Search

The European Commission intends to protect vertebrate wildlife populations by regulating plant protection product (PPP) active substances that have endocrine‐disrupting properties with a hazard‐based approach. In this paper we consider how the Commission's hazard‐based regulation and accompanying guidance can be operationalized to ensure that a technically robust process is used to distinguish between substances with adverse population‐level effects and those for which it can be demonstrated that adverse effects observed (typically in the laboratory) do not translate into adverse effects at the population level. Our approach is to use population models within the adverse outcome pathway framework to link the nonlinear relationship between adverse effects at the individual and population levels in the following way: (1) use specific protection goals for focal wildlife populations within an ecosystem services framework; (2) model the effects of changes in population‐related inputs on focal species populations with individual‐based population models to determine thresholds between negligible and nonnegligible (i.e., adverse) population‐level effects; (3) compare these thresholds with the relevant endpoints from laboratory toxicity tests to determine whether they are likely to be exceeded at hazard‐based limits or the maximum tolerated dose/concentration from the experimental studies. If the population threshold is not exceeded, then the substance should not be classified as an endocrine disruptor with population‐relevant adversity unless there are other lines of evidence within a weight‐of‐evidence approach to challenge this. We believe this approach is scientifically robust and still addresses the political and legal requirement for a hazard‐based assessment. Integr Environ Assess Manag 2019;15:278–291. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC) Key Points: In this paper we consider how the European Commission's hazard‐based Plant Protection Product Regulation can be operationalized to distinguish between substances with adverse population‐level effects and those for which observed adverse effects do not translate into adverse population‐level effects.Our approach is to use population models within the adverse outcome pathways framework to link the nonlinear relationship between adverse effects at the individual and population levels.Only if the population threshold is exceeded should the active substance be classified as an endocrine disruptor with population‐relevant adversity, unless this classification is challenged by other lines of evidence (e.g., from field studies) within a weight‐of‐evidence approach.We believe this approach is scientifically robust and addresses the political and legal requirement for a hazard‐based assessment. [ABSTRACT FROM AUTHOR]

ABSTRACT Ecosystems provide the conditions for producing food, regulating water, and providing wildlife habitats; these, among others, are known as ecosystem services (ESs). Food production is both economically and culturally important to southern European farmers, particularly in Italy where farmers grow flavorsome tomatoes with passion and pride. Growers rely on pesticides for crop protection, the potential environmental impact of which is often questioned by regulators and other stakeholders. The European regulatory system for the approval of pesticides includes a thorough evaluation of risks to the environment and is designed to be protective of ecosystems. The consideration of ESs in environmental decision making is a growing trend, and the present case study provides an example of how ESs evaluation could be used to enhance agricultural practices and regulatory policy for crop protection. By attacking plant roots, nematodes may affect the growth and yield of fruit and vegetable crops, and the income earned by farmers at harvest time. Available solutions include chemical treatments such as 1,3-dichloropropene (1,3-D), physical treatments (solarization), and biological treatments (biofumigation). In order to characterize the risks and benefits associated with the use of 1,3-D in crop protection, ESs and socioeconomic analyses were applied to its use in the control of nematodes in tomato cultivation in southern Italy. The present study confirmed the benefits of 1,3-D to tomato production in Italy, with significant positive effects on production yields and farm income when compared to limited and transient potential impacts on services such as soil function. It was confirmed that 1,3-D allows farm income to be maintained and secures tomato production in these regions for the future. Integr Environ Assess Manag 2016;12:801-810. © 2016 SETAC [ABSTRACT FROM AUTHOR]

Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite ( Colinus virginianus) or Japanese quail ( Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single-stage designs. Environ Toxicol Chem 2014;33:1578-1583. © 2014 The Authors. Published on behalf of SETAC by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Highlights: [•] Feasibility of the threshold approach for formulated PPPs fish acute toxicity tests. [•] Database analysis demonstrates that a reduction of approximately 38% of the fish might be achieved. [•] Proposal for the threshold approach in the development of a regulatory dataset. [Copyright &y& Elsevier]

Abstract: Ecotoxicity testing of pesticide active ingredients and formulated plant protection products (PPPs) prior to their commercial use is required by authorities around the world. Such studies are important for the conduct of risk assessments to protect wildlife and the environment, but they should only be conducted when their use is scientifically justified. One test of questionable scientific merit is the chronic fish toxicity test when conducted with formulated PPPs, which is a potential requirement under European legislation: chronic exposure to the formulated product per se rarely occurs in the environment and therefore it is generally not possible to use the data from chronic formulation studies in a meaningful risk assessment. A recent survey of European crop protection companies to explore the scientific merits and regulatory drivers for chronic fish toxicity studies has shown that current practice in deciding on the need for chronic fish toxicity testing of formulated PPPs varies substantially between companies. The most commonly cited reason for conducting such studies was solely to meet regulatory requirements. We conclude that chronic formulation testing is rarely if ever scientifically justified, and recommend that the forthcoming revision of the EU Aquatic Toxicology Guidance Document takes account of this by including a requirement that justification must be provided for conducting the test, rather than the current situation where the onus is on the registrant to provide a justification for not conducting the test. [ABSTRACT FROM AUTHOR]

The ongoing debate concerning the regulation of endocrine disruptors, has increasingly led to questions concerning the current testing of chemicals and whether this is adequate for the assessment of potential endocrine disrupting effects. This paper describes the current testing approaches for plant protection product (PPP) active substances in the European Union and the United States and how they relate to the assessment of endocrine disrupting properties for human and environmental health. This includes a discussion of whether the current testing approaches cover modalities other than the estrogen, androgen, thyroid and steroidogenesis (EATS) pathways, sensitive windows of exposure, adequate assessment of human endocrine disorders and wildlife species, and the determination of thresholds for endocrine disruption. It is concluded, that the scope and nature of the core and triggered data requirements for PPP active substances are scientifically robust to address adverse effects mediated through endocrine mode(s) of action and to characterise these effects in terms of dose response. [ABSTRACT FROM AUTHOR]

A Weight-of-evidence (WoE) evaluation should be applied in assessing all the available data for the identification of endocrine disrupting (ED) properties of chemicals. The European Commission draft acts specifying criteria under the biocidal products and plant protection products regulations require that WoE is implemented for the assessment of such products. However, only some general considerations and principles of how a WoE should be conducted are provided. This paper reviews WoE approaches to distil key recommendations specifically for the evaluation of potential ED properties of chemicals. In a manner, which is consistent with existing, published WoE frameworks, the WoE evaluation of ED properties can be divided into four phases: 1) Definition of causal questions and data gathering and selection, 2) Review of individual studies, 3) Data integration and evaluation, and 4) Drawing conclusions based on inferences. Recommendations are made on how to conduct each phase robustly and transparently to help guide the WoE evaluation of potential endocrine disrupting properties of chemicals within a European regulatory context. [ABSTRACT FROM AUTHOR]

Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions “What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?” and “Are there correlations between oral toxicity data for amphibians and data for mammals or birds?” Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. [ABSTRACT FROM AUTHOR]

The European Plant Protection Products Regulation 1107/2009 requires that registrants establish whether pesticide metabolites pose a risk to the environment. Fish acute toxicity assessments may be carried out to this end. Considering the total number of pesticide (re-) registrations, the number of metabolites can be considerable, and therefore this testing could use many vertebrates. EFSA's recent “Guidance on tiered risk assessment for plant protection products for aquatic organisms in edge-of-field surface waters” outlines opportunities to apply non-testing methods, such as Quantitative Structure Activity Relationship (QSAR) models. However, a scientific evidence base is necessary to support the use of QSARs in predicting acute fish toxicity of pesticide metabolites. Widespread application and subsequent regulatory acceptance of such an approach would reduce the numbers of animals used. The work presented here intends to provide this evidence base, by means of retrospective data analysis. Experimental fish LC 50 values for 150 metabolites were extracted from the Pesticide Properties Database ( http://sitem.herts.ac.uk/aeru/ppdb/en/atoz.htm ). QSAR calculations were performed to predict fish acute toxicity values for these metabolites using the US EPA's ECOSAR software. The most conservative predicted LC 50 values generated by ECOSAR were compared with experimental LC 50 values. There was a significant correlation between predicted and experimental fish LC 50 values (Spearman r s = 0.6304, p < 0.0001). For 62% of metabolites assessed, the QSAR predicted values are equal to or lower than their respective experimental values. Refined analysis, taking into account data quality and experimental variation considerations increases the proportion of sufficiently predictive estimates to 91%. For eight of the nine outliers, there are plausible explanation(s) for the disparity between measured and predicted LC 50 values. Following detailed consideration of the robustness of this non-testing approach, it can be concluded there is a strong data driven rationale for the applicability of QSAR models in the metabolite assessment scheme recommended by EFSA. As such there is value in further refining this approach, to improve the method and enable its future incorporation into regulatory guidance and practice. [ABSTRACT FROM AUTHOR]

Fish bioconcentration test guidelines generally require that bioconcentration factors (BCFs) are determined at two exposure concentrations. However, recent revisions to the OECD test guideline for bioconcentration testing (TG 305) provide the option to use only one exposure concentration, when justification is provided, although two concentrations may still be required for some regulatory purposes. Recently, this justification has been demonstrated for plant protection product active ingredients. To determine whether this justification has a broader validity for general chemicals, an analysis of 236 BCF studies on general chemicals was conducted. The results presented here again demonstrate that BCF values do not significantly differ between concentrations when more than one concentration is used. This relationship is particularly strong for BCFs ⩾1000 L/kg, which is beneficial, since only chemicals with BCFs >2000 L/kg may require regulatory action. This analysis therefore provides a data-driven rationale for using the one test concentration approach for general chemical substances and thus could contribute to a substantial reduction in the use of fish in bioconcentration tests. [ABSTRACT FROM AUTHOR]

Abstract: Fish bioconcentration tests are time consuming, expensive, and use many animals. Alternative methods that replace, reduce or refine the use of fish for BCF testing would therefore be of value. Test guidelines generally require that bioconcentration factors (BCFs) are determined at two exposure concentrations. However, recent revisions to the OECD Test Guideline for BCF testing (TG 305) provide the option to use only one exposure concentration, when justification is provided, although two concentrations may still be required for some regulatory purposes. Analysis of 55 studies on plant protection products demonstrates that BCF values do not significantly differ between the two exposure concentrations. This analysis therefore provides evidence to support the revision of OECD TG 305, and in particular provides justification for using the one test concentration approach for plant protection product active substances. [Copyright &y& Elsevier]

Abstract: 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. [ABSTRACT FROM AUTHOR]