HepG2 cells and disrupt their metabolic profile. There were 117 metabolites interfered by CPF exposure, which mainly affected ABC transporter, biosynthesis of amino acids, center carbon metabolism in cancer, fatty acid biosynthesis and other pathways, 95 metabolites interfered by EB exposure, which mainly affected center carbon metabolism in cancer, HIF-1 signaling pathway, valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis and other pathways. The cross analysis and further biological experiments confirmed that CPF and EB pesticide exposure may affect the HIF-1 signaling pathway and valine, leucine and isoleucine biosynthesis in HepG2 cells, providing reliable experimental evidence for the prevention and treatment of liver damage in greenhouse workers.

Nanoparticles-mediated entomotoxicology: lessons from biologica.

Nanotechnology has grown in importance in medicine, manufacturing, and consumer products. Nanoparticles (NPs) are also widely used in the field of insect pest management, where they show a variety of toxicological effects on insects. As a result, the primary goal of this review is to compile and evaluate available information on effects of NPs on insects, by use of a timely, bibliometric analysis. We also discussed the manufacturing capacity of NPs from insect tissues and the toxic effects of NPs on insects. To do so, we searched the Web of Science database for literature from 1995 to 2023 and ran bibliometric analyses with CiteSpace© and Bibliometrix©. The analyses covered 614 journals and identified 1763 relevant documents. We found that accumulation of NPs was one of the top trending topics. China, India, and USA had the most published papers. The most overall reported models of insects were those of Aedes aegypti (yellow fever mosquito), Culex quinquefasciatus (southern house mosquito), Bombyx mori (silk moth), and Anopheles stephensi (Asian malaria mosquito). The application and methods of fabrication of NPs using insect tissues, as well as the mechanism of toxicity of NPs on insects, were also reported. A uniform legal framework is required to allow nanotechnology to fully realize its potential while minimizing harm to living organisms and reducing the release of toxic metalloid nanoparticles into the environment.

Hormetic effects of thiamethoxam on Schizaphis graminum: demographics and feeding behavior.

In agroecosystems, insects contend with chemical insecticides often encountered at sublethal concentrations. Insects' exposure to these mild stresses may induce hormetic effects, which has consequences for managing insect pests. In this study, we used an electrical penetration graph (EPG) technique to investigate the feeding behavior and an age-stage, two-sex life table approach to estimate the sublethal effects of thiamethoxam on greenbug, Schizaphis graminum. The LC5 and LC10 of thiamethoxam significantly decreased longevity and fecundity of directly exposed adult aphids (F0). However, the adult longevity, fecundity, and reproductive days (RPd)-indicating the number of days in which the females produce offspring - in the progeny generation (F1) exhibited significant increase when parental aphids (F0) were treated with LC5 of the active ingredient. Subsequently, key demographic parameters such as intrinsic rate of increase (r) and net reproductive rate (R0) significantly increased at LC5 treatment. EPG recordings showed that total durations of non-probing (Np), intercellular stylet pathway (C), and salivary secretion into the sieve element (E1) were significantly increased, while mean duration of probing (Pr) and total duration of phloem sap ingestion and concurrent salivation (E2) were decreased in F0 adults exposed to LC5 and LC10. Interestingly, in the F1 generation, total duration of Np was significantly decreased while total duration of E2 was increased in LC5 treatment. Taken together, our results showed that an LC5 of thiamethoxam induces intergenerational hormetic effects on the demographic parameters and feeding behavior of F1 individuals of S. graminum. These findings have important implications on chemical control against S. graminum and highlight the need for a deeper understanding of the ecological consequences of such exposures within pest management strategies across the agricultural landscapes.

Persistent diazinon induced neurotoxicity: The effect on inhibitory avoidance memory performance, amyloid precursor proteins, and TNF-α levels in the prefrontal cortex of rats.

INTRODUCTION: Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex. MATERIALS AND METHODS: Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels. RESULTS: Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant. CONCLUSION: Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.

Single and combined exposure to 'bee safe' pesticides alter behaviour and offspring production in a ground-nesting solitary bee (Xenoglossa pruinosa).

Mounting evidence supporting the negative impacts of exposure to neonicotinoids on bees has prompted the registration of novel 'bee-friendly' insecticides for agricultural use. Flupyradifurone (FPF) is a butenolide insecticide that shares the same mode of action as neonicotinoids and has been assessed to be 'practically non-toxic to adult honeybees' using current risk assessment procedures. However, these assessments overlook some routes of exposure specific to wild bees, such as contact with residues in soil for ground-nesters. Co-exposure with other pesticides may also lead to detrimental synergistic effects. In a fully crossed experiment, we assessed the possible lethal and sublethal effects of chronic exposure to two pesticides used on Cucurbita crops, the insecticide Sivanto Prime (FPF) and the fungicide Quadris Top (azoxystrobin and difenoconazole), alone or combined, on solitary ground-nesting squash bees (Xenoglossa pruinosa). Squash bees exposed to Quadris Top collected less pollen per flower visit, while Sivanto-exposed bees produced larger offspring. Pesticide co-exposure induced hyperactivity in female squash bees relative to both the control and single pesticide exposure, and reduced the number of emerging offspring per nest compared to individual pesticide treatments. This study demonstrates that 'low-toxicity' pesticides can adversely affect squash bees under field-realistic exposure, alone or in combination.

Evaluation of multiple organophosphate insecticide exposure in relation to altered thyroid hormones in NHANES 2007-2008 adult population.

The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007-2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (ß = -0.209 (95% CI: -0.310, -0.114)), and caused an increased Tg concentration (ß = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and ß =-0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and ß =-0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.

Pet collars containing tetrachlorvinphos (TCVP): evaluation of the results of torsion and on-animal release studies and implications for post-application consumer exposure and risk analysis.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient found in some flea and tick collars for dogs and cats. Recent studies sponsored by The Hartz Mountain Corporation, confirm the safety of TCVP as an active ingredient in pet collars. Based upon data from these new studies and results previously relied upon by the U.S. Environmental Protection Agency, the following conclusions have been made: Torsion study data clearly indicate that approximately 93% of released formulation from TCVP containing pet collars is in a liquid phase immediately following activation.Further, even more relevant to human health risk analysis associated with post-application exposures, in vivo data from dogs wearing TCVP pet collars definitively document that TCVP dust released from the collar is rapidly absorbed into the sebum. The maximum ratio of dust to liquid was 0.023% dust to 99.977% liquid.In vivo fur data provide scientific evidence confirming that the mechanism of dissemination of TCVP from pet collars is as a liquid suspended or dissolved in the animal's sebum, even though it may be released from the collar as a solid. Thus, potential post-application exposure to TCVP, including immediately following collar placement, is almost entirely to a liquid phase.Based upon EPA's refined and conservative "untrimmed" collar risk assessment, post-application incidental oral hand-to-mouth activity by children aged 1 to <2 years of age results in margins of exposure significantly greater than the level of concern of 1000, and therefore do not present unreasonable health risk.