Internal Effect Concentrations Research Articles

Comparative toxicokinetics and toxicity of PFOA and its replacement GenX in the early stages of zebrafish

Perand poly-fluoroalkyl substances (PFAS) are receiving attention due to their persistence, and potential adverse effects on environmental and human health. Efforts to reduce long-chained PFAS (≥C8) compounds were implemented in 2006 as a part of “PFOA Stewardship Program Initiative” (PFOA–perfluorooctanoic acid). Short-chained PFAS (<C8) were introduced as replacements, which were believed to have lower potential for environmental persistence and bioaccumulation. Little is known about the uptake and elimination, and potential toxic effects of these replacement compounds. Hence, it is important to compare toxicokinetics and toxicity of long-chain PFAS to their replacement compounds. To this end, zebrafish (ZF), Danio rerio, embryos were exposed to PFOA and its short-chain replacement perfluoro (2-methyl-3-oxahexanoic) acid (GenX) with the aim to assess uptake and elimination kinetics, hatching success, morphology, startle response, and survival. At 24 hpf, LC50 was 82 μM for PFOA and 170 μM for GenX. At 54 hpf, GenX but not PFOA showed an increase in hatching success. At 120 hpf, no statistically significant differences were seen in white light startle response below the LC50. PFAS internal concentrations were measured at 72 and 120 hpf during exposure phase, and at 168 hpf during depuration phase. GenX and PFOA internal concentrations in 120 hpf larvae exposed to highest concentration (20 μM) were 35.02 and 44.51 μM, respectively. Concentrations were eliminated almost completely at 168 hpf for GenX up to 95%, while for PFOA up to 50%. As steady-state was not reached, we estimated kinetic bioconcentration factors (BCFkin). BCFkin for GenX was lower than PFOA at equimolar concentrations. However, bioconcentration factors were higher at the lower exposure concentrations for both chemicals, suggesting a concentration-dependent uptake of PFASs. The predicted internal effect concentrations, accounting for the differences in bioconcentration factors, were 229 μM for GenX and 226 μM for PFOA, suggesting similar toxic potencies.

Toxicokinetics and toxicodynamics of copper and cadmium in the soil invertebrate Enchytraeus crypticus (Oligochaeta)

The aim of this study was to evaluate the toxicokinetics-toxicodynamics (TKTD) of Cu and Cd in the soil model organism Enchytraeus crypticus, and assess the development of internal effect concentrations over time. Animals were exposed in LUFA 2.2 soil spiked with increasing concentrations of Cu and Cd. Survival, reproduction and internal metal concentrations in the animals were evaluated at different points in time over a period of 21 days. Internal concentrations increased with time, for Cu reaching a steady state after c. 10 days, except for the highest test concentration, and for Cd continuing to increase after 21 days. Applying a one-compartment model to all data together, estimated uptake and elimination rate constants for Cu and Cd were 0.08 and 0.45 kg soil/kg organism/day and 0.4 and 0.04 per day, respectively. Median lethal concentrations, based on total soil concentrations, decreased with time for Cu and did not reach a steady state level, but they did not change with time for Cd. The LC50inter (based on internal concentrations) was 75 mg Cu/kg body DW and > 800 mg Cd/kg body weight. Animals were able to regulate Cu internal concentrations, keeping them low, while for Cd internal concentrations continued to increase showing lack of regulation and also the importance of exposure time. This study highlights the advantages of using a TKTD approach to understand the relation between organism survival and internal Cu or Cd concentrations over time.

Recommendations for Improving Methods and Models for Aquatic Hazard Assessment of Ionizable Organic Chemicals.

Ionizable organic chemicals (IOCs) such as organic acids and bases are an important substance class requiring aquatic hazard evaluation. Although the aquatic toxicity of IOCs is highly dependent on the water pH, many toxicity studies in the literature cannot be interpreted because pH was not reported or not kept constant during the experiment, calling for an adaptation and improvement of testing guidelines. The modulating influence of pH on toxicity is mainly caused by pH-dependent uptake and bioaccumulation of IOCs, which can be described by ion-trapping and toxicokinetic models. The internal effect concentrations of IOCs were found to be independent of the external pH because of organisms' and cells' ability to maintain a stable internal pH milieu. If the external pH is close to the internal pH, existing quantitative structure-activity relationships (QSARs) for neutral organics can be adapted by substituting the octanol-water partition coefficient by the ionization-corrected liposome-water distribution ratio as the hydrophobicity descriptor, demonstrated by modification of the target lipid model. Charged, zwitterionic and neutral species of an IOC can all contribute to observed toxicity, either through concentration-additive mixture effects or by interaction of different species, as is the case for uncoupling of mitochondrial respiration. For specifically acting IOCs, we recommend a 2-step screening procedure with ion-trapping/QSAR models used to predict the baseline toxicity, followed by adjustment using the toxic ratio derived from in vitro systems. Receptor- or plasma-binding models also show promise for elucidating IOC toxicity. The present review is intended to help demystify the ecotoxicity of IOCs and provide recommendations for their hazard and risk assessment. Environ Toxicol Chem 2020;39:269-286. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

PH-Dependent Uptake and Sublethal Effects of Antihistamines in Zebrafish (Danio rerio) Embryos.

Reported off-target effects of antihistamines in humans draw interest in ecotoxicity testing of first- and second-generation antihistamines, the latter of which have fewer reported side effects in humans. Because antihistamines are ionizable compounds, the pH influences uptake and toxicity and thus is highly relevant when conducting toxicity experiments. Zebrafish embryo toxicity tests were performed with the 3 first-generation antihistamines ketotifen, doxylamine, and dimethindene and the 2 second-generation antihistamines cetirizine and levocabastine at pH 5.5, 7.0, and 8.0. We detected effects on survival, phenotype, swimming activity, and heart rate for 4 antihistamines with the exception of levocabastine, which did not show any lethal or sublethal effects. When compared to lethal concentrations, effect concentrations neither of phenotype malformation nor of swimming activity or heart rate deviated by more than a factor of 10 from lethal concentrations, indicating that all sublethal effects were fairly nonspecific. First-generation antihistamines are weak bases and showed decreasing external effect concentrations with increasing neutral fraction, accompanied by increased uptake in the fish embryo. As a result, internal effect concentrations were independent from external pH. The pH-dependent toxicity originates from speciation-dependent uptake, with neutral species taken up in higher amounts than the corresponding ionic species. Cetirizine, which shifts from a zwitterionic to an anionic state in the measured pH range, did not show any pH-dependent uptake or toxicity. Environ Toxicol Chem 2019;00:1-11. © 2019 SETAC.

Toxicokinetics of Perfluorinated Alkyl Acids Influences Their Toxic Potency in the Zebrafish Embryo ( Danio rerio).

Perfluorinated alkyl acids (PFAA) are highly persistent and bioaccumulative and have been associated with several adverse health effects. The chemical structure mainly differs in two ways: the length of the hydrophobic alkyl chain and the type of hydrophilic end group. Little is known how the chemical structure affects the toxicokinetics (TK) in different organisms. We studied the TK of four PFAA (PFOS, PFHxS, PFOA, and PFBA) with different chain lengths (4-8 carbons) and functional groups (sulfonic and carboxylic acid) in zebrafish ( Danio rerio) embryo. The time courses of the external (ambient water) and internal concentrations were determined at three exposure concentrations from 2 up to 120 h postfertilization (hpf). Three of the four PFAA showed a biphasic uptake pattern with slow uptake before hatching (around 48 hpf) and faster uptake thereafter. A two-compartment TK model adequately described the biphasic uptake pattern, suggesting that the chorion functions as an uptake barrier until 48 hpf. The bioconcentration factors (BCF) determined at 120 hpf varied widely between PFAA with averages of approximately 4000 (PFOS), 200 (PFHxS), 50 (PFOA), and 0.8 (PFBA) L kg dry weight-1, suggesting that both the alkyl chain length and the functional group influence the TK. The differences in toxic potency were reduced by 3 orders of magnitude when comparing internal effect concentrations instead of effective external concentrations.

Influence of pH on the uptake and toxicity of β-blockers in embryos of zebrafish, Danio rerio

ß-Blockers are weak bases with acidity constants related to their secondary amine group. At environmental pH they are protonated with the tendency to shift to their neutral species at more alkaline pH. Here we studied the influence of pH from 5.5 to 8.6 on the toxicity of the four ß-blockers atenolol, metoprolol, labetalol and propranolol in zebrafish embryos, relating toxicity not only in a conventional way to external aqueous concentrations but also to measured internal concentrations.Besides lethality, we evaluated changes in swimming activity and heartbeat, using the Locomotor Response (LMR) method and the Vertebrate Automated Screening Technology (VAST) for high throughput imaging.Effects of metoprolol, labetalol and propranolol were detected on phenotype, heart rate and swimming activity. External effect concentrations decreased with increasing neutral fraction for all three pharmaceuticals, attributed by an enhanced uptake of the neutral species in comparison to the corresponding charged form. The LC50 of metoprolol decreased by a factor of 35 from 1.91 mM with almost complete cationic state at pH 7.0 to 0.054 mM with 8% neutral fraction at pH 8.6. For propranolol the LC50 of 2.42 mM at pH 5.5 was even 100 fold higher than the LC50 at pH 8 with 0.023 mM where 3% were neutral fraction. No effects were detected in the zebrafish embryo exposed to atenolol.The internal concentrations for metoprolol and propranolol were quantified at non-toxic concentrations and at the LC10. Apparent bioconcentration factors (BCF) ranged from 1.96 at pH 7.0 to 32.0 at pH 8.6 for metoprolol and from 1.86 at pH 5.5 to 169 at pH 8.0 for propranolol. The BCFs served to predict the internal effect concentrations from the measured external effect concentrations.Internal effect concentrations of metoprolol and propranolol were in a similar range for all pH-values and for all endpoints. Interestingly, the internal effect concentrations were in the internal concentration range of baseline toxicity, which suggests that the effects of the ß-blockers are rather unspecific, even for sublethal effects on heart rate. In summary, our data confirm that the pH-dependent toxicity related to external concentrations can be explained by toxicokinetic effects and that the internal effect concentrations are pH-independent.

Maternally transferred dioxin-like compounds can affect the reproductive success of European eel.

Reported concentrations of dioxin-like compounds accumulated in the European eel (Anguilla anguilla) were used to perform a risk assessment for eel larval survival, taking into account a modeled amplification of tissue concentrations with a factor of 1.33 during spawning migration. The calculated concentrations of dioxin-like compounds finally deposited in the eggs were compared with the internal effect concentrations for survival of early life stages of the European eel; these concentrations, by lack of experimental data, were estimated from a sensitivity distribution based on literature data by assuming that eel larvae are among the 10% most sensitive teleost fish species. Given concentrations of dioxin-like contaminants and assuming a relatively high sensitivity, it can be expected that larvae from eggs produced by eel from highly contaminated locations in Europe will experience increased mortality as a result of maternally transferred dioxin-like contaminants. As historical persistent organic pollutant concentrations in eel tissue were higher, this impact must have been stronger in the past. Potential effects of other compounds or effects on the migration, condition, and fertility of the parental animals were not taken into account. It is important to further study the overall impact of contaminants on the reproductive success of the European eel as this may have been underestimated until now.

Effect propagation after silver nanoparticle exposure in zebrafish (Danio rerio) embryos: a correlation to internal concentration and distribution patterns

Internal silver concentrations were determined and combined with toxicological information to obtain critical internal effect concentrations triggering biological responses.

A toxicokinetic study of specifically acting and reactive organic chemicals for the prediction of internal effect concentrations in Scenedesmus vacuolatus.

The toxic potency of chemicals is determined by using the internal effect concentration by accounting for differences in toxicokinetic processes and mechanisms of toxic action. The present study examines toxicokinetics of specifically acting and reactive chemicals in the green algae Scenedesmus vacuolatus by using an indirect method. Concentration depletion in the exposure medium was measured for chemicals of lower (log KOW < 3: isoproturon, metazachlor, paraquat) and moderate (log KOW 4-5: irgarol, triclosan, N-phenyl-2-naphthylamine) hydrophobicity at 7 to 8 time points over 240 min or 360 min. Uptake and overall elimination rates were estimated by fitting a toxicokinetic model to the observed concentration depletions. The equilibrium of exposure concentrations was reached within minutes to hours or was even not observed within the exposure time. The kinetics of bioconcentration cannot be explained by the chemical's hydrophobicity only, but influential factors such as ionization of chemicals, the ion trapping mechanism, or the potential susceptibility for biotransformation are discussed. Internal effect concentrations associated with 50% inhibition of S. vacuolatus reproduction were predicted by linking the bioconcentration kinetics to the effect concentrations and ranged from 0.0480 mmol/kg wet weight to 7.61 mmol/kg wet weight for specifically acting and reactive chemicals. Knowing the time-course of the internal effect concentration may promote an understanding of toxicity processes such as delayed toxicity, carry-over toxicity, or mixture toxicity in future studies.

The discrimination of excess toxicity from baseline effect: Effect of bioconcentration

Toxic ratio TR is a valuable tool in the discrimination of excess toxicity from baseline effect. Although some authors realized that internal effect concentration or critical body residual (CBR) calculated from bioconcentration factor (BCF) should be used in the TR, the effect of BCF on the discrimination of excess toxicity from baseline effect has not been investigated. In this paper, 951 acute toxicity data to fish (LC50) and 1088 BCFs were used to investigate the relationship between TR and BCF. The results showed that some compounds identified as reactive compounds exhibit excess toxicity, but some do not. BCF is closely related to TR and can significantly affect the TR value. The real excess toxicity which is used to identify reactive chemicals from baseline should be based on the toxic ratio of internal effect concentrations, rather than on the ratio of external effect concentrations, TR. The use of LC50 alone to determine TR can result in errors in TR because toxicokinetics (as estimated by the BCF) are ignored. The foundation in the discrimination of excess toxicity from baseline effect is based on the linear relationship between log BCF and hydrophobicity expressed as log KOW. However, log BCF is not linearly related with log KOW for all the compounds. The BCFs with log KOW >7 or <0 are either overestimated or underestimated by the linear baseline BCF model. Parallel lines are observed from calculated log CBR values for baseline and less inert compounds. The log BCF values overestimated or underestimated by log KOW from the baseline BCF model can result in mis-prediction and mis-classification among baseline, less inert and reactive compounds.

Measured and modeled toxicokinetics in cultured fish cells and application to in vitro-in vivo toxicity extrapolation.

Effect concentrations in the toxicity assessment of chemicals with fish and fish cells are generally based on external exposure concentrations. External concentrations as dose metrics, may, however, hamper interpretation and extrapolation of toxicological effects because it is the internal concentration that gives rise to the biological effective dose. Thus, we need to understand the relationship between the external and internal concentrations of chemicals. The objectives of this study were to: (i) elucidate the time-course of the concentration of chemicals with a wide range of physicochemical properties in the compartments of an in vitro test system, (ii) derive a predictive model for toxicokinetics in the in vitro test system, (iii) test the hypothesis that internal effect concentrations in fish (in vivo) and fish cell lines (in vitro) correlate, and (iv) develop a quantitative in vitro to in vivo toxicity extrapolation method for fish acute toxicity. To achieve these goals, time-dependent amounts of organic chemicals were measured in medium, cells (RTgill-W1) and the plastic of exposure wells. Then, the relation between uptake, elimination rate constants, and log KOW was investigated for cells in order to develop a toxicokinetic model. This model was used to predict internal effect concentrations in cells, which were compared with internal effect concentrations in fish gills predicted by a Physiologically Based Toxicokinetic model. Our model could predict concentrations of non-volatile organic chemicals with log KOW between 0.5 and 7 in cells. The correlation of the log ratio of internal effect concentrations in fish gills and the fish gill cell line with the log KOW was significant (r>0.85, p = 0.0008, F-test). This ratio can be predicted from the log KOW of the chemical (77% of variance explained), comprising a promising model to predict lethal effects on fish based on in vitro data.

Internal effect concentrations of organic substances for early life development of egg-exposed fish

The present study investigates the likelihood that early life development of marine fish from contaminated areas is affected by maternally transferred persistent organic substances (POPs). The common sole (Solea solea) was used as model species. Fertilized eggs were exposed via the water until hatching, 6 days post fertilization. The newly hatched larvae were allowed to develop further under unexposed conditions until the end of the metamorphosis. Effects on the larvae were determined for the dioxin-like polychlorinated biphenyl PCB 126, the technical PCB-mixture Arochlor 1254, polybrominated diphenylethers (PBDEs), and hexabromocyclododecane (HBCD), for an artificial mixture of PCBs and PBDEs, and for ‘field mixtures’ extracted from sole from the North Sea and the contaminated Western Scheldt estuary. Effect levels were expressed as tissue concentrations in the newly hatched larvae at the end of the exposure period. Exposure to PCBs, PBDEs, and the artificial and field mixtures caused mortality that started to occur shortly after the larvae became free-feeding (10 days post fertilization) and continued to increase until the onset of metamorphosis, 15 days later. The effects induced by the field mixtures correlated well with the ΣPCB concentrations in the tissue of the exposed larvae. No indications were found for synergistic effects or for substantial contribution of other (unknown) substances in the field mixtures. HBCD did not induce toxic effects. As lipid normalized POP levels in fish eggs are in general comparable to the levels in the tissue of the female fish, fish tissue concentrations are indicative of the internal exposure of the developing larvae as a result maternally transferred POPs will occur in the field. In sole from the Western Scheldt estuary POP levels are about twenty times lower than the larval tissue concentration that produced 50 percent early life stage mortality. Levels in North Sea sole are an order of a magnitude lower. At more heavily contaminated sites negative effect of PCBs, especially of those with dioxin-like toxicity can be expected.

Crucial role of mechanisms and modes of toxic action for understanding tissue residue toxicity and internal effect concentrations of organic chemicals

This article reviews the mechanistic basis of the tissue residue approach for toxicity assessment (TRA). The tissue residue approach implies that whole-body or organ concentrations (residues) are a better dose metric for describing toxicity to aquatic organisms than is the aqueous concentration typically used in the external medium. Although the benefit of internal concentrations as dose metrics in ecotoxicology has long been recognized, the application of the tissue residue approach remains limited. The main factor responsible for this is the difficulty of measuring internal concentrations. We propose that environmental toxicology can advance if mechanistic considerations are implemented and toxicokinetics and toxicodynamics are explicitly addressed. The variability in ecotoxicological outcomes and species sensitivity is due in part to differences in toxicokinetics, which consist of several processes, including absorption, distribution, metabolism, and excretion (ADME), that influence internal concentrations. Using internal concentrations or tissue residues as the dose metric substantially reduces the variability in toxicity metrics among species and individuals exposed under varying conditions. Total internal concentrations are useful as dose metrics only if they represent a surrogate of the biologically effective dose, the concentration or dose at the target site. If there is no direct proportionality, we advise the implementation of comprehensive toxicokinetic models that include deriving the target dose. Depending on the mechanism of toxicity, the concentration at the target site may or may not be a sufficient descriptor of toxicity. The steady-state concentration of a baseline toxicant associated with the biological membrane is a good descriptor of the toxicodynamics of baseline toxicity. When assessing specific-acting and reactive mechanisms, additional parameters (e.g., reaction rate with the target site and regeneration of the target site) are needed for characterization. For specifically acting compounds, intrinsic potency depends on 1) affinity for, and 2) type of interaction with, a receptor or a target enzyme. These 2 parameters determine the selectivity for the toxic mechanism and the sensitivity, respectively. Implementation of mechanistic information in toxicokinetic-toxicodynamic (TK-TD) models may help explain time-delayed effects, toxicity after pulsed or fluctuating exposure, carryover toxicity after sequential pulses, and mixture toxicity. We believe that this mechanistic understanding of tissue residue toxicity will lead to improved environmental risk assessment.

The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model

Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent toxicity of the five basic pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine, and trimipramine. For all of them, the toxicity increased with increasing pH when aqueous effect concentrations were considered. Since these pharmaceuticals contain a basic amine group that is protonated and thus positively charged at physiological pH and because algae are capable of biological homeostasis, i.e., pH inside the algal cell remains virtually independent of variable external pH, the speciation of aliphatic amines can be different inside the algal cell compared to the external medium. Therefore, we hypothesized that the high toxicity of aliphatic amines in algae is a toxicokinetic effect caused by speciation and not a toxicodynamic effect caused by a specific mode of toxic action. This hypothesis also implies that internal effect concentrations are independent on external pH. On this basis we developed a simple toxicokinetic model, which assumes that only the neutral molecule is bioavailable and can pass the plasma membrane. This assumption is likely to be valid at pH values down to two units below the acidity constant (p K a). For lower pH values a more complex model would have to be evoked that includes, an, albeit smaller, permeability of the charged species. For pH > p K a − 2, we can safely assume that the outer membrane serves as insulator and that the charged species is formed inside the cell according to the pH in the cytoplasm. Thus this toxicokinetic model is an ion-trapping model. The input parameters of this model are the measured aqueous effect concentrations determined as a function of pH and the membrane–water partitioning, which was modelled by the liposome–water partition coefficients of the neutral and cationic species. They were deduced from experimentally determined liposome–water distribution ratios at various pH values measured with an equilibrium dialysis method. The modelled internal effect concentrations were independent of the external pH and effective membrane burdens were in the same range as for other baseline toxicants found in the literature for algae, daphnids and fish. These results confirm that the higher algal toxicity of pharmaceuticals with an aliphatic amine group can be explained by a toxicokinetic effect and that these pharmaceuticals do not exhibit a specific mode of action in algae but act as baseline toxicants.

Acute toxicity and bioaccumulation of arsenic in freshwater clam Corbicula fluminea

Arsenic is a potent human carcinogen of skin, lung, and urinary bladder. Freshwater clam Corbicula fluminea is a commercially important native species in Taiwan. C. fluminea is also a suitable biomonitoring test organism. Little is known, however, about the actual effects of arsenic on C. fluminea. The objectives of this study were to provide information on the acute toxicity and bioaccumulation kinetics of arsenic in C. fluminea. We carried out a 14-day exposure experiment to obtain bioaccumulation parameters. Uptake was very rapid when C. fluminea was first exposed and then slightly decayed during the uptake phase of the experiment and an uptake rate constant of 1.718 +/- 6.70 (mean +/- SE) mL g(-1) d(-1) was estimated. The elimination of arsenic from C. fluminea obeyed first-order depuration kinetics (r(2) = 0.85, p < 0.05) with a calculated half-life of 6.80 days. The derived bioaccumulation factor of 16.84 suggests that arsenic has a high potential for bioaccumulation in C. fluminea. This had important implications for dietary exposure of arsenic to humans who eat contaminated clams, because the soft tissue usually constitutes the majority of tissue consumed. The 96-h LC50 value was estimated to be 20.74 (95% CI: 11.74-30.79) mg L(-1) obtained from a 7-day acute toxicity bioassay. We also kinetically linked an acute toxicity model and a Hill sigmoid model to reconstruct an internal effect concentration based dose-response profile to assess the effect of soft tissue arsenic burden on the C. fluminea mortality. This result could be used to support the establishment of an ecological risk assessment to prevent possible ecosystem and human health consequences.

A biologically based damage assessment model to enhance aquacultural water quality management

The lethal concentration for 50% of aquacultural animals (LC 50)-based tests determines the external effect concentration (EEC) following certain statistical models, revealing that no biologically based mechanistic information and only statistical interpretations of its model parameters could be made. The purpose of this paper is to determine the survival risk of waterborne metals toward farmed species with respect to lethality based on biologically based mechanistic models. Here we study a biologically based mechanistic damage assessment model (DAM) compared with a pharmacodynamic (PD)-based critical area under the curve (CAUC) model to demonstrate the ability of predicting the internal effect concentration (IEC) and survival rate of farmed species. We tested the proposed models using published acute toxicity and accumulation data for two farmed species, tilapia ( Orechromis mossambicus) exposed to arsenic (As) and abalone ( Haliotis diversicolor supertexta) exposed to zinc (Zn), to compare observed and predicted LC 50 and IEC and, subsequently, to predict the survival rate. Our analyses demonstrate that the DAM- and PD-based survival models performed well and proved its usefulness as a tool in the quantification of risk assessment in aquacultural ecosystems. The study also supports the suggestion that replacing exposure-based EECs by IECs is a first step toward a measure for inherent toxicity and can be used to improve the construction of future environmental quality criteria programs aimed at protecting and restoring the rapidly degrading aquacultural ecosystems.

Site-specific environmental quality criteria for survival and growth of farmed abalone exposed to zinc

We develop a simple predictive environmental quality criteria (EQC) model for the survival and growth of farmed abalone Haliotis diversicolor supertexta exposed to waterborne zinc (Zn) based on a probabilistic internal effect concentration (IEC)-based modeling framework. We couple a first-order two-compartment bioaccumulation model and a reconstructed dose–response profile based on a three-parameter Hill equation model associated with a field bioaccumulation study to form a probabilistic model to determine acute and chronic EQC. The acute EQC (a-EQC) is predicted from IECs and a field-derived bioaccumulation factors, whereas a statistical procedure with an acute-to-chronic value is used to derive chronic EQC (c-EQC) based on bioaccumulation. Field bioaccumulation study demonstrates a linear relationship between water and tissue Zn concentrations in abalone and algae. Our model, designed for simplicity and theoretical insight, yields explicit mathematical results through a probabilistic analysis to capture EQC modeling methodology in a more realistic way by analyzing computationally through Monte Carlo simulations. Here we show that the median a-EQC ranges from 0.34–0.39 μg ml − 1, whereas the median c-EQC is 0.04–0.05 μg ml − 1 for selected abalone farms. We believe that this probabilistic EQC modeling framework is an effective method for conceptualizing a public policy decision vis-à-vis establishing a site-specific acceptable acute and chronic EQC for better management and restoration of the rapidly degrading aquacultural ecosystems.

Initial risk assessment for three β-blockers found in the aquatic environment

Daphnia magna, Desmodesmus subspicatus and Lemna minor were used to determine the ecotoxicity of beta-blockers. Propranolol was the most toxic substance, with EC 50s of 7.7 mg l −1 in the Daphnia test and 0.73 mg l −1 in the algal test. The toxicity of atenolol and metoprolol in the Daphnia test was very low, with EC 50s of 313 and 438 mg l −1, respectively. In the algal test, metoprolol (EC 50: 7.9 mg l −1) was more toxic than atenolol (EC 50: 620 mg l −1). Lemna minor was the least sensitive species. All substances showed PEC/PNEC ratios <1, whereas propranolol with a ratio of 0.81 seems to be the most relevant substance and I recommend to perform chronic biotests to refine the estimate of the environmental risk. Taking bioconcentration factors (BCF) into account, resulting internal effect concentrations (IEC) differ only slightly, which means that the differences in the EC 50 depend mainly on the diverse log P levels causing narcosis via disruption of membrane integrity. Predictions of toxicity using ECOSAR were close to the empirically measured data. Mixture toxicity of the three compounds could be predicted accurately using the concept of concentration addition.

Environmental quality criteria for organic chemicals predicted from internal effect concentrations and a food web model

Environmental quality criteria (EQC) for hydrophobic organic chemicals were calculated with a model for bioaccumulation in food webs. The model was calibrated and verified using polychlorinated biphenyl concentrations in food webs of shallow lakes. The EQCs in water and sediment were derived based on internal effect concentrations (IECs) for several modes of toxic action. By reverse calculation with the food web model for each organism in the web, a different water or sediment concentration is calculated corresponding to the IEC in each organism. A statistical procedure with an acute-to-chronic value is used to derive chronic EQCs based on bioaccumulation. The model-based chronic EQCs were compared with previously established EQCs. The EQCs calculated with the food web model generally are within an order of magnitude of the previously derived EQCs based on toxicity data on individual chemicals. Some previously derived EQCs are much lower than model predictions and usually based on small samples of toxicity data such as no-observed-effect concentrations (NOECs) with large assessment factors. When faced with data gaps, it is proposed to use model-based chronic EQCs for (polar) narcotic chemicals. Other modes of action require a different model concept to account for receptor-based toxicity.

Organ-Specific Toxicokinetics and Dose?Response of Arsenic in Tilapia Oreochromis mossambicus

We appraised organ-specific toxicokinetics and dose responses of arsenic burdens in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve (AUC)-based acute toxicity model and a pharmacodynamic model to derive dose-response relationships between equilibrium organ-specific arsenic concentrations and mortality effects. The AUC-based acute toxicity model was also used to derive organ-specific internal effect concentration (IEC)-time-response relationships, which can also be applied to predict a time-mortality profile. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based acute toxicity model was verified with LC50(t) data obtained from a 7-day acute toxicity bioassay. Our results demonstrated that 96-hour LC50 and incipient LC50 for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to 32.44) and 25.55 mg L(-1), respectively. Dose-response relationships followed the Hill equation, which could be expressed as organ-specific bioconcentration factors and incipient LC50. Organ-specific dose-response relationships showed that muscle, gill, and liver have a relatively steep sigmoid dose-response profile in that IEC50 were 26.6, 62.5, and 78.5 microg g(-1) dry wt (dw), respectively. Organ-specific arsenic internal lethal burdens were the highest in the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and target-organ concentrations derived in this study can be used in site-specific risk assessment.