Pyrethroid Exposure Research Articles

Lifelong exposure to pyrethroid insecticide cypermethrin at environmentally relevant doses causes primary ovarian insufficiency in female mice

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.

Developmental deltamethrin: Sex-specific hippocampal effects in Sprague Dawley rats

Pyrethroid pesticides are widely used and can cause long-term effects after early exposure. Epidemiological and animal studies reveal associations between pyrethroid exposure and altered cognition following prenatal and/or neonatal exposure. However, little is known about the cellular effects of such exposure. Sprague Dawley rats were gavaged with 0 or 1.0 mg/kg deltamethrin (DLM), a Type II pyrethroid, in corn oil (dose volume 5 mL/kg) once per day from postnatal day (P) 3–20 and assessed shortly after dosing ended or as adults. No effects of DLM exposure were found on striatal dopaminergic markers, nor on AMPA receptor subunits or on NMDA-NR1. However, DLM increased NMDA-NR2A and decreased NMDA-NR2B levels in the hippocampus, in males but not females. Additionally, adult hippocampal CA1 long-term potentiation was increased in DLM-treated males but not females. Potassium stimulated extracellular glutamate release in the hippocampus was not affected using in vivo microdialysis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed increased apoptotic cells in the dentate gyrus of male rats, in the absence of changes in cleaved caspase-3 at P21. Proinflammatory cytokines interferon gamma trended up in striatum, interleukin-1β trended down in nucleus accumbens, IL-13 trended up in hippocampus, and keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO or CXCL1) was significantly increased in the hippocampus in male DLM-treated rats on P20. The data point to the developing hippocampus as a susceptible region to DLM-induced adverse effects.

Association between Pyrethroids Exposure and Risk of Depressive Symptoms in U.S. Adults

Association between Pyrethroids Exposure and Risk of Depressive Symptoms in U.S. Adults

Transcriptomic analysis of resistance and short-term induction response to pyrethroids, in Anopheles coluzzii legs

BackgroundInsecticide-treated bed nets and indoor residual spraying comprise the major control measures against Anopheles gambiae sl, the dominant vector in sub-Saharan Africa. The primary site of contact with insecticide is through the mosquitoes’ legs, which represents the first barrier insecticides have to bypass to reach their neuronal targets. Proteomic changes and leg cuticle modifications have been associated with insecticide resistance that may reduce the rate of penetration of insecticides. Here, we performed a multiple transcriptomic analyses focusing on An. coluzzii legs.ResultsFirstly, leg-specific enrichment analysis identified 359 genes including the pyrethroid-binder SAP2 and 2 other chemosensory proteins, along with 4 ABCG transporters previously shown to be leg enriched. Enrichment of gene families included those involved in detecting chemical stimuli, including gustatory and ionotropic receptors and genes implicated in hydrocarbon-synthesis.Subsequently, we compared transcript expression in the legs of a highly resistant strain (VK7-HR) to both a strain with very similar genetic background which has reverted to susceptibility after several generations without insecticide pressure (VK7-LR) and a lab susceptible population (NG). Two hundred thirty-two differentially expressed genes (73 up-regulated and 159 down-regulated) were identified in the resistant strain when compared to the two susceptible counterparts, indicating an over-expression of phase I detoxification enzymes and cuticular proteins, with decrease in hormone-related metabolic processes in legs from the insecticide resistant population.Finally, we analysed the short-term effect of pyrethroid exposure on An. coluzzii legs, comparing legs of 1 h-deltamethrin-exposed An. coluzzii (VK7-IN) to those of unexposed mosquitoes (VK7-HR) and identified 348 up-regulated genes including those encoding for GPCRs, ABC transporters, odorant-binding proteins and members of the divergent salivary gland protein family.ConclusionsThe data on An. coluzzii leg-specific transcriptome provides valuable insights into the first line of defense in pyrethroid resistant and short-term deltamethrin-exposed mosquitoes. Our results suggest that xenobiotic detoxification is likely occurring in legs, while the enrichment of sensory proteins, ABCG transporters and cuticular genes is also evident. Constitutive resistance is primarily associated with elevated levels of detoxification and cuticular genes, while short-term insecticide-induced tolerance is linked with overexpression of transporters, GPCRs and GPCR-related genes, sensory/binding and salivary gland proteins.

Environmental Pyrethroid Exposure and Cognitive Dysfunction in U.S. Older Adults: The NHANES 2001-2002.

Pyrethroid compounds are widely used in household insecticides and agricultural pesticides. Recent studies, however, report that pyrethroid exposures affect neurobehavioral function in animals and may be associated with adverse neurocognitive development in children. This study aimed to examine the association between pyrethroid exposure and cognitive dysfunction in older adults using a well-defined general population. We analyzed data from 336 individuals, aged 60–84 years, who participated in the National Health and Nutrition Examination Survey 2001–2002. We used urinary 3-phenoxybenzoic acid (3-PBA) concentration as a biomarker of pyrethroid exposures and assessed cognitive function with the digit–symbol coding test. The geometric means (±geometric standard errors) of creatinine-uncorrected and corrected urinary 3-PBA were 0.30 (±0.87) μg/L and 0.36 (±0.89) μg/g. After adjusting for sociodemographic factors, higher 3-PBA concentrations (> vs. ≤0.30 μg/g creatinine (median)) were associated with lower scores of cognitive function (−3.83 95% confidence interval: −7.11, −0.54). Significance was persistent after additionally adjusting for physical activity and smoking pack-year (−3.76 95% CI: −7.16, −0.36) and further adjusting for BMI and presence of hypertension and diabetes (−3.82 95% CI: −6.92, −0.71). Our findings suggest that pyrethroid exposure is associated with cognitive dysfunction in older adults.

Pyrethroids exposure induces obesity and cardiometabolic diseases in a sex-different manner

People in the United States and around the world are widely exposed to pyrethroid pesticides. However, little is known about the effect of pyrethroids exposure on obesity in adults. This study examined the association between pyrethroids exposure and obesity in males and females and the role of obesity in the association of pyrethroids exposure with diabetes and cardiovascular disease (CVD). We used data from the National Health and Nutrition Examination Survey 1999–2002 and 2007–2014. Multivariate linear regression and logistic regression models were fitted to assess the association between urinary 3-Phenoxybenzoic Acid (3-PBA, a validated biomarker for pyrethroids exposure used in the primary analysis) and obesity. Mediation analyses were performed to investigate the mediation role of obesity on the associations of 3-PBA with diabetes and CVD. In this analysis, 7896 participants aged 20 years and above were included, of which 1235 (32.2%) males and 1623 (39.9%) females were diagnosed as obese. There was a significant interaction between sex and 3-PBA (Pinteraction = 0.004) for the risk of obesity. Among females, participants in the highest tertile of urinary 3-PBA had higher odds of obesity (OR = 1.22, 95% CI: 1.00, 1.48) compared to those in the lowest tertile after adjusting for covariates. Among males, the association was not statistically significant. Similar trends were found in the associations of log-transformed urinary 3-PBA level with body mass index in males and females. Further, we found that, in males and females, obesity explained the effect of 3-PBA exposure on diabetes by 1.1% (P = 0.850) and 13.6% (P = 0.004), as well as cardiovascular diseases by 5.9% (P = 0.785) and 25.0% (P = 0.016), respectively. In conclusion, 3-PBA was significantly associated with a higher risk of obesity, especially in females. In addition, obesity partially mediated the associations of 3-PBA exposure with diabetes and CVD.

Invited Perspective: How Can Studies of Chemical Mixtures and Human Health Guide Interventions and Policy?

Invited Perspective: How Can Studies of Chemical Mixtures and Human Health Guide Interventions and Policy?

Low-dose oral pyrethroid exposure induces gastrointestinal dysfunction and alters nigrostriatal dopamine signaling pathways in mice

BACKGROUND AND AIM: Insecticide exposure is associated with greater risk for developing Parkinson’s disease (PD). PD is characterized by motor impairments due to loss of nigrostriatal dopamine (DA) neurons in the midbrain, and patients commonly experience gastrointestinal (GI) dysfunction long before the onset of motor symptoms. Pyrethroids, synthetic insecticides commonly used around the world, disrupt DA signaling pathways. One of the most common routes of pyrethroid exposure is ingestion, so it is plausible that oral exposure acts locally within the GI tract and facilitates PD pathogenesis via the gut-brain axis. Here, we sought to determine the functional and molecular consequences of oral pyrethroid exposure in the adult mouse gut and brain in the context of idiopathic PD. METHODS: Adult mice were orally gavaged with 3 mg/kg deltamethrin weekly for 3 weeks. Intestinal behaviors were assessed to determine constipation phenotypes. Gut microbiome composition was determined by 16S rRNA sequencing. Intestinal and brain tissues were collected following the final dose to assess changes in gene expression and protein production pathways related to DA and other monoamine signaling, as determined by qPCR and western blot. RESULTS:Oral deltamethrin exposure significantly impaired GI function compared to vehicle controls. We observed reduced fecal output, changed gene and protein levels important for normal gut function, and altered gut microbial composition in deltamethrin-exposed mice, all of which are reflective of changes observed in PD patients. In the brain, oral deltamethrin exposure significantly altered production of proteins important for DA synthesis and reuptake compared to controls. CONCLUSIONS:Low-dose oral pyrethroid exposure induces GI dysfunction and alters DA pathways in the brain. These findings support the idea that pyrethroids induce functional and molecular changes relevant to PD pathology from within the gut, and further investigation is warranted to fully understand this phenomenon as a potential trigger in the etiology of PD. KEYWORDS: Pesticides, Chemical exposures, Neurodegenerative outcomes, Microbes/Microbiome

Phthalates and pyrethroids in infants and toddlers: concentrations, stability of repeat measures, and predictors of exposure

BACKGROUND AND AIM: Determinants of phthalate and pyrethroid exposures are not well understood in early life, a period of rapid brain development with heightened vulnerability to toxicant exposure. Our aims were to characterize concentrations, stability, and predictors of phthalate and pyrethroid metabolites in infants and toddlers. METHODS: We included a subset of participants in the UNC Baby Connectome Project, who provided≥1 urine sample(s) between birth and 77-months. We measured 8 phthalate and 4 pyrethroid metabolites in pediatric urines. At baseline, mothers completed an environmental questionnaire on household and personal care product usage and behaviors, during-and after-pregnancy. We calculated descriptive statistics of specific gravity unadjusted (Unadj) and adjusted (Adj) phthalate concentrations, estimated intraclass correlation coefficients (ICCs), and built predictive models. Detection frequencies of any pyrethroid metabolites and their Kappa statistics were calculated. RESULTS:62 children provided 125 urine samples, with near-ubiquitous detection of all phthalate metabolites (95%). Median concentrations were highest for monobutyl phthalate (MBP; Unadj: 15.35ug/L; Adj: 5.30ug/L), followed by mono-isobutyl phthalate (MiBP; 11.50ug/L; 4.59ug/L) and monobenzyl phthalate (MBzP; 4.03ug/L; 1.56ug/L). ICCs were higher for MBzP (0.58 [0.39, 0.72]; 0.46 [0.24, 0.63]) as compared to MBP (0.29 [0.05, 0.50]; 0.17 [-0.24, 0.53]) or MiBP (-0.05 [-0.29, 0.20]; 0.12 [-0.13, 0.35]). In the subset of first urine samples with questionnaire data (n=45), 54.86% of the variability in log(MBzP) was explained by specific gravity, pets, household/personal/child care product, income, pregnancy cosmetics use, race/ethnicity, pesticide use in and around the home, and infant birthweight. Besides specific gravity, having cat and dog in household was the strongest determinant. Any pyrethroid metabolites were detected in 35.2%, with a high agreement between second and third samples (0.86 [0.60, 1.00]) but not between other piecewise-comparisons. CONCLUSIONS:Phthalates, but not pyrethroids, were commonly detected during early childhood. MBzP had moderate ICCs and was partially explained by pets and household/personal care product preferences. KEYWORDS: Phthalates, pyrethroids, infants, toddlers, predictors

Do environmental and occupational exposure to pyrethroids and organophosphates affect human semen parameters? Results of a systematic review and meta-analysis.

Our purpose was to review and analyse the impact of pyrethroids and organophosphates exposure on human semen parameters. A comprehensive literature search was performed through MEDLINE via PubMed, Scopus and Webscience. Only cohort studies examining semen parameters in workers or general populations exposed to pyrethroids or organophosphates were included. Ejaculate volume, sperm count, concentration, motility, viability, normal morphology and seminal pH alterations were pooled using the Cochran-Mantel-Haenszel Method with the random effect model and expressed as weighted mean difference, risk ratios, 95% confidence intervals and p-values. Seven cross-sectional studies regarding pyrethroids were included. Four of them were eligible for meta-analysis. The only parameter affected by pyrethroid exposure was normal sperm morphology (WMD-7,61%, 95%CI -11,92 to -3,30;p=0,0,005). Nine studies were selected to evaluate the impact of organophosphates on semen parameters with six of them eligible for meta-analysis. A significant reduction was detected for the following: ejaculate volume (WMD -0,47ml, 95%CI -0,69 to -0,25; p<0,0001), sperm count (WMD-40,03, 95%CI -66,81 to -13,25;p=0,003), concentration (WMD-13,69 x10⁶/mL, 95%CI -23, 27 to-4,12;p=0,005) and motility (WMD -5,70%, 95%CI -12,89 to 1,50;p=0,12). Despite the increase in sperm abnormality, it has been shown that pyrethroids are unrelated to reduced sperm quality. However, the negative association of organophosphates with spermatogenesis is noteworthy.

Impact of sublethal pyrethroid exposure on resistant Anopheles gambiae mosquitoes' fitness

Impact of sublethal pyrethroid exposure on resistant Anopheles gambiae mosquitoes' fitness

Pyrethroids Toxicity to Male Reproductive System and Offspring as a Function of Oxidative Stress Induction: Rodent Studies.

Pyrethroids may be related to male reproductive system damage. However, the results of many previous studies are contradictory and uncertain. Therefore, a systematic review and a meta-analysis were performed to assess the relationship between pyrethroid exposure and male reproductive system damage. A total of 72 articles were identified, among which 57 were selected for meta-analysis, and 15 were selected for qualitative analysis. Pyrethroid exposure affected sperm count (SMD= -2.0424; 95% CI, -2.4699 to -1.6149), sperm motility (SMD=-3.606; 95% CI, -4.5172 to -2.6948), sperm morphology (SMD=2.686; 95% CI, 1.9744 to 3.3976), testis weight (SMD=-1.1591; 95% CI, -1.6145 to -0.7038), epididymal weight (SMD=-1.1576; 95% CI, -1.7455 to -0.5697), and serum testosterone level (SMD=-1.9194; 95% CI, -2.4589 to -1.3798) in the studies of rats. We found that gestational and lactational exposure to pyrethroids can reduce sperm count (SMD=1.8469; 95% CI, -2.9010 to -0.7927), sperm motility (SMD=-2.7151; 95% CI, -3.9574 to -1.4728), testis weight (SMD=-1.4361; 95% CI, -1.8873 to -0.9848), and epididymal weight (SMD=-0.6639; 95% CI, -0.9544 to -0.3733) of F1 offspring. Exposure to pyrethroids can increase malondialdehyde (SMD=3.3451; 95% CI 1.9914 to 4.6988) oxide in testes and can reduce the activities of glutathione (SMD=-2.075; 95% CI -3.0651 to -1.0848), superoxide dismutase (SMD=-2.4856; 95% CI -3.9612 to -1.0100), and catalase (SMD=-2.7564; 95% CI -3.9788 to -1.5340). Pyrethroid exposure and oxidative stress could damage male sperm quality. Gestational and lactational pyrethroid exposure affects the reproductive system of F1 offspring.

Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models.

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

Severe pulmonary toxicity associated with inhalation of pyrethroid-based domestic insecticides (Bop/Sapolio): a case series and literature review.

The current review focuses on serious pulmonary toxicity after inhalation of over the counter available pyrethroid-based insecticides. Pyrethroid is a synthetic product of pyrethrin, which in turn is the active ingredient of pyrethrum, a flower extract. On the contrary, a large gap of knowledge exists in the association of interstitial lung disease (ILD) with pyrethroids. So far, two cases of ILD, one associated with pyrethrin and one associated with pyrethrum, were described. Existing literature on both other (pulmo)toxic effects of pyrethroids in human and animals is summarized. We present three cases of severe pulmonary toxicity after inhalation of pyrethroid-based insecticides demanding hospitalization and oxygen therapy. One of these cases died. Although a causal relationship was hard to establish, these cases all demonstrated an obvious history of (repeated) pyrethroid exposure associated with ILD. Moreover, other causes of ILD as well as infections were excluded. Furthermore, studies in mammals as well as aquatic animals confirm (pulmonary) toxicity of pyrethroids. The occurrence of toxicity is dose-dependent but also associated with individual susceptibility. Therefore, we would like to acknowledge that awareness of potential hazards of commercially available insecticides containing pyrethroids to both medical physicians and the public is mandatory.

Transcriptomic analysis reveals pronounced changes in gene expression due to sub-lethal pyrethroid exposure and ageing in insecticide resistance Anopheles coluzzii

BackgroundMalaria control is heavily reliant on the use of insecticides that target and kill the adult female Anopheline vector. The intensive use of insecticides of the pyrethroid class has led to widespread resistance in mosquito populations. The intensity of pyrethroid resistance in some settings in Africa means mosquitoes can contact bednets treated with this insecticide class multiple times with minimal mortality effects. Furthermore, both ageing and diel cycle have been shown to have large impacts on the resistance phenotype. Together, these traits may affect other aspects of vector biology controlling the vectorial capacity or fitness of the mosquito.ResultsHere we show that sublethal exposure of a highly resistant Anopheles coluzzii population originally from Burkina Faso to the pyrethroid deltamethrin results in large and sustained changes to transcript expression. We identify five clear patterns in the data showing changes to transcripts relating to: DNA repair, respiration, translation, behaviour and oxioreductase processes. Further, we highlight differential regulation of transcripts from detoxification families previously linked with insecticide resistance, in addition to clear down-regulation of the oxidative phosphorylation pathway both indicative of changes in metabolism post-exposure. Finally, we show that both ageing and diel cycle have major effects on known insecticide resistance related transcripts.ConclusionSub-lethal pyrethroid exposure, ageing and the diel cycle results in large-scale changes in the transcriptome of the major malaria vector Anopheles coluzzii. Our data strongly supports further phenotypic studies on how transcriptional changes such as reduced expression of the oxidative phosphorylation pathway or pyrethroid induced changes to redox state might impact key mosquito traits, such as vectorial capacity and life history traits.

Epigenetic effects of parasites and pesticides on captive and wild nestling birds.

Anthropogenic changes to the environment challenge animal populations to adapt to new conditions and unique threats. While the study of adaptation has focused on genetic variation, epigenetic mechanisms may also be important. DNA methylation is sensitive to environmental stressors, such as parasites and pesticides, which may affect gene expression and phenotype. We studied the effects of an invasive ectoparasite, Philornis downsi, on DNA methylation of Galápagos mockingbirds (Mimus parvulus). We used the insecticide permethrin to manipulate P. downsi presence in nests of free‐living mockingbirds and tested for effects of parasitism on nestling mockingbirds using epiGBS, a reduced‐representation bisulfite sequencing (RRBS) approach. To distinguish the confounding effects of insecticide exposure, we conducted a matching experiment exposing captive nestling zebra finches (Taeniopygia guttata) to permethrin. We used zebra finches because they were the closest model organism to mockingbirds that we could breed in controlled conditions. We identified a limited number of differentially methylated cytosines (DMCs) in parasitized versus nonparasitized mockingbirds, but the number was not more than expected by chance. In contrast, we saw clear effects of permethrin on methylation in captive zebra finches. DMCs in zebra finches paralleled documented effects of permethrin exposure on vertebrate cellular signaling and endocrine function. Our results from captive birds indicate a role for epigenetic processes in mediating sublethal nontarget effects of pyrethroid exposure in vertebrates. Environmental conditions in the field were more variable than the laboratory, which may have made effects of both parasitism and permethrin harder to detect in mockingbirds. RRBS approaches such as epiGBS may be a cost‐effective way to characterize genome‐wide methylation profiles. However, our results indicate that ecological epigenetic studies in natural populations should consider the number of cytosines interrogated and the depth of sequencing in order to have adequate power to detect small and variable effects.

The contribution of detoxification pathways to pyrethroid resistance in Hyalella azteca

Chronic exposure to pyrethroid insecticides can result in strong selective pressures on non-target species in aquatic systems and drive the evolution of resistance and population-level changes. Characterizing the underlying mechanisms of resistance is essential to better understanding the potential consequences of contaminant-driven microevolution. The current study found that multiple mechanisms enhance the overall tolerance of Hyalella azteca to the pyrethroid permethrin. In H. azteca containing mutations in the voltage-gated sodium channel (VGSC), both adaptation and acclimation played a role in mitigating the adverse effects of pyrethroid exposures. Pyrethroid resistance is primarily attributed to the heritable mutation at a single locus of the VGSC, resulting in reduced target-site sensitivity. However, additional pyrethroid tolerance was conferred through enhanced enzyme-mediated detoxification. Cytochrome P450 monooxygenases (CYP450) and general esterases (GE) significantly contributed to the detoxification of permethrin in H. azteca. Over time, VGSC mutated H. azteca retained most of their pyrethroid resistance, though there was some increased sensitivity from parent to offspring when reared in the absence of pyrethroid exposure. Permethrin median lethal concentrations (LC50s) declined from 1809 ng/L in parent (P0) individuals to 1123 ng/L in the first filial (F1) generation, and this reduction in tolerance was likely related to alterations in acclimation mechanisms, rather than changes to target-site sensitivity. Enzyme bioassays indicated decreased CYP450 and GE activity from P0 to F1, whereas the VGSC mutation was retained. The permethrin LC50s in resistant H. azteca were still two orders-of-magnitude higher than non-resistant populations indicating that the largest proportion of resistance was maintained through the inherited VGSC mutation. Thus, the noted variation in tolerance in H. azteca is likely associated with inducible traits controlling enzyme pathways. A better understanding of the mechanistic and genomic basis of acclimation is necessary to more accurately predict the ecological and evolutionary consequences of contaminant-driven change in H. azteca.

Association between pyrethroid exposure and cardiovascular disease: A national population-based cross-sectional study in the US

ObjectivePyrethroids-containing products are widely used as commercial and household insecticides. While animal studies and clinical case reports have shown acute cardiovascular outcomes of pyrethroids exposure, little has been known on the effect of chronic pyrethroid exposure on cardiovascular disease (CVD). We aimed to examine the associations between chronic pyrethroid exposure and CVD in the US adults. MethodsCross-sectional data from the National Health and Nutrition Examination Survey 1999–2002 and 2007–2012 were analyzed. The exposure to pyrethroids was determined as the urinary level of 3-phenoxybenzoic acid (3-PBA), and CVD was ascertained based on self-reported physician diagnoses. Multivariable logistic regression models were fitted to evaluate associations of pyrethroid exposure with CVD, coronary heart disease (CHD), and stroke. ResultsIncluded were 6,471 participants with a mean age of 44.77 years (standard error, 0.39) for final analyses. The weighted prevalence of CVD, CHD, and stroke was 6.85%, 4.57% and 2.27%, respectively. With adjustments for major confounders, participants in the highest tertile of urinary 3-PBA had higher odds of CVD (odds ratio, 1.58; 95% confidence interval: 1.12, 2.23) and CHD (OR, 1.75; 95% CI: 1.17, 2.61) compared to those in the lowest tertile. There were linear associations for CVD (P for trend = 0.04) and CHD (P for trend = 0.02). However, no significant association was noted for stroke (1.29; 0.78, 2.16) in the main analyses. Conclusions3-PBA was adversely associated with CVD and CHD in the US adults. Our findings highlight potential cardiovascular risk of chronic exposure to pyrethroids, and should be validated in large prospective studies in different populations in future.

Influence of Pyrethroid Resistance on Vector Competency for Zika Virus by Aedes aegypti (Diptera: Culicidae).

The vector competence of mosquitoes for pathogens has been shown to be influenced by the status of insecticide resistance in the mosquito population. However, to date, only two studies has explored the impact of insecticide resistance on arbovirus transmission. The global and widespread use of pyrethroids has led to the development of insecticide resistance in many mosquito species, including Aedes aegypti (Linnaeus) (Diptera: Culicidae), the primary vector of Zika virus. Strains of Ae. aegypti that were genetically similar, but responded differently to pyrethroid exposure, were developed using backcrossing techniques. These populations were orally infected with Zika virus and susceptibility to infection, disseminated infection, and transmission potential were evaluated. Analyses revealed differences in susceptibility to infection and disseminated infection between the pyrethroid susceptible and resistant strains of Ae. aegypti during the infection period. Here, we identify an additional challenge to that of widespread pyrethroid resistance. Specifically, resistance is associated with altered phenotypic traits that influence susceptibility to arbovirus infection and progression of infection in the mosquito, factors which ultimately influence risk of arbovirus transmission. These findings support the need to 1) consider insecticide resistance status during times of arbovirus transmission and 2) to implement insecticide resistance management/ mitigation strategies in vector control programs.

Pyrethroid exposure among children residing in green versus non-green multi-family, low-income housing.

Background:There is growing concern about children’s chronic low-level pesticide exposure and its impact on health. Green building practices (e.g. reducing leakage of the thermal and pressure barrier that surrounds the structure, integrated pest management, improved ventilation) have the potential to reduce pesticide exposure. However, the potential impact of living in green housing on children’s pesticide exposure is unknown.Objective:To address this question, a longitudinal study of pyrethroid metabolites (3-phenoxybenzoic acid [3-PBA], 4-fluoro-3-phenoxybenzoic acid [4-F-3-PBA], trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid [trans-DCCA]) in first morning void urine, collected from 68 children from New Orleans, Louisiana residing in green and non-green housing was conducted.Methods:Children were followed for one year with three repeated measures of pesticide exposure. Generalized Estimating Equations examined associations between housing type (green v non-green) and urinary pyrethroid metabolite concentrations adjusting for demographic and household factors over the year.Results:Ninety-five percent of samples had detectable concentrations of 3-PBA (limit of detection [LOD]: 0.1 μg/L); 8% of 4-F-3-PBA (LOD: 0.1 μg/L), and 12% of trans-DCCA (LOD: 0.6 μg/L). In adjusted models, green housing was not associated with statistically significant differences in children’s 3-PBA urinary concentrations compared to non-green housing.Significance:In this study, green building practices had no impact on children’s pyrethroid urinary concentrations. Further studies with larger sample sizes are needed to confirm these findings.