Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

BACKGROUND: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. OBJECTIVES: To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. METHODS: The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. RESULTS: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. CONCLUSIONS: Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

Chronic exposure to drinking water nitrate and trihalomethanes in the French CONSTANCES cohort.

Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification. We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort. We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000-2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021. Median annual concentrations of total THMs and nitrate at study participants' homes for 2000-2020 were, respectively, 15.7 µg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68). These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data.

Pre-conception serum ferritin concentrations are associated with metal concentrations in blood during pregnancy: A cohort study in Benin.

BACKGROUND: Iron deficiency is a common nutritional deficiency that impacts maternal health and fetal development and is also associated with increased uptake of toxic metals. Women in sub-Saharan Africa are highly exposed to both iron deficiency and metals in the environment. As research on the developmental origins of health and disease increasingly shows impacts of pre-conception maternal health on pregnancy and fetal health, these environmental exposures are of concern. OBJECTIVES: This study investigated the association between iron status pre-pregnancy and blood metal concentrations in the first trimester of pregnancy with potential implications for iron supplementation. METHODS: Pre-conception and first trimester blood samples taken from 262 Beninese women were tested for serum ferritin, inflammation markers, manganese (Mn), cadmium (Cd), lead (Pb), copper, zinc, selenium, mercury and arsenic. Associations between serum ferritin adjusted for inflammation and metal concentrations were analyzed using multivariate linear regression. RESULTS: Women with iron deficiency before conception (13%) were more likely to remain iron deficient in the first trimester (4%) (adjusted OR = 41.2, 95%CI 6.2; 275.0) even within the context of routine iron supplementation during pregnancy. Lower pre-pregnancy serum ferritin concentrations were significantly related to higher concentrations of Mn, Cd and Pb in the first trimester. Every 1% increase in serum ferritin concentration was associated with a 0.13% decrease in Mn (adjusted ß = -0.13, 95%CI -0.18; -0.07), a 0.22% decrease in Cd (adjusted ß = -0.22, 95%CI -0.28; -0.15) and a 0.06% decrease in Pb concentration (adjusted ß = -0.06, 95%CI -0.12; -0.006). DISCUSSION: These results suggest that increasing iron stores prior to pregnancy may prevent excessive uptake of toxic concentrations of the metals Mn, Cd and Pb and argue in favour of testing the effects of iron supplementation prior to pregnancy on metal concentrations.

Semivolatile organic compounds in French schools: Partitioning between the gas phase, airborne particles and settled dust.

The indoor environmental quality in classrooms can largely affect children's daily exposure to indoor chemicals in schools. To date, there has not been a comprehensive study of the concentrations of semivolatile organic compounds (SVOCs) in French schools. Therefore, the French Observatory for Indoor Air Quality (OQAI) performed a field study of SVOCs in 308 nurseries and elementary schools between June 2013 and June 2017. The concentrations of 52 SVOCs, including phthalates, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), synthetic musks, and pesticides, were measured in air and settled dust (40 SVOCs in both air and dust, 12 in either air or dust). The results showed that phthalates had the highest concentrations among the SVOCs in both the air and dust. Other SVOCs, including tributyl phosphate, fluorene, phenanthrene, gamma-hexachlorocyclohexane (gamma-HCH, lindane), galaxolide, and tonalide, also showed high concentrations in both the air and dust. Theoretical equations were developed to estimate the SVOC partitioning between the air and settled dust from either the octanol/air partition coefficient or the boiling point of the SVOCs. The regression constants of the equations were determined using the data set of the present study for phthalates and PAHs.

Toward setting public health guidelines for chemicals in indoor settled dust?

Indoor settled dust may result in substantial human exposure to chemicals, especially by ingestion following hand-to-mouth or hand-to-object-to-mouth contact. As with other environmental media related to exposure, dust may thus be subject to regulation. An international scientific workshop was convened in Paris in September 2019 firstly to assess the relevance for public health of setting guidelines for indoor settled dust, and secondly to discuss scientific and technical challenges related to such guidelines. The main discussions and conclusions, with consensus achieved, are reported herein. Discussions concerned general considerations, objectives and definitions, relevance for a health-based guideline, units of measure, and finally derivation of the guideline. These points should be addressed when considering an indoor settled dust guideline as part of a policy to reduce exposure indoors to a given chemical or group of chemicals.

Emissions of VOCs, SVOCs, and mold during the construction process: Contribution to indoor air quality and future occupants' exposure.

Building materials and human activities are important sources of contamination indoors, but little information is available regarding contamination during construction process which could persist during the whole life of buildings. In this study, six construction stages on two construction sites were investigated regarding the emissions of 43 volatile organic compounds (VOCs), 46 semi-volatile organic compounds (SVOCs), and the presence of 4 genera of mold. Results show that the future indoor air quality does not only depend on the emissions of each building product but that it is also closely related to the whole implementation process. Mold spore measurements can reach 1400 CFU/m3 , which is particularly high compared with the concentrations usually measured in indoor environments. Relatively low concentrations of VOCs were observed, in relation to the use of low emissive materials. Among SVOCs analyzed, some phthalates, permethrin, and hydrocarbons were found in significant concentrations upon the delivery of building as well as triclosan, suspected to be endocrine disruptor, and yet prohibited in the treatment of materials and construction since 2014. As some regulations exist for VOC emissions, it is necessary to implement them for SVOCs due to their toxicity.

Toxics (Pb, Cd) and trace elements (Zn, Cu, Mn) in women during pregnancy and at delivery, South Benin, 2014-2015.

During pregnancy, fetal development can be hindered by maternal exposure to toxic elements and abnormal concentrations of trace elements. Few data are available in African countries. Our goal was to assess the body burden of lead (Pb), cadmium (Cd), manganese (Mn), zinc (Zn) and copper (Cu) in pregnant women in Benin. The study was carried out in Sô-Ava district, from November 2015 to April 2016. Sixty women were recruited from the RECIPAL pre-conceptional cohort study. In all women, blood samples were collected during the first trimester of pregnancy. Thirty-two women had additional maternal and cord blood samples collected at delivery. Blood samples were analyzed by inductively coupled plasma mass spectrometry. At delivery, Cd median (IQR) concentration in maternal blood was 0.34 µg/L (0.24-0.46) in this non-smoking population. Pb median (IQR) concentration in maternal blood at delivery was 37.4 µg/L (30.5-52.0), with 31.3% of blood Pb levels above the 50 µg/L threshold. These pregnant women lived in semi-rural lakeside villages. Potential sources of Pb exposure identified during pregnancy were having water supply by drill pump and activities such as smoking fish by the woman and fishing by the household head. At delivery, Zn, Cu, and Mn median (IQR) concentrations in maternal blood were, respectively, 5415 µg/L (4894-5822), 1609 µg/L (1295-1771) and 16.0 µg/L (12.5-20.8). Pb, Cd, Mn and Cu blood concentrations were significantly higher at delivery than during the first trimester of pregnancy. Pb, Cd, Zn and Cu concentrations were significantly lower in cord blood than in maternal blood, contrary to Mn concentration, which was significantly higher in cord blood than in maternal blood at delivery. This exploratory study is the first one performed in Benin, and warns us about exposition of women from Sô-Ava district to Pb and Cd during pregnancy.

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.

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

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.

Insights into the molecular mechanisms of pesticide tolerance in the Aporrectodea caliginosa earthworm.

Diffuse pollution of the environment by pesticides has become a major soil threat to non-target organisms, such as earthworms for which declines have been reported. However some endogeic species are still abundant and persist in intensively cultivated fields, suggesting they become tolerant to long-term anthropogenic pressure. We thus considered the working hypothesis that populations of Aporrectodea caliginosa earthworms from conventionally managed fields developed a tolerance to pesticides compared with those from organically managed fields. To investigate this hypothesis, we studied earthworm populations of the same genetic lineage from soils that were either lowly or highly contaminated by pesticides to detect any constitutive expression of differentially expressed molecular pathways between these populations. Earthworm populations were then experimentally exposed to a fungicide-epoxiconazole-in the laboratory to identify different molecular responses when newly exposed to a pesticide. State-of-the-art omics technology (RNA sequencing) and bioinformatics were used to characterize molecular mechanisms of tolerance in a non-targeted way. Additional physiological traits (respirometry, growth, bioaccumulation) were monitored to assess tolerance at higher levels of biological organization. In the present study, we generated the de novo assembly transcriptome of A. caliginosa consisting of 64,556 contigs with N50 = 2862 pb. In total, 43,569 Gene Ontology terms were identified for 21,593 annotated sequences under the three main ontologies (biological processes, cellular components and molecular functions). Overall, we revealed that two same lineage populations of A. caliginosa earthworms, inhabiting similar pedo-climatic environment, have distinct gene expression pathways after they long-lived in differently managed agricultural soils with a contrasted pesticide exposure history for more than 22 years. The main difference was observed regarding metabolism, with upregulated pathways linked to proteolytic activities and the mitochondrial respiratory chain in the highly exposed population. This study improves our understanding of the long-term impact of chronic exposure of soil engineers to pesticide residues.

Exposure to Disinfectants and Cleaning Products and Respiratory Health of Workers and Children in Daycares: The CRESPI Cohort Protocol.

Although cleaning tasks are frequently performed in daycare, no study has focused on exposures in daycares in relation to respiratory health. The CRESPI cohort is an epidemiological study among workers (n~320) and children (n~540) attending daycares. The purpose is to examine the impact of daycare exposures to disinfectants and cleaning products (DCP) on the respiratory health of workers and children. A sample of 108 randomly selected daycares in the region of Paris has been visited to collect settled dust to analyze semi-volatile organic compounds and microbiota, as well as sample indoor air to analyze aldehydes and volatile organic compounds. Innovative tools (smartphone applications) are used to scan DCP barcodes in daycare and inform their use; a database then matches the barcodes with the products' compositions. At baseline, workers/parents completed a standardized questionnaire, collecting information on DCP used at home, respiratory health, and potential confounders. Follow-up regarding children's respiratory health (monthly report through a smartphone application and biannual questionnaires) is ongoing until the end of 2023. Associations between DCP exposures and the respiratory health of workers/children will be evaluated. By identifying specific environments or DCP substances associated with the adverse respiratory health of workers and children, this longitudinal study will contribute to the improvement of preventive measures.

Lead contamination in French children's homes and environment.

Lead in homes is a well-known source of childhood lead exposure, which is still of concern due to the health effects of low lead doses. This study aims to describe lead contamination in the homes of children aged 6 months to 6 years in France (without overseas). Between October 2008 and August 2009, 484 housing units were investigated. Lead in tap water and total and leachable lead levels from floor dust, outdoor soils and paint chips were measured. X-ray fluorescence measurements were carried out on non-metallic and metallic substrates. Nationwide results are provided. The indoor floor dust lead (PbD) geometric mean (GM) was 8.8 µg/m² (0.8 µg/ft²) and 6.8 µg/m² (0.6 µg/ft²) for total and leachable lead respectively; 0.21% of homes had an indoor PbD loading above 430.5 µg/m² (40 µg/ft²). The outdoor play area concentration GM was 33.5 mg/kg and 21.7 mg/kg in total and leachable lead respectively; 1.4% of concentrations were higher than or equal to 400 mg/kg. Outdoor floor PbD GM was 44.4 µg/m² (4.1 µg/ft²) that was approximately 3.2 times higher than the GM of indoor PbD. Lead-based paint (LBP) was present in 25% of dwellings, LBP on only non-metallic substrates was present in 19% of homes and on metallic substrates in 10% of dwellings. The GM of lead concentrations in tap water was below 1 µg/L; 58% of concentrations were lower than 1 µg/L and 2.9% were higher than or equal to 10 µg/L. The age cut-off for homes with lead would be 1974 for paint and 1993 for indoor floor dust. This study provides, for the first time, a look at the state of lead contamination to which children are exposed in French housing. Moreover, it provides policy makers an estimate of the number of French dwellings sheltering children where abatement should be conducted.

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.

Organic contamination of settled house dust, a review for exposure assessment purposes.

People spend a considerable amount of time indoors. As a result, exposure to indoor contaminants is of great concern, notably via settled dust ingestion in particular for infants and toddlers. This paper proposes a critical review on the organic contamination of settled house dust and human exposure over the past 10 years and focused on sources, contaminations and measurement methods (sampling, pretreatment, storage and analysis). As many compounds were identified, arises the question of which ones to consider. Sensitive and selective analytical methods for simultaneous determination of targeted substances should be developed and evaluated. Various methods were described for sampling and sample preparation. Harmonization and standardization are needed to enable comparison of results from similar studies. Finally, an integrated multipollutant and multicompartment (settled dust, suspended particles and air) approach appears essential in order to determine the extent of the threat to public health posed by indoor contaminants.

Identification of sources of lead exposure in French children by lead isotope analysis: a cross-sectional study.

BACKGROUND: The amount of lead in the environment has decreased significantly in recent years, and so did exposure. However, there is no known safe exposure level and, therefore, the exposure of children to lead, although low, remains a major public health issue. With the lower levels of exposure, it is becoming more difficult to identify lead sources and new approaches may be required for preventive action. This study assessed the usefulness of lead isotope ratios for identifying sources of lead using data from a nationwide sample of French children aged from six months to six years with blood lead levels ≥25 µg/L. METHODS: Blood samples were taken from 125 children, representing about 600,000 French children; environmental samples were taken from their homes and personal information was collected. Lead isotope ratios were determined using quadrupole ICP-MS (inductively coupled plasma - mass spectrometry) and the isotopic signatures of potential sources of exposure were matched with those of blood in order to identify the most likely sources. RESULTS: In addition to the interpretation of lead concentrations, lead isotope ratios were potentially of use for 57% of children aged from six months to six years with blood lead level ≥ 25 µg/L (7% of overall children in France, about 332,000 children), with at least one potential source of lead and sufficiently well discriminated lead isotope ratios. Lead isotope ratios revealed a single suspected source of exposure for 32% of the subjects and were able to eliminate at least one unlikely source of exposure for 30% of the children. CONCLUSIONS: In France, lead isotope ratios could provide valuable additional information in about a third of routine environmental investigations.

Sequential digestion for measuring leachable and total lead in the same sample of dust or paint chips by ICP-MS.

House lead exposure is generally assessed using total lead, except in France, where acid-leachable lead is used for routine regulatory purposes. In order to allow an international comparison of French lead dust contamination, a sequential digestion protocol is developed to determine both leachable and total lead on the same sample with a two-step digestion stage: firstly, hydrochloric acid is added to the sample at 37°C to solubilize leachable lead; then nitric acid is added to an aliquot at 95°C to solubilize residual (i.e., non-leachable) lead. Both sample fractions are analyzed with inductively coupled plasma mass spectrometry (ICP-MS). The sum of the two fractions allows to determine total lead. This new protocol has been tested with wiped dust (n = 111) and paint chip (n = 46) samples collected in houses (n = 16). The leachability of lead ranged from 63 to 100% in dust and from 4 to 100% in paint. These findings confirm the strong variability of lead leachability in houses samples and thus the importance of considering it for lead poisoning prevention. This double determination of leachable and total lead for each wiped dust or paint sample appears to be a reproducible, simple, low-cost protocol and thus a useful tool for international comparison of house dust lead contamination.

The Isotopic Signature of Lead Emanations during the Fire at Notre Dame Cathedral in Paris, France.

When Notre Dame de Paris cathedral caught fire on 15 April 2019, lead particles were deposited in its surroundings. Our objective was to determine whether the lead plume had a homogeneous isotopic signature (i.e., a set of homogenous isotopic ratios), and whether, if so, this was different from common sources. In January 2020, dust samples were collected from six areas inside the cathedral, downwind of the fire, as well as from eight roof debris fragments. These samples were mineralized and analyzed using ICP-MS. Their isotopic ratios (207Pb/206Pb and 206Pb/204Pb) were determined and then compared both to each other and to previous published ratios measured in home dusts and blood samples collected in France. The isotopic ratios of dust samples collected inside the cathedral were compatible with each other and with the roof fragments. These isotopic ratios are common and differ neither from those of many other dusts collected in France during the period 2008-2009, nor from those of blood samples collected from children in France during the same period. Moreover, the fire's isotopic signature is close to the overall signature for Paris. Indeed, it would be difficult to attribute the fire at the cathedral to either lead poisoning or environmental contamination.

Improving Exposure Assessment Using Non-Targeted and Suspect Screening: The ISO/IEC 17025: 2017 Quality Standard as a Guideline.

The recent advances of novel methodologies such as non-targeted and suspect screening based on high-resolution mass spectrometry (HRMS) have paved the way to a new paradigm for exposure assessment. These methodologies allow to profile simultaneously thousands of small unknown molecules present in environmental and biological samples, and therefore hold great promises in order to identify more efficiently hazardous contaminants potentially associated with increased risks of developing adverse health outcomes. In order to further explore the potential of these methodologies and push the transition from research applications towards regulatory purposes, robust harmonized quality standards have to be implemented. Here, we discuss the feasibility of using ISO/IEC 17025: 2017 as a guideline to implement non-targeted and suspect screening methodologies in laboratories, whether it is for accreditation purposes or not. More specifically, we identified and then discussed how specificities of non-targeted HRMS methodology can be accounted for in order to comply with the specific items of ISO/IEC 17025: 2017. We also discussed other specificities of HRMS methodologies (e.g., need for digital storage capacity) that are so far not included in the ISO/IEC 17025 requirements but should be considered. This works aims to fuel and expand the discussion in order to subsidize new opportunities of harmonization for non-targeted and suspect screening.

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.