Public health assessment of hexachlorobenzene

Recently, hexachlorobenzene (HCB) was proposed for inclusion in the system of toxicity equivalency factors (TEFs) currently used for dioxin-like compounds. In this paper, we explore the practical implications of the proposition to the Agency for Toxic Substances and Disease Registry (ATSDR) programs by comparing respective health guidance values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and HCB (expressed as total toxicity equivalents [TEQs]), reviewing possible interactions between HCB and dioxin-like chemicals, and by providing information on actual co-existence of HCB and dioxin-like chemicals at hazardous waste sites. We found a good correlation between the TEF-adjusted oral exposure guidance values for HCB and guidance values for TCDD. The combination of HCB and other dioxin-like compounds was not found in soil, air, or water media at hazardous waste sites. Based on this fact, it is not necessary to include HCB in the total TEQ count at hazardous waste sites at this time.     

Near-road multipollutant profiles: associations between volatile organic compounds and a tracer gas surrogate near a busy highway

This research characterizes associations between multiple pollutants in the near-road environment attributed to a roadway line source. It also examines the use of a tracer gas as a surrogate of mobile source pollutants. Air samples were collected in summa canisters along a 300 m transect normal to a highway in Raleigh, North Carolina for five sampling periods spanning four days. Samples were subsequently measured for volatile organic compounds (VOCs) using an electron capture gas chromatograph. Sulfur hexafluoride (SF6) was released from a finite line source adjacent to the roadway for two of the sampling periods, collected in the canisters and measured with the VOCs. Associations between each VOC, and between VOCs and the tracer, were quantified with Pearson correlation coefficients to assess the consistency of the multi-pollutant dispersion profiles, and assess the tracer as a potential surrogate for mobile source pollutants. As expected, benzene, toluene, ethylbenzene, and m,p- and o-xylenes (collectively, BTEX) show strong correlations between each other; further BTEX shows a strong correlation to SF6. Between 26 VOCs, correlation coefficients were greater than 0.8, and 14 VOCs had coefficients greater than 0.6 with the tracer gas. Even under non-downwind conditions, chemical concentrations had significant correlations with distance. Results indicate that certain VOCs are representative of a larger multi-pollutant mixture, and many VOCs are well-correlated with the tracer gas.     

Proposals to overcome limitations in the EU chemical risk assessment scheme

The notification of new chemicals in the European Union requires a risk assessment. A Technical Guidance Document (TGD) was prepared for assistance. The TGD proposes QSARs, regressions and models from various sources. Each method has its own range of applicability and its own restrictions. Regressions used in the assessment of indirect human exposure have a common regression range from log K(OW), 3.0-4.6. Most models are compartment models, which do not consider a spatial distribution of the chemical, and were originally developed for non-dissociating, lipophilic persistent chemicals with measurable vapor pressure. Taking this into account, the TGD is only applicable for a minority of chemical classes. Dissociating compounds, ions, polar and very non-polar compounds do not belong to them. The effect of mixtures cannot be considered, except for hydrocarbons. Using the example of plant uptake, it is shown that in certain cases uptake is underestimated by the model due to processes not considered. This may lead to a wrong security in risk assessment. To overcome these limitations, a set of alternative models with different application ranges should be developed. When no applicable method is available, it might be better not to use a model at all instead of an inadequate model, and look for other sources of information.     

化学物质对发光菌的联合毒性评价方法

毒性单位法(TU)的理论基础来源于剂量加和模型(DA),目前仅在二元联合毒性评价中广泛应用。为了确定TU模型适合评价的混合物类型,实验选取5种剂量效应曲线类型不同的物质,采用微板光度计测试了一元、二元混合物对发光菌青海弧菌-Q67(Vibrio-qinghaiensis sp.-Q67)的急性毒性。根据物质的剂量效应曲线形状将物质分为A、B、C 3类,利用毒性单位法(TU)和联合作用定义法分别对AA类、AB类、AC类、BC类混合物进行分析。结果表明,TU法仅适合于由剂量效应曲线接近直线的物质组成的混合物进行联合毒性的评价。以效应为基准、TU模型为框架建立了TU’模型,该模型可以满足对任何类型已知成分的混合物或者未知成分的实际水样之间的多元联合作用的评价。     

Risk factors for increased BTEX exposure in four Australian cities

Benzene, toluene, ethylbenzene and xylenes (BTEX) are common volatile organic compounds (VOCs) found in urban airsheds. Elevated levels of VOCs have been reported in many airsheds at many locations, particularly those associated with industrial activity, wood heater use and heavy traffic. Exposure to some VOCs has been associated with health risks. There have been limited investigations into community exposures to BTEX using personal monitoring to elucidate the concentrations to which members of the community may be exposed and the main contributors to that exposure. In this cross sectional study we investigated BTEX exposure of 204 non-smoking, non-occupationally exposed people from four Australian cities. Each participant wore a passive BTEX sampler over 24h on five consecutive days in both winter and summer and completed an exposure source questionnaire for each season and a diary for each day of monitoring. The geometric mean (GM) and range of daily BTEX concentrations recorded for the study population were benzene 0.80 (0.04-23.8 ppb); toluene 2.83 (0.03-2120 ppb); ethylbenzene 0.49 (0.03-119 ppb); and xylenes 2.36 (0.04-697 ppb). A generalised linear model was used to investigate significant risk factors for increased BTEX exposure. Activities and locations found to increase personal exposure included vehicle repair and machinery use, refuelling of motor vehicles, being in an enclosed car park and time spent undertaking arts and crafts. A highly significant difference was found between the mean exposures in each of the four cities, which may be explained by differences in fuel composition, differences in the mix and density of industry, density of motor vehicles and air pollution meteorology.     

The interaction effects of binary mixtures of benzene and toluene on the developing heart of medaka (Oryzias latipes)

The United States Environmental Protection Agency (USEPA) has pursued the estimation of risk of adverse health effects from exposure to chemical mixtures since the early 1980s. Methods used to calculate risk estimates of mixtures were often based on single chemical information that required assumptions of dose-addition or response-addition and did not consider possible changes in response due to interaction effects among chemicals. Full factorial designs for laboratory studies can produce interactions information, but these are expensive to perform and may not provide the information needed to evaluate specific environmentally relevant mixtures. In this research, groups of Japanese medaka (Oryzias latipes) embryos were exposed to binary mixtures of benzene and toluene as well as to each of these chemicals alone. Endpoint specific dose-response models were built for the hydrocarbon mixture under an assumption of dose-additivity, using the single chemical dose-response information on benzene and toluene. The endpoints included heart rate, heart rate progression, and lethality. Results included a synergistic response for heart rate at 72 h of development, and either additivity or antagonism for all other endpoints at 96 h of development. This work uses an established statistical method to evaluate the toxicity of an environmentally relevant mixture to ascertain whether interaction effects are occurring, thus providing additional information on toxicity.     

Revealing source signatures in ambient BTEX concentrations

Management of ambient concentrations of Volatile Organic Compounds (VOCs) is essential for maintaining low ozone levels in urban areas where its formation is under a VOC-limited regime. The significant decrease in traffic-induced VOC emissions in many developed countries resulted in relatively comparable shares of traffic and non-traffic VOC emissions in urban airsheds. A key step for urban air quality management is allocating ambient VOC concentrations to their pertinent sources. This study presents an approach that can aid in identifying sources that contribute to observed BTEX concentrations in areas characterized by low BTEX concentrations, where traditional source apportionment techniques are not useful. Analysis of seasonal and diurnal variations of ambient BTEX concentrations from two monitoring stations located in distinct areas reveal the possibility to identify source categories. Specifically, the varying oxidation rates of airborne BTEX compounds are used to allocate contributions of traffic emissions and evaporative sources to observed BTEX concentrations.     

The joint effects of sulfonamides and their potentiator on Photobacterium phosphoreum: differences between the acute and chronic mixture toxicity mechanisms

Organisms are typically exposed to mixtures of chemicals over long periods of time; thus, chronic mixture toxicity analysis is the best way to perform risk assessment in regards to organisms. However, most studies focus on the acute mixture toxicity. To investigate the difference between chronic mixture toxicity and acute mixture toxicity, Photobacterium phosphoreum were exposed to chronic (24 h exposure) and acute (15 min exposure) toxicity of single sulfonamide (SA) and their potentiator (trimethoprim, TMP), both individually and mixtures (SA with TMP). A comparison of chronic vs. acute mixture toxicity revealed the presence of an interesting phenomenon, that is, that the joint effects vary with the duration of exposure; the acute mixture toxicity was antagonistic, whereas the chronic mixture toxicity was synergistic. Based on the approach of Quantitative Structure Activity Relationships (QSARs) and molecular docking, this phenomenon was proved to be caused by the presence of two points of dissimilarity between the acute and chronic mixture toxicity mechanism: (1) the receptor protein of SAs in acute toxicity was Luc, while in chronic toxicity it was Dhps, and (2) there is a difference between actual concentration of binding-Luc in acute toxicity and individual binding-Dhps in chronic toxicity. This deep insight into the difference between chronic and acute mixture toxicity will benefit environmental science, medical science, and other disciplines. The existence of these differences poses a challenge for the assessment of routine combinations in medicine, risk assessment, and mixture pollutant control, in which, previously, only a synergistic effect has been observed between SA and their potentiator.     

Mechanism of concentration addition toxicity: they are different for nonpolar narcotic chemicals, polar narcotic chemicals and reactive chemicals

According to the toxicity mechanism of the individual chemicals, the concentration addition toxicity mechanism is revealed for nonpolar-narcotic-chemical mixtures, polar-narcotic-chemical mixtures and reactive-chemical mixtures, respectively. For nonpolar-narcotic-chemical mixtures, the partitioning of individual chemicals from water to biophase was determined, and the result shows that their concentration additive effect results from no competitive partitioning among individual chemicals. For polar-narcotic-chemical mixtures, their toxicity are contributed by two factors (the total baseline toxicity and the hydrogen bond donor activity of individual chemicals), and it is the concentration additive effect for either of these two factors that leads to their concentration addition toxicity. In addition, the interactions between the reactive chemicals and the biological macromolecules are discussed thoroughly. The results suggest that the net effect of these interactions is zero, and it is this zero net effect that leads to the concentration addition toxicity mechanism for reactive-chemical mixtures.     

A novel method dependent only on the mixture information (MIM) for evaluating the toxicity of mixture

Compound contamination and toxicity interaction necessitate the development of models that have an insight into the combined toxicity of chemicals. In this paper, a novel and simple model dependent only on the mixture information (MIM), was developed. Firstly, the concentration-response data of seven groups of binary and multi-component (pseudo-binary) mixtures with different mixture ratios to Vibrio qinghaiensis sp.-Q67 were determined using the microplate toxicity analysis. Then, a desirable non-linear function was selected to fit the data. It was found that there are good linear correlations between the location parameter (α) and mixture ratio (p) of a component and between the steepness (β) and p. Based on the correlations, a mixture toxicity model independent of pure component toxicity profiles was built. The model can be used to accurately estimate the toxicities of the seven groups of mixtures, which greatly simplified the predictive procedure of the combined toxicity.     

Toxic masking and synergistic modulation of the estrogenic activity of chemical mixtures in a yeast estrogen screen (YES)

Background, aim and scope

Estrogenic and non-estrogenic chemicals typically co-occur in the environment. Interference by non-estrogenic chemicals may confound the assessment of the actual estrogenic activity of complex environmental samples. The aim of the present study was to investigate whether, in which way and how seriously the estrogenic activity of single estrogens and the observed and predicted joint action of estrogenic mixtures is influenced by toxic masking and synergistic modulation caused by non-estrogenic chemical confounders.

Materials and methods

The yeast estrogen screen (YES) was adapted so that toxicity and estrogenicity could be quantified simultaneously in one experimental run. Mercury, two organic solvents (dimethyl sulfoxide (DMSO) and 2,4-dinitroaniline), a surfactant (LAS-12) and the antibiotic cycloheximide were selected as toxic but non-estrogenic test chemicals. The confounding impact of selected concentrations of these toxicants on the estrogenic activity of the hormone 17ß-estradiol was determined by co-incubation experiments. In a second step, the impact of toxic masking and synergistic modulation on the predictability of the joint action of 17ß-estradiol, estrone and estriol mixtures by concentration addition was analysed.

Results

Each of the non-estrogenic chemicals reduced the apparent estrogenicity of both single estrogens and their mixtures if applied at high, toxic concentrations. Besides this common pattern, a highly substance- and concentration-dependent impact of the non-estrogenic toxicants was observable. The activity of 17ß-estradiol was still reduced in the presence of only low or non-toxic concentrations of 2,4-dinitroaniline and cycloheximide, which was not the case for mercury and DMSO. A clear synergistic modulation, i.e. an enhanced estrogenic activity, was induced by the presence of slightly toxic concentrations of LAS-12. The joint estrogenic activity of the mixture of estrogens was affected by toxic masking and synergistic modulation in direct proportion to the single estrogens, which allowed for an adequate adaptation of concentration addition and thus unaffected predictability of the joint estrogenicity in the presence of non-estrogenic confounders.

Discussion

The modified YES proved to be a reliable system for the simultaneous quantification of yeast toxicity and estrogen receptor activation. Experimental results substantiate the available evidence for toxic masking as a relevant phenomenon in estrogenicity assessment of complex environmental samples. Synergistic modulation of estrogenic activity by non-estrogenic confounders might be of lower importance. The concept of concentration addition is discussed as a valuable tool for estrogenicity assessment of complex mixtures, with deviations of the measured joint estrogenicity from predictions indicating the need for refined analyses.

Conclusions

Two major challenges are to be considered simultaneously for a reliable analysis of the estrogenic activity of complex mixtures: the identification of known and suspected estrogenic compounds in the sample as well as the substance- and effect-level-dependent confounding impact of non-estrogenic toxicants.

Recommendations and perspectives

The application of screening assays such as the YES to complex mixtures should be accompanied by measures that safeguard against false negative results which may be caused by non-estrogenic but toxic confounders. Simultaneous assessments of estrogenicity and toxicity are generally advisable.     

Characterization of emissions during the heating of tyre contaminated scrap

In order to characterize the compounds (type and quantities) emitted during melting of organic contaminated scrap and to investigate the mechanism of their formation, an experimental set-up has been designed and built to study precisely the influence of temperature and gas atmosphere in the conditions of an electric arc furnace. These experiments lead to the determination of mass balances (C, H, O, S) and to the quantification of unburnt compounds (tars, carbon monoxide, volatile organic compounds (VOCs), benzene, toluene, ethylbenzene and xylenes (BTEX), polyaromatic compounds (PAHs)). Degradation conditions (gas atmosphere and temperature) corresponding to different areas in the electric furnace have also been investigated. Such experiments lead to a better understanding of degradation mechanisms; this interpretation is not possible from investigations performed in an industrial furnace since there are many uncontrolled parameters (large dispersion of the results).     

Is an assessment factor of 10 appropriate to account for the variation in chemical toxicity to freshwater ectotherms under different thermal conditions?

Ecotoxicity tests are often conducted following standard methods, and thus carried out at a fixed water temperature under controlled laboratory conditions. Yet, toxicity of a chemical contaminant may vary in a temperature-dependent manner, depending on the physiology of the test organism and physicochemical properties of the chemical. Although an assessment factor of 10 (AF10) is commonly adopted to account for variability in toxicity data related to temperature in the development of water quality guidelines and/or ecological risk assessment, no one has ever rigorously assessed the appropriateness of AF10 to account for potential variation in temperature-dependent chemical toxicity to aquatic organisms. This study, therefore, aims to address this issue through a meta-analysis by comparing median lethal concentration data for nine chemicals (cadmium, copper, nickel, lead, silver, zinc, arsenic, selenium and DDT) on a range of freshwater ectothermic animal species at different temperatures, and to assess whether AF10 is under- or over-protective for tropical and temperate freshwater ecosystems. Our results reveal varying extents of interaction between temperature and different chemicals on organisms and the complexity of these interactions. Applying AF10 sufficiently protects 90 % of the animal species tested over a range of temperatures for cadmium, copper, nickel, silver, zinc and DDT in the tropics, but it is insufficient to adequately encompass a larger temperature variation for most studied chemicals in temperate regions. It is therefore important to set specific AFs for different climatic zones in order to achieve the desired level of ecosystem protection.     

Spatial and seasonal variations of atmospheric BTEX,sulfur dioxide,nitrogen dioxide,and ozone concentrations in Istanbul,and health risk assessment of BTEX

Volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene, and xylene (BTEX) along with inorganic gases such as sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and ozone (O₃) levels were found in the atmosphere of the Kemerburgaz region where environmental issues became a major concern due to nearby incineration plant and waste disposal facility in Istanbul. Ten sampling locations were selected considering possible sources in the study area. The sampling areas were classified as suburban, industrial, rural, and background regions. Sampling campaigns were carried out for four-week periods from March 2011 to August 2012 in all locations. Elevated concentrations of BTEX around roads and the industrial locations indicated that vehicle exhaust and industrial activities were the main sources of these pollutants in the region. Concentrations of NO₂ were also high around roads. A much more uniform distribution was observed for SO₂ during sampling periods. However higher levels were observed at suburban locations due to the use of coal for local heating especially during winter. Ozone concentrations were low at the industrial locations and roadsides, but high in suburban and rural locations downwind from the sources. The results of these organic and inorganic gases meet the national limit values. Furthermore, a lifetime risk assessment methodology was used to evaluate the potential adverse health effects of BTEX. The mean cancer risk level for benzene was estimated to be 7.71E-07 that is lower than assigned acceptable risk level of 1.0E-04. Toluene, ethylbenzene, and xylenes were lower than the specified level of 1.0 with respect to mean non-carcinogenic risks. The findings reveal that determined BTEX emissions do not pose a health threat to residents in the studied region.     

First report on development of quantitative interspecies structure-carcinogenicity relationship models and exploring discriminatory features for rodent carcinogenicity of diverse organic chemicals using OECD guidelines

Different regulatory agencies in food and drug administration and environmental protection worldwide are employing quantitative structure-activity relationship (QSAR) models to fill the data gaps related with properties of chemicals affecting the environment and human health. Carcinogenicity is a toxicity endpoint of major concern in recent times. Interspecies toxicity correlations may provide a tool for estimating sensitivity towards toxic chemical exposure with known levels of uncertainty for a diversity of wildlife species. In this background, we have developed quantitative interspecies structure-carcinogenicity correlation models for rat and mouse [rodent species according to the Organization for Economic Cooperation and Development (OECD) guidelines] based on the carcinogenic potential of 166 organic chemicals with wide diversity of molecular structures, spanning a large number of chemical classes and biological mechanisms. All the developed models have been assessed according to the OECD principles for the validation of QSAR models. Consensus predictions for carcinogenicity of the individual compounds are presented here for any one species when the data for the other species are available. Informative illustrations of the contributing structural fragments of chemicals which are responsible for specific carcinogenicity endpoints are identified by the developed models. The models have also been used to predict mouse carcinogenicities of 247 organic chemicals (for which rat carcinogenicities are present) and rat carcinogenicities of 150 chemicals (for which mouse carcinogenicities are present). Discriminatory features for rat and mouse carcinogenicity values have also been explored.     

Data ranges in aquatic toxicity of chemicals

A significant problem for effect assessment of aquatic ecosystems arises from the large ranges of toxicity data, which can be found in different databases and literature. Here, ranges are given for the aquatic toxicity of 27 high production volume chemicals. Based on these illustrative examples and on the current literature on uncertainty in aquatic effect assessment, toxicity ranges are discussed for their possible causes (variation in experimental condition, species, endpoint, time) and ways to handle them (safety factors). Implications and recommendations on the procedure of risk analysis of chemical substances are drawn. Two main requirements for a comprehensive risk assessment are identified, which often play a minor role in current practice (as they are often neglected) as well as in scientific discussion (as they are meant to be trivial). First, data quality must be checked critically before applying any result of a toxicity test. Secondly, experimental data should take into account different species and acute as well as chronic data. If these aspects are considered in risk analysis, which is common practice in ecotoxicology but not always in the context of practical applications in risk engineering, a more comprehensive picture of the environmental toxicity of a chemical substance can be obtained.     

Probabilistic approaches in the effect assessment of toxic chemicals. What are the benefits and limitations?

There is an ongoing discussion whether in the environmental risk assessment for chemicals the so called 'deterministic' approach using point estimates of exposure and effect concentrations is still appropriate. Instead, the more detailed and scientifically sounder probabilistic methods that have been developed over the last years are widely recommended. Here, we present the results of a probabilistic effect assessment for the aquatic environment performed for the pesticide methyl parathion and compare them with the results obtained with the common deterministic approach as described in the EU Technical Guidance Document. Methyl parathion was chosen because a sufficient data set (acute toxicity data for about 70 species) was available. The assumptions underlying the probabilistic effect assessment are discussed in the light of the results obtained for methyl parathion. Two important assumptions made by many studies are: (i) a sufficient number of ecologically relevant toxicity data is available, (ii) the toxicity data follow a certain distribution such as log-normal. Considering the scarcity of data for many industrial chemicals, we conclude that these assumptions would not be fulfilled in many cases if the probabilistic assessment was applied to the majority of industrial chemicals. Therefore, despite the well-known limitations of the deterministic approach, it should not be replaced by probabilistic methods unless the assumptions of these methods are carefully checked in each individual case, which would significantly increase the effort for the assessment procedure.     

Characterization of Volatile Organic Chemical Emissions From Carpet Cushions

Abstract

The U.S. Consumer Product Safety Commission is investigating chemical emissions from carpet systems in order to determine whether the emissions may be responsible for the numerous health complaints associated with carpet installation. As part of this effort, a study was conducted to identify and quantify volatile organic compounds (VOCs) released into the air by five major product types of new carpet cushions. Cushion samples were tested in small-volume dynamic chambers over a six-hour exposure period. Airborne VOCs collected on multisorbent samplers were identified using sensitive gas chromatography/mass spectrometry. The emissions of selected VOCs were quantitated with the small-scale chamber method and further characterized in larger environmental chambers conducted over a 96-hour period under conditions more representative of indoor environments. A separate chamber method was developed to screen polyurethane cushions for emissions of toluene diisocyanates (TDI). Over 100 VOCs, spanning a broad range of chemical classes, were emitted from 17 carpet cushions. The pattern of emitted VOCs varied between and among product types, which reflects probable differences in manufacturing processes and ingredients. No significant quantities of TDI or formaldehyde were released by any cushions. Emission profiles were characterized for total VOCs and for the predominant individual VOCs. As a group, the synthetic fiber cushion samples emitted the lowest quantities of VOCs. Cushion samples purchased from carpet retailers released lesser amounts of VOCs than samples of the same cushion types obtained directly from the manufacturing mills, suggesting that chemical losses from the bulk material may ensue as a result of transport, handling, and storage prior to installation. The data suggest that placement of carpet on top of a carpet cushion, as would occur in a residential installation, reduced the rate of some VOC emissions when compared to the cushion alone.     

Integration of biological responses from a suite of bioassays for the Venice Lagoon (Italy) through sediment toxicity index - Part A: Development and comparison of two methodological approaches

Marine and coastal quality assessment, based on test batteries involving a wide array of endpoints, organisms and test matrices, needs for setting up toxicity indices that integrate multiple toxicological measures for decision-making processes and that classify the continuous toxicity response into discrete categories according to the European Water Framework Directive.Two toxicity indices were developed for the lagoon environment such as the Venice Lagoon. Stepwise procedure included: the construction of a database that identified test-matrix pairs (indicators); the selection of a minimum number of ecotoxicological indicators, called toxicological core metrics (CMs-tox) on the basis of specific criteria; the development of toxicity scores for each CM-tox; the integration of the CMs-tox into two indices, the Toxicity Effect Index (TEI), based on the transformation of Toxic Unit (TU) data that were integrated as logarithmic sum, and the Weighted Average Toxicity Index (WATI), starting from toxicity classes integrated as weighted mean. Results from the indices are compared; advantages and drawbacks of both approaches are discussed.     

A guideline supplement for determining the aquatic toxicity of poorly water-soluble complex mixtures using water-accommodated fractions

Regulatory guideline methods for aquatic toxicity testing have generally been developed for pure chemicals tested at concentrations below the limit of their water solubility where exposure concentration can be quantified in terms of a concentration in solution. The same methods may also be applied to testing products which are complex chemical mixtures at product: water ratios that do not exceed the water-solubility of any of the product components. A different approach is required for testing complex mixtures at ratios which exceed water-solubilities of some of the components.