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Human immunology biomarkers and their association with organophosphate metabolites in children
Abstracts / Toxicology Letters 258S (2016) S62–S324
individuals was higher than non-exposed individuals, but it did not reach statistically significant level. All measured end-points in greenhouse workers were significantly higher than the open field pesticide applicators (P = 0.01, 0.002, 0.002, 0.0001 for MNL, BNMN, NPB, and NBUD, respectively). When MNL as dependent variable, multiple regression analysis also showed that age, gender, smoking habit and number of cigarettes per day affects the MN formation. The mentioned factor did not affect the NPB formation; however, smoking habit was positively associated with the NBUD formation. MNL and BNMN frequencies of females were significantly higher than the males. Such association was not found for NPB and NBUD. It can be concluded that chronic pesticide exposure can modulate the DNA integrity which may indicate a risk for health. http://dx.doi.org/10.1016/j.toxlet.2016.06.1820 P12-074 Identification and modeling of occupational exposure to heavy metals in sfax metropolis (Tunisia) F. Omrane 1,2,∗ , I. Gargouri 1 , I. Gargouri 3 , M. Khadhraoui 1 , B. Elleuch 1 , D. Zmirou Navier 4 , D. Zmirou Navier 5 1
Laboratory of Water, Energy and Environment, National School of Engineering of Sfax (ENIS), Sfax University, Sfax, Tunisia 2 INGRES, (EA) 7298, Medical School, Lorraine University, Vandœuvre-lès-Nancy, France 3 Department of Occupational Health, Medical School, Sfax University, Sfax, Tunisia 4 EHESP School of Public Health, Rennes, France 5 InsermU1085 (IRSET), Rennes, France
Pollution by heavy metals (HMs) is now well-established in the Sfax metropolis (Tunisia), threatening the health of residents, particularly for those exposed in the industrial activities. Several studies confirmed that this pollution is mainly originated from anthropogenic sources. The present study aims to assess health risks associated with occupational exposure in industries handling HMs. To do so, first of all, companies using HMs were identified and localized, amounting to 53 plants. Among them, 17 were selected and contacted. Six companies accepted to participate in our project. Then, we described those companies using a questionnaire which contains information about the activities, exposed employees, and materials and products used. Results enumerated 172 employees, including 95 men and 24 women who are directly handling metals. The main metals used in these companies are Cu, Zn, Ni, Pb, Al and Cr. In the third phase, we are now applying different models to estimate the exposure levels for each worker, using a second job/workplace questionnaire. Mathematical models for estimating occupational exposure to chemical are used in order to predict the indoor air concentrations of HMs. In order to calculate the models parameters, we performed some measurements (temperature, pressure, air velocity. . .). Potential exposure concentrations for each metal were calculated along a four-hour shift. In the next phase, we will conduct direct measurements of indoor air concentrations of HMs to compare them with the theoretical results. Lastly, we will carry out biological monitoring of HMs in urines of volunteer workers to assess their correlation with models estimates. http://dx.doi.org/10.1016/j.toxlet.2016.06.2119
S229
P13 – Immunotoxicology/immunogenicity P13-001 Human immunology biomarkers and their association with organophosphate metabolites in children A.F. Hernández Jerez 1,∗ , D. Lozano 1 , B. González Alzaga 2 , ˜ 2, D. Romero Molina 3 , I. López Flores 4 , C. Aguilar Garduno ˜ 2 M. Giménez Asensio 2 , M. Lacasana 1
Department of Legal Medicine and Toxicology, University of Granada, Spain 2 Escuela Andaluza de Salud Pública, Granada, Spain; ibs.GRANADA, Spain 3 Department of Mathematics, University of Granada, Spain 4 Department of Genetics, University of Granada, Spain
Limited evidence suggests that pesticides may target the immune system and deregulate the production of cytokines and chemokines. This study assessed the association between urine levels of organophosphate metabolites (dialkylphosphates, DAPs) and changes in immunological biomarkers in children. A cross-sectional study was conducted on 115 school children from an agriculture community (Almería, Southeast Spain). Urine levels of six DAPs (dimethylphosphate, dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) were measured by GC–MS/MS. A microsphere-based multiplexing luminex system (Bio-Plex human 27-Plex cytokine panel, Bio-Rad, Madrid) was used for the simultaneous quantification of IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17␣, basic-FGF, eotaxin, G-CSF, GM-CSF, IFN-␥, IP-10, MCP-1, MIP-1␣, MIP-1, PDGF-BB, RANTES, TNF-␣ and VEGF. Linear or logistic regression models were adjusted to assess the association between DAPs levels normalized by urinary creatinine and immunological parameters. Dimethylphosphate and diethylphosphate were significantly associated with the largest number of cytokines studied. While dimethylphosphate was either positively or inversely associated with these biomarkers, most of associations found for diethylphosphate were positive, suggesting a pro-inflammatory role. Sum-dimethyl-metabolites showed an inverse association and Sum-diethyl-metabolites showed a direct association with the immunological parameters studied. Three cytokines (IL13, RANTES and VEGH) failed to be significantly associated with any DAPs. Exposure to DAPs may have an impact on the immune system of children, although the direction of the effect (either pro- or anti-inflammatory) depends on the particular metabolite since a non-homogeneous profile was observed. Research funded by Consejería de Salud, Junta de Andalucía, Spain (PI-0682-2013). http://dx.doi.org/10.1016/j.toxlet.2016.06.1821
individuals was higher than non-exposed individuals, but it did not reach statistically significant level. All measured end-points in greenhouse workers were significantly higher than the open field pesticide applicators (P = 0.01, 0.002, 0.002, 0.0001 for MNL, BNMN, NPB, and NBUD, respectively). When MNL as dependent variable, multiple regression analysis also showed that age, gender, smoking habit and number of cigarettes per day affects the MN formation. The mentioned factor did not affect the NPB formation; however, smoking habit was positively associated with the NBUD formation. MNL and BNMN frequencies of females were significantly higher than the males. Such association was not found for NPB and NBUD. It can be concluded that chronic pesticide exposure can modulate the DNA integrity which may indicate a risk for health. http://dx.doi.org/10.1016/j.toxlet.2016.06.1820 P12-074 Identification and modeling of occupational exposure to heavy metals in sfax metropolis (Tunisia) F. Omrane 1,2,∗ , I. Gargouri 1 , I. Gargouri 3 , M. Khadhraoui 1 , B. Elleuch 1 , D. Zmirou Navier 4 , D. Zmirou Navier 5 1
Laboratory of Water, Energy and Environment, National School of Engineering of Sfax (ENIS), Sfax University, Sfax, Tunisia 2 INGRES, (EA) 7298, Medical School, Lorraine University, Vandœuvre-lès-Nancy, France 3 Department of Occupational Health, Medical School, Sfax University, Sfax, Tunisia 4 EHESP School of Public Health, Rennes, France 5 InsermU1085 (IRSET), Rennes, France
Pollution by heavy metals (HMs) is now well-established in the Sfax metropolis (Tunisia), threatening the health of residents, particularly for those exposed in the industrial activities. Several studies confirmed that this pollution is mainly originated from anthropogenic sources. The present study aims to assess health risks associated with occupational exposure in industries handling HMs. To do so, first of all, companies using HMs were identified and localized, amounting to 53 plants. Among them, 17 were selected and contacted. Six companies accepted to participate in our project. Then, we described those companies using a questionnaire which contains information about the activities, exposed employees, and materials and products used. Results enumerated 172 employees, including 95 men and 24 women who are directly handling metals. The main metals used in these companies are Cu, Zn, Ni, Pb, Al and Cr. In the third phase, we are now applying different models to estimate the exposure levels for each worker, using a second job/workplace questionnaire. Mathematical models for estimating occupational exposure to chemical are used in order to predict the indoor air concentrations of HMs. In order to calculate the models parameters, we performed some measurements (temperature, pressure, air velocity. . .). Potential exposure concentrations for each metal were calculated along a four-hour shift. In the next phase, we will conduct direct measurements of indoor air concentrations of HMs to compare them with the theoretical results. Lastly, we will carry out biological monitoring of HMs in urines of volunteer workers to assess their correlation with models estimates. http://dx.doi.org/10.1016/j.toxlet.2016.06.2119
S229
P13 – Immunotoxicology/immunogenicity P13-001 Human immunology biomarkers and their association with organophosphate metabolites in children A.F. Hernández Jerez 1,∗ , D. Lozano 1 , B. González Alzaga 2 , ˜ 2, D. Romero Molina 3 , I. López Flores 4 , C. Aguilar Garduno ˜ 2 M. Giménez Asensio 2 , M. Lacasana 1
Department of Legal Medicine and Toxicology, University of Granada, Spain 2 Escuela Andaluza de Salud Pública, Granada, Spain; ibs.GRANADA, Spain 3 Department of Mathematics, University of Granada, Spain 4 Department of Genetics, University of Granada, Spain
Limited evidence suggests that pesticides may target the immune system and deregulate the production of cytokines and chemokines. This study assessed the association between urine levels of organophosphate metabolites (dialkylphosphates, DAPs) and changes in immunological biomarkers in children. A cross-sectional study was conducted on 115 school children from an agriculture community (Almería, Southeast Spain). Urine levels of six DAPs (dimethylphosphate, dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) were measured by GC–MS/MS. A microsphere-based multiplexing luminex system (Bio-Plex human 27-Plex cytokine panel, Bio-Rad, Madrid) was used for the simultaneous quantification of IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17␣, basic-FGF, eotaxin, G-CSF, GM-CSF, IFN-␥, IP-10, MCP-1, MIP-1␣, MIP-1, PDGF-BB, RANTES, TNF-␣ and VEGF. Linear or logistic regression models were adjusted to assess the association between DAPs levels normalized by urinary creatinine and immunological parameters. Dimethylphosphate and diethylphosphate were significantly associated with the largest number of cytokines studied. While dimethylphosphate was either positively or inversely associated with these biomarkers, most of associations found for diethylphosphate were positive, suggesting a pro-inflammatory role. Sum-dimethyl-metabolites showed an inverse association and Sum-diethyl-metabolites showed a direct association with the immunological parameters studied. Three cytokines (IL13, RANTES and VEGH) failed to be significantly associated with any DAPs. Exposure to DAPs may have an impact on the immune system of children, although the direction of the effect (either pro- or anti-inflammatory) depends on the particular metabolite since a non-homogeneous profile was observed. Research funded by Consejería de Salud, Junta de Andalucía, Spain (PI-0682-2013). http://dx.doi.org/10.1016/j.toxlet.2016.06.1821