Search

Wild birds and mammals that feed in agricultural habitats are potentially exposed to pesticides through various routes. The European Food Safety Authority (EFSA) recently published a statement which concluded that the current EFSA risk assessment scheme for birds and mammals does not adequately cover bats (Chiroptera). In the present study, we take a more detailed look at the EFSA statement and assumptions made regarding direct (dermal) and indirect (dietary) exposure of bats to pesticides in terms of their realism and the potential implications for risk assessment outcomes. Regarding dietary exposure, errors in the residue per unit dose (RUD) values for flying insects (bat food), proposed in the EFSA bat statement, were identified and corrected. Lower RUD values based on a much broader data base are proposed. Using these more realistic RUD values, together with current assumptions regarding toxicity and exposure, the acute and long-term risk to bats appears to be within the range of those calculated for birds and ground-dwelling mammals under the current risk assessment scheme. Depending on the assumptions made, some uncertainties may remain and should be investigated further. According to the EFSA bat statement, dermal exposure of bats is the most significant route of exposure, resulting in the highest predicted daily doses. We demonstrated that the dermal exposure models in the EFSA bat statement predict much higher residues for bats than those measured for other flying organisms that have larger surface area to volume ratios, and thus would be expected to have the reverse relationship. We also illustrated that the amounts of spray liquid required to achieve the predicted dermal exposures of bats are implausibly high, with bats carrying an amount of spray liquid that exceeds their body weight many fold. It is recommended that a bat risk assessment framework should be based on realistic, sound science, allowing resources to be focused on those scenarios that are not already covered by the existing bird and mammal framework. Therefore, a quantitative risk assessment scheme should not be implemented until the many scientific uncertainties within the EFSA bat statement are addressed. Environ Toxicol Chem 2022;41:2595-2602. © 2022 Cambridge Environmental Assessments. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Waterbodies located in anthropogenically influenced environments, such as agricultural landscapes, may be exposed to different chemicals simultaneously, or sequentially. Yet, current environmental risk assessments focus on single active substances for unintended mixtures. For 3.5 years, the present study monitored the mixture of herbicides, within an intensively managed agricultural catchment, accompanied by a stewardship programme. Twelve herbicides and one metabolite were monitored on a daily to sub-daily basis, generating a unique, high temporal resolution dataset, enabling an assessment of cumulative exposure in a worst-case scenario. Analyses focused on the number of events at which the herbicide mixture concentration exceeded the regulatory accepted concentration for algae and macrophytes, based on concentration addition, and the potential factors influencing the frequency of these events are considered. A low number of individual herbicides drove the toxicity and only two of these overlapped for the two organism groups, algae and macrophytes. The observed exceedance events coincided with seasonal influences, and low rainfall during the 2011 season correlated with a highly reduced number of these events. The major influence was found to be the implementation of the stewardship programme, which directed farmers to use more advanced farming techniques, avoid spillages and other point sources. The number of exceedance events was reduced by more than half for algae (9% of daily mean samples in 2010 and 4% in 2013) and by approximately 10 times for macrophytes (36% in 2010 to 3% in 2013). This high-resolution monitoring data set illustrates how knowledge of the influencing factors can help reduce unintended exposure to chemicals and achieve real-world improvements. Overall, a single-substance assessment is protective of mixture effects. Where mixture effects do play a role, local measures to manage point sources are more effective than changes to the desk-based environmental risk assessments that focus on diffuse sources. This article is protected by copyright. All rights reserved. Integr Environ Assess Manag 2022;00:0-0. © 2022 SETAC.

The toxicity and ecotoxicity of pesticide active ingredients are evaluated by a number of standardized test methods using vertebrate animals. These standard test methods are required under various regulatory programs for the registration of pesticides. Over the past two decades, additional test methods have been developed with endpoints that are responsive to endocrine activity and subsequent adverse effects. This paper examines the available test methods and their endpoints that are relevant for an assessment of endocrine disrupting properties of pesticides. Furthermore, the paper highlights how weight of evidence approaches should be applied to determine whether an adverse response in (eco)toxicity tests are caused by an endocrine mechanism of action (MoA). The large number of endpoints in the current testing paradigms for pesticides make it unlikely that endocrine activity and adversity is being overlooked. This article is protected by copyright. All rights reserved. Integr Environ Assess Manag 2023;00:0-0. © 2023 SETAC.

Unintentional environmental mixtures happen when multiple chemicals co-occur in the environment. A generic mixture assessment factor (MAF), has been proposed to account for this. The MAF is a number by which safe exposure levels for single chemicals are divided to ensure protection against combined exposures to multiple chemicals. Two key elements to judge the appropriateness of a generic MAF are (1) defining the scope of mixtures that need to be addressed by a MAF (i.e.: simple mixtures vs complex mixtures), and (2) the existence of common risk drivers across large spatial scales. Simple mixtures with one to three risk drivers can easily be addressed by chemical-by-chemical regulatory action. Our work provides evidence on the prevalence and complexity of cumulative risk in EU freshwaters based on chemical monitoring data from one of the largest databases in the EU. With 334 chemicals being monitored, low complexity mixtures (one to 3 three risk drivers) dominated. After excluding metals, only 15 out of 307 chemicals (5 %) were most frequent chemical risk drivers. When these 15 chemicals were excluded from the analysis, 95 % of all monitoring site - year combinations did not pose a concern for cumulative risk. Most of these 15 chemicals are already banned or listed in various priority lists, showing that current regulatory frameworks were effective in identifying drivers of single chemical and cumulative risk. Although the monitoring data do not represent the entirety of environmental mixtures in the EU, the observed patterns of (1) limited prevalence of truly complex mixtures, and (2) limited number of overall risk drivers, argue against the need for implementing a generic MAF as a regulatory tool to address risk from unintentional mixtures in EU freshwaters.

Understanding the frequency of non-additive effects of pesticides (synergism and antagonism) is important in the context of risk assessment. The goal of this study was to investigate the prevalence of non-additive effects of pesticides to honey bees (Apis mellifera). We investigated a large set of mixtures including insecticides and fungicides of different chemical modes of action and classes. The mixtures included represent a relevant sample of pesticides that are currently used globally. We investigated whether the experimental toxicity of the mixtures could be predicted based on the Concentration Addition (CA) model for acute contact and oral adult bee toxicity tests. We measured the degree of deviation from the additivity predictions of the experimental toxicity based on the well-known Mixture Deviation Ratio (MDR). Further, we investigated the appropriate MDR thresholds that should be used for the identification of non-additive effects based on acceptable rates for false positive (alpha) and true positive (beta) findings. We found that a deviation factor of MDR = 5 is a sound reference for labeling potential non-additive effects in acute adult bee experimental designs when assuming a typical Coefficient of Variation (CV%) = 100 in the determination of the LD

Wild birds and mammals that feed in agricultural habitats are potentially exposed to pesticides through various routes. Until recently, it has been implicitly assumed that the existing European Union risk assessment scheme for birds and mammals also covered bats (Chiroptera). However, recent publications raised concerns and, in 2019, a scientific statement was published by the European Food Safety Authority (EFSA) that concluded that bats were not adequately covered by the current risk assessment scheme. We review the evidence presented and assumptions made in the EFSA bat statement relating to toxicity, bioaccumulation, and exposure pathways (oral, dermal, and inhalation), in terms of their relevance for bats potentially foraging in agricultural areas in the European Union; we highlight where uncertainties remain and how these could be addressed. Based on our review, it is clear that there is still much uncertainty with regard to the appropriateness of the assumptions made in the EFSA bat statement. Significantly more information needs to be gathered to answer fundamental questions regarding bat behavior in agricultural landscapes, together with the relative sensitivity of bats to pesticide exposure. Given the current critical information gaps, it is recommended that quantitative risk assessments for bats not be performed for pesticides until more robust, reliable, and relevant data are available. The risk to bats can then be compared with that for birds and ground-dwelling mammals, to determine the protectiveness of the existing scheme and thus whether a bat scenario is indeed required and under what circumstances. Environ Toxicol Chem 2021;40:2978-2989. © 2021 Cambridge Environmental Assessments, part of RSK ADAS Ltd. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Recent regulatory testing programs have been designed to evaluate whether a chemical has the potential to interact with the endocrine system and could cause adverse effects. Some endocrine pathways are highly conserved among vertebrates, providing a potential to extrapolate data generated for one vertebrate taxonomic group to others (i.e., biological read‐across). To assess the potential for biological read‐across, we reviewed tools and approaches that support species extrapolation for fish, amphibians, birds, and reptiles. For each of the estrogen, androgen, thyroid, and steroidogenesis (EATS) pathways, we considered the pathway conservation across species and the responses of endocrine‐sensitive endpoints. The available data show a high degree of confidence in the conservation of the hypothalamus–pituitary–gonadal axis between fish and mammals and the hypothalamus–pituitary–thyroid axis between amphibians and mammals. Comparatively, there is less empirical evidence for the conservation of other EATS pathways between other taxonomic groups, but this may be due to limited data. Although more information on sensitive pathways and endpoints would be useful, current developments in the use of molecular target sequencing similarity tools and thoughtful application of the adverse outcome pathway concept show promise for further advancement of read‐across approaches for testing EATS pathways in vertebrate ecological receptors. Environ Toxicol Chem 2020;39:739–753. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

The European legislation on plant protection products (Regulation (EC) No. 1107/2009) and biocides (Directive 98/8/EC), as well as the regulation concerning chemicals (Regulation (EC) No. 1907/2006 ‘REACH’) only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or non-target species. However, there is currently no agreed guidance on how to identify and evaluate endocrine activity and disruption. Consequently, an ECETOC task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. Specific scientific criteria for the determination of endocrine disrupting properties that integrate information from both regulatory (eco)toxicity studies and mechanistic/screening studies are proposed. These criteria combine the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. The criteria developed are presented in the form of flow charts for assessing relevant effects for both humans and wildlife species. In addition, since not all chemicals with endocrine disrupting properties are of equal hazard, assessment of potency is also proposed to discriminate chemicals of high concern from those of lower concern. The guidance presented in this paper includes refinements made to an initial proposal following discussion of the criteria at a workshop of invited regulatory, academic and industry scientists.

Fate and toxicity of the active ingredients (AI's) of plant protection products in surface waters is often influenced by pH. Although a general range of pH values is reported in literature, an evaluation targeting aquatic ecosystems with documented AI inputs is lacking at the larger scale. Results show 95% of European surface waters (n = 3075) with a documented history of AI exposure fall within a rather narrow pH range, between 7.0 and 8.5. Spatial and temporal variability in the data may at least be partly explained by the calcareous characteristics of parental rock material, the affiliation of the sampling site to a freshwater ecoregion, and the photosynthetic activity of macrophytes (i.e., higher pH values with photosynthesis). Nonetheless, the documented pH range fits well with the standard pH of most ecotoxicological test guidelines, confirming the fate and ecotoxicity of AIs are usually adequately addressed.

Coloured substances are often assumed to behave differently in the algal growth inhibition test due to shading of the algae. We have investigated EU-notifications of new substances and found no significant differences in algal test results between colours and non-colours. A modified method to differentiate between shading and toxicity is not satisfactory, because the method used to determine the shading effect is incorrect. Due to the shaking of the test flasks in the algal test intermittent light conditions are achieved which lead to a higher growth rate than expected from proposed tests with constant reduced light conditions. This will result in overestimation of the shading effect and thus to underestimation of chemical toxicity. Furthermore, we showed in experiments with the reference substance potassium dichromate that reduced light can reduce the measurable toxicity of chemicals. Comparing our results with approaches proposed in the literature, a simple approach to reduce effects of undesired shading when testing coloured substances is to achieve light saturation for the algae by increasing illumination at least to the upper limit given in test guidelines (120 μE s−1 m−2) and, optionally, to reduce the light path by choosing smaller test volumes.

An international ringtest of the enchytraeid reproduction test (ERT) was performed by 29 laboratories, with two substances (carbendazim and 4-nitrophenol) and two test designs (NOEC and ECx). Although many participants had no previous experience in enchytraeid ecotoxicology, the majority of tests were performed accurately and fulfilled the validity criteria, demonstrating method feasibility. However, variability in control reproduction was fairly high and exceeded the proposed validity criterion of a 50% coefficient of variation in 24% of the tests. Variability may be lowered with increasing experience and by using better defined animals, either through synchronized culture or by weighing animals before the test. In all tests, NOECs were higher than the EC10 values, sometimes by more than 1 order of magnitude and usually closer to the EC50. This shows that NOECs, due to their dependence on test design and variability, are an unsatisfactory measure of "no toxicity" for regulatory purposes. Preferably, differences to the control at NOEC concentrations should always be given. To achieve appropriate power and to avoid frequent false negatives, in the ERT, high numbers of replicates would be necessary. We favor using regression approaches with means of replicates whenever possible.

From the complete base set notifications of new substances currently available, we have investigated what effects the choice of using growth rate or biomass in the algal growth inhibition test has on the relative sensitivity of the three aquatic toxicity tests. Both parameters derived from the algal test were more sensitive than either fish or Daphnia tests. Changes in the classification of substances after the removal of either algae, Daphnia or fish data from the base set, when applying current legal practice, occur in 22.9%, 6.6% and 4.8% of the notifications, respectively. When always using growth rate as a parameter, these numbers change to 15.4%, 9.2% and 7.2%, respectively.

Model ecosystems are widely used to assess the fate and the effects of chemicals in the environment, because they yield reproducible data on higher levels of biological organization (populations, communities, ecosystems) at moderate cost. Still, there is a need for the development of complex terrestrial test systems which allow for the statistical evaluation of results. The variation ('normal range') of possible effect endpoints in such systems is of particular interest when comparing the ecotoxicological effects of chemicals. However, experiments designed to assess the variation of endpoint parameters are rarely performed, because they obviously do not yield data on the main topic, the effects of chemicals.

To use and implement an assessment scheme for the evaluation of endocrine disrupting properties of chemicals in ecotoxicology, the types of effect need to be agreed. Effects that merit further consideration in this context should fulfil the following three criteria: caused by an endocrine mode of action, be adverse, and be relevant at the population level to reflect the protection goal of ecotoxicological assessments. Thereafter, a comparison of effect values, regardless of the causative mechanisms, should be made, firstly to determine if endocrine toxicity generates the lowest endpoint within a taxon, and secondly if it is the lowest endpoint compared to that of other taxa living in the same compartment. These comparisons inform on two levels of specificity and determine if endocrine-mediated side-effects determine the ecotoxicological profile of a chemical. Various quantitative measures for the assessment of potency are also presented, which could assist in determining how to handle substances in the risk assessment when a regulatory concern is identified. Finally, derogation criteria should be defined for compounds that were designed as endocrine disruptors for non-vertebrates and those for which there is ‘negligible exposure’. This paper discusses and provides proposals on how to apply these concepts for assessment of substances.

The European regulation on plant protection products (1107/2009) (EC, 2009a), the revisions to the biocides Directive (COM[2009]267) (EC, 2009b), and the regulation concerning chemicals (Regulation (EC) No. 1907/2006 ‘REACH’) (EC.2006) only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. In the absence of agreed guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The resulting ECETOC technical report (ECETOC, 2009a) and the associated workshop (ECETOC, 2009b) presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. The synthesis of the technical report and the workshop report was published by the ECETOC task force (Bars et al., 2011a,b). Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory (eco)toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach. However, to be able to discriminate chemicals with endocrine properties of low concern from those of higher concern (for regulatory purposes), the task force recognised that the concept needed further refinement. Following a discussion of the key factors at a second workshop of invited regulatory, academic and industry scientists (ECETOC, 2011), the task force developed further guidance, which is presented in this paper. For human health assessments these factors include the relevance to humans of the endocrine mechanism of toxicity, the specificity of the endocrine effects with respect to other potential toxic effects, the potency of the chemical to induce endocrine toxicity and consideration of exposure levels. For ecotoxicological assessments the key considerations include specificity and potency, but also extend to the consideration of population relevance and negligible exposure. It is intended that these complement and reinforce the approach originally described and previously published in this journal (Bars et al., 2011a,b).

Acute toxicity data from the New Chemicals Database of the European Chemicals Bureau were compared for fish, Daphnia, and algae. The algal growth inhibition test was the most sensitive. Correlation between fish and Daphnia toxicity values was better than the correlation with algae. Toxicity values among the three organisms correlated more strongly than any with log P ow .

In 1998, the International Council of Chemical Associations (ICCA) launched a global initiative to investigate more than 1,000 HPV chemicals (High Production Volume,or = 1,000 t/a) within the refocused OECD HPV Chemicals Programme. Up to the OECD SIDS Initial Assessment Meeting in April 2004 (SIAM 18) 147 ICCA dossiers (ca. 230 CAS-No) have been assessed based on a harmonised data set. The environmental profile and an ecotoxicological characterisation of these chemicals are presented here. Data for acute aquatic toxicity were correlated among each other, as well as data for fish (LC50, LD50) and rodents (LD50). The data for acute aquatic toxicity are compared with other existing chemicals.Data of the ICCA HPV chemicals from the OECD SIAM 11-18 are presented for: log Kow (as an indicator for bioaccumulation potential), biodegradation, acute aquatic toxicity and availability of long-term toxicity data. Correlation analysis was performed with log transformed data and a linear regression model was fitted to the data, if a significant correlation was found. Acute toxicity for fish and acute oral toxicity for rodents were correlated on a molar basis. Acute aquatic toxicity of the chemicals is compared with data from BUA reports 1-234 and a random EINECS sample (Knacker et al. 1995).According to the dossier information, 71 of the 147 ICCA chemicals are not 'readily biodegradable', 21 have a log Kowor = 3, and 44 are 'toxic' (LC/EC50or = 10 mg/L) or 'very toxic' (LC/EC50or = 1 mg/L) to aquatic organisms. For 77, only the base set (acute fish, Daphnia and algae) is available, for the rest at least one long-term test (fish or Daphnia) is available and three tests for a mere 14 others. Based on the data presented, the SIAM gives recommendations for Environment and Human Health. 22 chemicals have been identified as a 'candidate for further work' for Environment and 16 for Human Health. The highest correlation coefficient was obtained correlating fish and Daphnia (r2 = 0.79). LC50 (fish) is significantly correlated with LD50 (rodent), but data are widely scattered. The correlation is not improved after transforming LC50 (fish) to LD50 (fish), using BCF QSAR. Based on acute aquatic toxicity, 25.1% of the chemicals from the BUA reports 1-234 are classified as 'very toxic' (LC/EC50or = 1 mg/L). This proportion is 2.5-fold higher than the ICCA HPV chemicals and 1.4-fold higher than the random EINECS sample.Correlation coefficients for aquatic toxicity data are rather uniform (0.57-0.79) compared with literature data, but also the best correlation was observed between fish and Daphnia. Because the scatter around the regression lines is still considerable, simple predictions of ecotoxicity between species are not possible. Correlation of LC50 (fish) and LD50 (rodent) indicates that toxicity is different. Surprisingly, the correlation of fish and rodent toxicity is not improved by transforming LC50 values to internal LD50s. The selection of ICCA chemicals by market significance (production volume) leads to a classification of toxicity, which is more comparable to a random sample of EINECS chemicals than to German BUA chemicals. The latter were chosen for concern (for Environment or Human Health).Of 147 dossiers assessed between SIAM 11-18, ca. 75% were sponsored by the three following countries: Germany (42), USA (37) and Japan (33). The current output is about 50 dossiers per year (70-100 CAS-No), but a trend for an increase of output is noticeable. Industry, national authorities, and OECD work on a further development to speed up the output. The number of chemicals with 'low priority for further work' and the work recommended for the 'candidates' (mainly exposure assessment) indicate that the data presented were adequate for an initial hazard assessment according to OECD requirements. From the ICCA HPV list (n = 880, state of 1999) 44% of the chemicals have data available to cover all SIDS endpoints for Environment and only 33% for Human Health (Allanou et al. 1999). This indicates the importance of the Initiative to provide information on existing chemicals. The authors agree with the expectation "...that the scientific information provided by this global initiative will be considered as an internationally accepted and harmonised basis for further steps of chemicals management." (ICCA 2002 b).

Risk assessment approaches within the regulatory framework of the European Union (EU) based on single species tests were compared to those using data from terrestrial model ecosystems (TMEs). In a case study with the fungicide carbendazim, single species data led to ratios of the predicted environmental concentration (PEC) and predicted no effect concentration (PNEC) of above 1000, depending on available data and related assessment factors, indicating concern for the terrestrial environment. Considering the high degree of realism of the TME studies with multiple endpoints measured, but also residual uncertainty related to higher variability of endpoints, an assessment factor of 5 was applied on TME data. The most sensitive reliable endpoint was earthworm biomass. With the TME studies yielding slightly higher effect thresholds compared to laboratory data, and due to the lower assessment factor, the PEC/PNEC ratio was lowered to 5. This means that there would be concern for high application rates of carbendazim.

Bayer CropScience, 355 Rue Dostoievsky, F-06903 Sophia Antipolis, France b Total Petrochemicals, Zone Industrielle Feluy C, B-7181 Seneffe, Brussels, Belgium BASF SE, Carl-Bosch-Str. 38, D-67056 Ludwigshafen, Germany Wca Environment Limited, Brunel House, Volunteer Way, Faringdon SN7 7YR, UK e ExxonMobil Petroleum and Chemical, Hermeslaan 2, B-1831 Machelen, Brussels, Belgium f SC Johnson, Frimley Green Road, Camberley, Surrey GU16 7AJ, UK g Syngenta Product Safety, Jealott’s Hill International Research Centre, Bracknell, Berkshire RG42 6EY, UK Unilever SEAC, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK AstraZeneca, Brixham Environmental Laboratory, Freshwater Quarry, Brixham TQ5 8BA, UK BASF SE, Crop Protection, Ecotoxicology, Speyerer Strasse 2, D-67117 Limburgerhof, Germany Currenta OHG, Geb. Q18, D-51368 Leverkusen, Germany ECETOC, 4 Avenue E. Van Nieuwenhuyse, B-1160 Brussels, Belgium