Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother–child cohort

International audiencePyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend = 0.04 and P-trend < 0.01, respectively) and with working memory scores (P-trend = 0.05 and P-trend < 0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6 years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importanc

Urinary Biomarkers of Prenatal Atrazine Exposure and Adverse Birth Outcomes in the PELAGIE Birth Cohort

Background: Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies—and fewer epidemiologic investigations—have examined the potential effects of prenatal exposure

Probabilistic dietary exposure to phycotoxins in a recreational shellfish harvester subpopulation (France).

International audiencePhycotoxins, secondary phytoplankton metabolites, are considered as an important food safety issue because their accumulation by shellfish may render them unfit for human consumption. However, the likely intakes of phycotoxins via shellfish consumption are almost unknown because both contamination and consumption data are very scarce. Thus, two 1-year surveys were conducted (through the same population: recreational shellfish harvesters and from the same geographical area) to assess: shellfish consumption and contamination by major toxins (domoic acid (DA) group, okadaic acid (OA) group and spirolides (SPXs)). Recreational shellfish harvesters had been targeted as an at-risk subpopulation because they consume more shellfish than general population and because they eat not only commercial shellfish species controlled by official authorities but also their own harvests of shellfish species may be in non-controlled areas and more over shellfish species non-considered in the official control species. Then, these two kinds of data were combined with deterministic and probabilistic approaches for both acute and chronic exposures, on considering the impact of shellfish species and cooking on phycotoxin levels. For acute risk, monitoring programs seem to be adequate for DAs, whereas OAs could be a matter of concern for high consumers (their acute intakes were up to ninefold the acute reference dose (ARfD)). About chronic risk, OAs are a matter of concern. The daily OAs intakes were close to the ARfD, which is, by definition, greater than the tolerable daily intake. Moreover, SPX contamination is low but regular, no (sub)chronic SPX toxicity data exist; but in case of (sub)chronic toxicity, SPX exposure should be considered.Journal of Exposure Science and Environmental Epidemiology advance online publication, 4 July 2012; doi:10.1038/jes.2012.44

Biomarqueurs urinaires d'exposition aux pesticides des femmes enceintes de la cohorte Pélagie réalisée en Bretagne (2002-2006)

International audienceBien qu'essentiellement agricole, l'usage des pesticides est varié et les sources d'exposition de la population aux pesticides sont multiples. Les niveaux d'imprégnation de la population générale aux pesticides sont méconnus en France et dans la majorité des pays européens. La mesure de l'exposition par des biomarqueurs d'exposition a l'avantage d'intégrer toutes les voies possibles d'exposition. Compte-tenu de la sensibilité particulière des fœtus aux toxiques, évaluer l'exposition des femmes enceintes est une question majeure de santé publique. La cohorte Pélagie a inclus près de 3 500 femmes enceintes en Bretagne entre 2002 et 2006. La collecte d'échantillons urinaires en début de grossesse et des dosages chimiques de pesticides pour 546 échantillons urinaires ont été réalisés. L'objectif était d'évaluer le niveau et l'étendue de l'imprégnation des femmes enceintes aux pesticides, en particulier aux herbicides de la familles des triazines, interdits d'usage en France depuis fin 2003 mais toujours présents dans l'environnement, et aux insecticides organophosphorés, d'usages agricoles et non agricoles. Les résultats indiquent la présence de traces de pesticides dans la majorité des urines des femmes enceintes, certaines molécules étant des produits de dégradation persistants dans l'environnement de molécules-mères. Ces résidus de pesticides sont généralement multiples et leurs impacts, individuels ou conjoints, sur le foetus et son développement sont encore incertains dans la littérature épidémiologique. Ils seront évalués prochainement dans la cohorte Pélagie

Domoic Acid, Okadaic Acid and Spirolides: Inter-Species Variability in Contamination and Cooking Effects

International audienceThe inter-species variability of contamination by domoic acid (DA), okadaic acid and analogues (OAs) and spirolides (SPX) in mussels, oysters, cockles, carpet shell clams and razor clams was assessed. DA concentrations were measured using both high performance liquid chromatography (HPLC) with Ultra Violet (UV) detection and HPLC coupled with tandem mass spectrometry (HPLC-MS/MS); OAs and SPX were measured using HPLC-MS/MS. Observations showed that for each phycotoxin, the contamination rates are species-dependent and the most contaminated species differ according to the kind of phycotoxin. For DA and SPX, cockles appear to be the most contaminated species whereas mussels seem to be the predominant vector for OAs. The effect of cooking process on DA concentrations was investigated in five different bivalve species by comparing toxin concentrations in whole raw flesh with concentrations in whole cooked flesh. The DA concentration decreased in cooked cockles and razor clams whereas it increased in cooked mussels, carpet shell clams and donax. Thus the impact of cooking is bivalve species-dependent. For OAs and SPX, the cooking process was studied on mussels and resulted in an increase in the toxin concentration because of their lipophilic nature. These results should be taken into consideration in exposure assessments and in the design of regulatory monitoring programs, as the current banning levels based on raw bivalves may over- or under-protect consumers when shellfish are eaten cooked

In-situ microcosms, a tool for assessment of pesticide impacts on oyster spat (Crassostrea gigas)

International audienceEffects of the herbicide Basamais (bentazon) and the fungicide Opus (epoxiconazole) on oyster spat (Crassostrea gigas) were assessed using in-situ microcosms in a field experiment lasting 13 days. Six-week-old hatchery spat (mean size 1.1 mm), previously collected on PVC plates, was immersed in glass bottles filled with 200 mu m filtered seawater. Bottles were maintained underwater at 6 m depth and their water content changed every other day. Growth, measured as shell area index increase, was 126 +/- 4% in the control bottles. While no growth differences were observed between control and individual pesticide treatments at 10 mu g l(-1), oysters treated with a mix of 10 mu g l(-1) Opus and 10 mu g l(-1) Basamais showed a 50% growth reduction compared with the control (P < 0.0001), suggesting a synergistic effect of these contaminants. Laboratory controls in microcosms maintained in a water bath with filtered natural light, were not significantly different from in-situ microcosm controls in the field, for organic weight content or growth. This in-situ experiment in microcosms allowed us to conclude that: (1) oyster spat can achieve significant growth in bottles immersed in situ without supplementary food; (2) this microcosm system is reliable and easy to use for environmental toxicity tests with C. gigas spat; (3) such microcosm systems can also be run in a laboratory water bath instead of more technically difficult immersed field experiments; (4) the synergistic effect observed here, at a concentration simulating a peak agricultural runoff event, suggests that the impacts of pesticides could be a real threat for oysters in estuarine areas

Prenatal exposure to organophosphate pesticides and autism spectrum disorders in 11-year-old children in the French PELAGIE cohort

International audienceBackground: Organophosphate (OP) pesticides act by inhibiting acetylcholinesterase activity at synaptic junctions and have already been linked with deleterious effects on neurodevelopment, including autism spectrum disorders (ASD).Objectives: To investigate the association of prenatal exposure to OP pesticides with traits related to ASD in 11-year-old children.Methods: The "Childhood Autism Spectrum Test" (CAST) parent questionnaire was used to screen for autistic traits in 792 children from the French PELAGIE cohort. Prenatal maternal urine samples were collected 80%), terbufos and its metabolites least often (<10%). No association with ASD was found for DAP, terbufos or its metabolites. Incidence rate ratios (IRRs) increased with maternal urinary diazinon concentrations, from 1.11 (95% CI: 0.87-1.42) to 1.17 (95% CI: 0.94-1.46). Higher CAST scores were statistically significantly associated with the maternal urine samples in which chlorpyrifos or two of its metabolites (chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol) were detected. The IRR for exposure to chlorpyrifos or chlorpyrifos-oxon was 1.27 (95%CI: 1.05-1.52) among all children, and 1.39 (95%CI: 1.07-1.82) among boys.Conclusion: These findings suggest an increase in autistic traits among 11-year-old children in association with prenatal maternal exposure to chlorpyrifos and possibly diazinon. These associations were previously suspected in the literature, in particular for chlorpyrifos. Further work establishing the causal mechanisms behind these risk association is needed

Air pollution by pesticides and maternal urinary biomarkers in association with head circumference at birth

International audienc

Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort

International audienceObjective The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds. Methods The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Results Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03). Conclusions The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age

Combined effects of antifouling biocides on the growth of three marine microalgal species

The toxicity of the antifouling compounds diuron, irgarol, zinc pyrithione (ZnPT), copper pyrithione (CuPT) and copper was tested on the three marine microalgae Tisochrysis lutea, Skeletonema marinoi and Tetraselmis suecica. Toxicity tests based on the inhibition of growth rate after 96-h exposure were run using microplates. Chemical analyses were performed to validate the exposure concentrations and the stability of the compounds under test conditions. Single chemicals exhibited varying toxicity depending on the species, irgarol being the most toxic chemical and Cu the least toxic. Selected binary mixtures were tested and the resulting interactions were analyzed using two distinct concentration-response surface models: one using the concentration addition (CA) model as reference and two deviating isobole models implemented in R software; the other implementing concentration-response surface models in Excel®, using both CA and independent action (IA) models as reference and three deviating models. Most mixtures of chemicals sharing the same mode of action (MoA) were correctly predicted by the CA model. For mixtures of dissimilarly acting chemicals, neither of the reference models provided better predictions than the other. Mixture of ZnPT together with Cu induced a strong synergistic effect on T. suecica while strong antagonism was observed on the two other species. The synergy was due to the transchelation of ZnPT into CuPT in the presence of Cu, CuPT being 14-fold more toxic than ZnPT for this species. The two modelling approaches are compared and the differences observed among the interaction patterns resulting from the mixtures are discussed