All Downloads from the category: “Technical”
Michail Gioutlakis et. al. (2025) Benchmark Dose Modelling in human tox and environmental risk assessment
Benchmark Dose Modelling in human tox and environmental risk assessment Benchmark Dose (BMD) Modelling is an approach used to derive toxicological endpoints for environmental (ERA) and human risk assessment. The aim of a BMD approach is to determine a dose-level that triggers a measurable change in a relevant toxicological parameter following exposure to a chemical, i.e. the Benchmark Response (BMR). The EFSA 2023 guidance on risk assessment for birds and mammals recommends the use of BMD for setting reproductive toxicity endpoints, rather than the current use of No-Observed-Adverse-Effect-Levels (NOAEL). The median BMD and a default response level for birds and mammals is set at 10% by EFSA 2023. However, further guidance on how to deal with different ecologically relevant parameters to be modelled and how to decide on the most appropriate BMR value is not available. Here, we report on analyses performed for real cases. First, the ecologically relevant parameters from mammalian toxicological studies were selected based on the EFSA 2023 guidelines. The data were then extracted from the toxicological study reports and their suitability for the BMD approach was assessed. The methodology outlined in the EFSA 2022 guidance on the use of BMD approach in risk assessment was followed, and results were obtained using the EFSA web tool for Bayesian BMD analysis. These results were checked against the EFSA 2023 validity criteria. For several active substances, the respective BMD values and their credible intervals were calculated for relevant parameters from mammalian toxicological studies. A key challenge with the BMD approach is that many toxicological studies are primarily designed to derive NOAELs, which are focused solely on identifying safe exposure levels. Consequently, not all extracted data sets were suitable for the BMD approach. In human risk assessment, the BMR level must be justified, and the lower limit of the credible interval should be used. In ERA the median BMD level is used and a default BMR level of 10% is recommended. However, these BMR levels of parameters of concern for ERA should be discussed in terms of ecological relevance. By presenting BMD approaches and their use in different areas of pesticide risk assessment we intend to initiate an open discussion on the selection process of ecologically relevant parameters and appropriate BMR levels, as well as the rationale behind these choices.
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Parvinder Kaur at al. (2025) Challenges in the interpretation of DNT endpoints and their regulatory implications
Challenges in the interpretation of DNT endpoints and their regulatory implications P. Kaur, A. Ochs, M. Gioutlakis, J. Schabacker, F. v. Blanckenhagen Developmental neurotoxicity (DNT) studies are designed to provide information on potential functional, behavioural and morphological effects on the developing nervous system after in utero and early-life exposure to chemical compounds. The current in vivo testing paradigm for DNT includes OECD TG 426, US EPA OPPTS 870.6300 and OECD TG 443 with the inclusion of DNT cohorts. However, several active substances have been impacted by methodological deficiencies, which adds to uncertainty in interpretation of results. We want to present and discuss several case studies from the pesticide regulatory framework where these challenges arise. The appraisal of these case studies using the Office of Health Assessment and Translation-National Toxicology Program Risk of Bias (RoB) assessment tool (NTP, 2015) in line with the EFSA Adverse Outcome Pathways-informed Integrated Approach to Testing and Assessment led to high RoB and non-acceptance of some endpoints. In view of these uncertainties, in certain instances the European commission has applied additional uncertainty factors. These case studies illustrate how differences in study design, number of doses, missing important key events and interpretation of behavioural and histopathological data can affect regulatory decisions. These case studies will emphasize the need for improved methodologies and robust uncertainty analysis to ensure reliable and consistent DNT assessments, which are crucial for regulatory toxicology decisions.
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Bauer et al. (2023) A Toxicokinetic–Toxicodynamic Modeling Workflow Assessing the Quality of Input Mortality Data
Toxicokinetic–toxicodynamic (TKTD) models simulate organismal uptake and elimination of a substance (TK) and its effects on the organism (TD). The Reduced General Unified Threshold model of Survival (GUTS‐RED) is a TKTD modeling framework that is well established for aquatic risk assessment to simulate effects on survival.
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Faupel et al. (2023) Precision farming and environmental pesticide regulation in the EU—How does it fit together?
Precision farming technology allows pesticides to be applied precisely to the target while leaving the rest of the field untreated. In the regulation of pesticides, however, a homogeneously sprayed field is considered as the standard scenario.
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113 KB
Wittwer, Jakoby (2023) Evaluation of wind speed measurements published by th German Meteorological Service (DWD) for the years 2004 to 2020
Sowing of seeds treated with agrochemicals is common practice in agriculture. German regulatory authorities are requesting that seeds treated with plant protection products must not be sown at average hourly wind speeds exceeding 5 m/s (at 2 m above ground) unless the environmental risk assessment indicates a large margin of safety.
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1 MB
Singer, Nickisch, Gergs (2022) Joint survival modelling for multiple species exposed to toxicants
In environmental risk assessment (ERA), the multitude of compounds and taxa demands cross-species extrapolation to cover the variability in sensitivity to toxicants. However, only the impact of a single compound to a single species is addressed by the general unified threshold model of survival (GUTS).
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2 MB
Sur, Herrmann (2022) Determination of transfer factors for solute concentrations from agricultural fields to drinking water abstraction points
The stepwise attenuation of solute concentrations has been determined, starting from the unsaturated zone underneath treated fields across the deeper aquifer, down to drinking water abstraction wells. The partial or overall transfer or attenuation factor may help to make informed decisions on the magnitude of the decrease in concentrations from shallow leachate to drinking water abstraction, which is largely caused by mixing.
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Faupel et al. (2022) Precision farming and environmental pesticide regulation in the EU—How does it fit together?
Precision farming technology allows pesticides to be applied precisely to the target while leaving the rest of the field untreated. In the regulation of pesticides, however, a homogeneously sprayed field is considered as the standard scenario.
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113 KB
Herrmann, Sur (2021) Natural attenuation along subsurface flow paths based on modeling and monitoring of a pesticide metabolite from three case studies
Groundwater—especially for the use as drinking water—is a strictly protected resource in the existing guidelines for pesticide registration and drinking water protection in the EU.
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Klopper et al. (2020) How to reduce computation effort for GUTS modelling while retaining output reliability for risk assessment use?
The practicability of approaches can influence their usability in environmental risk assessment (ERA). The anticipated 20- year data in aquatic RA would considerably amplify computational effort and therefore pose a challenge for General Unified Threshold Model of Survival (GUTS) applications in ERA.
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667 KB
Lückmann et al. (2020) Precision pesticide application as a tool to reduced exposure of crop visiting pollinators?
Recent publications on severe declines of insects moved the topic of biodiversity in agricultural landscapes into the focus of public attention. Consequently, European policy is under increasing public pressure to minimize the amount of synthetic pesticides applied and to reform the criteria for their authorization and use.
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Ludwigs et al. (2019) Response to David R. Crocker and Steven D. Langton “When Is It Legitimate to Downplay Individual Differences?”
In their letter, Crocker and Langton (2019) critically discuss the approach of 21‐dMonte Carlo PT (portion of diet from a pesticidetreated area) simulations proposed in Ludwigs et al. (2017). The aim of this method is to assess realistic 21‐d PT values by including daily variability in habitat use for individual animals.
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