Ronan Cariou

Chemical contaminants are widely dispersed in the environment in all its dimensions, posing significant public health problems. Comprehensive knowledge of these stressors is a prerequisite for assessing the associated risk and implementing public policy measures to reduce the level of population exposure. Nontargeted suspect screening approaches broaden the knowledge of the chemical human exposome. We developed and used a suspect screening method based on large spectral libraries. Chemical profiling was based on a combined LC- and GC-HRMS approach. The methodology was applied to 16 samples spanning the environment, food, and health continuum. Using a combination of matching and scoring data, a total of 547 compounds were likely identified, from which the chemical structure of 63 molecules was confirmed to the highest level of certainty. Wastewater, and more generally environmental samples, had the highest number of chemicals detected, while fish samples had a lower number. Pharmaceuticals, pesticides, and personal care product-related compounds were found to be the most common compounds in and between the extracts, particularly in water and serum samples. Many natural and endogenous compounds were consistently annotated in the samples submitted for analysis, regardless of the compartment investigated.

Bromochloro alkanes (BCAs) have been manufactured for use as flame retardants for decades, and preliminary environmental risk screening suggests they are likely to behave similarly to polychlorinated alkanes (PCAs), subclasses of which are restricted as Stockholm Convention Persistent Organic Pollutants (POPs). BCAs have rarely been studied in the environment, although some evidence suggests they may migrate from treated-consumer materials into indoor dust, resulting in human exposure via inadvertent ingestion. In this study, BCA-C₁₄ mixture standards were synthesized and used to validate an analytical method. This method relies on chloride-enhanced liquid chromatography-electrospray ionization-Orbitrap-high resolution mass spectrometry (LC-ESI-Orbitrap-HRMS) and a novel CP-Seeker integration software package for homologue detection and integration. Dust sample preparation via ultrasonic extraction, acidified silica cleanup, and fractionation on neutral silica cartridges was found to be suitable for BCAs, with absolute recovery of individual homologues averaging 66 to 78% and coefficients of variation ≤10% in replicated spiking experiments (n = 3). In addition, a total of 59 indoor dust samples from six countries, including Australia (n = 10), Belgium (n = 10), Colombia (n = 10), Japan (n = 10), Thailand (n = 10), and the United States of America (n = 9), were analyzed for BCAs. BCAs were detected in seven samples from the U.S.A., with carbon chain lengths of C₈, C₁₀, C₁₂, C₁₄, C₁₆, C₁₈, C₂₄ to C₂₈, C₃₀ and C₃₁ observed overall, though not detected in samples from any other countries. Bromine numbers of detected homologues in the indoor dust samples ranged Br_1-4 as well as Br₇, while chlorine numbers ranged Cl_2-11. BCA-C₁₈ was the most frequently detected, observed in each of the U.S.A. samples, while the most prevalent degrees of halogenation were homologues of Br₂ and Cl_4-5. Broad estimations of BCA concentrations in the dust samples indicated that levels may approach those of other flame retardants in at least some instances. These findings suggest that development of quantification strategies and further investigation of environmental occurrence and health implications are needed.

Despite the growing interest in PCNs and the dioxin-like toxicity exhibited by a number of congeners, a comprehensive assessment of their contribution to the cocktail of dioxin-like contaminants is still lacking. To address such a shortcoming, this study investigated the PCN contamination in foodstuffs recently acquired in France, together with that of the regulatory polychlorinated dibenzodioxins/furans (PCDD/Fs) and polychlorinated biphenyls (PCBs). PCNs were ubiquitous at levels (∑70 PCNs = 2.5-150 pg g^-1 wet weight) similar to those reported in other countries, with maximum concentrations observed in fish and fishery products from the North-East Atlantic Ocean. Their congener patterns further suggested unintentional releases of PCNs, while those of the other foodstuffs were correlated to the historical PCN profiles. Low risk from dietary exposure was estimated (∑70 PCNs-EDIs of 60-360 pg kg^-1 bw d^-1, ∑24 PCNs-TEQ-EDIs of 8 × 10^-3-2.2 × 10^-2 pg TEQ kg^-1 bw d^-1), with milk and dairy products being the highest contributors, followed by meat and meat products. Finally, the rather high contributions of PCNs to the total PCNs+PCDD/Fs+PCBs concentrations (0.9-50%, average of 9%) and the toxic equivalents (0.2-24%, average of 5%) show that these substances are not minor components of the PCNs+PCDD/Fs+PCBs cocktail.

Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or are added intentionally to our daily products. These complex mixtures of chemicals may pose a risk to human health. One of the goals of the European Union’s Green Deal and zero-pollution ambition for a toxic-free environment is to tackle the existent gaps in chemical mixture risk assessment by providing scientific grounds that support the implementation of adequate regulatory measures within the EU. We suggest dealing with this challenge by: (1) characterising ‘real-life’ chemical mixtures and determining to what extent they are transferred from the environment to humans via food and water, and from the mother to the foetus; (2) establishing a high-throughput whole-mixture-based in vitro strategy for screening of real-life complex mixtures of organic chemicals extracted from humans using integrated chemical profiling (suspect screening) together with effect-directed analysis; (3) evaluating which human blood levels of chemical mixtures might be of concern for children’s development; and (4) developing a web-based, ready-to-use interface that integrates hazard and exposure data to enable component-based mixture risk estimation. These concepts form the basis of the Green Deal project PANORAMIX, whose ultimate goal is to progress mixture risk assessment of chemicals.