Towards a non-animal risk assessment for anti-androgenic effects in humans

Toxicology testing is undergoing a transformation from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. We review the tools and approaches that could be used to develop a non-animal safety assessment for anti-androgenic effects in humans, with a focus on the molecular initiating events (MIEs) that human disorders indicate critical for normal functioning of the hypothalamus–pituitary–testicular (HPT) axis. In vitro test systems exist which can be used to characterize the effects of test chemicals on some MIEs such as androgen receptor antagonism, inhibition of steroidogenic enzymes or 5α-reductase inhibition. When used alongside information describing the pharmacokinetics of a specific chemical exposure, these could be used to inform a pathways-based safety assessment. However, some parts of the HPT axis such as events occurring in the hypothalamus or pituitary are not well represented by accepted in vitro methods. In vitro tools to characterize perturbations in these events need to be developed before a fully integrated model of the HPT axis can be described. Knowledge gaps also exist which prevent us from using in vitro data to predict the type and severity of in vivo effect(s) that could arise from a given level of in vitro anti-androgenic activity. This means that more work is needed to reliably link an MIE with an adverse outcome. However, especially for chemicals with low anti-androgenic activity, human exposure data can be used to put in vitro mode of action data into context for risk-based safety decision-making.     

Biota-sediment accumulation factors for Dechlorane Plus in bottom fish from an electronic waste recycling site,South China

Biota-sediment accumulation factors (BSAFs) for Dechlorane Plus (DP), a highly chlorinated flame retardant, were determined in three bottom fish species, i.e., crucian carp, mud carp, and northern snakehead from an electronic waste recycling site in South China. The average BSAFs are 0.007, 0.01, and 0.06 for syn-DP, and 0.003, 0.025, and 0.001 for anti-DP in crucian carp, mud carp, and northern snakehead, respectively, suggesting low bioaccumulation potential of DP isomers in these fish. However, the bioaccumulation factors (BAFs) determined previously in the same sample set indicated that both DP isomers were highly bioaccumulative (BAFs > 5000) in most of the samples. This implies that BSAF values may be inherently inconsistent affecting their reliability as a bioaccumulation indicator. The BSAFs for DP isomers are two orders of magnitude lower than those (average of 0.43–2.28) for extremely hydrophobic polychlorinated biphenyls (CBs 199, 203, 207 and 208), but are comparable to those (average of 0.0001–0.009) for decabromodiphenyl ether (BDE 209) determined in the same sample set. Despite of the different chemical structures of the three compound classes, significantly negative correlations between logarithm of octanol–water partition coefficients (log K_OWs) and BSAFs of these chemicals were found, indicating that hydrophobicity is one of the key factors influencing the bioaccumulation of these compounds.     

Applying network analysis and Nebula (neighbor-edges based and unbiased leverage algorithm) to ToxCast data

BackgroundToxCast data have been used to develop models for predicting in vivo toxicity. To predict the in vivo toxicity of a new chemical using a ToxCast data based model, its ToxCast bioactivity data are needed but not normally available. The capability of predicting ToxCast bioactivity data is necessary to fully utilize ToxCast data in the risk assessment of chemicals.ObjectivesWe aimed to understand and elucidate the relationships between the chemicals and bioactivity data of the assays in ToxCast and to develop a network analysis based method for predicting ToxCast bioactivity data.MethodsWe conducted modularity analysis on a quantitative network constructed from ToxCast data to explore the relationships between the assays and chemicals. We further developed Nebula (neighbor-edges based and unbiased leverage algorithm) for predicting ToxCast bioactivity data.ResultsModularity analysis on the network constructed from ToxCast data yielded seven modules. Assays and chemicals in the seven modules were distinct. Leave-one-out cross-validation yielded a Q² of 0.5416, indicating ToxCast bioactivity data can be predicted by Nebula. Prediction domain analysis showed some types of ToxCast assay data could be more reliably predicted by Nebula than others.ConclusionsNetwork analysis is a promising approach to understand ToxCast data. Nebula is an effective algorithm for predicting ToxCast bioactivity data, helping fully utilize ToxCast data in the risk assessment of chemicals.     

Phytoestrogens and mycoestrogens in surface waters — Their sources,occurrence, and potential contribution to estrogenic activity

This review discusses the potential contribution of phytoestrogens and mycoestrogens to in vitro estrogenic activities occurring in surface waters and in vivo estrogenic effects in fish. Main types, sources, and pathways of entry into aquatic environment of these detected compounds were summarized. Reviewed concentrations of phyto/mycoestrogens in surface waters were mostly undetectable or in low ng/L ranges, but exceeded tens of μg/L for the flavonoids biochanin A, daidzein and genistein at some sites. While a few phytosterols were reported to occur at relatively high concentrations in surface waters, information about their potencies in in vitro systems is very limited, and contradictory in some cases. The relative estrogenic activities of compounds (compared to standard estrogen 17β-estradiol) by various in vitro assays were included, and found to differ by orders of magnitude. These potencies were used to estimate total potential estrogenic activities based on chemical analyses of phyto/mycoestrogens. In vivo effective concentrations of waterborne phyto/mycoestrogens were available only for biochanin A, daidzein, formononetin, genistein, equol, sitosterol, and zearalenone. The lowest observable effect concentrations in vivo were reported for the mycoestrogen zearalenone. This compound and especially its metabolites also elicited the highest in vitro estrogenic potencies. Despite the limited information available, the review documents low contribution of phyto/mycoestrogens to estrogenic activity in vast majority of surface waters, but significant contribution to in vitro responses and potentially also to in vivo effects in areas with high concentrations.     

Bacillus thuringiensis, nucleopolyhedrosis virus,and pheromones: Environmental considerations and uncertainties in large-scale insect control

The mode of action, extent of use, and the current knowledge on environmental fate and toxicity of three biological insecticides [Bacillus thuringiensis (B.t.), nucleopolyhedrosis virus (NPV), and pheromones] are reviewed. Data gaps, environmental uncertainties in any large-scale use, and proposed registration guidelines which may lead to more extensive use are discussed. B.t. disappears rapidly from plant foliage on exposure to sunlight and/or moisture, although it may persist in dry soil for several months or years. Foliar-applied NPVs are also inactivated by sunlight; the halflife on cotton leaves is 20–25 h. In the soil, NPVs may remain active for several years. Pheromones volatilize readily and do not persist in plant or in soil. Limited available data indicate that B.t. and pheromones do not persist in aquatic environments; quantitative data are unavailable for NPVs. Based on bioassay data, the three insecticides exhibit undetectable to low toxicity to nontarget organisms; there are also no reports of human disease or injury due to exposure to these pesticides and no bioaccumulation is expected with normal application. Except for B.t. which has been used in a limited large-scale applications, pest control uses of NPVs and pheromones are still in experimental stages. Areas of uncertainties requiring research and development include potential adverse health and ecological impacts in any large-scale and widespread use and efficacy and cost relative to synthetic chemical pesticides.     

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: A review

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted.     

Determination of nonionic detergents in municipal wastewater

Hard (nonbiodegradable) nonionic surfactants are the most commonly used nonionics in Israel. This has no parallel in western industrial countries. Consequently, available methods for nonionic determination should be appropriately applied and validated under the particular local in vivo conditions. This study presents preliminary results of the application of modified available analycal hydrophilic and hydrophobic methods and procedures for nonionic detergents determination to the complex system of typical sewage effluents in Israel under in vitro (laboratory controlled), simulative, semi-in vivo, and in vivo (real, uncontrolled) local field conditions. Using the hydrophilic Cobalto thiocyanate method and applying several essential modifications and transformations have facilitated the obtaining of “summative,” averaged, factorized calibration curves which represent the local environmental reality. Based on the above in vitro-in vivo transformations, an unexpected low concentration of nonionic surfactants (3–4 mg/L) has been determined in typical local municipal sewage effluents.     

Bioaccumulation of PCDD/Fs,PCBs and PBDEs by earthworms in field soils of an E-waste dismantling area in China

A total of 60 paired samples of earthworm, corresponding soil and wormcast were collected to investigate the bioaccumulation tendency of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in earthworms from a typical E-waste dismantling area in east China. Significant correlations were observed for the total concentrations among different matrix types except for PCDD/Fs in soil and earthworm. The bioaccumulation tendency showed some differences among the contaminants. Calculated biota–soil accumulation factors (BSAFs) indicated that PCBs and PBDEs had higher bioaccumulation potential compared to PCDD/Fs, which was somewhat different from laboratory studies. The plot of mean BSAFs versus log K_ow values for PCBs and PBDEs was well fitted by a second-order polynomial with the maximum BSAF at approximately log K_ow of 6.5. While for PCDD/Fs, only a slightly decreasing trend was observed with increasing log K_ow. Composition analysis indicated that tetra-, penta- and hexa-halogenated homologs had higher bioaccumulation levels, indicating that medium-halogenated congeners with log K_ow around 6.5 are more easily accumulated by earthworms. Furthermore, the ratios of BDE-47/-99 and BDE-99/-100 showed some discrepancies with the technical products and other biotic species, suggesting different bioaccumulation potential of PBDEs in earthworm.     

Chemical contaminants in swimming pools: Occurrence,implications and control

A range of trace chemical contaminants have been reported to occur in swimming pools. Current disinfection practices and monitoring of swimming pool water quality are aimed at preventing the spread of microbial infections and diseases. However, disinfection by-products (DBPs) are formed when the disinfectants used react with organic and inorganic matter in the pool. Additional chemicals may be present in swimming pools originating from anthropogenic sources (bodily excretions, lotions, cosmetics, etc.) or from the source water used where trace chemicals may already be present. DBPs have been the most widely investigated trace chemical contaminants, including trihalomethanes (THMs), haloacetic acids (HAAs), halobenzoquinones (HBQs), haloacetonitriles (HANs), halonitromethanes (HNMs), N-nitrosamines, nitrite, nitrates and chloramines. The presence and concentrations of these chemical contaminants are dependent upon several factors including the types of pools, types of disinfectants used, disinfectant dosages, bather loads, temperature and pH of swimming pool waters. Chemical constituents of personal care products (PCPs) such as parabens and ultraviolet (UV) filters from sunscreens have also been reported. By-products from reactions of these chemicals with disinfectants and UV irradiation have been reported and some may be more toxic than their parent compounds. There is evidence to suggest that exposure to some of these chemicals may lead to health risks. This paper provides a detailed review of various chemical contaminants reported in swimming pools. The concentrations of chemicals present in swimming pools may also provide an alternative indicator to swimming pool water quality, providing insights to contamination sources. Alternative treatment methods such as activated carbon filtration and advanced oxidation processes may be beneficial in improving swimming pool water quality.     

A review of in vitro testing systems applicable to diesel health effects research

In vitro mutagenicity and carcinogenicity testing techniques are currently being used to assess the potential risk to man of exposure to diesel exhaust emissions. This paper examines general considerations of such systems, the types of in vitro tests currently available, the advantages and disadvantages of each cell line and type of test, the limitations of in vitro techniques, the alternative human cell lines that could be utilized for diesel health effects studies, and recommendations for future research employing in vitro methods.     

A new multimedia contaminant fate model for China: How important are environmental parameters in influencing chemical persistence and long-range transport potential?

We present a new multimedia chemical fate model (SESAMe) which was developed to assess chemical fate and behaviour across China. We apply the model to quantify the influence of environmental parameters on chemical overall persistence (P_OV) and long-range transport potential (LRTP) in China, which has extreme diversity in environmental conditions. Sobol sensitivity analysis was used to identify the relative importance of input parameters. Physicochemical properties were identified as more influential than environmental parameters on model output. Interactive effects of environmental parameters on P_OV and LRTP occur mainly in combination with chemical properties. Hypothetical chemicals and emission data were used to model P_OV and LRTP for neutral and acidic chemicals with different K_OW/D_OW, vapour pressure and pK_a under different precipitation, wind speed, temperature and soil organic carbon contents (f_OC). Generally for P_OV, precipitation was more influential than the other environmental parameters, whilst temperature and wind speed did not contribute significantly to P_OV variation; for LRTP, wind speed was more influential than the other environmental parameters, whilst the effects of other environmental parameters relied on specific chemical properties. f_OC had a slight effect on P_OV and LRTP, and higher f_OC always increased P_OV and decreased LRTP. Example case studies were performed on real test chemicals using SESAMe to explore the spatial variability of model output and how environmental properties affect P_OV and LRTP. Dibenzofuran released to multiple media had higher P_OV in northwest of Xinjiang, part of Gansu, northeast of Inner Mongolia, Heilongjiang and Jilin. Benzo[a]pyrene released to the air had higher LRTP in south Xinjiang and west Inner Mongolia, whilst acenaphthene had higher LRTP in Tibet and west Inner Mongolia. TCS released into water had higher LRTP in Yellow River and Yangtze River catchments. The initial case studies demonstrated that SESAMe performed well on comparing P_OV and LRTP of chemicals in different regions across China in order to potentially identify the most sensitive regions. This model should not only be used to estimate P_OV and LRTP for screening and risk assessments of chemicals, but could potentially be used to help design chemical monitoring programmes across China in the future.     

Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring

There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe results of a study that links HRMS data with exposure predictions from the U.S. EPA's ExpoCast™ program and in vitro bioassay data from the U.S. interagency Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. as part of the American Healthy Homes Survey (AHHS). Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC–TOF/MS) with electrospray ionization. On average, approximately 2000 molecular features were identified per sample (based on accurate mass) in negative ion mode, and 3000 in positive ion mode. Exact mass, isotope distribution, and isotope spacing were used to match molecular features with a unique listing of chemical formulas extracted from EPA's Distributed Structure-Searchable Toxicity (DSSTox) database. A total of 978 DSSTox formulas were consistent with the dust LC–TOF/molecular feature data (match score ≥ 90); these formulas mapped to 3228 possible chemicals in the database. Correct assignment of a unique chemical to a given formula required additional validation steps. Each suspect chemical was prioritized for follow-up confirmation using abundance and detection frequency results, along with exposure and bioactivity estimates from ExpoCast and Tox21, respectively. Chemicals with elevated exposure and/or toxicity potential were further examined using a mixture of 100 chemical standards. A total of 33 chemicals were confirmed present in the dust samples by formula and retention time match; nearly half of these do not appear to have been associated with house dust in the published literature. Chemical matches found in at least 10 of the 56 dust samples include Piperine, N,N-Diethyl-m-toluamide (DEET), Triclocarban, Diethyl phthalate (DEP), Propylparaben, Methylparaben, Tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and Nicotine. This study demonstrates a novel suspect screening methodology to prioritize chemicals of interest for subsequent targeted analysis. The methods described here rely on strategic integration of available public resources and should be considered in future non-targeted and suspect screening assessments of environmental and biological media.     

A novel abbreviation standard for organobromine,organochlorine and organophosphorus flame retardants and some characteristics of the chemicals

Ever since the interest in organic environmental contaminants first emerged 50 years ago, there has been a need to present discussion of such chemicals and their transformation products using simple abbreviations so as to avoid the repetitive use of long chemical names. As the number of chemicals of concern has increased, the number of abbreviations has also increased dramatically, sometimes resulting in the use of different abbreviations for the same chemical. In this article, we propose abbreviations for flame retardants (FRs) substituted with bromine or chlorine atoms or including a functional group containing phosphorus, i.e. BFRs, CFRs and PFRs, respectively. Due to the large number of halogenated and organophosphorus FRs, it has become increasingly important to develop a strategy for abbreviating the chemical names of FRs. In this paper, a two step procedure is proposed for deriving practical abbreviations (PRABs) for the chemicals discussed. In the first step, structural abbreviations (STABs) are developed using specific STAB criteria based on the FR structure. However, since several of the derived STABs are complicated and long, we propose instead the use of PRABs. These are, commonly, an extract of the most essential part of the STAB, while also considering abbreviations previously used in the literature. We indicate how these can be used to develop an abbreviation that can be generally accepted by scientists and other professionals involved in FR related work. Tables with PRABs and STABs for BFRs, CFRs and PFRs are presented, including CAS (Chemical Abstract Service) numbers, notes of abbreviations that have been used previously, CA (Chemical Abstract) name, common names and trade names, as well as some fundamental physico-chemical constants.     

The precautionary principle and chemicals management: The example of perfluoroalkyl acids in groundwater

Already in the late 1990s microgram-per-liter levels of perfluorooctane sulfonate (PFOS) were measured in water samples from areas where fire-fighting foams were used or spilled. Despite these early warnings, the problems of groundwater, and thus drinking water, contaminated with perfluoroalkyl and polyfluoroalkyl substances (PFASs) including PFOS are only beginning to be addressed. It is clear that this PFAS contamination is poorly reversible and that the societal costs of clean-up will be high. This inability to reverse exposure in a reasonable timeframe is a major motivation for application of the precautionary principle in chemicals management. We conclude that exposure can be poorly reversible; 1) due to slow elimination kinetics in organisms, or 2) due to poorly reversible environmental contamination that leads to continuous exposure. In the second case, which is relevant for contaminated groundwater, the reversibility of exposure is not related to the magnitude of a chemical's bioaccumulation potential. We argue therefore that all PFASs entering groundwater, irrespective of their perfluoroalkyl chain length and bioaccumulation potential, will result in poorly reversible exposures and risks as well as further clean-up costs for society. To protect groundwater resources for future generations, society should consider a precautionary approach to chemicals management and prevent the use and release of highly persistent and mobile chemicals such as PFASs.     

Environmental exposure to organophosphorus and pyrethroid pesticides in South Australian preschool children: A cross sectional study

Organophosphorus (OP) and pyrethroid (PYR) compounds are the most widely used insecticides. OPs and PYRs are developmental neurotoxicants. Understanding the extent of exposure in the general population and especially in young children is important for the development of public health policy on regulation and use of these chemicals. Presented here are the results of the first investigation into the extent of environmental exposure to neurotoxic insecticides in preschool children in South Australia (SA).Children were enrolled from different areas of SA and assigned into urban, periurban and rural groups according to their residential address. Residential proximity to agricultural activity, parental occupational contact to insecticides and use of insecticides within the household were investigated as potential indirect measures of exposure. We used liquid chromatography/tandem mass spectrometry to measure the following metabolites of OPs and PYRs in urine samples as direct indicators of exposure: dialkylphosphates, p-nitrophenol, 3-methyl-4-nitrophenol, 3,5,6-trichloro-2-pyridinol, cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid, cis-3-(2,2-dibromovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid, 2-methyl-3phenylbenzoic acid and 3-phenoxybenzoic acid. Results were analysed to assess factors affecting the risk and level of exposure. Results were also compared to the published data in similar age groups from US and German studies.The results of this study demonstrate that there was widespread chronic exposure to OPs and and PYRs in SA children. OP metabolites were detected more commonly than PYR. Exposure to more than one chemical and contemporaneous exposure to chemicals from both OP and PYR groups was common in the study population. There were some differences in risks and levels of exposure between the study groups. Exposure to some restricted use of chemicals, for example, fenitrothion, was higher in periurban and rural children. There was no difference among the study groups in exposure to chlorpyrifos, used commonly in agriculture and in domestic settings and most frequently found OP pesticide in food in Australia. South Australian children appear to have higher levels of exposure compared their peers in US and Germany.     

A multidisciplinary weight of evidence approach for classifying polluted sediments: Integrating sediment chemistry, bioavailability, biomarkers responses and bioassays

Evaluation of chemical bioavailability and onset of biological alterations is fundamental to assess the hazard of environmental pollutants, particularly when associated to sediments which need to be removed. In the present work, five sediment samples were collected from the Venice Lagoon and data from sediment chemistry were integrated with those of bioaccumulation of chemicals in European eel (Anguilla anguilla) exposed under laboratory conditions, responses of a wide battery of biomarkers, and standardized ecotoxicological bioassays. The overall results were elaborated within a recently developed, software-assisted weight of evidence (WOE) model which provides synthetic indices for each of considered line of evidence (LOE), before a general evaluation of sediment hazard. Levels of chemicals in sediments were not particularly elevated when compared to sediment quality guidelines of Venice Protocol. On the other hand, bioavailability was evident in some samples for Cd, Cu, Zn and, especially, polycyclic aromatic hydrocarbons. The ecotoxicological approach provided further evidence on the biological and potentially harmful effects due to released contaminants, and oxidative-mediated responses appeared of primary importance in modulating sublethal responses and the onset of cellular alterations. Biomarkers variations were sensitive, and more evident variations included significant changes of cytochrome P450 biotransformation pathway, antioxidant responses, onset of oxidative damages, lysosomal membrane stability and genotoxic effects. The results obtained from the battery of bioassays indicated that responses measured at organism level were in general accordance but less marked compared to the onset of sublethal changes measured through biomarkers. Overall this study revealed differences when comparing evaluations obtained from different LOEs, confirming the importance of considering synergistic effects between chemicals in complex mixtures. Compared to a qualitative pass-fail approach toward normative values, the proposed WOE model allowed a quantitative characterization of sediment hazard and a better discrimination of on the basis of various types of chemical and biological data.     

Bioassays as one of the Green Chemistry tools for assessing environmental quality: A review

For centuries, mankind has contributed to irreversible environmental changes, but due to the modern science of recent decades, scientists are able to assess the scale of this impact. The introduction of laws and standards to ensure environmental cleanliness requires comprehensive environmental monitoring, which should also meet the requirements of Green Chemistry. The broad spectrum of Green Chemistry principle applications should also include all of the techniques and methods of pollutant analysis and environmental monitoring. The classical methods of chemical analyses do not always match the twelve principles of Green Chemistry, and they are often expensive and employ toxic and environmentally unfriendly solvents in large quantities. These solvents can generate hazardous and toxic waste while consuming large volumes of resources. Therefore, there is a need to develop reliable techniques that would not only meet the requirements of Green Analytical Chemistry, but they could also complement and sometimes provide an alternative to conventional classical analytical methods. These alternatives may be found in bioassays. Commercially available certified bioassays often come in the form of ready-to-use toxkits, and they are easy to use and relatively inexpensive in comparison with certain conventional analytical methods. The aim of this study is to provide evidence that bioassays can be a complementary alternative to classical methods of analysis and can fulfil Green Analytical Chemistry criteria. The test organisms discussed in this work include single-celled organisms, such as cell lines, fungi (yeast), and bacteria, and multicellular organisms, such as invertebrate and vertebrate animals and plants.     

Assessment of the endocrine-disrupting effects of short-chain chlorinated paraffins in in vitro models

Short-chain chlorinated paraffins (SCCPs), which are candidate persistent organic pollutants (POPs) according to the Stockholm Convention, are of great concern because of their persistent bioaccumulation, long-range transport and potential adverse health effects. However, data on the endocrine-disrupting effects of SCCPs remain scarce. In this study, we first adopted two in vitro models (reporter gene assays and H295R cell line) to investigate the endocrine-disrupting effects of three SCCPs (C10-40.40%, C10-66.10% and C11-43.20%) via receptor mediated and non-receptor mediated pathway. The dual-luciferase reporter gene assay revealed that all test chemicals significantly induced estrogenic effects, which were mediated by estrogen receptor α (ERα), in the following order: C11-43.20% > C10-66.10% > C10-40.40%. Notably, C10-40.40% and C10-66.10% also demonstrated remarkable anti-estrogenic activities. Only C11-43.20% showed glucocorticoid receptor-mediated (GR) antagonistic activity, with a RIC₂₀ value of 2.6 × 10^− 8 mol/L. None of the SCCPs showed any agonistic or antagonistic activities against thyroid receptor β (TRβ). Meanwhile, all test SCCPs stimulated the secretion of 17β-estradiol (E₂). Both C10-66.10% and C11-43.20% increased the production of cortisol at a high level in H295R cell lines. In order to explore the possible mechanism underlying the endocrine-disrupting effects of SCCPs through the non-receptor pathway, the mRNA levels of 9 steroidogenic genes were measured by real-time polymerase chain reaction (RT-PCR). StAR, 17βHSD, CYP11A1, CYP11B1, CYP19 and CYP21 were upregulated in a concentration-dependent manner by all chemicals. The data provided here emphasized that comprehensive assessments of the health and ecological risks of emerging contaminants, such as SCCPs, are of great concern and should be investigated further.     

In vivo contaminant partitioning to silicone implants: Implications for use in biomonitoring and body burden

Silicone polymers are used for a wide array of applications from passive samplers in environmental studies, to implants used in human augmentation and reconstruction. If silicone sequesters toxicants throughout implantation, it may represent a history of exposure and potentially reduce the body burden of toxicants influencing the risk of adverse health outcomes such as breast cancer. Objectives of this research included identifying a wide variety of toxicants in human silicone implants, and measuring the in vivo absorption of contaminants into silicone and surrounding tissue in an animal model. In the first study, eight human breast implants were analyzed for over 1400 organic contaminants including consumer products, chemicals in commerce, and pesticides. A total of 14 compounds including pesticides such as trans-nonachlor (1.2–5.9 ng/g) and p,p′-DDE (1.2–34 ng/g) were identified in human implants, 13 of which have not been previously reported in silicone prostheses. In the second project, female ICR mice were implanted with silicone and dosed with p,p′-DDE and PCB118 by intraperitoneal injection. After nine days, silicone and adipose samples were collected, and all implants in dosed mice had p,p′-DDE and PCB118 present. Distribution ratios from silicone and surrounding tissue in mice compare well with similar studies, and were used to predict adipose concentrations in human tissue. Similarities between predicted and measured chemical concentrations in mice and humans suggest that silicone may be a reliable surrogate measure of persistent toxicants. More research is needed to identify the potential of silicone implants to refine the predictive quality of chemicals found in silicone implants.