Chlordecone Exposure Research Articles

Impact of chlordecone exposure on reproductive system: A concise review

Impact of chlordecone exposure on reproductive system: A concise review

The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms.

Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson's disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode C. elegans as an in vivo model organism. We established that CLD kills cultured DA neurons in a concentration- and time-dependent manner while exerting no direct proinflammatory effects on glial cells. DA cell loss was not impacted by the degree of maturation of the culture. The use of fluorogenic probes revealed that CLD neurotoxicity was the consequence of oxidative stress-mediated insults and mitochondrial disturbances. In C. elegans worms, CLD exposure caused a progressive loss of DA neurons associated with locomotor deficits secondary to alterations in food perception. L-DOPA, a molecule used for PD treatment, corrected these deficits. Cholinergic and serotoninergic neuronal cells were also affected by CLD in C. elegans, although to a lesser extent than DA neurons. Noticeably, CLD also promoted the phosphorylation of the aggregation-prone protein tau (but not of α-synuclein) both in midbrain cell cultures and in a transgenic C. elegans strain expressing a human form of tau in neurons. In summary, our data suggest that CLD is more likely to promote atypical forms of Parkinsonism characterized by tau pathology than classical synucleinopathy-associated PD.

Prenatal and childhood chlordecone exposure, cognitive abilities and problem behaviors in 7-year-old children: the TIMOUN mother–child cohort in Guadeloupe

BackgroundChlordecone is a highly persistent organochlorine insecticide that was intensively used in banana fields in the French West Indies, resulting in a widespread contamination. Neurotoxicity of acute exposures in adults is well recognized, and empirical data suggests that prenatal exposure affects visual and fine motor developments during infancy and childhood, with greater susceptibility in boys.ObjectiveTo assess the associations between pre- and postnatal exposures to chlordecone and cognitive and behavioral functions in school-aged children from Guadeloupe.MethodsWe examined 576 children from the TIMOUN mother–child cohort in Guadeloupe at 7 years of age. Concentrations of chlordecone and other environmental contaminants were measured in cord- and children’s blood at age 7 years. Cognitive abilities of children were assessed with the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing and internalizing problem behaviors documented with the Strengths and Difficulties Questionnaire (SDQ) completed by the child’s mother. We estimated covariate-adjusted associations between cord- and 7-years chlordecone concentrations and child outcomes using structural equations modeling, and tested effect modification by sex.ResultsGeometric means of blood chlordecone concentrations were 0.13 µg/L in cord blood and 0.06 µg/L in children’s blood at age 7 years. A twofold increase in cord blood concentrations was associated with 0.05 standard deviation (SD) (95% Confidence Interval [CI]: 0.0, 0.10) higher internalizing problem scores, whereas 7-years chlordecone concentrations were associated with lower Full-Scale IQ scores (FSIQ) and greater externalized behavioral problem scores. A twofold increase in 7-year chlordecone concentrations was associated with a decrease of 0.67 point (95% CI: -1.13, -0.22) on FSIQ and an increase of 0.04 SD (95% CI: 0.0, 0.07) on externalizing problems. These associations with Cognitive abilities were driven by decreases in perceptive reasoning, working memory and verbal comprehension. Associations between 7-year exposure and perceptive reasoning, working memory, and the FSIQ were stronger in boys, whereas cord blood and child blood associations with internalizing problems were stronger in girls.ConclusionsThese results suggests that cognitive abilities and externalizing behavior problems at school age are impaired by childhood, but not in utero, exposure to chlordecone, and that prenatal exposure is related to greater internalizing behavioral problems.

Abstract 15286: Prolonged Exposure to Pesticides and the Risk of Atrial Fibrillation: The Particular Case of Chlordecone

Introduction: Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Chlordecone (CLD) is a pesticide known for its carcinogenic effects. Data suggest that CLD may disrupt the activity of myocardial Na + /K + -ATPase, deregulate mitochondrial Mg2+/ATPase in cardiomyocytes (CM), and inhibit CM Ca 2+ /ATPase. Little is known about the link between CLD and AF. Hypothesises: 1. Prolonged exposure to CLD induces arrhythmogenic cardiac remodeling in rats. 2.Cycle of CLD-withdrawal is accompanied by reduction of CLD-induced AF vulnerability. Methods: Male Wistar rats (250g) were exposed to CLD (0.1 μg/L or 1 μg/L) diluted in their daily water for 28 days. Control rats (CTRL) received water without CLD. Starting on day 29, all animals were exposed to CLD-free water. Electrophysiological study (EPS), echocardiography, and cardiac optical mapping (OM) were performed at days 28 and 56 to study cardiac function and atrial conduction. Expression levels of genes and proteins involved in inflammation, fibrosis and senescence were quantified by histology, immunoblot and qPCR. Results: At D28, all CLD-rats developed AF while CTRL rats did not. Compared to CTRL, weight up-take and water consumption were lower in animals exposed to CLD, although their food consumption was higher. Echocardiography revealed that CLD animals showed increased left ventricular contractility and atrial filling compared to CTRL. Acute CLD contamination caused a decrease in atrial conduction velocity and atrial action potential durations determined by cardiac OM ex-vivo . A 28-days CLD-withdrawal cycle was accompanied by weight normalization, and attenuation of AF inducibility, without improving atrial fibrosis and AF duration. CLD also decreased right and left atrial p21 mRNA expression, an effect not reversed by CLD weaning. Conclusion: CLD exposure is associated with increased AF vulnerability. CLD-weaning decreased (without abolishing), cardiac fibrosis and AF susceptibility.

Soil ingestion, a key determinant of exposure to environmental contaminants. The case study of chlordecone exposure in free-range pigs in the French West Indies.

Ingested soil may expose free-range animals to environmental pollutants. In pigs, soil ingestion is few described whereas their burrowing behaviour suggests that it could be high. Although highly productive pigs are generally reared indoor, free-range farming is increasing in view of ethical considerations for animal welfare and is a common practice for subsistence agriculture systems. The experiment lasted 8 weeks (2 for adaptation, 6 for measurements) with 24 growing pigs of Guadeloupean Creole (CR) or Large White (LW) breeds. Pigs were assigned to 3 outdoor treatments: high pasture HP (>60 days of regrowth), low pasture LP (35 days of regrowth), and sweet potato SP (sweet potato field). Titanium (soil marker) and chromium (faecal output marker) contents of faeces, vegetation and soil samples were used to estimate individual daily soil ingestions. The average, 10th and 90th percentiles were 440, 200 and 726 g of dry soil per 100 kg body weight, respectively, without significant differences between the 3 outdoor treatments or the 2 breeds but with a significant period (i.e. week of measurements) × treatment interaction (P < 0.001). In the French West Indies, animals may be exposed to chlordecone (CLD), a very persistent organochlorine insecticide. Simulations of CLD tissue contamination due to ingestion of contaminated soil were carried out and compared to the maximum residue limit. These results show that grazing management needs to be adapted to effectively limit soil ingestion by pigs and the impact of a contaminated environment on the sustainability of pig systems.

Prenatal and childhood exposure to chlordecone and adiposity of seven-year-old children in the Timoun mother\u2013child cohort study in Guadeloupe (French West Indies)

BackgroundExposure to persistent environmental organic pollutants may contribute to the development of obesity among children. Chlordecone is a persistent organochlorine insecticide with estrogenic properties that was used in the French West Indies (1973–1993) and is still present in the soil and the water and food consumed by the local population. We studied the association between prenatal and childhood exposure to chlordecone and the adiposity of prepubertal children.MethodsWithin the Timoun Mother–Child Cohort Study in Guadeloupe (French West Indies), 575 children had a medical examination at seven years of age, including adiposity measurements. A Structural Equation Modeling approach was used to create a global adiposity score from four adiposity indicators: the BMI z-score, percentage of fat mass, sum of the tricipital and subscapular skinfold thickness, and waist-to-height ratio. Chlordecone concentrations were measured in cord blood at birth and in the children’s blood at seven years of age. Models were adjusted for prenatal and postnatal covariates. Sensitivity analyses accounted for co-exposure to PCB-153 and pp’-DDE. Mediation analyses, including intermediate birth outcomes, were conducted.ResultsPrenatal chlordecone exposure tended to be associated with increased adiposity at seven years of age, particularly in boys. However, statistical significance was only reached in the third quartile of exposure and neither linear nor non-linear trends could be formally identified. Consideration of preterm birth or birth weight in mediation analyses did not modify the results, as adjustment for PCB-153 and pp’-DDE co-exposures.ConclusionGlobally, we found little evidence of an association between chlordecone exposure during the critical in utero or childhood periods of development and altered body-weight homeostasis in childhood. Nevertheless, some associations we observed at seven years of age, although non-significant, were consistent with those observed at earlier ages and would be worth investing during further follow-ups of children of the Timoun Mother–Child Cohort Study when they reach puberty.

Soil Ingestion, a Key Determinant of Exposure to Environmental Contaminants. The Case Study of Chlordecone Exposure in Free-Range Pigs in the French West Indies

Soil Ingestion, a Key Determinant of Exposure to Environmental Contaminants. The Case Study of Chlordecone Exposure in Free-Range Pigs in the French West Indies

Visuospatial processing and fine motor function among 7-years old Guadeloupe children pre- and postnatally exposed to the organochlorine pesticide chlordecone

BackgroundChlordecone is an organochlorine that was largely used as an insecticide to control a species of root borers, the Banana weevil (Cosmopolites sordidus), in the French West Indies, Guadeloupe and Martinique. Its molecules have been shown to be very persistent in the environment as pollution in soils leading to contamination of water sources and foodstuff will last for several decades. Our team previously reported associations between prenatal chlordecone exposure and poorer fine motor development at two points in time during infancy. ObjectiveTo document whether effects of prenatal exposure to chlordecone previously reported persists until middle-childhood, and whether deleterious effects are observed in domain of visual processing. Associations with postnatal exposure and sex-specific vulnerabilities were also investigated. MethodsWe examined 410 children from the TIMOUN mother-child cohort in Guadeloupe at 7 years of age. Concentrations of chlordecone and other environmental contaminants were measured in cord- and children’s blood at age 7 years. Fine motor function was assessed using the Bruininks Oseretsky Test of Motor Proficiency Second Edition (BOT-2). The Computerized Adaptive Testing System (CATSYS) was used to evaluated postural hand tremor, while non-verbal visuospatial processing was measured using the Stanford Binet copying (S-B copying) test. We used adjusted multiple linear regressions to test the relationship between children’s scores and both continuous and categorical blood chlordecone concentrations, adding child sex as a moderator in continuous models. ResultsCord chlordecone concentrations are associated with a regular frequency pattern of subtle hand tremors in both hands, and not related to visual processing and fine motor precision. Chlordecone concentrations in blood sample collected at testing time are associated with poorer visual processing when copying geometric figures, but not significantly related to poorer fine movement precision in tasks requiring pencil, scissors and paper. No sex-specific vulnerability was reported in any of the outcomes. ConclusionsThese results at school aged expand those previously reported in the same cohort during infancy at age 7- and 18 months, and corroborate the negative effects of chlordecone exposure on fine motor function in absence of intoxication. Our results support the need to continue public health efforts aimed at reducing exposure especially among women of child bearing age and young children.

In Utero Chlordecone Exposure and Thyroid, Metabolic, and Sex-Steroid Hormones at the Age of Seven Years: A Study From the TIMOUN Mother-Child Cohort in Guadeloupe.

BackgroundChlordecone is an endocrine-disrupting chemical with well recognized estrogenic and progestagenic properties. This organochlorine insecticide was extensively used in the French West Indies from 1973 to 1993 to control the banana root borer. Due to its poor degradation in the environment, permanently polluted soil is responsible for the current contamination of the food chain and human beings. We aimed to examine the relationship of in utero exposure to chlordecone and thyroid (thyroid stimulating hormone [TSH], free tri-iodothyronine [FT3], free thyroxine [FT4]), metabolic (insulin growth-factor 1, leptin, adiponectin), and sex-steroid (dehydroepiandrosterone [DHEA], total testosterone [TT], dihydrotestosterone [DHT], estradiol [E2]) hormone levels in children at the age of seven years who participated in TIMOUN, an ongoing birth cohort in Guadeloupe.MethodsChlordecone concentrations were measured in cord-blood at delivery. Thyroid, metabolic, and sex-steroid hormone levels were determined in the blood of children at seven years of age. Associations between in utero chlordecone exposure and hormone levels at seven years of age were assessed by multiple linear or logistic regression, controlling for confounding factors.ResultsAmong the study population (210 boys and 228 girls), chlordecone and hormone measurements were available for 124 boys and 161 girls. We found the third quartile of in utero chlordecone exposure relative to the lowest quartile to be associated with elevated TSH levels in girls and elevated DHEA, TT, and DHT levels in both sexes. Complementary non-linear analysis (spline regression) confirmed a significant non-linear trend for TSH in girls and DHEA and DHT in boys.Conclusion In utero chlordecone exposure was associated with elevated levels of selected thyroid (TSH) and sex-steroid (DHEA, TT, and DHT) hormones at seven years in a non-monotonic dose response (inverted U) relationship. The implications for future health and reproductive function in puberty and adulthood should be determined.

In utero exposure to chlordecone affects histone modifications and activates LINE-1 in cord blood.

Environmental factors can induce detrimental consequences into adulthood life. In this study, we examined the epigenetic effects induced by in utero chlordecone (CD) exposure on human male cord blood as well as in blood-derived Ke-37 cell line. Genome-wide analysis of histone H3K4me3 distribution revealed that genes related to chromosome segregation, chromatin organization, and cell cycle have altered occupancy in their promoters. The affected regions were enriched in ESR1, SP family, and IKZF1 binding motifs. We also observed a global reduction in H3K9me3, markedly in repeated sequences of the genome. Decrease in H3K9me3 after CD exposure correlates with decreased methylation in LINE-1 promoters and telomere length extension. These observations on human cord blood were assessed in the Ke-37 human cell line. H3K4me3 and the expression of genes related to immune response, DNA repair, and chromatin organization, which were affected in human cord blood were also altered in CD-exposed Ke-37 cells. Our data suggest that developmental exposure to CD leads to profound changes in histone modification patterns and affects the processes controlled by them in human cord blood.

Characterization of chlordecone distribution and elimination in ewes during daily exposure and depuration

To reduce the exposure of the French West Indies population to the pollutant chlordecone (CLD), the contamination of consumed products must be reduced. One of the strategies to secure safe animal products is related to the depuration of contaminated animals. In order to set up this strategy in situ, characterizing CLD distribution and elimination appears to be essential. The aim of this study is to characterize CLD distribution and elimination in ewes, and establish correlations between CLD concentrations in tissues following a continuous oral contamination period and a depuration period. The experiment consisted in a 90-d period of CLD exposure via daily feeding at 0.01 mg kg−1 body weight, followed by a 127-d period of depuration. A total of 24 ewes were sequentially slaughtered and serum, liver, perirenal fat, subcutaneous fat, shaft muscle, longissimus dorsi muscle and heart samples were collected. CLD concentrations in serum and tissues were analyzed by GC-MS/MS and LC-MS/MS, respectively. Whatever the time of sampling, CLD concentrations in liver were significantly higher than in other collected tissues. However, the results showed that fat tissues stored the higher portion of CLD body burden, followed by muscle, liver, serum and heart. CLD half-lives did not differ significantly between tissues including serum and ranged between 20.2 ± 4.0 and 24.1 ± 4.9 d. Two linear models were developed to estimate CLD concentration in tissues from a blood sample. This study illustrates the theoretical methodology to estimate the time required to decontaminate farm animals from a blood sample.

Evaluation and mechanistic study of chlordecone-induced thyroid disruption: Based on in vivo, in vitro and in silico assays.

The present study aimed to evaluate the thyroid-disrupting potency of chlordecone, and reveal the underlying mechanism. In the in vivo assays, rare minnow embryos were exposed to 0, 0.01, 0.1, 1 and 10μg·L-1 chlordecone until sexually mature. The results showed decreased T4 but increased T3 concentrations in plasma, upregulated mRNA levels of thyrotropin-releasing hormone receptor (trhr) and sodium-iodide symporter (nis) in the brain, and transthyretin (ttr), thyroid hormone receptor α (trα) and deiodinase enzymes (dio1 and dio2) in the liver of adult fish. In the in vitro assays, single chlordecone treatments promoted growth hormone (GH) and prolactin (PRL) secretion in GH3 cells. Transcription of thyroid receptor (trβ) was inhibited, but this is not likely responsible for chlordecone-induced GH secretion and altered transcription. When co-treated with T3, chlordecone acted independently of the effect of T3 on GH secretion; chlordecone-induced GH/PRL secretion and mRNA expression were further promoted when co-treated with E2, but inhibited when co-treated with ICI, indicating an important role for estrogen receptors (ERs) in chlordecone-induced changes in GH3 cells. Furthermore, in silico prediction suggested no stable interactions between chlordecone and thyroid hormone-related proteins, as well as a regulatory role for ERs in thyroid systems. Overall, our results indicated that chlordecone may have adverse effects on thyroid systems upon long-term exposure. However, rather of TRs, ERs may be responsible for thyroid disruption following chlordecone exposure.

Chlordecone exposure and risk of congenital anomalies: the Timoun Mother-Child Cohort Study in Guadeloupe (French West Indies).

Chlordecone is an organochlorine pesticide that was extensively used to control the banana root borer population in the French West Indies until 1993. Its persistence in soil has led to widespread pollution of the environment, and human beings, including pregnant women, are still exposed to this chemical. High levels of exposure to chlordecone during gestation have been shown to cause congenital anomalies, including undescended testes in rodents. We assessed the associations between chlordecone concentrations in maternal and cord plasma and the risk of congenital anomalies in the Timoun Mother-Child Cohort Study (2004-2007) that included 1068 pregnant women in Guadeloupe. Odds ratios were estimated using unconditional logistic regression analysis, controlling for confounding factors. The median plasma concentrations in maternal and cord plasma were 0.39 μg/L and 0.20 μg/L, respectively. Thirty-six children were diagnosed with malformations according to the European Registration of Congenital Anomalies guidelines and 25 with undescended testes. There was no association between maternal or cord plasma concentration of chlordecone and the risk of overall malformations nor undescended testes. These results suggest that prenatal exposure to the currently observed environmental levels of chlordecone in French West Indies does not increase the risk of birth defects.

In vivo comparison of the proangiogenic properties of chlordecone and three of its dechlorinated derivatives formed by in situ chemical reduction.

In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by chlordecone (CLD). Evidences provided by the literature indicate an association between the development of prostate cancer and CLD exposure (Multigner et al. 2010). In a previous in vitro study, we demonstrated that the two main dechlorinated CLD derivatives formed by ISCR, CLD-1Cl, and CLD-3Cl have lower cytotoxicity and proangiogenic properties than CLD itself (Legeay et al. 2017). By contrast, nothing is known on the in vivo proangiogenic effect of these dechlorinated derivatives. Based on in vitro data, the aims of this study were therefore to evaluate the in vivo influence of CLD and three of its dechlorinated metabolites in the control of neovascularization in a mice model of prostate cancer. The proangiogenic effect of CLD and three of its dechlorinated derivatives, CLD-1Cl, CLD-3Cl, and CLD-4Cl, was evaluated on a murine model of human prostate tumor (PC-3) treated, at two exposure levels: 33μg/kg and 1.7μg/kg respectively reflecting acute and chronic toxic exposure in human. The results of serum measurements show that, for the same ingested dose, the three metabolite concentrations were significantly lower than that of CLD. Dechlorination of CLD lead therefore to molecules that are biologically absorbed or metabolized, or both, faster than the parent molecule. Prostate tumor growth was lower in the groups treated by the three metabolites compared to the one treated by CLD. The vascularization measured on the tumor sections was inversely proportional to the rate of dechlorination, the treatment with CLD-4Cl showing no difference with control animals treated with only the vehicle oil used for all substances tested. We can therefore conclude that the proangiogenic effect of CLD is significantly decreased following the ISCR-resulting dechlorination. Further investigations are needed to elucidate the molecular mechanisms by which dechlorination of CLD reduces proangiogenic effects in prostate tumor.

Evidence for Chlordecone-Stimulated Oxidative Stress in Different Tissues of the Cichlid Fish, Pseudetroplus Maculatus (Bloch, 1795)

Abstract The present study was designed to assess the effect of chlordecone on the stimulation of oxidative stress in gill, liver and brain tissues of the cichlid fish, Pseudetroplus maculatus. Fishes were exposed to chlordecone at two sublethal concentrations, 3.5 and 7 μg/L, for 24, 72 and 96 h, maintaining ten animals in each group. Chlordecone treatment did not alter the body weight of the animal. However, significant increase in the secretion of mucous and decrease in the weights of gill, brain and hepatosomatic index were observed at 7 μg/L of chlordecone treatment only after 96 h. Gill tissue showed significant increase in the activities of superoxide dismutase, catalase and glutathione reductase along with elevated levels of hydrogen peroxide and lipid peroxidation in concentration and timedependent manner. This could be the defensive mechanism of gill tissue to escape the toxic effects of chlordecone. In the liver tissue, superoxide dismutase activity was increased by 39% at 3.5 μg/L and by 73% at 7 μg/L of chlordecone treatment. Activities of catalase and glutathione reductase were decreased 3 to 9 times at 3.5 and 7 μg/L concentrations, respectively, with concomitant increase in hydrogen peroxide generation (17 to 28 times) and lipid peroxidation (3 to 7 times) at the end of 96 h, which reveals the failure of hepatic antioxidant system to prevent free radical generation owing to chlordecone exposure. Activities of all antioxidant enzymes in the brain were inhibited by 29 to 80% along with the induction of hydrogen peroxide (13 to 20 times) and lipid peroxidation (6 to 11 times), thereby indicating imbalance in the antioxidant status. Activities of gill and liver marker enzyme - alkaline phosphatase - and acetylcholinesterase in brain were decreased. Therefore, imbalance in the antioxidant defence system as a result of chlordecone toxicity could lead to susceptible oxidative stress in various tissues of the fish.

Prenatal exposure to chlordecone, gestational weight gain, and birth weight in a Guadeloupean birth cohort

BackgroundChlordecone is a persistent organochlorine insecticide with well-defined estrogenic properties. It was intensively used in the French West Indies until 1993 to control the banana root borer. Because of the long-term contamination of soils and water, the population is currently exposed to chlordecone through food consumption. Chlordecone has been found in the blood of pregnant women and in cord blood. It has been shown to be an endocrine-disrupting chemical and exposure during pregnancy may affect fetal growth. ObjectivesThe objective of our study was to examine the association between prenatal exposure to chlordecone and fetal growth based on the TIMOUN birth cohort conducted in Guadeloupe, with a focus on the potential modification of this relationship by maternal body mass index (BMI) and gestational weight gain (GWG). MethodsChlordecone was determined in cord plasma at birth in 593 babies. Birth weight was the indicator of fetal growth. Maternal pre-pregnancy BMI and GWG were determined. Adherence to GWG recommendations of the US Institute of Medicine based on maternal pre-pregnancy BMI was assessed. Birth weight was analyzed relative to cord blood chlordecone levels using linear and non-linear regression models. ResultsOverall chlordecone in cord blood was not associated with birth weight, but we found an interaction between chlordecone exposure with GWG and adherence to GWG recommendations. After stratification by GWG, we found a significant U-shaped association between birth weight and chlordecone exposure, within the upper quartiles of GWG or excessive GWG. ConclusionChlordecone exposure may affect fetal growth, particularly when excessive GWG is present.

Public health and chronic low chlordecone exposure in Guadeloupe, Part 1: hazards, exposure-response functions, and exposures.

BackgroundInhabitants of Guadeloupe are chronically exposed to low dose of chlordecone via local food. The corresponding health impacts have not been quantified. Nevertheless the public authority implemented an exposure reduction program in 2003. We develop methods for quantifying the health impacts of chlordecone and present the results in 2 articles: 1. hazard identification, exposure-response functions (ERF) and exposure in Guadeloupe, 2. Health impacts and benefits of exposure reduction. Here is the first article.MethodsRelevant data are extracted from publications searched in Medline and Toxline. Available knowledges on mode of action and key-event hazards of chlordecone are used to identify effects of chlordecone that could occur at low dose. Then a linear ERF is derived for each possible effect. From epidemiological data, ERF is the delta relative risk (RR-1) divided by the corresponding delta exposure. From animal studies, ERF is the benchmark response (10 %) divided by the best benchmark dose modeled with BMDS2.4.0. Our goal is to obtain central values for the ERF slopes, applicable to typical human populations, rather than lower or upper bounds in the most sensitive species or sex.ResultsWe derive ERFs for 3 possible effects at chronic low chlordecone dose: cancers, developmental impairment, and hepatotoxicity. Neurotoxicity in adults is also a possible effect at low dose but we lack quantitative data for the ERF derivation. A renal toxicity ERF is derived for comparison purpose. Two ERFs are based on epidemiological studies: prostate cancer in men aged >44y (0.0019 per μg/Lblood) and altered neurodevelopment in boys (−0.32 QIpoint per μg/Lcord-blood). Two are based on animal studies: liver cancer (2.69 per mg/kg/d), and renal dysfunction in women (0.0022 per mg/kg/d).ConclusionThe methodological framework developed here yields ERFs for central risk estimates for non-genotoxic effects of chemicals; it is robust with regard to models used. This framework can be used generally to derive ERFs suitable for risk assessment and for cost-benefit analysis of public health decisions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0160-x) contains supplementary material, which is available to authorized users.

Transcriptome analysis of the copepod Eurytemora affinis upon exposure to endocrine disruptor pesticides: Focus on reproduction and development

Copepods—which include freshwater and marine species—represent the most abundant group of aquatic invertebrates. Among them, the calanoid copepod Eurytemora affinis is widely represented in the northern hemisphere estuaries and has become a species of interest in ecotoxicology. Like other non-target organisms, E. affinis may be exposed to a wide range of chemicals such as endocrine disruptors (EDs). This study investigated the gene expression variation in E. affinis after exposure to ED pesticides—chosen as model EDs—in order to (i) improve the knowledge on their effects in crustaceans, and (ii) highlight relevant transcripts for further development of potential biomarkers of ED exposure/effect. The study focused on the reproduction function in response to ED. Copepods were exposed to sublethal concentrations of pyriproxyfen (PXF) and chlordecone (CLD) separately. After 48h, males and females (400 individuals each) were sorted for RNA extraction. Their transcriptome was pyrosequenced using the Illumina® technology. Contigs were blasted and functionally annotated using Blast2GO®. The differential expression analysis between ED- and acetone-exposed organisms was performed according to sexes and contaminants. Half of the 19,721 contigs provided by pyrosequencing were annotated, mostly (80%) from arthropod sequences. Overall, 2,566 different genes were differentially expressed after ED exposures in comparison with controls. As many genes were differentially expressed after PXF exposure as after CLD exposure. In contrast, more genes were differentially expressed in males than in females after both exposures. Ninety-seven genes overlapped in all conditions. Finally, 31 transcripts involved in reproduction, growth and development, and changed in both chemical exposures were selected as potential candidates for future development of biomarkers.

Evaluation of the ecotoxicological impact of the organochlorine chlordecone on soil microbial community structure, abundance, and function.

The insecticide chlordecone applied for decades in banana plantations currently contaminates 20,000 ha of arable land in the French West Indies. Although the impact of various pesticides on soil microorganisms has been studied, chlordecone toxicity to the soil microbial community has never been assessed. We investigated in two different soils (sandy loam and silty loam) exposed to different concentrations of CLD (D0, control; D1 and D10, 1 and 10 times the agronomical dose) over different periods of time (3, 7, and 32 days): (i) the fate of chlordecone by measuring (14)C-chlordecone mass balance and (ii) the impact of chlordecone on microbial community structure, abundance, and function, using standardized methods (-A-RISA, taxon-specific quantitative PCR (qPCR), and (14)C-compounds mineralizing activity). Mineralization of (14)C-chlordecone was inferior below 1 % of initial (14)C-activity. Less than 2 % of (14)C-activity was retrieved from the water-soluble fraction, while most of it remained in the organic-solvent-extractable fraction (75 % of initial (14)C-activity). Only 23 % of the remaining (14)C-activity was measured in nonextractable fraction. The fate of chlordecone significantly differed between the two soils. The soluble and nonextractable fractions were significantly higher in sandy loam soil than in silty loam soil. All the measured microbiological parameters allowed discriminating statistically the two soils and showed a variation over time. The genetic structure of the bacterial community remained insensitive to chlordecone exposure in silty loam soil. In response to chlordecone exposure, the abundance of Gram-negative bacterial groups (β-, γ-Proteobacteria, Planctomycetes, and Bacteroidetes) was significantly modified only in sandy loam soil. The mineralization of (14)C-sodium acetate and (14)C-2,4-D was insensitive to chlordecone exposure in silty loam soil. However, mineralization of (14)C-sodium acetate was significantly reduced in soil microcosms of sandy loam soil exposed to chlordecone as compared to the control (D0). These data show that chlordecone exposure induced changes in microbial community taxonomic composition and function in one of the two soils, suggesting microbial toxicity of this organochlorine.

Chlordecone exposure and adverse effects in French West Indies populations.

Chlordecone (Kepone) is an organochlorine insecticide that has been used as insecticide and fungicide. In the French West Indies, Guadeloupe and Martinique, it was intensively applied to banana fields from 1973 to 1993 to control root borers. This pesticide undergoes no significant biotic or abiotic degradation in the environment and is still present in soils where it was applied. It was only in 1999 that health and environmental authorities became aware of the extent of the chlordecone pollution of environmental media, including soils, waterways, and the food chain. Earlier observations and toxicological studies have demonstrated that chlordecone is a reproductive and developmental toxicant, neurotoxic and carcinogenic in rodents, and is an endocrine-disrupting chemical because of its estrogenic properties both in vitro and in vivo. Several surveys have confirmed that the French West Indian population continues to be exposed to this chemical though consumption of contaminated foodstuffs. Here, we report the findings of various epidemiological studies conducted in the French West Indies to assess the impact of environmental exposure to chlordecone on the health of the population.