Environmental Risk Assessment Of Chemicals Research Articles

Promoting effects on reproduction increase population vulnerability of Daphnia magna

Environmental risk assessment of chemicals is based on single species tests at the individual level with single compounds. However, the protection goal is the sustainability of a population, which faces several natural stressors and mixtures of chemicals in the environment. Therefore, experiments were undertaken to quantify the combined effects of chemicals with different modes of action on Daphnia magna populations. Populations continuously exposed to dispersogen A and at abundance equilibrium were treated with a 2-d pulse of p353-nonylphenol. In previous studies, dispersogen A was shown to act as a natural info-chemical, promoting the reproduction of daphnids (higher offspring quantity) coupled with reduced offspring fitness, whereas nonylphenol in pulsed-exposure caused size-selective mortality. Dispersogen A caused accelerated population growth to maximum abundance, shifted the population structure towards smaller individuals, and increased the population sensitivity to nonylphenol. The authors showed that a positive effect observed at the individual level can be transposed to a negative effect when monitored at the population level. So far, positive effects are not addressed in environmental risk assessment, and even in higher-tier testing, population structure is not quantified. Both factors indicate a potential mismatch between protection aim and risk assessment practice.

Risk Assessment of Environmental Chemicals: If It Ain't Broke …

Risk Assessment of Environmental Chemicals: If It Ain't Broke …

Fungal composition on leaves explains pollutant-mediated indirect effects on amphipod feeding

The energy stored in coarse particulate organic matter, e.g. leaf litter, is released to aquatic ecosystems by breakdown processes involving microorganisms and leaf shredding invertebrates. The palatability of leaves and thus the feeding of shredders on leaf material are highly influenced by microorganisms. However, implications in the colonization of leaves by microorganisms (=conditioning) caused by chemical stressors are rarely studied. Our laboratory experiments, therefore, investigated for the first time effects of a fungicide on the conditioning process of leaf material by means of food-choice experiments using Gammarus fossarum (Crustacea: Amphipoda). Additionally, microbial analyses were conducted to facilitate the mechanistic understanding of the observed behavior. Gammarids significantly preferred control leaf discs over those conditioned in presence of the fungicide tebuconazole at concentrations of 50 and 500 μg/L. Besides the decrease of fungal biomass with increasing fungicide concentration, also the leaf associated fungal community composition showed that species preferred by gammarids, such as Alatospora acumunata, Clavariopsis aquatica, or Flagellospora curvula, were more frequent in the control. Tetracladium marchalianum, however, which is rejected by gammarids, was abundant in all treatments suggesting an increasing importance of this species for the lower leaf palatability – as other more palatable fungal species were almost absent – in the fungicide treatments. Hence, the food-choice behavior of G. fossarum seems to be a suitable indicator for alterations in leaf associated microbial communities, especially fungal species composition, caused by chemical stressors. Finally, this or similar test systems may be a reasonable supplement to the environmental risk assessment of chemicals in order to achieve its protection goals, as on the one hand, indirect effects may occur far below concentrations known to affect gammarids directly, and on the other hand, the observed shifts in leaf associated microbial communities may have perpetuating implications in leaf shredding invertebrates.

General Unified Threshold Model of Survival - a Toxicokinetic-Toxicodynamic Framework for Ecotoxicology

Toxicokinetic-toxicodynamic models (TKTD models) simulate the time-course of processes leading to toxic effects on organisms. Even for an apparently simple endpoint as survival, a large number of very different TKTD approaches exist. These differ in their underlying hypotheses and assumptions, although often the assumptions are not explicitly stated. Thus, our first objective was to illuminate the underlying assumptions (individual tolerance or stochastic death, speed of toxicodynamic damage recovery, threshold distribution) of various existing modeling approaches for survival and show how they relate to each other (e.g., critical body residue, critical target occupation, damage assessment, DEBtox survival, threshold damage). Our second objective was to develop a general unified threshold model for survival (GUTS), from which a large range of existing models can be derived as special cases. Specific assumptions to arrive at these special cases are made and explained. Finally, we illustrate how special cases of GUTS can be fitted to survival data. We envision that GUTS will help increase the application of TKTD models in ecotoxicological research as well as environmental risk assessment of chemicals. It unifies a wide range of previously unrelated approaches, clarifies their underlying assumptions, and facilitates further improvement in the modeling of survival under chemical stress.

Effect of 2,4‐dihydroxybenzophenone (BP1) on early life‐stage development of the marine copepod Acartia tonsa at different temperatures and salinities

Benzophenone (BP)-type ultraviolet (UV) filters are widely used in cosmetic and sunscreen products and can enter the aquatic environment. Therefore, we investigated the subchronic toxicity of 2,4-dihydroxybenzophenone (BP1) on the marine calanoid copepod Acartia tonsa in an early life-stage development study. Since developmental endpoints depend on environmental conditions, a preceding study of A. tonsa development was performed at three temperatures, four salinities, four light:dark regimes, six food densities, and four culture densities. Times elapsed until 50% of the population had reached a copepodite stage (DT(½) ) at the different conditions were calculated. The DT(½) values decreased from 296 h at 15°C to 89 h at 25°C and were also affected by salinity (126 h at 15‰ and 167 h at 30‰), whereas the light:dark regime and culture density influenced development only to a minor extent. BP1 was found acutely toxic at 2.6 mg/L (48-h median lethal concentration [LC50]). The toxicity of BP1 on early life-stage development was studied in combinations of three temperatures (15, 20, 25°C) and three salinities (15, 20, 25‰) using five toxicant concentrations between 0.051 and 2 mg/L in each scenario. Concentrations causing 10 and 50% inhibition of development (EC10 and EC50) were determined. Acartia tonsa was most resistant towards BP1 at 20°C where an EC50 of 1.1 mg/L was found, whereas EC50 values were significantly lower at 15°C (0.49 mg/L) and 25°C (0.77 mg/L), respectively. The EC50 also decreased with increasing salinity. Our results demonstrate that environmental conditions do influence toxicity test results; thus, they need to be considered carefully when developing test protocols as well as for environmental risk assessments of chemicals.

Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment.

Epidemiologic Review of Long-Term, Low-Level Exposure to Environmental Chemicals and Cardiovascular Disease: An Exposure-Response Relationship

The effects of exposure to environmental chemicals, such as heavy metals and fine particulates, on cardiovascular diseases have been reported. To set a permissible exposure standard, an exposure-response relationship should be elucidated. Thus, epidemiologic evidence in relation to long-term, low-level exposure to environmental chemicals (i.e., lead, cadmium, mercury, arsenic, PM(2.5), carbon disulfide) was reviewed. As a result, there exists a clear exposure-response relationship between exposure to lead or PM(2.5) and cardiovascular diseases, but those cohort studies were carried out in the US only. From epidemiologic viewpoint, "consistency" of the observed relationship must be clarified, especially findings of a study in the Japanese population. It is well known that the distribution pattern of cardiovascular risk factors are quite different between two countries, which could modify the true relationship. This will require studies of large samples from the general Japanese population with control for potential confouders. Moreover, to detect a small effect of exposure within low-level range, random misclassification of exposure as well as that of effect must be minimized. Thus, for studies of heavy metals, sensitive biomarkers identified in toxicological studies would be applied. For PM(2.5), a wide range of population samples should be covered by a national sampling network in the near future. Finally, the integration of epidemiologic and toxicological evidence would be more important for risk assessment of environmental chemicals at low exposure levels, because an exposure-response relationship from only epidemiologic observation may be unstable with a wide confidence interval around the threshold.

Modelling 36Cl in soil-plant system: A phenomenological approach and its application to the discharge of 36Cl in groundwater from radioactive waste deep storage site

Chlorine 36 is considered as part of the group III of radioactive wastes composed of the moderate radiotoxic radionuclides such as Carbon 14. As such and along with its long half-life (3.01 × 10 5 years) and its chemical form (chloride anion), it is a very important radionuclide to be taken into account in the environment thereby making its modelling an important goal. We present in this paper the phenomenological approach developed at IRSN for modelling the behaviour of chloride 36 in the continental ecosystems. This model is a part of the SYMBIOSE programme (SYstemic approach for Modelling the fate of chemicals in the BIOSphere and the Ecological systems) whose main goal is to develop a modelling platform able to sustain an environmental chemical risk assessment. Such an approach has been found necessary for Chlorine 36 when the classic models (conventional transfer factor models and specific activity models) fail (for instance in case of acute release of radionuclides). Only the part of the model dealing with the agricultural soil-plant system is described here in detail: interaction matrices, components description, components equations, independent variables, and data. Then, we present an application of this model to investigate chlorine 36 behaviour in soils and uptake by plants after its discharge in groundwater from a radioactive waste deep storage site. Finally, we present results from an intercomparison study performed under the BIOPROTA international cooperation framework.

Use of neurodevelopmental data in children for risk assessment of environmental chemicals

Use of neurodevelopmental data in children for risk assessment of environmental chemicals

Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era

The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA) — i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on “augmentation” of weight of evidence — using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards “integration” of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for “expansion” of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual “reorientation” of QRA towards approaches that more directly link environmental exposures to human outcomes.

Potential application of ecological models in the European environmental risk assessment of chemicals I: Review of protection goals in EU directives and regulations

Several European directives and regulations address the environmental risk assessment of chemicals. We used the protection of freshwater ecosystems against plant protection products, biocidal products, human and veterinary pharmaceuticals, and other chemicals and priority substances under the Water Framework Directive as examples to explore the potential of ecological effect models for a refined risk assessment. Our analysis of the directives, regulations, and related guidance documents lead us to distinguish the following 5 areas for the application of ecological models in chemical risk assessment: 1) Extrapolation of organism-level effects to the population level: The protection goals are formulated in general terms, e.g., avoiding "unacceptable effects" or "adverse impact" on the environment or the "viability of exposed species." In contrast, most of the standard ecotoxicological tests provide data only on organism-level endpoints and are thus not directly linked to the protection goals which focus on populations and communities. 2) Extrapolation of effects between different exposure profiles: Especially for plant protection products, exposure profiles can be very variable and impossible to cover in toxicological tests. 3) Extrapolation of recovery processes: As a consequence of the often short-term exposures to plant protection products, the risk assessment is based on the community recovery principle. On the other hand, assessments under the other directives assume a more or less constant exposure and are based on the ecosystem threshold principle. 4) Analysis and prediction of indirect effects: Because effects on 1 or a few taxa might have consequences on other taxa that are not directly affected by the chemical, such indirect effects on communities have to be considered. 5) Prediction of bioaccumulation within food chains: All directives take the possibility of bioaccumulation, and thus secondary poisoning within the food chain, into account.

Application of OMICS data to human health risk assessment of environmental chemicals

Application of OMICS data to human health risk assessment of environmental chemicals

Study on Collection and Communication of Information for Environmental Risk Assessment of Chemicals

Study on Collection and Communication of Information for Environmental Risk Assessment of Chemicals

The zebrafish embryo model in environmental risk assessment—applications beyond acute toxicity testing

The use of fish embryos is not regulated by current legislations on animal welfare and is therefore considered as a refinement, if not replacement of animal experiments. Fish embryos represent an attractive model for environmental risk assessment of chemicals since they offer the possibility to perform small-scale, high-throughput analyses. Beyond their application for determining the acute toxicity, fish embryos are also excellent models for studies aimed at the understanding of toxic mechanisms and the indication of possible adverse and long-term effects. Therefore, we have reviewed the scientific literature in order to indicate alternative applications of the fish embryo model with focus on embryos of the zebrafish. The analysis of the mode of action is important for the risk assessment of environmental chemicals and can assist in indicating adverse and long-term effects. Toxicogenomics present a promising approach to unravel the potential mechanisms. Therefore, we present examples of the use of zebrafish embryos to study the effect of chemicals on gene and protein patterns, and the potential implications of differential expression for toxicity. The possible application of other methods, such as kinase arrays or metabolomic profiling, is also highlighted. Furthermore, we show examples of toxicokinetic studies (bioconcentration, ABC transporters) and discuss limitations that might be caused by the potential barrier function of the chorion. Finally, we demonstrate that biomarkers of endocrine disruption, immune modulation, genotoxicity or chronic toxicity could be used as indicators or predictors of sub-acute and long-term effects. The zebrafish embryo represents a model with an impressive range of possible applications in environmental sciences. Particularly, the adaptation of molecular, system-wide approaches from biomedical research is likely to extend its use in ecotoxicology. Challenges for future research are (1) the identification of further suitable molecular markers as indicators of the mode of action, (2) the establishment of strong links between (molecular) effects in short-term assays in embryos and long-term (toxic) effects on individuals, (3) the definition of limitations of the model and (4) the development of tests that can be used for regulatory purposes.

Integrating individual ecdysteroid content and growth-related stressor endpoints to assess toxicity in a benthic harpacticoid copepod

Anthropogenic chemicals released into the environment may have so-called endocrine disruptive effects. For instance, innumerous observations on subtle alterations of fish reproductive systems have been published in the scientific literature during the last decades. At the same time, the evidence is scarce regarding similar effects in crustaceans, which is probably related to the limited understanding of basic crustacean endocrine systems and pathways, rather than absence of endocrine disruption within the crustacean subphylum. This knowledge gap is particularly evident in micro-crustacean species, which are frequently used in environmental risk assessment of chemicals, and adequate tools for identification of potential endocrine disrupters are missing in current chemicals regulation. The main objective of the current study was therefore to utilize an enzyme immunoassay to establish a stable protocol for analysis of individual ecdysteroid levels in the benthic harpacticoid copepod Nitocra spinipes, a species which has been used in ecotoxicological investigations for more than 30 years. Further, to assess the usefulness of the individual ecdysteroid level as a stressor endpoint, it was integrated with a growth-related stressor endpoint battery, i.e. individual RNA content, mean development times, and growth rate, by exposing individual N. spinipes to the insecticide and known ecdysteroid antagonist lindane at 25–400 μg L −1. The results showed that the ecdysteroid levels were significantly different from the control (71 pg individual −1) in the 100 μg L −1 treatment (124 pg individual −1). Although the ecdysteroid levels were not significantly different from the control in the 25–50 μg L −1 treatments (83–93 pg individual −1), these results still show a clear concentration-related trend. In the 200 μg L −1 treatment, the ecdysteroid content was the highest (165 pg individual −1), however not significantly different from the control due to high variation. The 400 μg L −1 treatment resulted in lowered ecdysteroid levels (107 pg individual −1), indicating a profound lindane-induced stress, which was confirmed by high mortality in the same treatment (79%). For all other endpoints there were clear concentration-related effects of lindane, with development time and growth rate as the most sensitive endpoints. In conclusion, this study presents for the first time a tool for identification of endocrine alterations in N. spinipes. By using the established enzyme immunoassay protocol, we obtained individual ecdysteroid levels that integrated well with the growth-related stressor endpoints previously used on this species.

An ecological perspective in aquatic ecotoxicology: Approaches and challenges

Abstract This paper aims to highlight the considerable potential of a better integration of ecological theory in aquatic ecotoxicology. It outlines how community ecology, studies on trophic interaction and disturbance ecology could provide an enhanced theoretical basis for aquatic ecotoxicology and increase ecological relevance in environmental risk assessment of chemicals. Based on the literature and own research, approaches from aquatic ecotoxicology are presented, which are based on ecological considerations and address a higher level of biological complexity for risk assessment strategies of chemicals. The concepts of species-sensitivity distribution (SSD), pollution-induced community tolerance (PICT), the use of model ecosystems and the sediment quality triad (SQT) in ecological risk assesment as well as inputs from ecotoxicology into landscape ecology are illustrated. These examples aim to evidence aquatic ecotoxicology as a rewarding field of ecological research.

Seasonal variations in spontaneous levels of DNA damage; implication in the risk assessment of environmental chemicals

The alkaline comet assay was used to investigate DNA damage levels in white blood cells of 45 normal healthy subjects. Therefore blood was sampled at four different periods, namely in February, June, August and November of the same year. Higher DNA damage levels were found in summertime, as well as higher levels of 1-hydroxypyrene in urine in this period. This suggests a higher exposure to polycyclic hydrocarbons in the summer compared with other periods of the year. The observed seasonal variation in DNA damage levels is in agreement with some, but in contradiction with other data. Seasonal variations in DNA damage levels can easily be explained by the existence of different confounders that may influence the results of a biomonitoring study. Besides sunlight and environmental pollution, also diet, allergy and physical exercise, for example, were already identified as important influencing factors. The investigation confirms that the blood sampling period is crucial in the planning and interpretation of biomonitoring studies.

Bacterial lipopolysaccharides induce genes involved in the innate immune response in embryos of the zebrafish ( Danio rerio)

The innate immune response in fish represents an early, rapid defence against pathogens. Environmental contaminants could disturb this defence and negatively influence the ability to protect against infection. However, analysis of immune-modulation has not yet been included in testing strategies for environmental risk assessment of chemicals. In order to establish an efficient, small scale test system, the ability to induce the innate immune response by bacterial lipopolysaccharides in zebrafish embryos was investigated. The level of expression of various genes involved in inflammation was used as the endpoint. We could show that immersion of embryos in LPS induced the gene expression of two key pro-inflammatory cytokines, tumor necrosis factor α and interleukin 1β in 32 h old zebrafish embryos. The gene induction required the removal of the chorion prior to lipopolysaccharide exposure.

Biomonitoring equivalents: A screening approach for interpreting biomonitoring results from a public health risk perspective

Advances in both sensitivity and specificity of analytical chemistry have made it possible to quantify substances in human biological specimens, such as blood, urine, and breast milk, in specimen volumes that are practical for collection from individuals. Research laboratories led by the Centers for Disease Control and Prevention (CDC) in its series National Report on Human Exposure to Environmental Chemicals [Centers for Disease Control and Prevention (CDC), 2005. Third National Report on Human Exposure to Environmental Chemicals. NCEH Pub. No. 05-0570.] are dedicating substantial resources to designing and conducting human biomonitoring studies and compiling biomonitoring data for the general population. However, the ability to quantitatively interpret the results of human biomonitoring in the context of a health risk assessment currently lags behind the analytical chemist’s ability to make such measurements. The traditional paradigm for human health risk assessment of environmental chemicals involves comparing estimated daily doses to health-based criteria for acceptable, safe, or tolerable daily intakes (for example, reference doses [RfDs], tolerable daily intakes [TDIs], or minimal risk levels [MRLs]) to assess whether estimated doses exceed such health screening levels. However, biomonitoring efforts result in measured chemical concentrations in biological specimens (the result of absorption, distribution, metabolism and excretion of administered doses) rather than estimated intake doses. Quantitative benchmarks of acceptable or safe concentrations in biological specimens (analogous to RfDs, TDIs, or MRLs) needed to interpret these levels exist for very few chemicals of environmental interest. This paper discusses issues inherent in converting existing health screening benchmarks based on intake doses to screening levels for evaluating biomonitoring data, and presents methods and approaches that can be used to derive such screening levels (termed “Biomonitoring Equivalents,” or BEs) for a range of chemicals and biological media.

Alternative approaches can greatly reduce the number of fish used for acute toxicity testing

Acute toxicity tests with algae, daphnids, and fish are required for the classification and environmental risk assessment of chemicals. The degree of risk is determined by the lowest of these acute toxicity values. Many ecotoxicological programs are seeking to reduce the numbers of fish used in acute toxicity testing. The acute threshold test is a recently proposed strategy that uses, on average, only 10 (instead of 54) fish per chemical. We examined the consequences of reducing the number of fish used in toxicity testing on the ultimate outcome of risk assessments. We evaluated toxicity data sets for 507 compounds, including agrochemicals, industrial chemicals, and pharmaceuticals from our internal database. Theoretical applications of the acute threshold test gave similar results to those obtained with the standard fish median lethal concentration (LC50) test but required only 12% as many fish (3195 instead of 27,324 fish used for all compounds in the database). In 188 (90%) of the 208 cases for which a complete data set was available, the median effect concentration for algae or daphnids was lower than the LC50 for fish. These results show that replacement of the standard fish LC50 test by the acute threshold test would greatly reduce the number of fish needed for acute ecotoxicity testing without any loss of reliability.