Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Due to their geographic location and traditional diet, rich in seafood and marine mammals, the Inuit living in Arctic Quebec are exposed to high amounts of pollutants, including organochlorine pesticides (OCPs). While the adverse developmental effects of these pesticides on child cognitive functions are well known, the effects of developmental exposure to OP on sensory processes have not been investigated. The aim of this longitudinal study was to assess the effects of prenatal and childhood exposure to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its major metabolite 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), on visual processing in Inuit children in Nunavik (Arctic Québec). p,p'-DDT and p,p'-DDE concentrations were determined from umbilical cord and 5- and 11-year plasma samples. Visual evoked potentials (VEPs) were successfully recorded in 150 children at 4 contrast levels (95%, 30%, 12%, and 4%). Hierarchical multiple regressions were conducted to determine the association between p,p'-DDT, or p,p'-DDE, exposure and VEPs while controlling for the effects of various confounders, including fish nutrients and other contaminants. p,p'-DDE measured in umbilical cord plasma was significantly related to the amplitude of the N150 response at the lowest contrast (4%). In addition, 5-year p,p'-DDE plasma concentration was significantly associated with decreased N75 amplitude. These findings indicate that p,p'-DDE exposure, both pre- and postnatally, during early childhood is associated with visual processing impairment later in life.
ISSN: 0161-813X

hal-01061309
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061309
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061309/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061309/file/Prenatal_and_5-year-NEUTOX-D-13-00192R2_v4.pdf
DOI : 10.1016/j.neuro.2014.04.009

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
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 population's 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 population's exposure to herbicides.
Environment International

hal-00966842
https://hal.archives-ouvertes.fr/hal-00966842
https://hal.archives-ouvertes.fr/hal-00966842/document
DOI : 10.1016/j.envint.2013.10.010
PUBMED : 24246238

Éditeur(s) : HAL CCSD
Résumé : International audience
Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolised to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here we show through steroidogenic profiling that exposure to aniline led to increased levels of the Δ4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into anti-androgenic paracetamol, impairs male reproductive development
Toxicological Sciences: An Official Journal of the Society of Toxicology

hal-01187305
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187305
DOI : 10.1093/toxsci/kfv179
PUBMED : 26259604

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Humans may be exposed via their environment to multiple chemicals as a consequence of human activities and use of synthetic products. Little knowledge is routinely generated on the hazards of these chemical mixtures. The metabolomic approach is widely used to identify metabolic pathways modified by diseases, drugs, or exposures to toxicants. This review, based on the state of the art of the current applications of metabolomics in environmental health, attempts to determine whether metabolomics might constitute an original approach to the study of associations between multiple, low-dose environmental exposures in humans. Studying the biochemical consequences of complex environmental exposures is a challenge demanding the development of careful experimental and epidemiological designs, in order to take into account possible confounders associated with the high level of interindividual variability induced by different lifestyles. The choices of populations studied, sampling and storage procedures, statistical tools used, and system biology need to be considered. Suggestions for improved experimental and epidemiological designs are described. Evidence indicates that metabolomics may be a powerful tool in environmental health in the identification of both complex exposure biomarkers directly in human populations and modified metabolic pathways, in an attempt to improve understanding the underlying environmental causes of diseases. Nevertheless, the validity of biomarkers and relevancy of animal-to-human extrapolation remain key challenges that need to be properly explored.
ISSN: 1093-7404

hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/file/Potential_input_from_metabolomics_accepted.pdf
DOI : 10.1080/10937404.2013.860318

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
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 population's 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 population's exposure to herbicides.
ISSN: 0160-4120

hal-01107546
https://hal.archives-ouvertes.fr/hal-01107546
DOI : 10.1016/j.envint.2013.10.010
PUBMED : 24246238

Éditeur(s) : Communication, ICES Conference and Meeting (CM), 2010, Nantes
Résumé : Chlordecone is a very persistent insecticide used in banana plantations of the French West Indies between 1972 and 1993. Chlordecone residues were found in inland water, in agricultural and freshwater products, and in marine organisms. This pollution has become of great concern in 2007. Therefore, a governmental action Plan was launched to better assess the pollution and to improve the consumer’s protection. Within this plan, 1048 samples from 69 different species of marine fishes and crustaceans were collected all around both the Guadeloupe and the Martinique Islands and analyzed. The results confirm the presence of chlordecone in marine organisms, with highly variable concentrations (from the detection limit to 1000 μg.kg-1). In 17.9 % of the samples, concentrations exceeded 20 μg.kg-1, the maximum acceptable level in fish according to the French regulation (Anon, 2008). Two main features of this contamination were characterized. 1) Because of the sedimentation of contaminated suspended soil particles, the sheltered bays are more exposed to chlordecone than the open coast where terrigenous flux are dispersed. 2) Species biology, particularly their lifestyle and diet, appear to influence contamination levels. Thus, the more contaminated species live in relation with sediment or are at high trophic level. These results have directly supported political decisions in order to prevent too high exposure of consumers to chlordecone. Fishing activities in sheltered bays have been forbidden for potentially highly contaminated species like benthic crustaceans and top predators. Further studies are under way to assess the importance of the trophic transport of chlordecone within the foodweb, and to evaluate the historical deposition of this insecticide in sediment and its further bioavailability.

Droits : 2010 ICES/CIEM ; Ifremer
http://archimer.ifremer.fr/doc/00014/12511/9361.pdf
http://archimer.ifremer.fr/doc/00014/12511/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In addition to dietary exposure, children are exposed to metals via ingestion of soils and indoor dust, contaminated by natural or anthropogenic outdoor and indoor sources. The objective of this nationwide study was to assess metal contamination of soils and dust which young French children are exposed to. A sample of 484 children (6 months to 6 years) was constituted in order to obtain representative results for young French children. In each home indoor settled dust was sampled by a wipe in up to five rooms. Outdoor playgrounds were sampled with a soil sample ring (n=315) or with a wipe in case of hard surfaces (n=53). As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V were measured because of their potential health concern due to soil and dust ingestion. The samples were digested with hydrochloric acid, and afterwards aqua regia in order to determine both leachable and total metal concentrations and loadings by mass spectrometry with a quadrupole ICP-MS. In indoor settled dust most (total) loadings were below the Limit of Quantification (LOQ), except for Pb and Sr, whose median loadings were respectively 9 and 10 μg/m². The 95th percentile of loadings were 2 μg/m² for As, <0.8 for Cd, 18 for Cr, 49 for Cu, <64 for Mn, 63 for Pb, 2 for Sb, 56 for Sr, and <8 for V. Median/95th percentile of loadings in settled dust on outdoor playgrounds were 2/16, <0.8/1.3, 17/53, 49/330, 99/424, 32/393, 2/13, 86/661 and 10/37 μg/m² for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. In outdoor playground soil median/95th percentile of concentrations (μg/g) were 8/26, <0.65/1, 25/52, <26/53,391/956, 27/254, 0.7/4, 54/295, 23/57 for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. These results are comparable with those observed in other countries. Because of their representative nature, we can assess children's exposures to these metals via soil and dust and the associated risks in urban and rural environments. Ratios of leachable/total concentrations and loadings, calculated on >LOQ measurements, differed among metals. To a lesser extent, they were also affected by type of matrix, with (except for Cd) a greater leachability of dust (especially indoor) compared to soils.
ISSN: 0160-4120

hal-00732136
https://hal.archives-ouvertes.fr/hal-00732136
PUBMED : 22613504
DOI : 10.1016/j.envint.2012.04.010

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Plasma membrane is an early target of polycyclic aromatic hydrocarbons (PAH). We previously showed that the PAH prototype, benzo[a]pyrene (B[a]P), triggers apoptosis via DNA damage-induced p53 activation (genotoxic pathway) and via remodeling of the membrane cholesterol-rich microdomains called lipid rafts, leading to changes in pH homeostasis (non-genotoxic pathway). As omega-3 (n-3) fatty acids can affect membrane composition and function or hamper in vivo PAH genotoxicity, we hypothesized that addition of physiologically relevant levels of polyunsaturated n-3 fatty acids (PUFAs) might interfere with B[a]P-induced toxicity. The effects of two major PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were tested on B[a]P cytotoxicity in the liver epithelial cell line F258. Both PUFAs reduced B[a]P-induced apoptosis. Surprisingly, pre-treatment with DHA increased the formation of reactive B[a]P metabolites, resulting in higher levels of B[a]P-DNA adducts. EPA had no apparent effect on B[a]P metabolism or related DNA damage. EPA and DHA prevented B[a]P-induced apoptotic alkalinization by affecting Na(+)/H(+) exchanger 1 activity. Thus, the inhibitory effects of omega-3 fatty acids on B[a]P-induced apoptosis involve a non-genotoxic pathway associated with plasma membrane remodeling. Our results suggest that dietary omega-3 fatty acids may have marked effects on the biological consequences of PAH exposure.
ISSN: 0009-2797

hal-00950341
https://hal.archives-ouvertes.fr/hal-00950341
https://hal.archives-ouvertes.fr/hal-00950341/document
https://hal.archives-ouvertes.fr/hal-00950341/file/DENDELE_et_al_2013-unmarked.pdf
PUBMED : 24246761

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides (n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines (n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds (n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects.
ISSN: 1660-4601

hal-01560242
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560242
PUBMED : 28665355
DOI : 10.3390/ijerph14070708