Gaël Durand

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. Objectives: We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor). Methods: This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation. Results: We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0–2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0–2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor. Conclusions: This study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use.

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

Pyrethroid 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 childrens 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 6years 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 childrens 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 6years 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 importance.

Impact on fetal growth of prenatal exposure to pesticides due to agricultural activities: a prospective cohort study in Brittany, France

BackgroundPesticide use is widespread in agriculture. Several studies have shown that pesticides used in agricultural fields can contaminate the domestic environment and thus be an important source of pesticide exposure of populations residing nearby. Epidemiological studies that have examined the health effects of in utero pesticide exposure from residence near agricultural activities suggest adverse effects, but the results are inconsistent. Our purpose was to investigate the effect on intrauterine growth of such exposure due to agricultural activities in the residential municipality.MethodsA prospective birth cohort recruited 3421 pregnant women in a French agricultural region (Brittany, 2002-2006) through gynecologists, ultrasonographers, and maternity hospitals during routine prenatal care visits before 19 weeks of gestation. The national agricultural census in 2000 provided the percentages of the municipality area devoted to cultivation of corn, wheat, colza, peas, potatoes, and fresh vegetables.ResultsBirth weight and the risk of fetal growth restriction were not associated with agricultural activities in the municipality of residence in early pregnancy. Children whose mother lived in a municipality where peas were grown had a smaller head circumference at birth than those in municipalities not growing peas (-0.2 cm, p = 0.0002). Head circumference also tended to be lower when wheat was grown, but not to a statistically significant degree (p-trend = 0.10). Risk of an infant with a small head circumference was higher for mothers living in a municipality where peas (OR = 2.2; 95% CI = 1.2-3.6) or potatoes (OR = 1.5; 95% CI = 0.9-2.4) were grown.ConclusionsAgricultural activities in the municipality of residence may have negative effects on cranial growth. Cultivation of pea crops and, to a lesser degree, potato and wheat crops, may negatively affect head circumference. Insecticides, including organophosphate insecticides, were applied to most of the area devoted to pea and potato crops; this was less true for corn and wheat crops. These results must be interpreted in light of the studys limitations, in particular, the scale at which we could assess pesticide exposure.

Environmental determinants of the urinary concentrations of herbicides during pregnancy: The PELAGIE mother–child cohort (France)

Herbicides are generally the most extensively used of the pesticides applied to agricultural crops. However, the literature contains little evidence useful in assessing the potential sources of the general populations exposure to herbicides, including by residential proximity to crops. The objective of this study was to take advantage of data from the PELAGIE mother-child cohort to identify the main determinants of the body burden of exposure to the chloroacetanilide and triazine herbicides commonly used on corn crops in Brittany, France, before 2006. Urine samples from a randomly selected subcohort of women in the first trimester of pregnancy (n=579) were assayed for herbicide metabolites. The residential exposure resulting from proximity to corn crops was assessed with satellite-image-based scores combined with meteorological data. Data on diet, drinking tap water (from the public water supply), occupations, and household herbicide use were collected by questionnaires. Herbicides were quantified in 5.3% to 39.7% of urine samples. Alachlor and acetochlor were found most frequently in the urine of women living in rural areas. The presence of dealkylated triazine metabolites in urine samples was positively associated with residential proximity to corn crops (OR=1.38, 95% CI: 1.05-1.80). Urinary metabolites of both atrazine and dealkylated triazine were correlated with tap water consumption (OR=2.94, 1.09-7.90, and OR=1.82, 1.10-3.03, respectively); hydroxylated triazine metabolites were correlated with fish intake (OR=1.48, 1.09-1.99). This study reinforces previous results that suggest that environmental contamination resulting from agricultural activities may contribute to the general populations exposure to herbicides.

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

Phycotoxins, 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.

Organophosphate Insecticide Metabolites in Prenatal and Childhood Urine Samples and Intelligence Scores at 6 Years of Age: Results from the Mother–Child PELAGIE Cohort (France)

Background: Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children. Objectives: We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort. Methods: In 2002–2006, the PELAGIE mother–child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks’ gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) were administered when the children were 6 years of age to evaluate cognitive function (n = 231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used. Results: WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate (DE) metabolites (5.5; 95% CI: 0.8, 10.3 for > 13.2 nmol/L vs. < LOQ), whereas WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (–3.6; 95% CI: –7.8, –0.6 for > 11.1 nmol/L vs. < LOD). Conclusion: We found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the population’s socioeconomic status, which was higher than in previous studies, though other causal and noncausal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure. Citation: Cartier C, Warembourg C, Le Maner-Idrissi G, Lacroix A, Rouget F, Monfort C, Limon G, Durand G, Saint-Amour D, Cordier S, Chevrier C. 2016. Organophosphate insecticide metabolites in prenatal and childhood urine samples and intelligence scores at 6 years of age: results from the mother–child PELAGIE cohort (France). Environ Health Perspect 124:674–680; http://dx.doi.org/10.1289/ehp.1409472

Children’s contrast sensitivity function in relation to organophosphate insecticide prenatal exposure in the mother-child PELAGIE cohort

HIGHLIGHTSVery few studies in children have investigated the potential impact of prenatal exposure to organophosphate pesticides (OP) on sensory functions.The association between urinary OP metabolite levels collected in pregnant women and child’s visual contrast sensitivity was evaluated.Although no associations were observed in the entire sample, a OP‐related decrease in contrast sensitivity was observed in boys only. ABSTRACT Human exposure to organophosphate pesticides (OP) is widespread. Several studies suggest that OP prenatal exposure alters the development of cognitive and behavioural functions in children, but the effects of OP prenatal exposure on child sensory functions are largely unknown. The aim of the study was to evaluate the association between OP prenatal exposure and visual processing in school‐aged children from the mother‐child PELAGIE cohort (France). OP biomarkers of exposure were measured in maternal urine samples at the beginning of pregnancy. The Functional Acuity Contrast Test (FACT) was used to assess visual contrast sensitivity in 180 children at 6 years of age. Linear regression models were performed on all children, and separately for boys and girls, taking into account various potential confounders, including maternal education and breastfeeding. No associations were observed in the whole sample, while maternal OP urinary metabolite levels were associated with a decrease of FACT scores in boys. These findings indicate that OP prenatal exposure might impair visual processing later in life in boys only.

Urinary pesticide concentrations in French adults with low and high organic food consumption: results from the general population-based NutriNet-Santé

An organic diet may reduce dietary exposure to pesticides but findings based on observational data are scant. We aimed to compare urinary pesticide concentrations between “organic” and “conventional” consumers from the NutriNet-Santé study. Organic food consumption was determined using a self-reported food frequency questionnaire. Individuals with a proportion of organic food in the whole diet (in g/d) below 10% were defined as low organic food consumers and those whose proportion was above 50% as high organic food consumers. A propensity score matching procedure was then used to obtain two similar subsets of 150 participants, differing mostly by the organic valence of their diet. Urinary pesticide and metabolite concentrations (organophosphorus, pyrethroid, and azole compounds) were determined by UPLC-MS/MS, standardized with respect to creatinine. The molar sums of total diethylphosphates, dimethylphosphates, and dialkylphosphates were also computed. Differences in distributions across groups were tested using Wilcoxon signed-rank test for matched data. Mean age was 58.5 years and 70% of participants were women. Significantly lower urinary levels of diethylthiophosphate, dimethylthiophosphate, dialkylphosphates, and free 3-phenoxybenzoic acid were observed among organic consumers compared to conventional consumers. Our findings confirm that exposure to certain organophosphate and pyrethroïd pesticides in adults may be lowered by switching from conventional to organic foods. This is particularly of high interest among conventional fruit and vegetable consumers, as their exposure may be the highest.

Probabilistic Exposure Assessment to Phycotoxins by Recreational Shellfish Harvesters: Results and Influence of Shellfish Species and the Cooking Process

Phycotoxins, secondary phytoplankton metabolites, are considered as an important food safety issue because of their accumulation by shellfish until they becoming unfit for human consumption. However, the likely intakes of phycotoxins via shellfish consumption are almost unknown. The aim of this study is to assess both acute and chronic exposure levels to phycotoxins for high shellfish consumers (i.e. recreational shellfish harvesters), to develop a realistic probabilistic exposure assessment model, and to evaluate the influence of shellfish species and cooking process on exposure levels. Exposure assessment requires data on shellfish consumption and contamination. Two one-year surveys were conducted (by the same population, from the same geographical area) to assess shellfish consumption and shellfish contamination by major toxins (Domoic Acid group (DAs), Okadaic Acid group (OAs) and Spirolides (SPXs)) (Picot, Evaluation du risque lie a l’exposition aux phycotoxines via la consommation de coquillages chez les pecheurs a pied du Finistere, Ph.D. thesis, Universite de Bretagne Occidentale, Brest, France, 2010). These two kinds of data were combined with a probabilistic MCMC (Markov-Chain, Monte-Carlo) method. Assessments were made for both acute and chronic-exposures considering the impact of shellfish species and cooking on phycotoxin levels. For acute exposures, according to the shellfish species considered, the mean exposure levels ranged from 20 to 740; from 3.8 to 702; and from 0.7 to 78.4 ng/kg pc, for DAs, OAs and SPXs, respectively. Results reveal inter-species variabilities have a considerable impact on exposure levels and consequently should be considered to choose the monitored species in monitoring programs. Concerning chronic exposures, mean exposures were equal to 110; 54 and 5.4 ng/kg pc/day for DAs, OAs and SPXs, respectively. The impact of cooking differs according to the phycotoxin. For lipophilic toxins, the cooking increased the exposure by a factor about 1.5–2. For DAs, considering the cooking process, the exposures decreased for cockles and razor clams but increased for mussels, donax and hard shell clams. Thus, the actual banning levels based on raw bivalves might over or under protect the consumers when they cooked shellfish.