Background:

Aryl phosphate esters (APEs) are widely used and commonly present in the environment. Health hazards associated with these compounds remain largely unknown and the effects of diphenyl phosphate (DPhP), one of their most frequent derivatives, are poorly characterized.

Objective:

Our aim was to investigate whether DPhP per se may represent a more relevant marker of exposure to APEs than direct assessment of their concentration and determine its potential deleterious biological effects in chronically exposed mice.

Methods:

Conventional animals (FVB mice) were acutely or chronically exposed to relevant doses of DPhP or to triphenyl phosphate (TPhP), one of its main precursors. Both molecules were measured in blood and other tissues by liquid chromatography–mass spectrometry (LC-MS). Effects of chronic DPhP exposure were addressed through liver multi-omics analysis to determine the corresponding metabolic profile. Deep statistical exploration was performed to extract correlated information, guiding further physiological analyses.

Results:

Multi-omics analysis confirmed the existence of biological effects of DPhP, even at a very low dose of 0.1mg/mL in drinking water. Chemical structural homology and pathway mapping demonstrated a clear reduction of the fatty acid catabolic processes centered on acylcarnitine and mitochondrial β-oxidation in mice exposed to DPhP in comparison with those treated with vehicle. An interesting finding was that in mice exposed to DPhP, mRNA, expression of genes involved in lipid catabolic processes and regulated by peroxisome proliferator–activated receptor alpha (PPARα) was lower than that in vehicle-treated mice. Immunohistochemistry analysis showed a specific down-regulation of HMGCS2, a kernel target gene of PPARα. Overall, DPhP absorption disrupted body weight–gain processes.

Conclusions:

Our results suggest that in mice, the effects of chronic exposure to DPhP, even at a low dose, are not negligible. Fatty acid metabolism in the liver is essential for controlling fast and feast periods, with adverse consequences on the overall physiology. Therefore, the impact of DPhP on circulating fat, cardiovascular pathologies and metabolic disease incidence deserves, in light of our results, further investigations. https://doi.org/10.1289/EHP6826

Background:

Testicular germ cell tumors (TGCT) were suggested to have a prenatal environmentally related origin. The potential endocrine disrupting properties of certain solvents may interfere with the male genital development in utero.

Objectives:

We aimed to assess the association between maternal and paternal occupational exposures to organic solvents during the prenatal period and TGCT risk in their offspring.

Methods:

This registry-based case control study included TGCT cases aged 14–49 y (n=8,112) diagnosed from 1978 to 2012 in Finland, Norway, and Sweden. Controls (n=26,264) were randomly selected from the central population registries and were individually matched to cases on year and country of birth. Occupational histories of parents prior to the child’s birth were extracted from the national censuses. Job codes were converted into solvent exposure using the Nordic job-Nordic Occupational Cancer Study Job-Exposure Matrix. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results:

Overall, no association was found between prenatal maternal exposure to solvents and TGCT risk. In subset analyses using only mothers for whom occupational information was available in the year of or in the year prior to the child’s birth, there was an association with maternal exposure to aromatic hydrocarbon solvents (ARHC) (OR=1.53; CI: 1.08, 2.17), driven by exposure to toluene (OR=1.67_; CI: 1.02, 2.73). No association was seen for any paternal occupational exposure to solvents with the exception of exposure to perchloroethylene in Finland (OR=2.42; CI: 1.32, 4.41).

Conclusions:

This study suggests a modest increase in TGCT risk associated with maternal prenatal exposure to ARHC. https://doi.org/10.1289/EHP864

Background and Aims: Chronic exposure to pesticides has endocrine, immunologic and neurologic disrupting properties and other toxic effects believed to be associated with certain cancers, unfavorable reproductive outcomes, neurologic disorders and other health outcomes. Farming and other agricultural jobs are among the occupations with the highest exposures to pesticides. AGRICOH is a consortium of agricultural cohort studies that offers the opportunity to investigate the role of pesticides, and other exposures, in the etiology of several health outcomes. This poster presentation provides a description of AGRICOH to disseminate its formation and future research plans.

Methods: Characteristics of the cohorts integrating AGRICOH, data harmonization plans and research concepts to be studied will be illustrated in the poster presentation including the construction of pesticide crop exposure matrices.

Results: AGRICOH is a consortium of 22 agricultural cohort studies initiated by the US National Cancer Institute (NCI) and coordinated by the International Agency for Research on Cancer (IARC) since October 2010. The consortium includes cohorts from 9 countries: South Africa (1), Canada (3), Costa Rica (2), USA (6), Korea (1), New Zealand (2), Denmark (1), France (3) and Norway (3). AGRICOH aspires to promote and sustain collaboration and pooling of data to investigate the association between a wide range of agricultural exposures and a wide range of health outcomes, with a particular focus on associations that cannot easily be addressed in individual studies because of rare exposures (e.g. use of infrequently applied pesticides) or relatively rare outcomes (e.g. certain types of cancer, neurologic and auto-immune diseases).

Conclusions: AGRICOH represents a great resource for studying cancer, respiratory, neurologic, and auto-immune diseases as well as reproductive and allergic disorders, injuries and overall mortality in association with a wide array of exposures, prominent among these the application of pesticides.

Background:General population spent about 85 to 90 % of their time in indoor environment and higher indoor pesticides level might be related to adverse health effect. It has been suggested that the indoor exposure level to pesticides is increased by residential proximity to agricultural pesticide use, but information on overall domestic pesticides contamination is lacking in the literature. In 2012, we sampled indoor dust of 239 French houses to validate a GIS approach aiming to estimate agricultural contribution to pesticide in household dusts. Aim: To characterize domestic pesticide contamination in the Rhône-Alpes region (France) depending on type of dominant farming in surrounding fields, thus accounting for non-agricultural sources by our measurement data.

Methods: We sampled 239 houses: 69 in orchards production area, 66 near corns and grains, 68 near vineyards and 36 houses in an urban area (at least 2000 meters from agricultural fields). During the main period of pesticides applications, we used a polypropylene dust trap (30 days) and isopropanol floor wipes to collect recent (7 days) and older dust (at least 6 month). Farmer and pesticides applicators were excluded from the study. Questionnaires were used to assess household characteristics and related domestic pesticide use. We conducted multi-residue laboratory analyses for 413 pesticides and 102 organic compounds in each sample. Results: 126 pesticides were detected at least one time in houses, and at least 1 in 97% of homes. Of 30 predominant compounds, 10 were non-authorized and 5 non-agricultural pesticides. Of the remaining, 9 were authorized for domestic purpose. Highest detection of agricultural-exclusive pesticides (47%) was in the homes near vineyards. Older dust samples are still under analysis. Conclusion: Our results confirmed previous studies in US assessing the household pesticides contamination from surrounding fields. However, our findings indicate non-agricultural use contributes substantially to the total contamination observed in our study homes.

Background : Dioxins are produced during incomplete combustion of chlorine compounds in several industrial processes. They are suspected to play a role in the development of hormone-related cancers such as breast cancer.

Aims : The Geo3N project aims to analyse the relation between environmental dioxin exposure from multiple sources and breast cancer in the French E3N cohort. A pilot study is conducted in the Rhône-Alpes Region (France). To estimate dioxin exposure through a geographic information system (GIS), a first step aims to make an inventory of dioxin emissions from 1990 to 2008.

Methods : Inventory of relevant sources and dioxin emissions through public and institutional information sources were performed. We used the United Nations Environment Programme (UNEP) Toolkit for Identification and Quantification of Dioxin and Furan Releases to assess relevant sources known to release dioxins and estimate annual dioxin emissions. Results : Based on the Toolkit, more than 200 relevant industries and activities in the Rhône-Alpes Region were included and detailed information on key parameters gathered (exact location, activity periods and levels, process characteristics and technologies). For some sources and periods, reliable data were lacking or nonexistent, in particular for closed sites and no measured releases were available prior to 1997 for larger plants. Based on the default UNEP emission factors, we estimated dioxin emissions for the 200 sources identified in the Rhône-Alpes Region and compared them when available, with dioxin release data. Source characteristics and emission estimates were reviewed by a panel of 8 experts. We will present and discuss results of applying the UNEP Tollkit to France to estimate dioxin releases from multiple sources. Conclusion : Although default emission factors may be prone to uncertainties, the Toolkit provides a standardized methodology, to estimate dioxin emissions. Combined with a GIS, it will contribute to improve characterization of dioxin exposures in epidemiology study design.

Background: There is growing trend in use of GIS in health risk analysis. A number of studies have used GIS to assess proximity to crop production and environmental pesticides exposure. However, most of these studies lacked spatial information on known factors such as wind direction, and barriers to transport from field to receptor. France, with publicly available spatial data on these critical factors presents a unique opportunity to advance understanding the relationship between proximity to crop production and residential pesticides exposure. Aim: SIGEXPO is a pilot study in the Rhone-Alpes Region for developing and validating a metric for an epidemiological study concerning exposure to agricultural pesticides across France.

Methods: For 239 homes in 3 differing agriculture territories, we developed a GIS taking into account the residential proximity to pesticide source areas (fields), meteorological data, and mapped vegetative, topographic, and structural barriers between homes and fields. We linked crop, pesticide use, and transport factor data to create an exposure metric based on mechanisms of pesticide drift. We collected and analyzed house dust samples from each home representing short (30 days) and long-term deposition of pesticides for use in calibrating and validating of our metric. Results: We will present 1) Our methodology for combining data layers of the above factors to create potential pesticide transport area for each residence based on prevailing wind direction, 2) Probability of detection/ relative level of pesticides expected to be captured by the samplers in each home over a 30 day period during the 2012 growing season, and 3) Results of our validation based on pesticides in house dust samples.

Conclusions: We have demonstrated the ability to construct and assess a metric for environmental pesticides exposure in epidemiological studies across France.

Background: Breast cancer incidence increased in France during the past thirty years, which cannot only be explained by population ageing or organised breast cancer screening. It has thus been hypothesized that some of the increase could be related to environmental exposure to endocrine disrupting chemicals such as dioxins. Dioxin emissions occur during combustion of chlorinated products (fires, municipal waste incinerators, production of herbicides, or metal industry). Seventeen dioxin congeners are toxic and one of them, tetrachlorodibenzo-p-dioxin, has been classified as a human carcinogen Group 1 by the International Agency for Research on Cancer. Dioxins can contaminate and accumulate in the food chain; therefore diet is considered the main source of exposure to dioxins in humans. Objective: We aimed to estimate the association between dietary exposure to dioxins and risk of incident breast cancer among women from the French E3N prospective cohort.

Methods: The E3N prospective cohort involves nearly 100,000 French female volunteers, adherent to a single health insurance plan and followed since 1990, with the aim of identifying cancer risk factors. Our study focused on 68,995 women of the E3N study who responded to the self-administered food frequency questionnaire (FFQ) in 1993. We used dioxin contamination data in foodstuffs consumed in the general French population collected by the French High Council on Public Health in 1998. Dietary exposure to dioxins was calculated by multiplying concentrations of dioxins (pg TEQ/g fat content) in each food group with the amount reported in the FFQs. We used Cox proportional hazard models to estimate breast cancer risk associated with dietary exposure to dioxins, adjusting for known breast cancer risk factors. Results: Analyses are under way and results will be presented at the ISEE 2013 Annual Conference.

Background: Exposure to agricultural pesticides has been shown to impact human health and is associated with several diseases, e.g. cancer. Assessment, in particular retrospectively, is difficult due to lack of exposure data at the individual level and limits of classical epidemiological methods (recall bias). Geographic Information Systems (GIS) offer the possibility of analysing exposure at a fine scale, reducing misclassification and thus improving health risk estimates.

Aims: To analyze GIS methods for pesticides exposure assessment and to highlight differences and overlaps in data and techniques across peer-reviewed published studies.

Methods: We conducted a systematic literature review combining terms related to GIS, exposure, pesticides and health, producing 1161 papers published 1980 to 2013. Based on review of title and abstract, we selected 50 papers using GIS to assess agricultural pesticide exposure in the general population, including epidemiological and environmental health studies. We analysed the 50 studies in terms of design, data sources and analytical methods. Results: Most were epidemiology studies conducted in California where pesticide use reporting (PUR) is mandatory. Studies were mostly case-control design regarding cancer and neurological disorders. Populations were derived from disease registries or other recruitment, resulting in high variation in geocoding accuracy. Most studies included land use and pesticide data varying in geographic resolution, and from PUR (1 mi2) to field level applications. Most used 500m circular buffers to define pesticide source area. Methodological studies using larger buffers found improved prediction in metric validation. Use of meteorological and topographic data was rare and heterogeneous. Conclusion: GIS improves assessment of agricultural pesticides exposure in the general population when accurate geocoding, source location, and metric design are used and particularly with mandatory reporting (PUR).

Dioxins are environmental pollutants emitted from many sources including industrial combustion (waste incinerators, metal and cement industries). Known to be endocrine disrupting chemicals, dioxins are suspected to increase breast cancer (BC) risk: TCDD has been classified as Group 1 carcinogen by the International Agency for Research on Cancer. The GEO3N project aims to investigate the hypothesis of an association between environmental dioxin exposure and BC risk in a case-control study nested within the French E3N prospective cohort (‘Etude Epidémiologique auprès de femmes de l’Education Nationale’, involving 98,995 women aged 40-65 in 1990). We conducted a pilot study in the Rhône-Alpes region with 521 BC cases and 1,161 controls (matched on age, place of residence and date of inclusion in E3N) to optimize study design and identification of dioxin emitting sources, and to develop and test the Geographic Information System (GIS) to assess dioxin exposure from 1990 to 2008. Dioxin emitting sources were identified through national and regional databases and their emission level was determined with the United National Environment Program (UNEP) Toolkit (www.unep.org/tnt-unep/toolkit/). We used the ArcGIS software to geocode dioxin emitting sources and consecutive participant addresses. Our environmental dioxin exposure score was based on: the distance between dioxin emitting sources and participants, the UNEP Toolkit emission level and exposure duration. We will use conditional logistic regression to estimate BC risk associated with dioxin exposure adjusting for individual BC risk factors (menopausal status, smoking, alcohol, Body Mass Index…). Statistical analyses are currently ongoing and results will be presented and discussed at the ISEE 2014 Conference. This pilot study will demonstrate the feasibility, in France, to use GIS based methods in a large prospective cohort to estimate the association between environmental exposure to dioxins and BC risk.