Nonpolar Narcosis Research Articles

NSO-heterocyclic PAHs – Controlled exposure study reveals high acute aquatic toxicity

Environmental occurrence and hazardous nature of heterocyclic polyaromatic hydrocarbons (heterocyclic PAHs) has the potential to threaten the health of aquatic ecosystems. Here, we investigate the acute toxicity of heterocyclic PAHs (log KOW 3.7–6.9) to aquatic organisms: marine bacteria (Aliivibrio fischeri), freshwater green algae (Raphidocelis subcapitata), and water fleas (Daphnia magna) using passive dosing to maintain stable exposure. The membrane-water partition coefficient (KMW) of the heterocycles was measured to elucidate its relationship with toxicity. Our findings show that the tested heterocycles had little inhibitory effect on A. fischeri, while most compounds were highly toxic to R. subcapitata and D. magna. Toxicity generally increased with increasing KMW values, and nonpolar narcosis was identified as the most likely mode of toxic action of the heterocycles. Comparison of standard protocols with passive dosing emphasizes the importance of maintaining a constant concentration during toxicity testing, as very high losses occurred in standard tests and passive dosing experiments revealed higher toxicities. These results indicate a potentially high risk to aquatic life and call for more in-depth investigation of the (eco)toxic effects of NSO-PAHs.

Sublethal Effect Concentrations for Nonpolar Narcosis in the Zebrafish Embryo.

Nonpolar narcosis, also known as baseline toxicity, has been described as the minimal toxicity that an organic chemical may elicit based on its lipophilicity. Although lethal effects of narcosis-inducing chemicals (NICs) have been thoroughly investigated, knowledge of sublethal effects is still very limited. We investigated the effects of 3 well-known NICs (phenanthrene, 1,3,5-trichlorobenzene, and pentachlorobenzene) on a variety of organismal endpoints (malformations, swim bladder inflation, respiration, heart rate, swimming activity, and turning angles), which can be plausibly linked to narcosis in zebrafish embryos. Baseline toxicity recorded as mortality is typically observed in similar exposure ranges in a wide variety of species including fish, corresponding to a chemical activity range between 0.01 and 0.1. In the present study, we found that sublethal effects occurred at concentrations approximately 5 times below lethal concentrations. Altered swimming activity and impaired swim bladder inflation were the most sensitive endpoints occurring at exposure levels below the generally accepted threshold for baseline toxicity for 2 out of 3 compounds. Overall, most effective exposure levels across the sublethal endpoints and compounds did fall within the range typically associated with baseline toxicity, and deviations were generally limited to a factor 10. Although there could be benefit in adding sublethal endpoints to toxicity tests, such as the fish embryo acute toxicity (FET) test, based on the present sublethal endpoints and available evidence from our and other studies, the underestimation of toxicity as a result of the sole assessment of mortality as an endpoint in an FET test may be limited for narcosis. Environ Toxicol Chem 2021;40:2802-2812. © 2021 SETAC.

One uncertainty factor does not fit all: Identifying mode of action and species specific acute to chronic ratios for aquatic life

In ecological risk assessment, acute to chronic ratio (ACR) uncertainty factors are routinely applied to acute mortality benchmarks to estimate chronic toxicity thresholds. To investigate variability of aquatic ACRs, we first compiled and compared 56 and 150 pairs of acute and subchronic/chronic growth/reproductive toxicity data for fishes (Pimephales promelas (53), Danio rerio (2), and Oryzias latipes (1)) and the crustacean Daphnia magna, respectively, for 172 chemicals with different modes of action (MOA). We found that there were only significant relationships between P. promelas acute median lethal concentrations and growth lowest-observed effect concentrations for class 1 (nonpolar narcosis) chemicals, though significant relationships were demonstrated for D. magna to all Verhaar et al. MOA classes (Class 1: nonpolar narcosis, Class 2: polar narcosis, Class 3: reactive chemicals, and Class 4: AChE inhibitors and estrogenics). Probabilistic ecological hazard assessment using chemical toxicity distributions was subsequently employed for each MOA class to estimate acute and chronic thresholds, respectively, to identify MOA and species specific ecological thresholds of toxicological concern. Finally, novel MOA and species specific ACRs using both chemical toxicity distribution comparison and individual ACR probability distribution approaches were identified using representative MOA and chemical categories. Our data-driven approaches and newly identified ACR values represent robust alternatives to application of default ACR values, and can also support future research and risk assessment and management activities for other chemical classes when toxicity information is limited for chemicals with specific MOAs within invertebrates and fish.

Extrapolation Factors for Characterizing Freshwater Ecotoxicity Effects

Various environmental and chemical assessment frameworks including ecological risk assessment and life cycle impact assessment aim at evaluating long-term ecotoxicity effects. Chronic test data are reported under the European Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation for various chemicals. However, chronic data are missing for a large fraction of marketed chemicals, for which acute test results are often available. Utilizing acute data requires robust extrapolation factors across effect endpoints, exposure durations, and species groups. We propose a decision tree based on strict criteria for curating and selecting high-quality aquatic ecotoxicity information available in REACH for organic chemicals, to derive a consistent set of generic and species group-specific extrapolation factors. Where ecotoxicity effect data are not available at all, we alternatively provide extrapolations from octanol-water partitioning coefficients as suitable predictor for chemicals with nonpolar narcosis as mode of action. Extrapolation factors range from 0.2 to 7 and are higher when simultaneously extrapolating across effect endpoints and exposure durations. Our results are consistent with previously reported values, while considering more endpoints, providing species group-specific factors, and characterizing uncertainty. Our proposed decision tree can be adapted to curate information from additional data sources as well as data for other environments, such as sediment ecotoxicity. Our approach and robust extrapolation factors help to increase the substance coverage for characterizing ecotoxicity effects across chemical and environmental assessment frameworks. Environ Toxicol Chem 2019;38:2568-2582. © 2019 SETAC.

Petroleum hydrocarbon mixture toxicity and a trait-based approach to soil invertebrate species for site-specific risk assessments.

Although petroleum hydrocarbons released to the environment typically occur as mixtures, petroleum hydrocarbon remediation guidelines often reflect individual substance toxicity. It is well documented that groups of aliphatic petroleum hydrocarbons act via the same mechanism of action (nonpolar narcosis) and, theoretically, concentration addition mixture toxicity principles apply. To assess this theory, 10 standardized acute and chronic soil invertebrate toxicity tests on a range of organisms (Eisenia fetida, Lumbricus terrestris, Enchytraeus crypticus, Folsomia candida, Oppia nitens, and Hypoaspis aculeifer) were conducted with a refined petroleum hydrocarbon binary mixture. Reference models for concentration addition and independent action were applied to the mixture toxicity data with consideration of synergism, antagonism, and dose level toxicity. Both concentration addition and independent action, without further interactions, provided the best fit with observed response to the mixture. Individual fraction effective concentration values were predicted from optimized, fitted reference models. Concentration addition provided a better estimate than independent action of individual fraction effective concentrations based on comparison with available literature and species trends observed in toxic responses to the mixture. Interspecies differences in standardized laboratory soil invertebrate species responses to petroleum hydrocarbon-contaminated soil was reflected in unique traits. Diets that included soil, large body size, permeable cuticle, low lipid content, lack of ability to molt, and no maternal transfer were traits linked to a sensitive survival response to petroleum hydrocarbon-contaminated soil in laboratory tests. Traits linked to sensitive reproduction response in organisms tested were long life span and small clutch size. By deriving single-fraction toxicity endpoints considerate of mixtures, we can reduce the resources and time required to conduct site-specific risk assessments for the protection of a soil organism's exposure pathway. Environ Toxicol Chem 2018;37:2222-2234. © 2018 SETAC.

Comparative behavioral toxicology with two common larval fish models: Exploring relationships among modes of action and locomotor responses

Behavioral responses inform toxicology studies by rapidly and sensitively detecting molecular initiation events that propagate to physiological changes in individuals. These behavioral responses can be unique to chemical specific mechanisms and modes of action (MOA) and thus present diagnostic utility. In an initial effort to explore the use of larval fish behavioral response patterns in screening environmental contaminants for toxicity and to identify behavioral responses associated with common chemical specific MOAs, we employed the two most common fish models, the zebrafish and the fathead minnow, to define toxicant induced swimming activity alterations during interchanging photoperiods. Though the fathead minnow (Pimephales promelas) is a common model for aquatic toxicology research and regulatory toxicology practice, this model has received little attention in behavioral studies compared to the zebrafish, a common biomedical model. We specifically compared behavioral responses among 7 different chemicals (1-heptanol, phenol, R-(-)-carvone, citalopram, diazinon, pentylenetetrazole (PTZ), and xylazine) that were selected and classified based on anticipated MOA (nonpolar narcosis, polar narcosis, electrophile, specific mechanism) according to traditional approaches to examine whether these comparative responses differ among chemicals with various structure-based predicted toxicity. Following standardized experimental guidelines, zebrafish embryos and fathead minnow larvae were exposed for 96 h to each compound then were observed using digital behavioral analysis. Behavioral observations included photomotor responses, distance traveled, and stimulatory, refractory and cruising locomotor activity. Though fathead minnow larvae displayed greater behavioral sensitivity to 1-heptanol, phenol and citalopram, zebrafish were more sensitive to diazinon and R-(-)-carvone. Both fish models were equally sensitive to xylazine and PTZ. Further, the pharmaceuticals citalopram and xylazine significantly affected behavior at therapeutic hazard values, and each of the seven chemicals elicited unique behavioral response profiles. Larval fish behaviors appear useful as early tier diagnostics to identify mechanisms and pathways associated with diverse biological activities for chemicals lacking mechanistic data.

Read-across of 90-day rat oral repeated-dose toxicity: A case study for selected 2-alkyl-1-alkanols

2-Alkyl-1-alkanols offer an example whereby the category approach to read-across can be used to predict repeated-dose toxicity for a variety of derivatives. Specifically, the NOAELs of 125mg/kg bw/d for 2-ethyl-1-hexanol and 2-propyl-1-heptanol, the source substances, can be read across with confidence to untested 2-alkyl-1-alkanols in the C5 to C13 category based on a LOAEL of low systemic toxicity. These branched alcohols, while non-reactive and exhibiting unspecific, reversible simple anaesthesia or nonpolar narcosis mode of toxic action, have metabolic pathways that have significance to repeated-dose toxic potency. In this case study, the chemical category is limited to the readily bioavailable analogues. The read-across premise includes rapid absorption via the gastrointestinal tract, distribution in the circulatory system and first-pass metabolism in the liver via Phase 2 glucuronidation prior to urinary elimination. 2-Ethyl-1-hexanol and 2-propyl-1-heptanol, the source substances, have high quality 90-day oral repeated-dose toxicity studies (OECD TG 408) that exhibit qualitative and quantitative consistency. Findings include only mild changes consistent with low-grade effects including decreased body weight and slightly increased liver weight, which in some cases is accompanied by clinical chemical and haematological changes but generally without concurrent histopathological effects at the LOAEL. These findings are supported by results from the TG 408 assessment of a semi-defined mixture of isotridecanols. Chemical similarity between the analogues is readily defined and data uncertainty associated with toxicokinetic and toxicodynamics similarities are low. Uncertainty associated with mechanistic relevance and completeness of the read-across is reduced by the concordance of in vivo and in vitro results, as well as high throughput and in silico methods data. As shown in detail, the 90-day rat oral repeated-dose NOAEL values for the two source substances can be read across to fill the data gaps of the untested analogues in this category with uncertainty deemed equivalent to results from a TG 408 assessment.

Read-across of 90-day rat oral repeated-dose toxicity: A case study for selected n-alkanols

n-Alkanols provide an excellent example where a category-approach to read-across may be used to estimate the repeated-dose endpoint for a number of untested derivatives (target chemicals) using experimental data for tested derivatives (source chemicals). n-Alkanols are non-reactive and exhibit the unspecific, reversible simple anaesthesia or non-polar narcosis mode of toxic action in that the metabolic products of the parent alcohols do not contribute to the toxic endpoint evaluated. In this case study, the chemical category is limited to the readily bioavailable (C5–C13) analogues. The toxicokinetic premise includes rapid absorption via the gastrointestinal tract, distribution in the circulatory system, and first-pass metabolism in the liver resulting in metabolism via oxidation to CO2 and with minor elimination of oxidative intermediate as glucuronides. Two analogues have experimental 90-day oral repeated-dose toxicity data which exhibit qualitative and quantitative consistency. Typical findings include decreased body weight, slightly increased liver weight which, in some cases, is accompanied by clinical chemical and haematological changes but generally without concurrent histopathological effects at the Lowest Observed Effect Level (LOEL). Chemical similarity between the analogues is readily defined by a variety of structure-related properties; data uncertainty associated with toxicokinetic and toxicodynamic similarities is low. Uncertainty associated with mechanistic relevance and completeness of the read-across is reduced by the concordance of in vivo and in vitro results, as well as high throughput and in silico methods data. As shown in detail, the 90-day oral repeated-dose toxicity No Observed Effect Level (NOEL) value of 1000mg/kgbw/d for 1-pentanol and 1-hexanol based on a LOEL of very low systemic toxicity can be read across to fill the data gaps of the untested analogues in this category with acceptable uncertainty.

Waiving chronic fish tests: possible use of acute-to-chronic relationships and interspecies correlations

ABSTRACTEU chemicals legislation requires the use of all available information for hazard and risk assessment before new tests on vertebrates are proposed or conducted. In this context, extrapolation approaches for avoiding chronic fish testing on the basis of existing data have been explored. Simple linear relationships and interspecies sensitivity ratios between Daphnia and fish were calculated and acute-to-chronic relationships and ratios were calculated for fish, taking into consideration the mode of action. The best fitted relationships for the prediction of chronic fish toxicity are obtained based on acute fish and Daphnia data. Chemicals acting by unspecific reactivity and non-polar narcosis give the strongest acute and chronic Daphnia-to-chronic fish relationship. With acute fish data, strong relationships are obtained for all mode of action. Daphnia was found to be more sensitive than fish to several aniline derivatives and pesticides acting through cholinesterase inhibition, and less sensitive than fish to known endocrine disruptors. Extreme (i.e. <1 or >100) interspecies sensitivity ratios were mainly evident for chemicals acting by polar narcosis and specific reactivity. The safety factor of 100 commonly applied in environmental risk assessment does not seem to be equally protective for each mode of action.

Evaluation of acute-to-chronic ratios of fish and Daphnia to predict acceptable no-effect levels.

BackgroundAcute-to-chronic extrapolation is an important approach to predict acceptable no-effect levels from acute data which has some uncertainties, but is valuable for risk assessment of chemical substances. With regard to the still limited and heterogenic data of chronic fish tests, conclusions on aquatic hazard estimation need to be checked and the question arises whether the chronic toxicity to fish can be adequately derived from acute data. A comprehensive dataset including ecotoxicological studies of 203 substances was used to investigate acute-to-chronic ratios (ACR) for both fish and Daphnia. To address potential uncertainty parameters of the approach, the influence of the octanol–water partition coefficient Kow, the mode of action, and the acute toxicity levels on the ACR was evaluated.ResultsFor industrial chemicals, median ACRs of 12.0 for fish and 8.8 for Daphnia and 90th percentiles of 68.0 and 50.2, respectively, were determined. The ACR for the most sensitive aquatic trophic level (ACRaqu) is derived by comparing the lowest acute and chronic effect value of Daphnia and fish. The median ACRaqu was 9.9, and the 90th percentile was determined to 58.5. The influence of the Kow on the ACR value was analysed and a correlation could not be confirmed. Non-polar narcosis was associated with a lower ACR, whereas polar narcosis was associated with an increased ACR.ConclusionsThe result suggests that an acute-to-chronic extrapolation factor of 100 is protective for more than 90 % of the chemicals. Polar narcosis may represent a predictor for an increased ACR and an increased uncertainty of the approach. The result further suggests that a high Kow is probably not associated with increased ACRs and does not necessarily represent a determinant for chronic toxicity testing within this context.

Critical body residue to fish of organic pollutants

The internal concentration represented by critical body residue(CBR) is an ideal indicator of the intrinsic toxicity of a chemical that can be used to assess toxicity to aquatic organisms. In this study, we systematically summarized the method for calculation of CBR in fish, CBR values with different modes of toxic action, the relationship between CBR and BCF, and the factors influencing the CBR based on the progress in this field as a result of studies conducted worldwide and our own investigations. The CBRs could be calculated by the LC50 and BCF based on the toxicokinetic model. The modes of toxic action of fish are usually recognized based on classification of organic compounds as acting by non-polar narcosis(baseline compounds), polar narcosis(less inert compounds), or reactive and specific acting mechanisms. Baseline toxicity is associated with chemicals acting narcosis mechanism, which is the reversible suppression of physiological function brought about by hydrophobic binding of chemicals to cell membranes and proteins. The CBRs to fish for narcotic chemicals vary in a narrow range and are close to constant. The CBRs for non-polar narcotic chemicals are higher than those for polar narcotic chemicals. Moreover, non-polar and polar narcotic compounds have different underlying mechanisms. Polar compounds intercalate less deeply into membranes, leading to lower CBR values than non-polar narcotic compounds. Reactive compounds interact and/or react with biological molecules, leading to enhanced toxicity relative to that associated with narcosis, and their CBRs are lower than those of narcotic compounds. Because the CBRs of narcotic compounds are close to constant, their toxicities are mainly affected by bioconcentration and linearly related to hydrophobicity. Conversely, the CBRs of reactive compounds are closely related to the reactivity of chemicals with biomolecules at the target site, with different values being observed for different reactive compounds. Their toxicities are not only related to the bioconcentration factor, but also to the descriptors used to describe the reactivity of chemicals with biomolecules(CBRs). Many factors can affect the CBRs of chemicals. For example, linear models of the relationship between log BCF and log Kow can underestimate the log BCF for compounds with log Kow 0.5 and overestimate the log BCF for compounds with log Kow 7, resulting in larger errors for CBRs calculated from the BCF and LC50 of highly hydrophilic and hydrophobic compounds. Organism size, lipid content, exposure time, metabolism and transformation, and uncertainty of toxic data can also affect the calculation or determination of CBRs.

QSAR models and their corresponding toxicity mechanism for mixture toxicity of organic pollutants

Environmental contaminants are frequently encountered as mixtures rather than single chemicals. However, current environmental quality standards and ecological risk assessments are mainly based on single toxicities, and pay little attention to the potential hazards of mixture exposure. The study of mixture toxicity is therefore not only of theoretical value, but also of deep practical significance. This review mainly focuses on quantitative structure-activity relationship (QSAR) models for mixture toxicities of organic pollutants and the corresponding toxicity mechanisms. The organic pollutants are classified as non-polar narcosis chemicals, polar narcosis chemicals, and reactive chemicals, according to their modes of action. QSAR models of the three types of chemical are described based on their toxicity mechanisms respectively. QSAR models of non-polar narcosis chemicals are described. The QSAR models of the mixture toxicities of non-polar narcosis chemicals are the simplest. The toxicity only depends on the total hydrophobicity of the mixture and can be predicted using a uniform model. QSAR models for polar narcosis chemicals are summarized. The toxicities of narcosis chemicals are determined not only by the total hydrophobicity but also by hydrogen-bonding effects. QSAR models for reactive chemicals are described in detail. There is no uniform model, because the toxicity mechanisms of the reactive chemicals are complicated. However, three aspects of the latest research on quantitative prediction methods for toxicities of mixtures containing reactive chemicals are summarized: the factors affecting multicomponent mixtures containing reactive chemicals; the interactions among the single chemicals in the mixture; and the interactions between the chemicals and the target protein. It is pointed out that identifying the molecular biological mechanisms of chemicals using advanced experimental methods (such as genomics and metabolomics) and formulating a common prediction model based on these mechanisms should be the direction of future developments.

Aquatic hazard assessment of a commercial sample of naphthenic acids

This paper presents chemical composition and aquatic toxicity characteristics of a commercial sample of naphthenic acids (NAs). Naphthenic acids are derived from the refining of petroleum middle distillates and can contribute to refinery effluent toxicity. NAs are also present in oil sands process-affected water (OSPW), but differences in the NAs compositions from these sources precludes using a common aquatic toxicity dataset to represent the aquatic hazards of NAs from both origins. Our chemical characterization of a commercial sample of NAs showed it to contain in order of abundance, 1-ring>2-ring>acyclic>3-ring acids (∼84%). Also present were monoaromatic acids (7%) and non-acids (9%, polyaromatic hydrocarbons and sulfur heterocyclic compounds). While the acyclic acids were only the third most abundant group, the five most abundant individual compounds were identified as C10–14n-acids (n-decanoic acid to n-tetradecanoic acid). Aquatic toxicity testing of fish (Pimephales promelas), invertebrate (Daphnia magna), algae (Pseudokirchneriella subcapitata), and bacteria (Vibrio fischeri) showed P. promelas to be the most sensitive species with 96-h LL50=9.0mgL−1 (LC50=5.6mgL−1). Acute EL50 values for the other species ranged 24–46mgL−1 (EC50 values ranged 20–30mgL−1). Biomimetic extraction via solid-phase-microextraction (BE–SPME) suggested a nonpolar narcosis mode of toxic action for D. magna, P. subcapitata, and V. fischeri. The BE analysis under-predicted fish toxicity, which indicates that a specific mode of action, besides narcosis, may be a factor for fishes.

Methods for assigning confidence to toxicity data with multiple values — Identifying experimental outliers

The assessment of data quality is a crucial element in many disciplines such as predictive toxicology and risk assessment. Currently, the reliability of toxicity data is assessed on the basis of testing information alone (adherence to Good Laboratory Practice (GLP), detailed testing protocols, etc.). Common practice is to take one toxicity data point per compound — usually the one with the apparently highest reliability. All other toxicity data points (for the same experiment and compound) from other sources are neglected. To show the benefits of incorporating the “less reliable” data, a simple, independent, statistical approach to assess data quality and reliability on a mathematical basis was developed. A large data set of toxicity values to Aliivibrio fischeri was assessed. The data set contained 1813 data points for 1227 different compounds, including 203 identified as non-polar narcotic. Log KOW values were calculated and non-polar narcosis quantitative structure–activity relationship (QSAR) models were built. A statistical approach to data quality assessment, which is based on data outlier omission and confidence scoring, improved the linear QSARs. The results indicate that a beneficial method for using large data sets containing multiple data values per compound and highly variable study data has been developed. Furthermore this statistical approach can help to develop novel QSARs and support risk assessment by obtaining more reliable values for biological endpoints.

1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil.

1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS) in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg) for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS), betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA) of contaminants is not clearly defined.

Priority and emerging flame retardants in rivers: Occurrence in water and sediment, Daphnia magna toxicity and risk assessment

The occurrence, partitioning and risk of eight polybrominated diphenyl ethers (PBDEs), nine new brominated (NBFRs) and ten organophosphorus flame retardants (OPFRs) were evaluated in three Spanish rivers suffering different anthropogenic pressures (Nalón, Arga and Besòs). OPFRs were ubiquitous contaminants in water (ΣOPFRs ranging from 0.0076 to 7.2μgL−1) and sediments (ΣOPFRs ranging 3.8 to 824μgkg−1). Brominated flame retardants were not detected in waters, whereas ΣPBDEs ranged from 88 to 812μgkg−1 and decabromodiphenyl ethane (DBDPE) reached 435μgkg−1 in sediments from the River Besòs, the most impacted river. The occurrence of flame retardants in river water and sediment was clearly associated with human activities, since the highest levels occurred near urban and industrial zones and after wastewater treatment plants discharge. Daphnia magna toxicity was carried out for OPFRs, the most ubiquitous flame retardants, considering individual compounds and mixtures. Toxicity of nine tested OPFRs differed largely among compounds, with EC50 values ranging over three magnitude orders (0.31–381mgL−1). Results evidenced that these compounds act by non-polar narcosis, since their toxicity was proportional to their lipophilicity (Kow). Furthermore, their joint toxicity was additive, which means that single and joint toxicity can be predicted knowing their concentration levels in water using quantitative structure activity relationships (QSARs) and predictive mixture models. Based on these results, a risk assessment considering joint effect was performed calculating and summing risk quotients (RQs) for the water and sediment samples. No significant risk to D. magna (ΣRQs <1) was observed for any of the monitored rivers.

Acute toxicity of chlorobenzenes in Tetrahymena: Estimated by microcalorimetry and mechanism

The toxicity of chlorobenzenes to Tetrahymena growth metabolism was studied by microcalorimetry. The growth constant (k), peak time (T) and generation times (TG) were calculated. IC50 of chlorobenzenes was obtained through the kinetic parameters. The results suggested that the order of toxicity was 1,2,4-trichlorobenzene>o-dichlorobenzene>p-dichlorobenzene>m-dichlorobenzene>chlorobenzene. ATR-FTIR spectra revealed that amide groups and PO2− of the phospholipid phospho-diester, both in the hydrophobic end exposed to the outer layer, were the easiest to be damaged. The relationship between IC50 and chemicals structure parameters (ELUMO, EHOMO, logKOW, ∑QR, ΔQπR and ΔE), indicated that the more chlorine atoms were substituted, the greater the toxicity was. Chlorobenzenes have toxicity of non-polar narcosis. Their toxicity is proportional to their concentrations at the site of action, and caused by membrane perturbation.

Toxic effects of nine polycyclic aromatic compounds on Enchytraeus crypticus in artificial soil in relation to their properties

The aim of this study was to compare the toxic effects of selected two- and three-ringed PAHs (naphthalene, phenanthrene, and anthracene) and their N-heterocyclic analogs with one (quinoline, acridine, and phenanthridine) or two (quinoxaline, phenazine, and 1,10-phenanthroline) nitrogen atoms on the survival and reproduction of Enchytraeus crypticus in artificial soil. Toxicity of compounds was recalculated to soil pore-water concentrations using the data of chemical analyses of 0.01 M CaCl 2 extracts of spiked soils. When toxicity was based on molar concentrations in pore water (μmol/L), it significantly increased with increasing K ow value. This relationship indicates nonpolar narcosis as the general toxicity mechanism of the tested compounds. In addition, significant correlation between the toxicity of PACs and their ionization potential has been identified by multidimensional QSAR models.

1-D and 2-D NMR metabolomics of earthworm responses to sub-lethal trifluralin and endosulfan exposure

Environmental contextEnvironmental metabolomics is an emerging field that examines the metabolic changes in organisms in response to potential environmental stressors. In this study, nuclear magnetic resonance spectroscopy is used to investigate earthworm metabolic responses to sub-lethal exposure of environmentally persistent pesticides. The study identifies two toxic modes of action elicited by the pesticides, and highlights the potential of metabolomics for the chemical assessment of persistent environmental contaminants. Abstract1-D and 2-D nuclear magnetic resonance (NMR) spectroscopy is used to examine the metabolic response of the earthworm (Eisenia fetida) after contact test exposure to an organofluorine pesticide, trifluralin, and an organochlorine pesticide, endosulfan. Three sub-lethal concentrations were used for each pesticide (0.1, 0.5 and 1.0 mg cm–2 for trifluralin and 0.5, 1.0 and 2.0 μg cm–2 for endosulfan). Principal component analysis of the trifluralin and endosulfan NMR datasets showed separation between the unexposed and the exposed earthworm groups. Alanine, glycine, maltose and ATP were significant in the highest concentration (1.0 mg cm–2) for trifluralin-exposed earthworms and may result from a non-polar narcosis toxic mode of action (MOA). Leucine, phenylalanine, tryptophan, lysine, glutamate, valine, glycine, isoleucine, methionine, glutamine, alanine, maltose, glucose, meibiose, malate, fumarate and ATP were detected as significant for the two highest concentrations (1.0 and 2.0 μg cm–2) for endosulfan-exposed earthworms and a neurotoxic MOA is postulated. This study highlights the use of 1-D and 2-D metabolomics for understanding the biochemical response of environmental contaminants to model organisms such as earthworms.

A baseline inhalation toxicity model for narcosis in mammals

This paper presents the results of an analysis of the rodent inhalation literature and the development of a quantitative structure–activity relationships (QSAR) model for 4-hour LC50 as baseline toxicity to complement the baseline toxicity model for aquatic animals. We used the same literature review criteria developed for the ECOTOX database which selects only primary references with explicit experimental methods to form a high-quality database. Our literature review focused on the primary references reporting a 4-hour exposure for a single species of rodent in which the chemical had been clearly tested as a vapour and for which the exposure concentrations were not ambiguous. An expert system was used to remove reactive chemicals, receptor-mediated toxicants, and any test that produced symptoms inconsistent with non-polar narcosis. The QSAR model derived for narcosis in rodents was log LC50 = 0.69 × log VP + 1.54 which had an r 2 of 0.91, which is significantly better than the baseline toxicity model for aquatic animals. This simple model suggests that there is no intrinsic barrier to estimating baseline toxicity for in vivo endpoints in mammalian or terrestrial toxicology.