One planet: one health. A call to support the initiative on a global science-policy body on chemicals and waste.

The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science-policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science-policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science-policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health.

SIPIBEL observatory: Data on usual pollutants (solids, organic matter, nutrients, ions) and micropollutants (pharmaceuticals, surfactants, metals), biological and ecotoxicity indicators in hospital and urban wastewater, in treated effluent and sludge from wastewater treatment plant, and in surface and groundwater.

The Bellecombe pilot site - SIPIBEL - was created in 2010 in order to study the characterisation, treatability and impacts of hospital effluents in an urban wastewater treatment plant. This pilot site is composed of: i) the Alpes Léman hospital (CHAL), opened in February 2012, ii) the Bellecombe wastewater treatment plant, with two separate treatment lines allowing to fully separate the hospital wastewater and the urban wastewater, and iii) the Arve River as the receiving water body and a tributary of the Rhône River and the Geneva aquifer. The database includes in total 48 439 values measured on 961 samples (raw and treated hospital and urban wastewater, activated sludge in aeration tanks, dried sludge after dewatering, river and groundwater, and a few additional campaigns in aerobic and anaerobic sewers) with 44 455 physico-chemistry values (including 15 pharmaceuticals and 14 related transformation products, biocides compounds, metals, organic micropollutants), 2 193 bioassay values (ecotoxicity), 1 679 microbiology values (including microorganisms and antibioresistance indicators) and 112 hydrobiology values.

Impact of peri-urban landscape on the organic and mineral contamination of pond waters and related risk assessment.

Ponds are important for their ecological value and for the ecosystem services they provide to human societies, but they are strongly affected by human activities. Peri-urban development, currently one of the most pervasive processes of land use change in Europe, exposes ponds to both urban and agricultural contaminants, causing a potential combination of adverse effects. This study, focused on 12 ponds located in a peri-urban area, has two main objectives: (1) to link the physico-chemical characteristics of the waters and the nature of their contaminants, either organic or mineral, with the human activities around ponds, and (2) to estimate the environmental risk caused by these contaminants. The ponds were sampled during two consecutive years in both spring and in autumn. Although the ponds were distributed over a limited geographical area, their contamination profiles were different and more correlated with the agricultural than the urban land use. In terms of aptitude for biology, half of the ponds were classified in degraded states due to their physico-chemical parameters, but without correlation with the endocrine disrupting activities and the levels of organic pollutants as indicators. The main quantified organic pollutants, however, were pesticides with sufficiently high levels in certain cases to induce an environmental risk exceeding the classical thresholds of risk quotient.

Removal efficiency of emerging micropollutants in biofilter wastewater treatment plants in tropical areas.

We studied the removal of 61 emerging micropollutants, including illicit drugs, in a biofilter wastewater treatment plant located in the French Indies (Martinique). Raw wastewater concentrations were the highest for paracetamol followed by caffeine, naproxen, ibuprofen, its metabolite 2-hydroxyibuprofen, atenolol, ketoprofen, furosemide, methylparaben, cocaine, benzoylecgonine, and 11-nor-delta-9-carboxytetrahydrocannabinol (THC-COOH). The calculated removals were better than those reported in the literature, while the cumulative removal efficacy (i.e., removal of the total mass load) was estimated to be 92 ± 4%. However, this good performance may be partly explained by the removal of paracetamol (also named acetaminophen) and caffeine, which represented 86.4% of the total mass load. Our results point to the adsorption of some molecules on sludge, thus raising the question about local soil pollution from sludge spreading.

Modelling daily and hourly loads of pharmaceuticals in urban wastewater.

Pharmaceuticals are known contaminants of the environment. Assessing and managing the risk associated to this contamination has become an important field of study in environmental sciences. Accurately sampling and measuring pharmaceuticals concentrations in wastewater or in the environment is still costly and difficult. Thus only a few studies have looked at the temporal variability of the concentrations. In parallel, models have been proposed to predict the occurrence of pharmaceuticals. They usually assume that the loads of pharmaceuticals entering a wastewater treatment plant (WWTP) are proportional to the pharmaceuticals sales. However, most of the time, the results are difficult to interpret. The main problem with those models is the lack of data at WWTP. In this context, a stochastic model predicting daily and hourly loads is proposed to better understand the processes influencing the occurrence of pharmaceuticals in wastewater. Using accurate statistical pharmaceutical sales data, the mass consumed daily in the catchment is randomly picked from empirical probability density functions. Then, patients are randomly generated until the picked total mass is reached. For each patient, posology, metabolism and excretion rates of pharmaceuticals to the sewer system are randomly generated according to relevant literature data. In particular, time-use data are used to generate the time-use of patients to pick the times when patients consume pharmaceuticals and also when they excrete them in toilets. Applied to 9 molecules in a French catchment, results show that the model accurately and reliably predicts both the daily and hourly loads of pharmaceuticals at the inlet of the WWTP.

Wastewater-based epidemiology in low Human Development Index states: bias in consumption monitoring of illicit drugs.

Wastewater-based epidemiology is a promising approach worldwide, and its application is currently being developed in non-advanced economies. This technology, based on known toxicokinetic data initially used to detect illicit drugs in well-managed and maintained local sewer networks, has been extended to assess other products such as pesticides, alcohol, flame retardants, nicotine, and other substances. This technology is also used in countries with non-advanced economies. The present review aims to support future wastewater-based epidemiology in such countries by providing toxicokinetic data for locally used narcotic drugs that are expected or known to be emerging in developed countries, outlining the excretion differences due to human polymorphism, and summarising the practical obstacles due to the coverage, maintenance efficiency, or type of local sewage network.Case study feedback from Martinique is presented as an example; the Martinique field study complies with the Organisation for Economic Co-operation and Development standards for health issues, but not with regard to population and urban dynamics.

Exposure of an urban population to pesticides assessed by wastewater-based epidemiology in a Caribbean island.

Wastewater-based epidemiology is an innovative approach to estimate the consumption of chemicals and their exposure patterns in a population, on the basis of measurements of biomarkers in wastewater. This method can provide objective real-time information on xenobiotics directly or indirectly ingested by a population. This approach was used to examine the exposure of the Martinique population to the three classes of pesticides: triazines, organophosphates and pyrethroids. Martinique island (French West Indies) is a closed market and has been closely monitored since the early 2000's when contamination with chlordecone, an organochlorine insecticide widely applied between 1972 and 1993 in banana plantations, became a critical political issue. The aim of this study was to identify and quantify the patterns of human exposure and compare the results to those from other countries. Wastewater was collected as 24-h composite samples and analysed for selected urinary pesticide metabolites by liquid chromatography-tandem mass spectrometry. Organophosphate and pyrethroid metabolites were found in all the samples up to 330 ng/L, while triazines were found only at trace levels. Mass loads indicated higher exposure to pyrethroids than in some cities in Europe, but lower exposure to triazines and organophosphates. The estimated human intake for pyrethroids was close to the Acceptable Daily Intake, but importation of these pesticides to Martinique was low. This study illustrates the high human exposure with indoor pesticide use in comparison to its use in agriculture.

Pemetrexed degradation by photocatalytic process: Kinetics, identification of transformation products and estimation of toxicity.

This study employed a UV-A/visible/TiO2 system to investigate the degradation of pemetrexed, an antifolate agent used in chemotherapy. The laboratory-scale method employed a photostability chamber that could be used to study multiple samples. Reversed-phase HPLC coupled with high-resolution ESI-LTQ-Orbitrap mass spectrometry was used to determine the transformation products (TPs) of PEME. Based on the identified TPs and existing chemical knowledge, the mechanism of degradation of the target compound was proposed. Concentrations were monitored as a function of time, and the degradation kinetics were compared. The structures of seven TPs, four of which have not been described to date, were proposed. Most of the TPs stemmed from OH radical additions to the dihydropyrrole moiety and oxidative decarboxylation of the glutamate residue. Based on the elucidated structures, a computational toxicity assessment was performed, showing that the TPs with higher log D values than the parent compound are more toxic than the PEME itself. To support these findings, the toxicities of irradiated samples on Vibrio fischeri were monitored over time. The experimental results corresponded well with the results of previous computational studies.

Enrichment of free-living amoebae in biofilms developed at upper water levels in drinking water storage towers: An inter- and intra-seasonal study.

Free-living amoebae (FLA) are ubiquitous organisms present in various natural and artificial environments, such as drinking water storage towers (DWST). Some FLA, such as Acanthamoeba sp., Naegleria fowleri, and Balamuthia mandrillaris, can cause severe infections at ocular or cerebral level in addition to being potential reservoirs of other pathogens. In this work, the abundance and diversity of FLA was evaluated in two sampling campaigns: one performed over five seasons in three DWST at three different levels (surface, middle and bottom) in water and biofilm using microscopy and PCR, and one based on the kinetics analysis in phase contrast and confocal microscopy of biofilm samples collected every two weeks during a 3-month period at the surface and at the bottom of a DWST. In the seasonal study, the FLA were detected in each DWST water in densities of ~20 to 25amoebaeL-1. A seasonal variation of amoeba distribution was observed in water samples, with maximal densities in summer at ~30amoebaeL-1 and minimal densities in winter at ~16amoebaeL-1. The FLA belonging to the genus Acanthamoeba were detected in two spring sampling campaigns, suggesting a possible seasonal appearance of this potentially pathogenic amoeba. Interestingly, a 1 log increase of amoebae density was observed in biofilm samples collected at the surface of all DWST compared to the middle and the bottom where FLA were at 0.1-0.2amoebae/cm2. In the kinetics study, an increase of amoebae density, total cell density, and biofilm thickness was observed as a function of time at the surface of the DWST, but not at the bottom. To our knowledge, this study describes for the first time a marked higher FLA density in biofilms collected at upper water levels in DWST, constituting a potential source of pathogenic micro-organisms.

Theory versus practice, bacteriological efficiency versus personal habits: A bacteriological and user acceptability evaluation of filtering tools for people who inject drugs.

INTRODUCTION AND AIMS: People who inject drugs (PWID) are exposed to associated viral, bacterial and fungal risks. These risks can be reduced by filtration. Large disparities in the quality of filtration exist between the various available filters. This paper compares both performance and user acceptability of three filters for drug injection (cotton filters, Sterifilt® and wheel filters) by combining epidemiological and bacteriological analyses. DESIGN AND METHODS: A cross-sectional epidemiological study (ANRS-Coquelicot) using time-location sampling combined with the generalised weight sampling method was conducted among 985 PWID in France. Two filtration-based bacteriological studies of 0.20- and 0.45-µm wheel filters, Sterifilt filters and cotton filters were also conducted. RESULTS: The bacteriological study highlighted the value of using wheel filters with a porosity of less than 0.5 µm, as they limit the risk of bacterial and fungal infection. The results of this study clearly highlight a distinction between the efficiency of Sterifilt and wheel filters, the latter being more effective. Our epidemiological study highlighted that the use of cotton filters is widespread and routine, but is the subject of much criticism among PWID. Sterifilt is not widely used, and its adoption is slow. Finally, the wheel filter remains a largely untested tool. DISCUSSION AND CONCLUSIONS: Low product retention and ease of use are the two most important factors for filters for PWID. Bacterial and fungal risk filtration is less important. It is essential to educate PWID about the benefits of wheel filters. [Jauffret-Roustide M, Chollet A, Santos A, Benoit T, Péchiné S, Duplessy C, Bara J-L, Lévi Y, Karolak S, Néfau T. Theory versus practice, bacteriological efficiency versus personal habits: A bacteriological and user acceptability evaluation of filtering tools for people who inject drugs. Drug Alcohol Rev 2018;37:106-115].

Application of a multidisciplinary and integrative weight-of-evidence approach to a 1-year monitoring survey of the Seine River.

Quality assessment of environments under high anthropogenic pressures such as the Seine Basin, subjected to complex and chronic inputs, can only be based on combined chemical and biological analyses. The present study integrates and summarizes a multidisciplinary dataset acquired throughout a 1-year monitoring survey conducted at three workshop sites along the Seine River (PIREN-Seine program), upstream and downstream of the Paris conurbation, during four seasonal campaigns using a weight-of-evidence approach. Sediment and water column chemical analyses, bioaccumulation levels and biomarker responses in caged gammarids, and laboratory (eco)toxicity bioassays were integrated into four lines of evidence (LOEs). Results from each LOE clearly reflected an anthropogenic gradient, with contamination levels and biological effects increasing from upstream to downstream of Paris, in good agreement with the variations in the structure and composition of bacterial communities from the water column. Based on annual average data, the global hazard was summarized as "moderate" at the upstream station and as "major" at the two downstream ones. Seasonal variability was also highlighted; the winter campaign was least impacted. The model was notably improved using previously established reference and threshold values from national-scale studies. It undoubtedly represents a powerful practical tool to facilitate the decision-making processes of environment managers within the framework of an environmental risk assessment strategy.

The SIPIBEL project: treatment of hospital and urban wastewater in a conventional urban wastewater treatment plant.

Hospital wastewater (HWW) receives increasing attention because of its specific composition and higher concentrations of some micropollutants. Better knowledge of HWW is needed in order to improve management strategies and to ensure the preservation of wastewater treatment efficiency and freshwater ecosystems. This context pushed forward the development of a pilot study site named Site Pilote de Bellecombe (SIPIBEL), which collects and treats HWW separately from urban wastewater, applying the same conventional treatment process. This particular configuration offers the opportunity for various scientific investigations. It enables to compare hospital and urban wastewater, the efficiency of the two parallel treatment lines, and the composition of the resulting hospital and urban treated effluents, as well as the evaluation of their effects on the environment. The study site takes into account environmental, economic, and social issues and promotes scientific and technical multidisciplinary actions. ᅟ.

Validation of an ultra-high-performance liquid chromatography-tandem mass spectrometry method to quantify illicit drug and pharmaceutical residues in wastewater using accuracy profile approach.

The analysis of biomarkers in wastewater has become a common approach to assess community behavior. This method is an interesting way to estimate illicit drug consumption in a given population: by using a back calculation method, it is therefore possible to quantify the amount of a specific drug used in a community and to assess the consumption variation at different times and locations. Such a method needs reliable analytical data since the determination of a concentration in the ngL-1 range in a complex matrix is difficult and not easily reproducible. The best analytical method is liquid chromatography - mass spectrometry coupling after solid-phase extraction or on-line pre-concentration. Quality criteria are not specially defined for this kind of determination. In this context, it was decided to develop an UHPLC-MS/MS method to analyze 10 illicit drugs and pharmaceuticals in wastewater treatment plant influent or effluent using a pre-concentration on-line system. A validation process was then carried out using the accuracy profile concept as an innovative tool to estimate the probability of getting prospective results within specified acceptance limits. Influent and effluent samples were spiked with known amounts of the 10 compounds and analyzed three times a day for three days in order to estimate intra-day and inter-day variations. The matrix effect was estimated for each compound. The developed method can provide at least 80% of results within ±25% limits except for compounds that are degraded in influent.

Applying sewage epidemiology approach to estimate illicit drug consumption in a tropical context: Bias related to sewage temperature and pH.

Illicit drug consumption can be estimated from drug target residue (DTR) in wastewater, with the reliability of results being partly linked to DTR stability in the sewage network. However, wastewater temperature and pH drive the stability of molecules and, in this context, tropical conditions must be studied to specify the impact of residence time in the sewage network on DTR degradation. Warmth enhances biotic and abiotic processes such as degradation, leading to a decrease in oxygen content, and consequently, early diagenesis conditions in wastewater. In this study, we conduct laboratory studies under acidic pH and high temperature (30°C) conditions to determine the degradation half-lives of cocaine (COC), tetrahydrocannabinol, and heroine targets, allowing COC/benzoylecgonine (BZE) ratio variations to be predicted in sewage networks. A rapid COC degradation is observed, as already reported in the literature but without a short-term significant difference between 20°C and 30°C. Acidic pH seems to prevent degradation. Thus, theoretically, the use of COC as DTR is only reliable in acidic conditions, with the decrease in COC concentration being 6% at 8h, but over 40% in other conditions. By contrast, the use of BZE as DTR to estimate COC consumption, which is performed in practice, can be undertaken with the same back-calculation equation as used in temperate countries. However, 11-nor-delta-9-carboxytetrahydrocannabinol stability is more influenced by high temperature: concentration levels after 24h are 20% lower at 30°C than at 20°C, corresponding to a 20% and 40% decrease, respectively. Based on a mean residence time of 8h, underestimated cannabis consumption is close to 15% in tropical contexts, which is double that of temperate areas.

The removal of illicit drugs and morphine in two waste water treatment plants (WWTPs) under tropical conditions.

The consumption of drugs of abuse has been recently investigated in Martinique using the back-calculation approach, also called the "sewage epidemiology" method. Results demonstrated a very high consumption considering the international data. Wastewater treatment plants (WWTPs) are located just behind the Martinique island shoreline, and effluents could impact the vulnerable corals and marine seagrass ecosystem. The present article aims to determine a WWTP's efficiency by comparing the influent and effluent of two WWTPs, with different residence times and biological treatments, located either outdoors or indoors. In parallel, a degradation study is conducted using spiked wastewater exposed to tropical and ambient temperatures. Results demonstrate the consistent efficiency of the two processes, especially for the outdoor WWTP which uses the activated sludge process. The positive effect of the tropical temperature is showed by the increase of cocaine degradation at 31 °C. Thus, low illicit drug residue concentrations in effluent would indicate that wastewater treatment is efficient and even enhanced under tropical context. This fact should be confirmed with others molecules. Furthermore, our results highlight the need for subsequent studies of sludge contamination because of their local recycling as compost.

First characterization of the endocrine-disrupting potential of indoor gaseous and particulate contamination: comparison with urban outdoor air (France).

The composition of endocrine-disrupting compounds (EDCs) in the ambient air of indoor environments has already been described, but little is known about the inherent endocrine-disrupting potential of indoor air contamination. We therefore aimed to study the distribution of bioactive EDCs in the gaseous and particulate phases of indoor air using a cellular bioassay approach that integrates the interaction effects between chemicals. Organic air extracts, both gaseous and particulate, were taken from three indoor locations (office, apartment, and children's day care) in France and sampled in two different seasons in order to study their interference with the signaling of estrogen, androgen, and thyroid receptors. The experiments were also conducted on aerial extracts from an outdoor site (urban center). We found that gaseous and/or particulate extracts from all locations displayed estrogenicity, anti-androgenicity, and thyroidicity. Overall, indoor air extracts had a higher endocrine-disrupting potential compared to outdoor ones, especially during winter and in the day care. The biological activities were predominant for the gaseous extracts and tended to increase for the particulate extracts in cool conditions. In conclusion, our data confirmed the presence of bioactive EDCs in a gaseous state and highlighted their indoor origin and concentration, especially in the cold season.

Drug analysis of residual content of used syringes: a new approach for improving knowledge of injected drugs and drug user practices.

BACKGROUND: Since their inception, harm reduction services, including needle exchange programs, have aimed to improve and update knowledge about illicit drug consumption and injection practices in order to assess and regularly revise the effectiveness of preventive strategies. METHODS: In this paper we describe the development of a scientific approach to obtaining this type of information through analysis of the residual content of used syringes. This was done using a validated liquid chromatography method with mass spectrometry detection to identify different molecules. Used syringes were collected from automatic injection kit dispensers at 17 sites in Paris and the surrounding suburbs each month for one year. RESULTS: In total, 3489 syringes were collected. No compounds were detected in 245 syringes. Heroin was the most commonly observed compound (42%), followed by cocaine (41%), buprenorphine (29%) and 4-methylethylcathinone (23%). These analyses also showed the increased appearance of 4-methylethylcathinone between the summer and winter of 2012. CONCLUSIONS: Despite the bias involved in this approach, the method can provide rapid data on patterns of drug consumption for specific time periods and for well-defined locations. This kind of analysis enables the detection of new substances being injected and thus enables harm reduction services to revise and adapt prevention strategies.

Presence of illicit drugs and metabolites in influents and effluents of 25 sewage water treatment plants and map of drug consumption in France.

Consumption of illicit drugs is a new concern for water management that must be considered not only because of the social and public health aspects but also in an environmental context in relation with the contamination of surface waters. Indeed, sewage treatment plant (STP) effluents contain drug residues that have not been eliminated since STP treatments are not completely efficient in their removal. We developed and validated an HPLC-MS/MS analytical method to assess the concentrations of 17 illicit drugs and metabolites in raw urban wastewaters: cocaine and its metabolites, amphetamine and amphetamine-likes (methamphetamine, MDMA, MDEA, MDA), opiates and opiate substitutes (methadone and buprenorphine), and THC-COOH cannabis metabolite. This method has been applied to the analysis of influent and effluent samples from 25 STPs located in France all over the country. The results allowed evaluating the drug consumption in the areas connected to the STPs and the efficiency of the treatment technology implied. We selected STPs according to their volume capacity, their treatment technologies (biofilters, activated sludges, MBR) and their geographical location. In influents, the concentrations varied between 6 ng/L for EDDP (main metabolite of methadone) and 3050 ng/L for benzoylecgonine (cocaine metabolite). Consumption maps were drawn for cocaine, MDMA, opiates, cannabis and amphetamine-like compounds. Geographical significant differences were observed and highlighted the fact that drug consumption inside a country is not homogeneous. In parallel, comparisons between STP technology processes showed differences of efficiency. More, some compounds appear very resistant to STP processes leading to the contamination of receiving water.

Calibration and field evaluation of Polar Organic Chemical Integrative Sampler (POCIS) for monitoring pharmaceuticals in hospital wastewater.

The Polar Organic Chemical Integrative Sampler (POCIS) is a new tool for the sampling of organic pollutants in water. We tested this device for the monitoring of pharmaceuticals in hospital wastewater. After calibration, a field application was carried out in a French hospital for six pharmaceutical compounds (Atenolol, Prednisolone, Methylprednisolone, Sulfamethoxazole, Ofloxacin, Ketoprofen). POCIS were calibrated in tap water and wastewater in laboratory conditions close to relevant environmental conditions (temperature, flow velocity). Sampling rates (R(s)) were determined and we observed a significant increase with flow velocity and temperature. Whatever the compound, the R(s) value was lower in wastewater and the linear phase of uptake was shorter. POCIS were deployed in a hospital sewage pipe during four days and the estimated water concentrations were close to those obtained with twenty-four hour composite samples.

Tetrabromobisphenol-A disrupts thyroid hormone receptor alpha function in vitro: use of fluorescence polarization to assay corepressor and coactivator peptide binding.

Thyroid hormone receptors (TRs) recruit corepressor or coactivator factors to the promoters of target genes to regulate their transcription. Corepressors such as nuclear hormone receptor corepressor (NCoR) are recruited by unliganded TRs, whereas coactivators such as steroid receptor coactivator-2 (SRC2) are recruited when triiodothyronine (T3) is bound to TRs. These coregulator proteins interact with the ligand binding domain (LBD) of TRs via short, conserved peptide sequences that can be used to probe the conformational changes induced in TR LBD by TR ligands. Recombinant LBD of the human TRα1 isoform (hTRα1 LBD) was produced as a fusion with glutathione S-transferase, and used to develop assays based on fluorescence polarization to quantify the binding of either NCoR- or SRC2-derived fluorescent peptides to the hTRα1 LBD. The optimum concentrations of recombinant hTRα1 LBD, and of peptide probes were adjusted in order to produce the greatest possible T3-dependent signal variations in fluorescence polarization. Under these conditions, T3 induced a dose-dependent decrease in NCoR peptide binding, and a reciprocal dose-dependent increase in SRC2 peptide binding, in both cases at similar 50%-effective doses. The TR agonists triiodothyroacetic acid and thyroxine were also effective in preventing NCoR peptide binding and increasing SRC2 peptide binding, whereas reverse-triiodothyronine was less efficient and the biologically inactive thyronine had no effect on either process. These experiments validate cell-free assays based on the use of binding of corepressor or coactivator peptide probes, as measured by fluorescence polarization, for investigating the conformational changes of TRα1 LBD induced by potentially TR-interfering compounds. Both these methods were used to elucidate the mechanism of the disrupting effects of tetrabromobisphenol-A (TBBPA) on the hTRα1 LBD conformation related to the transcriptional activity of the receptor. TBBPA is a flame retardant that is released into the environment, and is a suspected disrupter of thyroid homeostasis. The present results indicate that TBBPA did indeed interfere with the ability of the hTRα1 LBD to bind both NCoR and SRC2. TBBPA behaved similarly to T3 in promoting the release of NCoR from LBD, whereas it failed to promote LBD interactions with SRC2. However, it did reduce the T3-induced interactions between LBD and the coactivator peptide. This study therefore suggests that TBBPA in the micromolar range can affect the regulation of transcription by both the apo- and the holo-TRα1, with potential disruption of the expression of genes that are either up- or down-regulated by T3.