Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism.

BACKGROUND AND AIMS: Chlordecone is a persistent organochlorinated insecticide, extensively used in the French West Indies and has been contaminating the population for more than thirty years. Its potentiation effect on hepatotoxic agents has been demonstrated in animal models. We investigated the relationship between environmental exposure to chlordecone and the progression of liver fibrosis. METHODS: This study included 182 consecutive patients with chronic alcoholic hepatitis whose liver fibrosis was assessed using non-invasive methods. Measured plasma chlordecone concentrations at inclusion were used as surrogate of long-term exposure under steady-state conditions. As the pharmacokinetic processing of chlordecone is largely determined by the liver, we used a human physiologically based pharmacokinetic model to predict plausible changes in the steady-state blood chlordecone concentrations induced by liver fibrosis. RESULTS: With a median follow-up of 27.1 years after the onset of alcohol consumption, we found a significant decrease in the risk of advanced liver fibrosis with increasing plasma chlordecone concentration (adjusted hazard ratio = 0.56; 95% confidence interval: 0.34-0.95 for the highest vs. lowest tertile, p = 0.04). Changes induced by liver fibrosis influenced the pharmacokinetic processing of chlordecone, resulting in substantial modifications in its steady-state blood concentrations. CONCLUSION: According to this human model of coexposure to alcohol, reverse causality is the most plausible explanation of this inverse association between plasma chlordecone concentrations and progression of liver fibrosis. This study underlines the importance of considering the pharmacokinetic of environmental contaminants in epidemiological studies when biomarkers of exposure are used to investigate their own impact on the liver. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03373396.

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

BACKGROUND: Chlordecone 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. OBJECTIVE: To assess the associations between pre- and postnatal exposures to chlordecone and cognitive and behavioral functions in school-aged children from Guadeloupe. METHODS: We 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. RESULTS: Geometric 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. CONCLUSIONS: These 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.

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

BACKGROUND: Exposure 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. METHODS: Within 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. RESULTS: Prenatal 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. CONCLUSION: Globally, 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.

Endocrine disrupting-chemicals and biochemical recurrence of prostate cancer after prostatectomy: A cohort study in Guadeloupe (French West Indies).

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39-4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.

Persistent Organic Pollutant Burden, Experimental POP Exposure, and Tissue Properties Affect Metabolic Profiles of Blubber from Gray Seal Pups.

Persistent organic pollutants (POPs) are toxic, ubiquitous, resist breakdown, bioaccumulate in living tissue, and biomagnify in food webs. POPs can also alter energy balance in humans and wildlife. Marine mammals experience high POP concentrations, but consequences for their tissue metabolic characteristics are unknown. We used blubber explants from wild, gray seal ( Halichoerus grypus) pups to examine impacts of intrinsic tissue POP burden and acute experimental POP exposure on adipose metabolic characteristics. Glucose use, lactate production, and lipolytic rate differed between matched inner and outer blubber explants from the same individuals and between feeding and natural fasting. Glucose use decreased with blubber dioxin-like PCBs (DL-PCB) and increased with acute experimental POP exposure. Lactate production increased with DL-PCBs during feeding, but decreased with DL-PCBs during fasting. Lipolytic rate increased with blubber dichlorodiphenyltrichloroethane and its metabolites (DDX) in fasting animals, but declined with DDX when animals were feeding. Our data show that POP burdens are high enough in seal pups to alter adipose function early in life, when fat deposition and mobilization are vital. Such POP-induced alterations to adipose metabolic properties may significantly alter energy balance regulation in marine top predators, with the potential for long-term impacts on fitness and survival.

Proteomic response of Macrobrachium rosenbergii hepatopancreas exposed to chlordecone: Identification of endocrine disruption biomarkers?

The present work is the first study investigating the impacts of chlordecone, an organochlorine insecticide, on the proteome of the decapod crustacean Macrobrachium rosenbergii, by gel-free proteomic analysis. The hepatopancreas protein expression variations were analysed in organisms exposed to three environmental relevant concentrations of chlordecone (i.e. 0.2, 2 and 20µg/L). Results revealed that 62 proteins were significantly up- or down-regulated in exposed prawns compared to controls. Most of these proteins are involved in important physiological processes such as ion transport, defense mechanisms and immune system, cytoskeleton dynamics, or protein synthesis and degradation. Moreover, it appears that 6% of the deregulated protein are involved in the endocrine system and in the hormonal control of reproduction or development processes of M. rosenbergii (e.g. vitellogenin, farnesoic acid o-methyltransferase). These results indicate that chlordecone is potentially an endocrine disruptor compound for decapods, as already observed in vertebrates. These protein modifications could lead to disruptions of M. rosenbergii growth and reproduction, and therefore of the fitness population on the long-term. Besides, these disrupted proteins could be suggested as biomarkers of exposure for endocrine disruptions in invertebrates. However, further investigations are needed to complete understanding of action mechanisms of chlordecone on proteome and endocrine system of crustaceans.

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

BACKGROUND: Chlordecone 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. OBJECTIVES: The 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). METHODS: Chlordecone 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. RESULTS: Overall 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. CONCLUSION: Chlordecone exposure may affect fetal growth, particularly when excessive GWG is present.

Optimizing the design of a reproduction toxicity test with the pond snail Lymnaea stagnalis.

This paper presents the results from two ring-tests addressing the feasibility, robustness and reproducibility of a reproduction toxicity test with the freshwater gastropod Lymnaea stagnalis (RENILYS strain). Sixteen laboratories (from inexperienced to expert laboratories in mollusc testing) from nine countries participated in these ring-tests. Survival and reproduction were evaluated in L. stagnalis exposed to cadmium, tributyltin, prochloraz and trenbolone according to an OECD draft Test Guideline. In total, 49 datasets were analysed to assess the practicability of the proposed experimental protocol, and to estimate the between-laboratory reproducibility of toxicity endpoint values. The statistical analysis of count data (number of clutches or eggs per individual-day) leading to ECx estimation was specifically developed and automated through a free web-interface. Based on a complementary statistical analysis, the optimal test duration was established and the most sensitive and cost-effective reproduction toxicity endpoint was identified, to be used as the core endpoint. This validation process and the resulting optimized protocol were used to consolidate the OECD Test Guideline for the evaluation of reproductive effects of chemicals in L. stagnalis.

POPs in free-ranging pilot whales, sperm whales and fin whales from the Mediterranean Sea: Influence of biological and ecological factors.

The pilot whale Globicephala melas, the sperm whale Physeter macrocephalus, and the fin whale Balaenoptera physalus are large cetaceans permanently inhabiting the Mediterranean Sea. These species are subjected to numerous anthropogenic threats such as exposure to high levels of contaminants. Therefore, selected persistent organic pollutants POPs (29 PCBs, 15 organochlorine compounds, 9 PBDEs and 17 PCDD/Fs) were analysed in blubber biopsies of 49 long-finned pilot whales, 61 sperm whales and 70 fin whales sampled in the North Western Mediterranean Sea (NWMS) from 2006 to 2013. Contamination profile and species feeding ecology were then combined through the use of stable isotopes. δ(13)C, δ(15)N values and POPs levels were assessed through IR-MS and GC-MS respectively. To assess the toxic potency of the dioxin-like compounds, the TEQ approach was applied. δ(15)N values were 12.2±1.3‰ for sperm whales, 10.5±0.7‰ for pilot whales and 7.7±0.8‰ in fin whales, positioning sperm whales at higher trophic levels. δ(13)C of the two odontocetes was similar and amounted to -17.3±0.4‰ for sperm whales and -17.8±0.3‰ for pilot whales; whilst fin whales were more depleted (-18.7±0.4‰). This indicates a partial overlap in toothed-whales feeding habitats, while confirms the differences in feeding behaviour of the mysticete. Pilot whales presented higher concentrations than sperm whales for ΣPCBs (38,666±25,731 ng g(-1)lw and 22,849±15,566 ng g(-1) lw respectively), ΣPBDEs (712±412 ng g(-1) lw and 347±173 ng g(-1) lw respectively) and ΣDDTs (46,081±37,506 ng g(-1) lw and 37,647±38,518 ng g(-1) lw respectively). Fin whales presented the lowest values, in accordance with its trophic position (ΣPCBs: 5721±5180 ng g(-1) lw, ΣPBDEs: 177±208 ng g(-1) lw and ΣDDTs: 6643±5549 ng g(-1) lw). Each species was characterized by large inter-individual variations that are more related to sex than trophic level, with males presenting higher contaminant burden than females. The discriminant analysis (DA) confirmed how DDTs and highly chlorinated PCBs were influential in differentiating the three species. Pollutant concentrations of our species were significantly higher than both their Southern Hemisphere and North Atlantic counterparts, possibly due to the particular Mediterranean geomorphology, which influences pollutants distribution and recycle. Dioxin-like PCBs accounted for over 80% of the total TEQ. This study demonstrated (1) an important exposure to pollutants of Mediterranean cetaceans, often surpassing the estimated threshold toxicity value of 17,000 ng g(-1) lw for blubber in marine mammals; and (2) how the final pollutant burden in these animals is strongly influenced not only by the trophic position but also by numerous other factors such as sex, age, body size and geographical distribution.

Changes in antitoxic defense systems of the freshwater amphipod Gammarus pulex exposed to BDE-47 and BDE-99.

Polybrominated diphenyl ethers (PBDEs) are emerging pollutants widely distributed in aquatic environment. Although the bioaccumulation of this compound has been well studied, few studies have investigated their impacts on antitoxic systems of invertebrates, considering both genders. Here, we have evaluated the effects of BDE-47 and BDE-99 congeners on the antitoxic defence systems of the freshwater amphipod Gammarus pulex, and especially on the multixenobiotic resistance (MXR) activity, as well as the activities of two antitoxic enzymes, the glutathione-S-transferase (GST) and the glutathione peroxidases (GPx). Results revealed that BDE-47 and BDE-99 have inhibited the MXR activity whatever the gammarid gender, which could lead to a reduction of the pollutant elimination from the organism. In addition, a gender-biased response and a congener-biased effect on the antitoxic enzymes activities were observed. Indeed, both BDE congener exposures increased the GST activity in males, whereas in females, only BDE-99 congener modified this activity by decreasing it. On the contrary, BDE exposures did not impact the GPx activity in females, while in males BDE-99 has increased it. Results of the present study highlight that a PBDE exposure at 0.1 µg L(-1) modify antitoxic enzymes activities differently according to gender, which could lead to a change in G. pulex sensitivity on the long term. Finally, this work confirms the ecotoxicological implication of gender in the pollutant toxicity assessment, in order to evaluate impact on populations.

Chlordecone exposure, length of gestation, and risk of preterm birth.

Persistent organic pollutants have not been conclusively associated with length of gestation or with preterm birth. Chlordecone is an organochlorine pesticide that has been extensively used to control the banana root borer population in the French West Indies. Data from the Timoun Mother-Child Cohort Study conducted in Guadeloupe between 2004 and 2007 were used to examine the associations of chlordecone concentrations in maternal plasma with the length of gestation and the rate preterm birth in 818 pregnant women. Data were analyzed using multivariate linear regression for length of gestation and a Cox model for preterm birth. The median plasma chlordecone concentration was 0.39 µg/L (interquartile range, 0.18-0.83). No correlation was observed with plasma concentrations of p,p'-dichlorodiphenyl dichloroethene (ρ = 0.017) or polychlorinated biphenyl 153 (ρ = -0.016), the other main organochlorine compounds detected. A 1-log10 increase in chlordecone concentration was associated with a decreased length of gestation (-0.27 weeks; 95% confidence interval: -0.50, -0.03) and an increased risk of preterm birth (60%; 95% confidence interval: 10, 130). These associations may result from the estrogen-like and progestin-like properties of chlordecone. These results are of public health relevance because of the prolonged persistence of chlordecone in the environment and the high background rate of preterm births in this population.

Localization and in situ absolute quantification of chlordecone in the mouse liver by MALDI imaging.

Chlordecone is an organochlorine pesticide that was extensively used in the French West Indies to fight weevils in banana plantations from 1973 to 1993. This has led to a persistent pollution of the environment and to the contamination of the local population for several decades with effects demonstrated on human health. Chlordecone accumulates mainly in the liver where it is known to potentiate the action of hepatotoxic agents. However, there is currently no information on its in situ localization in the liver. We have thus evaluated a matrix-assisted laser desorption ionization (MALDI) imaging quantification method based on labeled normalization for the in situ localization and quantification of chlordecone. After validating the linearity and the reproducibility of this method, quantitative MALDI imaging was used to study the accumulation of chlordecone in the mouse liver. Our results revealed that normalized intensities measured by MALDI imaging could be first converted in quantitative units. These quantities appeared to be different from absolute quantities of chlordecone determined by gas chromatography (GC), but they were perfectly correlated (R(2) = 0.995). The equation of the corresponding correlation curve was thus efficiently used to convert quantities measured by MALDI imaging into absolute quantities. Our method combining labeled normalization and calibration with an orthogonal technique allowed the in situ absolute quantification of chlordecone by MALDI imaging. Finally, our results obtained on the pathological mouse liver illustrate the advantages of quantitative MALDI imaging which preserves information on in situ localization without radioactive labeling and with a simple sample preparation.

Effect of a Mediterranean diet during pregnancy on fetal growth and preterm delivery: results from a French Caribbean Mother-Child Cohort Study (TIMOUN).

BACKGROUND: Recent studies suggest that a Mediterranean dietary pattern during pregnancy may influence pregnancy outcomes. The aim of this study was to evaluate the effect of adherence to a Mediterranean diet (MD) during pregnancy on fetal growth restriction (FGR) and preterm delivery (PTD) in a French Caribbean island where the population is largely of African descent and presents dietary patterns similar to MD. METHODS: Using data from the TIMOUN Mother-Child Cohort Study conducted in Guadeloupe (French West Indies) between 2004 and 2007, we analysed data for 728 pregnant women who delivered liveborn singletons without any major congenital malformations. Degree of adherence to MD during pregnancy was evaluated with a semi-quantitative food frequency questionnaire based on nine dietary criteria. Multiple logistic regression models were used to analyse birth outcomes while taking potential confounders into account. RESULTS: Overall there was no association between MD adherence during pregnancy and the risk of PTD or FGR. However, pre-pregnancy body mass index was a strong effect modifier, and MD adherence was associated with a decreased risk of PTD specifically in overweight and obese women (adjusted odds ratio 0.7, 95% confidence interval 0.6, 0.9) (P heterogeneity <0.01). CONCLUSIONS: These results suggest that Caribbean diet during pregnancy may carry some benefits of MD and may contribute to reduce the risk of PTD in overweight and obese pregnant women.

Validation of an HPLC-MS/MS method with QuEChERS extraction using isotopic dilution to analyze chlordecone in human serum.

Until 1993, chlordecone (CLD) was extensively used in banana fields in French West Indies. In a previous study, CLD was detected in 90 % of Martinican and Guadeloupean adult's serum. In order to simplify the analyses of CLD in the serum, a new QuEChERS-HPLC-MS/MS method was implemented and validated by the Pasteur Institute of Guadeloupe (IPG). This method was validated with accuracy profiles according to the French Standard NF V03-110 plus the ISO 15189 and European guidelines. Linearity, repeatability, accuracy, intermediate precision, specificity, limit of detection (LOD), limit of quantification (LOQ) and uncertainty were determined. The accuracy profile allowed the method to be validated between 0.06  µg L-1 and 1.00  µg L-1 of serum. The LOD was 0.02  µg L-1, the LOQ was 0.06  µg L-1 and the uncertainty of the method was 21 %. A comparison of 49 serum samples between the IPG (LC-MS/MS) and the LEAE-CART (GC-HRMS) laboratories demonstrated that this new method can reliably determine CLD in human serum. Stability tests were performed and duration of the storage of raw samples and extracts before analysis by HPLC-MS/MS. Raw samples were stable after collection for at least one week at 5 °C or 25 °C and for at least 3 months at -20 °C. Extracts in acetonitrile were stable for at least 1 month at -20 °C. These stability results facilitate the daily use of the method. This method should help the entire population of Guadeloupe and Martinique by allowing a routinely analyzed for CLD and will be useful for future projects aimed at improving population health monitoring.

Precision-cut liver slices to investigate responsiveness of deep-sea fish to contaminants at high pressure.

While deep-sea fish accumulate high levels of persistent organic pollutants (POPs), the toxicity associated with this contamination remains unknown. Indeed, the recurrent collection of moribund individuals precludes experimental studies to investigate POP effects in this fauna. We show that precision-cut liver slices (PCLS), an in vitro tool commonly used in human and rodent toxicology, can overcome such limitation. This technology was applied to individuals of the deep-sea grenadier Coryphaenoides rupestris directly upon retrieval from 530-m depth in Trondheimsfjord (Norway). PCLS remained viable and functional for 15 h when maintained in an appropriate culture media at 4 °C. This allowed experimental exposure of liver slices to the model POP 3-methylcholanthrene (3-MC; 25 µM) at levels of hydrostatic pressure mimicking shallow (0.1 megapascal or MPa) and deep-sea (5-15 MPa; representative of 500-1500 m depth) environments. As in shallow water fish, 3-MC induced the transcription of the detoxification enzyme cytochrome P4501A (CYP1A; a biomarker of exposure to POPs). This induction was diminished at elevated pressure, suggesting a limited responsiveness of C. rupestris toward POPs in its native environment. This very first in vitro toxicological investigation on a deep-sea fish opens the route for understanding pollutants effects in this highly exposed fauna.

Cognitive, visual, and motor development of 7-month-old Guadeloupean infants exposed to chlordecone.

BACKGROUND: The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally. OBJECTIVES: The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. METHODS: Infants were tested at 7 months (n=153). Visual recognition memory and processing speed were assessed with the Fagan Tests of Infant Intelligence (FTII), visual acuity with the Teller Acuity Card, and fine motor development with the Brunet-Lezine. Samples of cord blood and breast milk at 3 months (n=88) were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. RESULTS: Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group (ß=-0.19, p=0.02). Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference (ß=-0.14, p=0.07), and longer processing speed (ß=0.16, p=0.07). Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale (OR=1.25, p<0.01). CONCLUSION: These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.

Differential changes of fat-soluble vitamins and pollutants during lactation in northern elephant seal mother-pup pairs.

We investigated the changes of vitamins A and E as well as PCBs and DDTs during lactation in northern elephant seal (Mirounga angustirostris) mother-pup pairs. On average, milk vitamin A concentrations were 6 times higher during late lactation than during early lactation, a pattern that differs dramatically from terrestrial mammals. Vitamin A concentrations also significantly increased in the inner blubber throughout lactation, whereas they remained constant in the outer blubber. Similar dynamics were observed for PCBs and DDTs in maternal blubber and milk. Blubber appears to be an important storage site for vitamin A and organochlorines in seals and a direct transfer of those molecules to the mammary gland may occur. The dynamics of vitamin A, PCBs and DDTs differed from those of vitamin E. There was a significant drop in milk vitamin E concentrations between early and late lactation, which is the usual pattern observed in terrestrial mammals. The dynamics of vitamin E in the blubber layers also differed from those of vitamin A, suggesting different mechanisms of mobilization and transfer into the milk.

Using sets of behavioral biomarkers to assess short-term effects of pesticide: a study case with endosulfan on frog tadpoles.

Pesticides and other chemicals often have detrimental effects at environmental concentrations. Many amphibian species are particularly threatened because of their susceptibility but also because wetlands are often polluted. Behavioral assessments of toxicity have the advantage of showing sublethal effects but quantitative measures at varied scales of integrations are rarely considered together. In this study, we aimed at showing that these behavioral endpoints could be differently affected across time and concentrations, and be biomarkers of toxicity. To this end, we tested the effects of an organochlorine pesticide (endosulfan) on amphibians during a standard 96 h test. We evaluated possible lag effects in continuing the analyses after removal of the pesticide. The study was based on 240 tadpoles (4 pesticide treatments: 0.4, 3, 22, and 282 µg/l, 1 control and 1 solvent-control). Abnormal behaviors such as lying and swirling rapidly were exhibited only in the presence of the pesticide. Essential functions such as breathing and feeding were deeply affected by the pesticide: contaminated tadpoles breathed and fed less than control tadpoles. They also moved less and occupied a more central position in the aquariums in the presence of the pesticide. A higher mortality was only found at the highest concentration. These results suggest that endosulfan is toxic to amphibians at environmental concentrations. Behavioral markers showed potential as early warning systems. They should thus be used in complement to other markers to detect sublethal effects only a few days after application of the pesticide and at concentrations where mortality does not occur.

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

BACKGROUND: Chlordecone 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. OBJECTIVE: To 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. METHODS: We 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. RESULTS: Cord 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. CONCLUSIONS: These 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.

Environmental fate of chlordecone in coastal habitats: recent studies conducted in Guadeloupe and Martinique (Lesser Antilles).

The organochlorine pollution by chlordecone, an insecticide spread in the past in banana plantations, is now recognized as a major ecological, economic, and social crisis in Guadeloupe and Martinique Islands. Due to its physical and chemical properties, this molecule is particularly persistent in the natural environment. Volcanic soil of Guadeloupe and Martinique contain allophanes (amorphous clays), which favor chlordecone trapping due to their structure and physical properties. Thus, with this trapping ability, allophanes serve as a vector allowing chlordecone to contaminate runoff waters and, finally, the sea. In the present publication, several studies recently conducted in the Lesser Antilles have been compiled in order to evaluate the desorption of chlordecone from allophanes when arriving in the estuarine environment and to determine the transfer of chlordecone along marine trophic food webs. The experiments showed that 20% of the initial quantity of chlordecone was released from allophanes in estuarine conditions and 10% in the marine environment. These results could explain the high level of contamination found in the suspended organic matter and zooplankton in the coastal areas located downstream of the contaminated watersheds. The contamination of the marine food webs of mangroves, seagrass beds, and coral reefs is dominated by a contamination "by bath" in littoral waters containing chlordecone and by bioamplification seawards.