Biocide and other semi-volatile organic compound concentrations in settled indoor dust of CRESPI daycare centers and implication for public health.

This study investigates the presence of biocides and other semi-volatile organic compounds (SVOCs) in cleaning products used in daycare centers and health impact through ingestion of settled dust by young children. In Paris metropolitan area, 106 daycares area were investigated between 2019-2022. Fifteen substances were analyzed in settled indoor dust by gas chromatography-tandem mass spectrometry. Detection rates and concentrations ranged from 5 to 100%, and

Prevalence of occupational co-exposure to biomechanical factors and neurotoxic chemicals in French workers.

OBJECTIVES: Little is known about occupational co-exposure. The objective was to assess the prevalence of exposure and co-exposure to biomechanical factors and neurotoxic chemicals in French workers in 2017. METHODS: Data from the French representative survey SUMER 2017 (SUrveillance Médicale des Expositions aux Risques professionnels) were analyzed. A total of 25 118 workers were included. Exposure to 4 biomechanical factors (manual handling of loads, forceful joint exertion, repetitive movements, and hand-arm transmitted vibrations) and 18 neurotoxic chemicals (n-hexane, perchloroethylene, trichloroethylene, etc.) were assessed using a questionnaire during face-to-face interviews with occupational physicians. RESULTS: Among men, 22.9% were exposed to at least one biomechanical factor and 10.2% were exposed to at least one neurotoxic chemical, mainly single exposures. Among women, 10.8% were exposed to at least one biomechanical factor and 3.1% were exposed to at least one neurotoxic chemical, also mainly single exposures. Occupational co-exposure to biomechanical factors and neurotoxic chemicals was observed among 4.8% of men and 0.7% of women. Workers under 30 yr old, blue-collar workers and those working in small companies were more co-exposed than other workers. In men, the prevalence of co-exposure was higher in the construction sector compared to other economic activities. DISCUSSION: This study stresses the importance of considering multiple occupational exposures while the current prevention measures are designed to focus on preventing occupational factors individually.

Characterization of organic contaminants in hair for biomonitoring purposes.

Biological monitoring is one way to assess human exposure to contaminants. Blood and urine are often used as biological matrices, but hair is an innovative and effective tool for quantifying more biomarkers over a wider exposure window. In order to improve the use of hair in exposure assessment, this article identifies relevant compounds in the literature to investigate hair contamination. Statistical analysis was performed to correlate the physical-chemical properties of the relevant compounds and their concentration levels in hair. Phthalates, pyrethroids and organophosphate flame retardants were chosen for further study of the interpretation of hair measurements for exposure assessment. No significant correlation was found between the average concentration levels in the literature and the physical-chemical properties of the selected compounds. This work also explores the properties of hair and the analytical process that may impact the quantification of organic contaminants in hair. The sample preparation method (sampling, storage, washing) were also studied and adaptations were suggested to improve the existing methods.

A control banding method for chemical risk assessment in occupational settings in France.

Background: This study describes a method whose aim is to help companies assess the chemical occupational risks related to labeled products and industrial chemical emissions. The method is intended to be used by industrial hygienists at the scale of one company. Both inhalation and cutaneous exposure routes are taken into account. Methods: The method relies on a control-banding scheme. A work situation is described by exposure parameters such as the process or the local exhaust ventilation and by the hazard of the product. Each possible value of the parameters is associated with a "band," which is associated with an integer value. The multiplication of these values results in a score, which represents a priority for intervention. The higher the score, the more the situation warrants investigation for implementing prevention measures, such as chemical substitution and the addition of local exhaust ventilation. To simplify communication, the priority is associated with a colored priority band: red for "very high priority," orange for "high priority," and green for "moderate priority." The priority bands are computed for all work situations performed in a company. Results: An example of the use of this method is described in a French façade insulation company. Conclusion: A tool named Seirich was developed to implement this method and promote good practices for helping industrial hygienists in the prioritization of interventions for reducing chemical risk in France.

Determination of glyphosate and AMPA in indoor settled dust by hydrophilic interaction liquid chromatography with tandem mass spectrometry and implications for human exposure.

The widespread application of glyphosate leads to significant contamination of outdoor environmental compartments, notably air and soil, which can contaminate indoor air and dust. This study assessed the contamination of indoor household dust for the first time in France and potential exposure to glyphosate through the inadvertent ingestion of dust. A specific and new analytical method was developed using HILIC MS/MS (hydrophilic interaction liquid chromatography with tandem mass spectrometry) to measure polar pesticides, such as glyphosate, aminomethylphosphonic acid, and glufosinate, in indoor dust, with a low quantification limit (25 ng/g). The dust from vacuum cleaner bags of 60 rural and urban households (Brittany, France) was analyzed. All samples contained glyphosate (median 1675 ng/g for rural dwellings (n = 29), 457 ng/g for urban dwellings (n = 31)), more than 90 % contained aminomethylphosphonic acid, and none contained glufosinate. Concentrations were influenced by the rural or urban setting, the proximity of crops, and the use of weed killers on driveways or lawns. Glyphosate exposure via indoor dust ingestion was < 1 % of both acceptable daily intake and dietary intake. However, the high quantification limit of the glyphosate concentration in the food analysis method probably leads to overestimation of the dose from food.

Characterization of multiple pesticide exposure in pregnant women in Brittany, France.

BACKGROUND: France is one of the biggest users of pesticides in Europe and exposure to pesticides is a current concern, especially when it occurs early in life. OBJECTIVE: The aim of this study was to assess the exposure of pregnant women in Brittany (western France) with high pesticide use. METHODS: The pesticides were selected according to agricultural practices. Forty pesticides or metabolites were measured in urine samples collected in 2004 from 296 pregnant women in Brittany. The samples were analyzed by ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) after a solid phase extraction (SPE) step. RESULTS: Twenty seven pesticides were detected: the most frequently detected were the metabolites of organophosphate and pyrethroid insecticides (>89%) and several herbicides (phenoxypropionic acid derivatives and fluazifop >60%). Organophosphate and pyrethroid metabolites were also quantified in highest levels with maximum values of 590 µg/l for dimethylphosphate and 5.4 µg/l for 3- phenoxybenzoic acid. For the other parent compounds, such as prochloraz, bromoxynil and procymidone, they were also detected in 10-29% of the samples. SIGNIFICANCE: Our results are consistent with pesticide use at the time of collection. The median concentrations of organophosphorus and pyrethroids were of the same order of magnitude as those reported in other countries. Herbicides and fungicides (fluazifop-p-butyl, bromoxynil, and prochloraz) were measured for the first time in this biomonitoring study, showing the usefulness of measuring widely used pesticides locally to improve knowledge of exposure. IMPACT: The objective of this study is to assess the exposure of pregnant women in a region of Europe with high pesticide use.

Analytical strategies to profile the internal chemical exposome and the metabolome of human placenta.

As a non-invasive biological matrix, the placenta offers great and novel opportunities to monitor fetal exposure to exogenous chemicals and their biotransformation products (the internal chemical exposome), as well as the biological responses associated, in large-scale epidemiological studies. However, it is first crucial to ensure that analytical methods based on high-resolution mass spectrometry (HRMS) can detect the low abundant components of the internal chemical exposome present in these complex biological matrices. In this study, we aimed to develop a robust analytical method (extraction and sample preparation) sensitive enough to profile the internal chemical exposome and the metabolome of placenta using high-resolution mass spectrometry (HRMS) for future application in mother child cohorts. Several extraction solvents (methanol, methanol/H2O (50/50 v/v), methyl tert-butyl ether/methanol/H2O) were tested and their ability to extract components of the internal exposome and metabolome were compared. Then, sample preparation methods commonly used for metabolomics application (methanolic protein precipitation) were compared with solid phase extraction (SPE), protein and phospholipid removal plates (PPRP) and combination of SPE and PPRP. The methods were compared and validated using qualitative (i.e., numbers of features and chemical classes ID), quantitative parameters adopted from targeted multi-residue analysis (recovery experiments, repeatability and matrix effect) as well as the ability of these methods to be implemented for high-throughput applications. The analytical repeatability of the two most effective methods (methanolic extraction followed by either protein precipitation or PPRP) were tested at the batch level to determine the best concentration factors to be used for improving detection of components of the internal chemical exposome and metabolome without impacting on the analytical response. Finally, these two methods based on protein precipitation and PPRP were tested on 40 placenta samples from the French PELAGIE birth cohort, and annotation was performed on the related datasets to compare the respective impacts of PPT and PPRP. A wide range of exogenous (e.g., biocides, pharmaceuticals, personal care products) and endogenous chemicals (steroids, prostanoids, lipids, carnitins) could be detected and annotated (some of them for the first time in placenta). We show that both methods are complementary but that PPRP allows the injection of more concentrated extracts without impacting the LC repeatability and therefore improve the detection (presence and signal area fold change) of many exogenous and endogenous chemicals.

[Occupational exposome: An organisational model]. / Un modèle organisationnel de l'exposome professionnel.

This article describes the concept of occupational exposome in highlighting the value of the concept in understanding the complexity of workplace exposures and their determinants. An organizational approach to the occupational exposome is proposed. The organizational approach is intended, from an interdisciplinary perspective, to broaden the levels of analysis of the exposures (whether they are) of the individual to the work situation (individual or collective), the work situation in the workshop or in the service, the company and the socio-economic environment of the company, the socio-economic environment of the company to the Society as a whole. The organizational approach of the occupational exposome helps to broaden the spectrum of health risk assessment and to promote a comprehensive and integrated approach to the prevention of arduousness at work and occupational wear and tear.

Title: Un modèle organisationnel de l'exposome professionnel. Abstract: Dans cette revue, nous décrivons le concept d'exposome professionnel, en soulignant son intérêt pour appréhender la complexité des expositions en milieu de travail et saisir l'ensemble de leurs déterminants. Une approche organisationnelle de cet exposome est par ailleurs proposée. Elle vise, en lui donnant une perspective interdisciplinaire, à élargir les niveaux d'analyse des expositions, quelles qu'elles soient, de l'individu à la situation de travail, individuelle ou collective, de la situation de travail à l'atelier ou au service dans l'entreprise1 et son environnement socio-économique, et, enfin, de l'environnement socio-économique de l'entreprise à l'ensemble de la Société. Cette approche organisationnelle de l'exposome professionnel contribue également à élargir le spectre de l'évaluation des risques sanitaires et à promouvoir une approche globale et intégrée de la prévention de la pénibilité au travail et de l'usure professionnelle.

The design of a matrix linking work situations to chemical health risk at the workplace.

In France, laws require each company to draw up an inventory of the risks that may threaten employees' health in order to prioritize the preventive actions to be implemented. Focusing on chemical risk, databases on hazards or exposures are widely available but they lack information regarding chemical risks resulting from combining the hazards of chemicals with their conditions of use, thus generating exposures. Our objective is to build a matrix of French work situations associated with their chemical risk. Eighty-eight work situations were collected from reports written by professionals from the French public health insurance service. Each work situation is defined by descriptive parameters of the task, the exposure, and the hazard. According to an expert elicitation method (Delphi, n = 21 experts), each work situation was assessed and a chemical risk score defined, taking into account all the descriptive exposure and hazard parameters. Chemical risk scores were expressed as a range of values from 0 to 100, with the size of the range chosen by the experts themselves according to their uncertainty. The experts' assessments were merged to assign one risk score for each work situation, variability, and confidence. The results showed that 50% of the work situations had a risk score between 40 and 60. The average variability and confidence were around 15% and 82%, respectively. This work situation matrix constructed from French data can be used by occupational safety and health managers that have similar work situations in their company (Western European industrial sector). In this context, it may be useful to easily determine the level of risks for similar tasks and prioritize those that are most risky. Moreover, it could be used to compare and define the differences between a risk assessment performed by "expertise" and another defined by a software.

Proposal for a neurotoxic classification for chemicals at work.

Many neurotoxic chemicals are used in the workplace but there is currently no database dedicated to neurotoxicity. We aimed to develop a classification method for neurotoxicity based on a weight-of-evidence approach, similar to the IARC classification for carcinogenicity. Human and animal lines of evidence were collected from recent toxicological profiles and a literature search and were combined into six groups from neurotoxic to potentially not neurotoxic. The method was tested on 26 chemicals, mixtures or group of products used in the workplace in France: 31% were considered neurotoxic, 31% probably and 11% possibly neurotoxic, and 27% not classifiable because of insufficient data. This operational method suggests that many chemicals used in the workplace are neurotoxic and that questionnaires used to collect data on occupational chemical exposure should propose items with more targeted compounds that have common chemical or toxic properties to improve risk assessment.

Organophosphorus Flame Retardants: A Global Review of Indoor Contamination and Human Exposure in Europe and Epidemiological Evidence.

We aimed to identify high-priority organophosphorus flame retardants for action and research. We thus critically reviewed literature between 2000 and 2019 investigating organophosphorus flame retardants' presence indoors and human exposure in Europe, as well as epidemiological evidence of human effects. The most concentrated compounds indoors were tris(2-butoxyethyl)phosphate (TBOEP), tris(1-chloro-2-propyl)phosphate (TCIPP), tris(2,3-dichloropropyl)phosphate (TDCIPP). TBOEP and TCIPP were the most consistently detected compounds in humans' urine, hair or breast milk as well as tris (butyl) phosphate (TNBP) and tris (phenyl) phosphate (TPHP). Notably, epidemiological evidence concerned reprotoxicity, neurotoxicity, respiratory effects and eczema risk for TDCIPP, eczema increase for TBOEP, and neurodevelopmental outcomes for Isopropylated triarylphosphate isomers (ITPs). Given the ubiquitous presence indoors and the prevalence of exposure, the growing health concern seems justified. TDCIPP and TPHP seem to be of particular concern due to a high prevalence of exposure and epidemiological evidence. TBOEP and TNBP require epidemiological studies regarding outcomes other than respiratory or dermal ones.

Occupational co-exposure to biomechanical factors and neurotoxic chemicals in a representative sample of French employees.

OBJECTIVES: Musculoskeletal disorders, mainly carpal tunnel syndrome, represent a leading cause of compensation claims of workers worldwide. Despite this, and the fact that occupational exposures to biomechanical factors and neurotoxic chemicals have been individually associated with peripheral nerve damage, the prevalence of occupational co-exposure to biomechanical factors and neurotoxic chemicals has rarely been explored. Therefore, our aim was to assess the prevalence of occupational co-exposure to biomechanical factors and neurotoxic chemicals in a national representative sample of the French working population. METHODS: The study was based on the French representative cross-sectional survey SUMER 2010. A total of 47 983 employees who had worked in their current job for at least one year were included. Occupational exposure to biomechanical factors and neurotoxic chemicals within the previous week of work were assessed using a questionnaire during face-to-face interviews with occupational physicians. RESULTS: Approximately 5% of male employees and 1% of female employees were co-exposed to biomechanical factors and neurotoxic chemicals. This prevalence was up to 10% among male blue-collar workers and 13%, 8%, and 6%, respectively, among male employees in the construction, agriculture, and industry sectors. Male employees under 30 years old, in apprenticeships, and working in small companies were more co-exposed to biomechanical factors and neurotoxic chemicals than their counterparts. CONCLUSIONS: Occupational co-exposure to biomechanical factors and neurotoxic chemicals was observed in a significant proportion of French male employees, suggesting that further studies are required to investigate its potential adverse effects on peripheral neuropathies.

Multiple Exposures and Coexposures to Occupational Hazards Among Agricultural Workers: A Systematic Review of Observational Studies.

BACKGROUND: Workers may be exposed to various types of occupational hazards at the same time, potentially increasing the risk of adverse health outcomes. The aim of this review was to analyze the effects of multiple occupational exposures and coexposures to chemical, biomechanical, and physical hazards on adverse health outcomes among agricultural workers. METHODS: Articles published in English between 1990 and 2015 were identified using five popular databases and two complementary sources. The quality of the included publications was assessed using the methodology developed by the Effective Public Health Practice Project assessment tool for quantitative studies. RESULTS: Fifteen articles were included in the review. Multiple chemical exposures were significantly associated with an increased risk of respiratory diseases, cancer, and DNA and cytogenetic damage. Multiple physical exposures seemed to increase the risk of hearing loss, whereas coexposures to physical and biomechanical hazards were associated with an increased risk of musculoskeletal disorders among agricultural workers. CONCLUSION: Few studies have explored the impact of multiple occupational exposures on the health of agricultural workers. A very limited number of studies have investigated the effect of coexposures among biomechanical, physical, and chemical hazards on occupational health, which indicates a need for further research in this area.

Metabolome disruption of pregnant rats and their offspring resulting from repeated exposure to a pesticide mixture representative of environmental contamination in Brittany.

The use of pesticides exposes humans to numerous harmful molecules. Exposure in early-life may be responsible for adverse effects in later life. This study aimed to assess the metabolic modifications induced in pregnant rats and their offspring by a pesticide mixture representative of human exposure. Ten pregnant rats were exposed to a mixture of eight pesticides: acetochlor (246 µg/kg bw/d) + bromoxynil (12 µg/kg bw/d) + carbofuran (22.5 µg/kg bw/d) + chlormequat (35 µg/kg bw/d) + ethephon (22.5 µg/kg bw/d) + fenpropimorph (15.5 µg/kg bw/d) + glyphosate (12 µg/kg bw/d) + imidacloprid (12.5 µg/kg bw/d) representing the main environmental pesticide exposure in Brittany (France) in 2004. Another group of 10 pregnant rats served as controls. Females were fed ad libitum from early pregnancy, which is from gestational day (GD) 4 to GD 21. Urine samples were collected at GD 15. At the end of the exposure, mothers and pups were euthanized and blood, liver, and brain samples collected. 1H NMR-based metabolomics and GC-FID analyses were performed and PCA and PLS-DA used to discriminate between control and exposed groups. Metabolites for which the levels were significantly modified were then identified using the Kruskal-Wallis test, and p-values were adjusted for multiple testing correction using the False Discovery Rate. The metabolomics analysis revealed many differences between dams of the two groups, especially in the plasma, liver and brain. The modified metabolites are involved in TCA cycle, energy production and storage, lipid and carbohydrate metabolism, and amino-acid metabolism. These modifications suggest that the pesticide mixture may induce oxidative stress associated with mitochondrial dysfunction and the impairment of glucose and lipid metabolism. These observations may reflect liver dysfunction with increased relative liver weight and total lipid content. Similar findings were observed for glucose and energy metabolism in the liver of the offspring, and oxidative stress was also suggested in the brains of male offspring.

Chemical-by-chemical and cumulative risk assessment of residential indoor exposure to semivolatile organic compounds in France.

BACKGROUND: The toxic effects of environmental exposure to chemicals are increasingly being studied and confirmed, notably for semivolatile organic compounds (SVOCs). These are found in many products and housing materials, from which they are emitted to indoor air, settled dust and other surfaces. OBJECTIVES: The objective of this work is to assess the human health risk posed by residential indoor exposure to 32 SVOCs, assessed in previous nationwide studies. METHODS: A chemical-by-chemical risk assessment, using a hazard quotient (HQ) or excess risk (ER) method, was supplemented by a cumulative risk assessment (CRA). For CRA, a hazard index (HI) method, as well as higher tier approaches using relative potency factors (RPFs) or toxic equivalency factors (TEFs) were used for the following endpoints: neurotoxicity, reproductive toxicity, genotoxicity and immunotoxicity. RESULTS: HQs were above 1 for 50% of French children from birth to 2 years for BDE 47, and for 5% of children for lindane and dibutyl phthalate (DBP). Corresponding hazards are reprotoxic for BDE 47 and DBP, and immunotoxic for lindane. The CRA approach provided additional information of reprotoxic risks (HI > 1) that may occur for 95% of children and for 5% of the offspring for pregnant women's exposure. The SVOCs contributing most to these risks were PCB 101 and 118, BDE 47, and DBP. The higher tier CRA approaches showed that exposure to dwellings' SVOC mixtures were of concern for 95% of children for neurotoxic compounds having effects linked with neuronal death. To a lesser extent, effects mediated by the aryl hydrocarbon receptor (AhR) or by a decrease in testosterone levels may concern 5% of children and adults. Lastly, unacceptable immunotoxic risk related to exposure to 8 indoor PCBs was also observed for 5% of children. CONCLUSIONS: In view of uncertainties related to compounds' toxicity for humans, these results justify the implementation of preventive measures, as well as the production of more standardized and comprehensive toxicological data for some compounds.

Bioaccessibility and bioavailability of environmental semi-volatile organic compounds via inhalation: A review of methods and models.

Semi-volatile organic compounds (SVOCs) present in indoor environments are known to cause adverse health effects through multiple routes of exposure. To assess the aggregate exposure, the bioaccessibility and bioavailability of SVOCs need to be determined. In this review, we discussed measurements of the bioaccessibility and bioavailability of SVOCs after inhalation. Published literature related to this issue is available for 2,3,7,8-tetrachlorodibenzo-p-dioxin and a few polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and phenanthrene. Then, we reviewed common modeling approaches for the characterization of the gas- and particle-phase partitioning of SVOCs during inhalation. The models are based on mass transfer mechanisms as well as the structure of the respiratory system, using common computational techniques, such as computational fluid dynamics. However, the existing models are restricted to special conditions and cannot predict SVOC bioaccessibility and bioavailability in the whole respiratory system. The present review notes two main challenges for the estimation of SVOC bioaccessibility and bioavailability via inhalation in humans. First, in vitro and in vivo methods need to be developed and validated for a wide range of SVOCs. The in vitro methods should be validated with in vivo tests to evaluate human exposures to SVOCs in airborne particles. Second, modeling approaches for SVOCs need to consider the whole respiratory system. Alterations of the respiratory cycle period and human biological variability may be considered in future studies.

TOXsIgN: a cross-species repository for toxicogenomic signatures.

Motivation: At the same time that toxicologists express increasing concern about reproducibility in this field, the development of dedicated databases has already smoothed the path toward improving the storage and exchange of raw toxicogenomic data. Nevertheless, none provides access to analyzed and interpreted data as originally reported in scientific publications. Given the increasing demand for access to this information, we developed TOXsIgN, a repository for TOXicogenomic sIgNatures. Results: The TOXsIgN repository provides a flexible environment that facilitates online submission, storage and retrieval of toxicogenomic signatures by the scientific community. It currently hosts 754 projects that describe more than 450 distinct chemicals and their 8491 associated signatures. It also provides users with a working environment containing a powerful search engine as well as bioinformatics/biostatistics modules that enable signature comparisons or enrichment analyses. Availability and implementation: The TOXsIgN repository is freely accessible at http://toxsign.genouest.org. Website implemented in Python, JavaScript and MongoDB, with all major browsers supported. Supplementary information: Supplementary data are available at Bioinformatics online.

Indoor residential exposure to semivolatile organic compounds in France.

Multiple chemicals are emitted in residential accommodation. Aggregate Daily Doses (ADD) (ng/kg-bw/d) were estimated for 32 semivolatile organic compounds (SVOCs) of different chemical families that are frequently detected in French dwellings in both air and settled dust. Daily doses were determined using steady-state models for the population, categorized into 11 age groups covering birth to age 30. Three routes of exposure were taken into account: dust ingestion, inhalation (gaseous and particulate phases) and dermal contact with the gaseous phase of air. Contamination levels were preferentially retrieved from large, nationwide representative datasets. A two-dimensional probabilistic approach was used to assess parametric uncertainty and identify the most influential factors. For children aged 2 to 3years, ADD estimates spanned orders of magnitude, with median values ranging from 8.7pg/kg-bw/d for 2,2',3,4,4'-pentabromodiphenylether (BDE 85) to 1.3µg/kg-bw/d for di-isobutyl phthalate (DiBP). Inhalation, ingestion and dermal pathway contributed at varying levels, and depending on compound, air was the dominant medium for 28 of the 32 compounds (either by inhalation or dermal contact). Indoor exposure estimate variance was mainly driven by indoor contamination variability, and secondarily by uncertainty in physical and chemical parameters. These findings lend support to the call for cumulative risk assessment of indoor SVOCs.

Aggregating exposures & cumulating risk for semivolatile organic compounds: A review.

Increasingly, health risk assessment is addressing multiple pathway exposures to multiple contaminants. We reviewed aggregated exposure and cumulative risk approaches for contemporary and ubiquitous semivolatile organic compounds (SVOC). We identified 22 studies aggregating exposure pathways, and 31 cumulating risk. Exposure aggregation is based on the addition of pathway-specific doses, using kinetic modeling where it exists, and classic external dose equations otherwise. In most cases, exposure is dominated by a single route or source of exposure - mainly the oral pathway - via dietary or non-dietary exposure. Preferential routes and sources of exposure are influenced by SVOC physical-chemical properties such as vapor pressure. The cumulative risk approach for contaminants is based on dose addition. Simple sum of hazard quotient (Hazard Index: HI) is the most commonly used cumulative risk assessment approach, while Relative Potency Factor (RPF) appeared to the best suited - although this calls for a level of toxicological information that limits the number of compounds that can be studied simultaneously. Where both were performed, moving from HI to more refined approach produced similar results. In conclusion, both approaches - exposure aggregation and cumulative risk - rely on simple assumptions. Nevertheless, they allow uncertainty to be reduced, in comparison with source-by-source or chemical-by-chemical approaches.

Relative toxicity for indoor semi volatile organic compounds based on neuronal death.

BACKGROUND: Semi Volatile Organic Compounds (SVOCs) are contaminants commonly found in dwellings as a result of their use as plasticizers, flame retardants, or pesticides in building materials and consumer products. Many SVOCs are suspected of being neurotoxic, based on mammal experimentation (impairment of locomotor activity, spatial learning/memory or behavioral changes), raising the question of cumulative risk assessment. The aim of this work is to estimate the relative toxicity of such SVOCs, based on neuronal death. METHOD: SVOCs fulfilling the following conditions were included: detection frequency >10% in dwellings, availability of data on effects or mechanism of action for neurotoxicity, and availability of dose-response relationships based on cell viability assays as a proxy of neuronal death. Benchmark concentration values (BMC) were estimated using a Hill model, and compared to assess relative toxicity. RESULTS: Of the 58 SVOCs selected, 28 were suspected of being neurotoxic in mammals, and 21 have been documented as inducing a decrease in cell viability in vitro. 13 have at least one dose-response relationship that can be used to derive a BMC based on a 10% fall in neuronal viability. Based on this in vitro endpoint, PCB-153 appeared to be the most toxic compound, having the lowest BMC10 (0.072µM) and diazinon the least toxic compound, having the highest BMC10 (94.35µM). We showed that experimental designs (in particular choice of cell lines) had a significant influence on BMC calculation. CONCLUSION: For the first time, the relative in vitro toxicity of 13 indoor contaminants belonging to different chemical families has been assessed on the basis of neuronal cell viability. Lack of comparable toxicity datasets limits the number of SVOCs that can be included. More standardized protocols in terms of cell lines, species and exposure duration should be developed with a view to cumulative risk assessment.