In Silico Identification of Potential Thyroid Hormone System Disruptors among Chemicals in Human Serum and Chemicals with a High Exposure Index.

Data on toxic effects are at large missing the prevailing understanding of the risks of industrial chemicals. Thyroid hormone (TH) system disruption includes interferences of the life cycle of the thyroid hormones and may occur in various organs. In the current study, high-throughput screening data available for 14 putative molecular initiating events of adverse outcome pathways, related to disruption of the TH system, were used to develop 19 in silico models for identification of potential thyroid hormone system-disrupting chemicals. The conformal prediction framework with the underlying Random Forest was used as a wrapper for the models allowing for setting the desired confidence level and controlling the error rate of predictions. The trained models were then applied to two different databases: (i) an in-house database comprising xenobiotics identified in human blood and ii) currently used chemicals registered in the Swedish Product Register, which have been predicted to have a high exposure index to consumers. The application of these models showed that among currently used chemicals, fewer were overall predicted as active compared to chemicals identified in human blood. Chemicals of specific concern for TH disruption were identified from both databases based on their predicted activity.

Fate of Per- and Polyfluoroalkyl Substances from Durable Water-Repellent Clothing during Use.

To make outdoor clothing water- or dirt-repellent, durable water-repellent (DWR) coatings based on side-chain fluorinated polymers (SFPs) are used. During use of outdoor clothing, per- and polyfluoroalkyl substances (PFASs) can be emitted from the DWR to the environment. In this study, the effects of aging, washing, and tumble drying on the concentration of extractable PFASs in the DWR of perfluorohexane-based short-chain SFPs (FC-6 chemistry) and of perfluorooctane-based long-chain SFPs (FC-8 chemistry) were assessed. For this purpose, polyamide (PA) and polyester (PES) fabrics were coated with FC-6- and FC-8-based DWRs. Results show that aging of the coated fabrics causes an increase in concentration and formation of perfluoroalkyl acids (PFAAs). The effect of aging on the volatile PFASs depends on the type of fabric. Washing causes a decrease in PFAA concentrations, and in general, volatile PFASs are partly washed out of the textiles. However, washing can also increase the extractable concentration of volatile PFASs in the fabrics. This effect becomes stronger by a combination of aging and washing. Tumble drying does not affect the PFAS concentrations in textiles. In conclusion, aging and washing of fabrics coated with the DWR based on SFPs release PFASs to the environment.

Source characterisation and distribution of selected PCBs, PAHs and alkyl PAHs in sediments from the Klip and Jukskei Rivers, South Africa.

A study of the distribution of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) utilising 16 priority PAHs, benzo(e)pyrene, perylene, 19 alkylated PAHs and 31 ortho substituted PCBs in South Africa is presented. It was aimed to (a) deduce characteristic contamination patterns for both PCBs and PAHs and (b) provide the first comprehensive dataset for establishment of source characterisation of PCBs and PAHs. This is in line with new South African legislation on mandatory monitoring of PCB and PAH emissions. Bar charts, principal component analysis (PCA) and biplots were utilised to identify signature contamination patterns and distribution of PCBs and PAHs within the Jukskei and Klip Rivers. Sediments from the Jukskei and Klip River catchments both showed distinct contamination signatures for hexa to nonachlorinated PCBs, characteristic of contamination by Aroclor 1254 and 1260 technical mixtures. PCB signature patterns in order of abundance were 138 > 180 > 206 > 153 > 187 > 149 and 138 > 153 > 180 > 149 > 187 > 110 > 170 for the Jukskei and Klip River sediments, respectively. The upstream Alberton point had the highest Σ31 PCB and Σ (parent+alkyl) PAH concentrations in the Klip River of 61 and 6000 µg kg-1 dry weight (dw), respectively. In the Jukskei River, the upstream Marlboro point had the highest Σ31 PCB concentration of 19 µg kg-1 dw and the N14 site recorded the highest Σ (parent+alkyl) PAH concentration of 2750 µg kg-1 dw. PAH concentrations in both the Jukskei and Klip Rivers were significantly higher than the PCB concentrations. Fluoranthene, phenanthrene and pyrene were found in the highest concentrations in both the Jukskei and Klip River sediments. Both the Jukskei and Klip River sediments showed trends of a mixed pyrogenic-petrogenic PAH source contamination.

In Silico Approach To Identify Potential Thyroid Hormone Disruptors among Currently Known Dust Contaminants and Their Metabolites.

Thyroid hormone disrupting chemicals (THDCs) interfere with the thyroid hormone system and may induce multiple severe physiological disorders. Indoor dust ingestion is a major route of THDCs exposure in humans, and one of the molecular targets of these chemicals is the hormone transporter transthyretin (TTR). To virtually screen indoor dust contaminants and their metabolites for THDCs targeting TTR, we developed a quantitative structure-activity relationship (QSAR) classification model. The QSAR model was applied to an in-house database including 485 organic dust contaminants reported from literature data and their 433 in silico derived metabolites. The model predicted 37 (7.6%) dust contaminants and 230 (53.1%) metabolites as potential TTR binders. Four new THDCs were identified after testing 23 selected parent dust contaminants in a radio-ligand TTR binding assay; 2,2',4,4'-tetrahydroxybenzophenone, perfluoroheptanesulfonic acid, 3,5,6-trichloro-2-pyridinol, and 2,4,5-trichlorophenoxyacetic acid. These chemicals competitively bind to TTR with 50% inhibition (IC50) values at or below 10 µM. Molecular docking studies suggested that these THDCs interacted similarly with TTR via the residue Ser117A, but their binding poses were dissimilar to the endogenous ligand T4. This study identified new THDCs using an in silico approach in combination with bioassay testing and highlighted the importance of metabolic activation for TTR binding.

Tracing thyroid hormone-disrupting compounds: database compilation and structure-activity evaluation for an effect-directed analysis of sediment.

A variety of anthropogenic compounds has been found to be capable of disrupting the endocrine systems of organisms, in laboratory studies as well as in wildlife. The most widely described endpoint is estrogenicity, but other hormonal disturbances, e.g., thyroid hormone disruption, are gaining more and more attention. Here, we present a review and chemical characterization, using principal component analysis, of organic compounds that have been tested for their capacity to bind competitively to the thyroid hormone transport protein transthyretin (TTR). The database contains 250 individual compounds and technical mixtures, of which 144 compounds are defined as TTR binders. Almost one third of these compounds (n = 52) were even more potent than the natural hormone thyroxine (T4). The database was used as a tool to assist in the identification of thyroid hormone-disrupting compounds (THDCs) in an effect-directed analysis (EDA) study of a sediment sample. Two compounds could be confirmed to contribute to the detected TTR-binding potency in the sediment sample, i.e., triclosan and nonylphenol technical mixture. They constituted less than 1% of the TTR-binding potency of the unfractionated extract. The low rate of explained activity may be attributed to the challenges related to identification of unknown contaminants in combination with the limited knowledge about THDCs in general. This study demonstrates the need for databases containing compound-specific toxicological properties. In the framework of EDA, such a database could be used to assist in the identification and confirmation of causative compounds focusing on thyroid hormone disruption.

In vivo effect confirmation of anti-androgenic compounds in sediment contact tests with Potamopyrgus antipodarum.

In order to investigate the sensitivity of Potamopyrgus antipodarum to anti-androgenic compounds, three spiked sediment tests were performed. The substances benzanthrone (7H-benz[de]anthracen-7-one), traseolide (ATII) and androstenone (5α-Androst-16-en-3-one) were previously identified in an effect-directed analysis study of the river Schijn in the north of Belgium. Although, in previous studies, all of the three compounds exhibited anti-androgenic activities in vitro, only the oxy-PAH benzanthrone had significant stimulating effects on the snails' reproduction. The reproduction of P. antipodarum was significantly stimulated, following a sigmoidal dose response curve, whereby an EC(50) of 10 ng/g dry sediment was calculated. Mortality was significantly increased at the highest concentration (69 ng/g dry sediment). The results indicate different relative potencies for the in vivo test with P. antipodarum and the in vitro anti-AR-CALUX assay, performed in a previous study. This highlights the importance of combined in vitro and in vivo assays for the effect assessment of field sediments.

Estimated daily intake of per- and polyfluoroalkyl substances related to different particle size fractions of house dust.

Indoor environmental pollutants are a threat to human health. In the current study, we analysed 25 per- and polyfluoroalkyl substances (PFASs) in seven different size fraction of house dust including the two relevant for exposure via ingestion and inhalation. The highest PFAS concentration is found in the inhalable particulate fraction which is explained by the increased surface area as the particulate's sizes decrease. The estimated daily intake (EDI) of the individual PFAS and exposure pathways were calculated for children and adults. In addition, the total EDI for PFOA and its precursors was estimated. The polyfluoroalkyl phosphoric acid diesters (diPAP), followed by PFOA and PFHxA fluortelomer, showed the highest concentrations of PFAS analysed. The cumulative EDI of PFAS for children was 3.0 ng/kg bw per day, a worst-case scenario, which is 17 times higher than the calculated EDI for adults. For children, ingestion of dust was found to result in 800 times higher PFOA exposure than via inhalation. The contribution from PFOA precursors corresponded to only 1% of the EDI from dust indicating PFOA as the main source of exposure. The EDI's of PFOA and PFOS from dust were lower than the calculated EDI's from food ingestion reported by the Swedish Food Agency. Our data indicate that the EDI for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS from dust intake alone is close to the established tolerable weakly intake of 4.4 ng/kg bw in children, set by European Food Safety Authority (EFSA) in 2020. The combined EDI levels PFOA and PFOS from both dust and food exceeded the EFSA TWI for both children and adults. This study demonstrates that dust is a relevant exposure pathway for PFAS intake and that analysis of relevant particle size fractions is important for evaluation of dust as an exposure pathway.

Polar compounds dominate in vitro effects of sediment extracts.

Sediment extracts from three polluted sites of the river Elbe basin were fractionated using a novel online fractionation procedure. Resulting fractions were screened for mutagenic, aryl hydrocarbon receptor (AhR)-mediated, transthyretin (TTR)-binding, and estrogenic activities and their potency to inhibit gap junctional intercellular communication (GJIC) to compare toxicity patterns and identify priority fractions. Additionally, more than 200 compounds and compound classes were identified using GC-MS/MS, LC-MS/MS, and HPLC-DAD methods. For all investigated end points, major activities were found in polar fractions, which are defined here as fractions containing dominantly compounds with at least one polar functional group. Nonpolar PAH fractions contributed to mutagenic and AhR-mediated activities while inhibition of GJIC and estrogenic and TTR-binding activities were exclusively observed in the polar fractions. Known mutagens in polar fractions included nitro- and dinitro-PAHs, azaarenes, and keto-PAHs, while parent and monomethylated PAHs such as benzo[a]pyrene and benzofluoranthenes were identified in nonpolar fractions. Additionally, for one sample, high AhR-mediated activities were determined in one fraction characterized by PCDD/Fs, PCBs, and PCNs. Estrone, 17ß-estradiol, 9H-benz[de]anthracen-7-one, and 4-nonylphenol were identified as possible estrogenic and TTR-binding compounds. Thus, not only nonpolar compounds such as PAHs, PCBs, and PCDD/Fs but also the less characterized and investigated more polar substances should be considered as potent mutagenic, estrogenic, AhR-inducing, TTR-binding, and GJIC-inhibiting components for future studies.

Identification strategy for unknown pollutants using high-resolution mass spectrometry: androgen-disrupting compounds identified through effect-directed analysis.

Effect-directed analysis has been applied to a river sediment sample of concern to identify the compounds responsible for the observed effects in an in vitro (anti-)androgenicity assay. For identification after non-target analysis performed on a high-resolution LTQ-Orbitrap, we developed a de novo identification strategy including physico-chemical parameters derived from the effect-directed analysis approach. With this identification strategy, we were able to handle the immense amount of data produced by non-target accurate mass analysis. The effect-directed analysis approach, together with the identification strategy, led to the successful identification of eight androgen-disrupting compounds belonging to very diverse compound classes: an oxygenated polyaromatic hydrocarbon, organophosphates, musks, and steroids. This is one of the first studies in the field of environmental analysis dealing with the difficult task of handling the large amount of data produced from non-target analysis. The combination of bioassay activity assessment, accurate mass measurement, and the identification and confirmation strategy is a promising approach for future identification of environmental key toxicants that are not included as priority pollutants in monitoring programs.

Per- and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats.

Per- and polyfluoroalkyl substances (PFASs) are used in a wide range of products and have been found ubiquitously in our indoor environment, and there is evidence that exposure to PFAS can lead to adverse endocrine effects, such as thyroid hormone disruption. Pet cats have a high dust intake due to their grooming behavior and have been shown to be a suitable sentinel species for assessment of toddler's exposure. Here we used paired household dust (n=46) and cat serum (n=27) samples to establish whether dust is a relevant exposure pathway to PFASs. An analytical method for PFAS analysis was optimized using a low volume of cat serum samples, combining solid-phase extraction and online sample cleanup. Dust was extracted with methanol by sonication and cleaned up by addition of active carbon. In total, 27 PFASs were analyzed by liquid chromatography/mass spectrometry analysis. The correlation between PFAS levels in dust and serum, serum lipids and thyroid hormone levels, and PFAS levels in dust between different rooms were statistically evaluated. PFOS and PFDA could be quantified in all cat serum samples (median 2300 pg/mL and 430 pg/mL, respectively), followed by PFOA (median 1100 pg/mL), quantified in 96% of the samples. The levels of 6:2 and 8:2 diPAPs were determined in 65% and 92% of the serum samples, respectively, and were an order of magnitude lower (1.4-160 pg/mL). Household dust on the other hand was dominated by 6:2 and 8:2 diPAPs, with a median of 65 ng/g dust and 49 ng/g dust, respectively. PFOS (median 13 ng/g dust) and PFOA (median 9 ng/g dust) were quantified in 93% of the dust samples. Only eight PFASs were detected (>LOD) in at least 50% of the samples of both matrices and could be paired. Significant correlations between cat serum and dust were found for PFOA (rS=0.32, p<0.049) and PFUnDA (rS=0.55, p<0.001). Significant positive correlations were found between serum total thyroxine (rS=0.11, p<0.05) and PFNA and between serum cholesterol and PFHpA (rS=0.46, p<0.01), PFUnDA (rS=0.40, p<0.05), PFDoDA (rS=0.44, p<0.01), and sum PFAS (rS=0.48, p<0.01). In conclusion, this study confirmed that dust is a relevant exposure pathway for the ingestion of some PFASs for cats, and the serum levels of PFASs could be of relevance for the cat's health.

Testing endocrine disruption in biota samples: a method to remove interfering lipids and natural hormones.

A cleanup method was developed to remove coextracted lipids and natural hormones from biota samples in order to test the endocrine-disrupting (ED) capacity of their extracts in in vitro bioassays. Unspiked and spiked fish tissues were cleaned with a combination of dialysis, gel permeation chromatography (GPC), and normal-phase liquid chromatography (NP-HPLC). The spiking mixture consisted of a broad range of environmental pollutants (endocrine disruptors and genotoxic compounds). Chemical recoveries of each test compound, and thyroid-hormone-like and (anti)androgenic activities of the cleaned extracts were investigated. Despite the chemical and toxicological complexity of the spiking mixture and the sequential sample treatment, chemical analysis revealed acceptable recoveries on average: 89 ± 8% after each cleanup step separately and 75 ± 3% after the whole extraction and cleanup procedure in the extracts. In addition, recovered activities in the bioassays were in good agreement with the spiking levels. The developed cleanup method proved to be capable of lipid and natural hormone removal from fish extracts, enabling the measurement of selected endocrine-hormone-like activities in T(4)*-TTR and AR-CALUX bioassays. The method can be used as a sample preparation method of biota samples for toxicity profiling and effect-directed analysis (EDA).

Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum.

BACKGROUND: House dust contains many organic contaminants that can compete with the thyroid hormone (TH) thyroxine (T4) for binding to transthyretin (TTR). How these contaminants work together at levels found in humans and how displacement from TTR in vitro relates to in vivo T4-TTR binding is unknown. OBJECTIVES: Our aims were to determine the TTR-binding potency for contaminant mixtures as found in house dust, maternal serum, and infant serum; to study whether the TTR-binding potency of the mixtures follows the principle of concentration addition; and to extrapolate the in vitro TTR-binding potency to in vivo inhibition levels of T4-TTR binding in maternal and infant serum. METHODS: Twenty-five contaminants were tested for their in vitro capacity to compete for TTR-binding with a fluorescent FITC-T4 probe. Three mixtures were reconstituted proportionally to median concentrations for these chemicals in house dust, maternal serum, or infant serum from Nordic countries. Measured concentration-response curves were compared with concentration-response curves predicted by concentration addition. For each reconstituted serum mixture, its inhibitor-TTR dissociation constant (Ki) was used to estimate inhibition levels of T4-TTR binding in human blood. RESULTS: The TTR-binding potency of the mixtures was well predicted by concentration addition. The ∼20% inhibition in FITC-T4 binding observed for the mixtures reflecting median concentrations in maternal and infant serum was extrapolated to 1.3% inhibition of T4-TTR binding in maternal and 1.5% in infant blood. For nontested mixtures reflecting high-end serum concentrations, these estimates were 6.2% and 4.9%, respectively. DISCUSSION: The relatively low estimated inhibition levels at median exposure levels may explain why no relationship between exposure to TTR-binding compounds and circulating T4 levels in humans has been reported, so far. We hypothesize, however, that 1.3% inhibition of T4-TTR binding may ultimately be decisive for reaching a status of maternal hypothyroidism or hypothyroxinemia associated with impaired neurodevelopment in children. https://doi.org/10.1289/EHP5911.

Short-, medium-, and long-chain chlorinated paraffins in South African indoor dust and cat hair.

Polychlorinated n-alkanes or chlorinated paraffins (CPs) contain a magnitude of structural isomers and are categorized as short-chain (SCCPs), medium-chain (MCCPs), and long-chain (LCCPs) CPs, according to the carbon chain lengths. In this study the Æ©SCCPs, Æ©MCCPs, and Æ©LCCP concentrations are reported for South African indoor dust and pet cat hair. The median concentrations of the Æ©CPs (C9-C37) ranged from 33 to 663 µg/g for freshly collected dust (FD), 36-488 µg/g for dust collected from household vacuum cleaner bags (VD), and 1.2-15 µg/g for cat hair (CH) samples. MCCPs were the dominant CP group, followed by SCCPs and LCCPs. The Æ©MCCP concentration ranged from 13 to 498 µg/g in dust and 0.6-6.5 µg/g in cat hair. SCCPs with shorter carbon chains and lower chlorine substitution were observed in cat hair. LCCPs with carbon chains > C20 were detected in dust and hair samples, possibly indicating the use of wax grade LCCP formulations. Non-traditional Kendrick mass defect plots were used to obtain information on the magnitude of CPs and provide evidence of possible interfering compounds. This is the first report on the occurrence of SCCPs, MCCPs, and LCCPs in the South African indoor environment.

The effect of weathering on per- and polyfluoroalkyl substances (PFASs) from durable water repellent (DWR) clothing.

To assess the effects of weathering on per- and polyfluoroalkyl substances (PFASs) from durable water repellent (DWR) clothing, thirteen commercial textile samples were exposed to elevated ultra violet (UV) radiation, humidity, and temperature in an aging device for 300 h, which mimics the lifespan of outdoor clothing. Before and after aging, the textile samples were extracted and analysed for the ionic PFASs (perfluoroalkyl acids (PFAAs), perfluorooctane sulfonamide (FOSA)) and volatile PFASs (fluorotelomer alcohols (FTOHs), acrylates (FTACs) and methacrylates (FTMACs)). Results showed that weathering can have an effect on PFASs used in DWR of outdoor clothing, both on the PFAS profile and on the measured concentrations. In most weathered samples the PFAA concentrations increased by 5- to more than 100-fold, while PFAAs not detected in the original textiles were detected in the weathered samples. DWR chemistries are based on side-chain fluorinated polymers. A possible explanation for the increase in concentration of the PFAAs is hydrolysis of the fluorotelomer based polymers (FTPs), or degradation of the FTOHs, which are used in the manufacturing of the FTPs. The concentrations of volatile PFASs also increased, by a factor up to 20. Suggested explanations are the degradation of the DWR polymers, making non-extractable fluorines extractable, or the transformation or degradation of unknown precursors. Further research is needed to unravel the details of these processes and to determine the transformation routes. This study shows that setting maximum tolerance limits only for a few individual PFASs is not sufficient to control these harmful substances in outdoor clothing.

Masking effect of anti-androgens on androgenic activity in European river sediment unveiled by effect-directed analysis.

This study shows that the androgen receptor agonistic potency is clearly concealed by the effects of androgen receptor antagonists in a total sediment extract, demonstrating that toxicity screening of total extracts is not enough to evaluate the full in vitro endocrine disrupting potential of a complex chemical mixture, as encountered in the environment. The anti-androgenic compounds were masking the activity of androgenic compounds in the extract with relatively high anti-androgenic potency, equivalent to 200 nmol flutamide equivalents/g dry weight. A two-step serial liquid chromatography fractionation of the extract successfully separated anti-androgenic compounds from androgenic compounds, resulting in a total androgenic potency of 3,820 pmol dihydrotestosterone equivalents/g dry weight. The fractionation simplified the chemical identification analysis of the original complex sample matrix. Seventeen chemical structures were tentatively identified. Polyaromatic hydrocarbons, a technical mixture of nonylphenol and dibutyl phthalate were identified to contribute to the anti-androgenic potency observed in the river sediment sample. With the GC/MS screening method applied here, no compounds with AR agonistic disrupting potencies could be identified. Seventy-one unidentified peaks, which represent potentially new endocrine disrupters, have been added to a database for future investigation.

Brominated and organophosphorus flame retardants in South African indoor dust and cat hair.

Flame retardants (FRs), such as brominated flame retardants (BFRs) and organophosphorus flame retardants (OPFRs), are diverse groups of compounds used in various products related to the indoor environment. In this study concentrations of eight polybrominated diphenyl ethers (PBDEs), two alternative BFRs and ten OPFRs were determined in indoor dust (n = 20) and pet cat hair (n = 11) from South Africa. The OPFRs were the major FRs, contributing to more than 97% of the total FR concentration. The median Ʃ10OPFRs concentrations were 44,800 ng/g in freshly collected dust (F-dust), 19,800 ng/g in the dust collected from vacuum cleaner bags (V-dust), and 865 ng/g in cat hair (C-hair). Tris(1-chloro-2-propyl) phosphate (TCIPP) was the dominant OPFR in the dust samples with median concentrations of 7,010 ng/g in F-dust and 3,590 ng/g in V-dust. Tris(2-butoxyethyl) phosphate (TBOEP) was the dominant OPFR in C-hair, with a median concentration of 387 ng/g. The concentrations of Ʃ8PBDEs were higher in F-dust than in V-dust. BDE209 was the dominant BFR in all three matrices. Bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5- tetrabromobenzoate (EH-TBB) showed notable contributions to the BFR profile in cat hair. A worst-case dust exposure estimation was performed for all analytes. The estimated TCIPP daily intake through dust ingestion was up to 1,240 ng/kg bw for toddlers. The results indicate that OPFRs are ubiquitous in South African indoor environment. Indoor dust is a major source of human exposure to environmental contaminants. This can for example occur through hand-to-mouth contact of toddlers, and is an important route of exposure to currently used FRs accumulated on dust particles. The presence of FRs, in particular high concentrations of OPFRs, suggests that children and indoor pet cats may have greater exposure to FRs than adults.

Seasonal variation of chloro-s-triazines in the Hartbeespoort Dam catchment, South Africa.

Seasonal variation of eight chloro-s-triazine herbicides and seven major atrazine and terbuthylazine degradation products was monitored in the Hartbeespoort Dam catchment using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS/MS). Lake, river and groundwater were sampled from the Hartbeespoort Dam catchment over four seasons and the downstream Jukskei River was monitored during the winter season. Triazine herbicide concentrations in the Hartbeespoort Dam were in the order atrazine>simazine>propazine>ametryn>prometryn throughout the four seasons sampled. Triazine herbicide concentrations in the Hartbeespoort Dam surface water were highest in summer and gradually decreased in successive seasons of autumn, winter and spring. Terbuthylazine was the only triazine herbicide detected at all sampling sites in the Jukskei River, though atrazine recorded much higher concentrations for the N14 and Kyalami sites, with concentrations of 923 and 210ngL-1 respectively, compared to 134 and 74ngL-1 for terbuthylazine. Analytical results in conjunction with river flow data indicate that the Jukskei and Crocodile Rivers contribute the greatest triazine herbicide loads into the Hartbeespoort Dam. No triazine herbicides were detected in the fish muscle tested, showing that bioaccumulation of triazine herbicides is negligible. Atrazine and terbuthylazine metabolites were detected in the fish muscle with deethylatrazine (DEA) being detected in both catfish and carp muscle at low concentrations of 0.2 and 0.3ngg-1, respectively. Desethylterbuthylazine (DET) was detected only in catfish at a concentration of 0.3ngg-1. With atrazine herbicide groundwater concentrations being >130ngL-1 for all seasons and groundwater ∑triazine herbicide concentrations ranging between 527 and 367ngL-1, triazine compounds in the Hartbeespoort Dam catchment may pose a risk to humans and wildlife in light findings of endocrine and immune disrupting atrazine effects by various researchers.

Contaminants of emerging concern in the Hartbeespoort Dam catchment and the uMngeni River estuary 2016 pollution incident, South Africa.

A quantitative assessment of pollutants of emerging concern in the Hartbeespoort Dam catchment area was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to establish the occurrence, source and distribution of 15 environmental pollutants, including 10 pharmaceuticals, 1 pesticide and 4 steroid hormones. Seasonal sampling was conducted in the Hartbeespoort Lake using sub-surface grab sampling to determine the lake's ecological status and obtain data for establishment of progressive operational monitoring. The Jukskei River, which lies upstream of the Hartbeespoort Dam, was sampled in the winter season. Five year old carp (Cyprinus carpio) and catfish (Clarias gariepinus) were also sampled from the Hartbeespoort Dam to study bioaccumulation in biota as well as to estimate risk associated with fish consumption. In the Jukskei River, the main source of 11 emerging pollutants (EPs) was identified as raw sewage overflow, with the highest ∑11 EP concentration of 593ngL-1 being recorded at the Midrand point and the lowest ∑11 EP concentration of 164ngL-1 at the N14 site located 1km downstream of a large wastewater treatment plant. The Jukskei River was found to be the largest contributor of the emerging contaminants detected in the Hartbeespoort Dam. In the Hartbeespoort Dam EP concentrations were generally in the order efavirenz>nevirapine>carbamazepine>methocarbamol>bromacil>venlafaxine. Water and sediment were sampled from the uMngeni River estuary within 24h after large volumes of an assortment of pharmaceutical waste had been discovered to be washed into the river estuary after flash rainfall on 18 May 2016. Analytical results revealed high levels of some emerging pollutants in sediment samples, up to 81ngg-1 for nevirapine and 4ngg-1 for etilefrine HCL. This study shows that efavirenz, nevirapine, carbamazepine, methocarbamol, bromacil and venlafaxine are contaminants that require operational monitoring in South African urban waters.

Comprehensive two-dimensional gas chromatography coupled to high resolution time-of-flight mass spectrometry for screening of organohalogenated compounds in cat hair.

The coupling of comprehensive two-dimensional gas chromatography with high-resolution time-of-flight mass spectrometry offers the best separation efficiency combined with accurate mass measurements over a wide mass range. The tremendous power of this screening tool is illustrated by trace qualitative screening analysis of organohalogenated compounds (OHCs) in pet cat hair. Tentative identification was supported by mass spectral database searches and elemental formula prediction from the experimentally determined accurate mass data. This screening approach resulted in the first tentative identification of pentabromoethylbenzene, decabromodiphenyl ethane, hexabromocyclododecane, trisbromoneopentyl alcohol, tris(2-chloroethyl) phosphate and tris(2-chloroisopropyl)phosphate in the South African indoor environment. A total of seventy-two OHCs were identified in the samples and include known flame retardants, such as polybrominated diphenyl ethers, and legacy contaminants such as polychlorinated biphenyls and organochlorine, organophosphorous and pyrethroid pesticides. The results obtained from cat hair indicate that these pets are exposed to complex mixtures of OHCs and the detection of these compounds suggests that non-invasive cat hair samples can be used to model indoor exposure with reference to external deposition of OHCs present in the air and dust surrounding people. Toddlers share the same environment as pet cats and therefore also the same health risks.

Daily intake of phthalates, MEHP, and DINCH by ingestion and inhalation.

Phthalate esters, suspected endocrine disrupting chemicals, are used in a wide range of applications. Because phthalate esters are not covalently bound, they can easily leach into the indoor environment and associate to dust particles. Thus, exposure may occur through inhalation, ingestion, or contact with the skin. However, it is unclear to what degree indoor dust contributes to the daily intake of phthalate esters. This study investigates household dust as an exposure pathway for seven phthalate esters, the monoester MEHP, and the plasticizer DINCH. Household dust collected from children's sleeping rooms and from living rooms were analysed using gas and liquid chromatography tandem mass spectrometry. To compare two exposure pathways, different dust particle sizes were generated: a respirable fraction (<5 µm) and an ingested particle fraction in the anticipated size range of skin adherence (<75 µm). Modelling of dust inhalation and ingestion showed that the daily intake of dust-bound phthalate esters was likely to be 2 times (inhalation) to 12 times (ingestion) higher for 21-month-old children than for adults. These children's daily uptake of phthalate esters was 40-140 times higher through ingestion than inhalation. Furthermore, dust may be an exposure pathway for phthalate esters as well as for MEHP. Therefore, phthalate monoesters could be environmental contaminants of their own and need to be considered in health risk assessments.