Application of General Unified Threshold Models of Survival Models for Regulatory Aquatic Pesticide Risk Assessment Illustrated with an Example for the Insecticide Chlorpyrifos

Abstract

Mathematical models within the General Unified Threshold models of Survival (GUTS) framework translate time-variable chemical exposure information into expected survival of animals. The GUTS models are species and compound specific and explicitly describe the internal exposure dynamics in an organism (toxicokinetics) and the related damage and effect dynamics (toxicodynamics), thereby connecting the external exposure concentration dynamics with the simulated mortality or immobility over time. In a recent scientific opinion on toxicokinetic-toxicodynamic (TKTD) models published by the European Food Safety Authority (EFSA), the GUTS modeling framework was considered ready for use in the aquatic risk assessment for pesticides and aquatic fauna. The GUTS models are suggested for use in risk assessment, if they are sufficiently validated for a specific substance-species combination. This paper aims to illustrate how they can be used in the regulatory environmental risk assessment for pesticides for a specific type of refinement, that is, when risks are triggered by lower tiers in acute as well as in chronic risk assessment and mortality or immobility is the critical endpoint. This approach involves the evaluation of time-variable exposure regimes in a so-called "Tier-2C" assessment. The insecticide chlorpyrifos was selected as an example compound because a large data set was available. The GUTS models for 13 different freshwater arthropods and 8 different theoretical aquatic exposure profiles were used to calculate a series of GUTS-based risk estimates, including exposure profile-specific multiplication factors leading to 50% mortality or immobility at the end of the tested profile (LP50/EP50) as "margins of safety." To put the use of GUTS models within the tiered aquatic risk assessment into perspective, GUTS models for the 13 aquatic arthropods were also used to predict the environmental risks of a measured chlorpyrifos exposure profile from an experimental ditch study (Tier-3 approach), and the results are discussed in the context of calibration of the tiered approach. Integr Environ Assess Manag 2020;00:1-16.

Application of General Unified Threshold Models to Predict Time-Varying Survival of Mayfly Nymphs Exposed to Three Neonicotinoids

“…Both the present study and the study by Focks et al [9] stress the need to shed better light on the applicability of (eventually adapted) GUTS models for implementation in regulatory risk assessments of neonicotinoids. Such studies should also account for the various parameters that are known to influence the modeling results, such as differences in the test compounds, experimental durations, and test species, including their size/sensitive life stage and sex [13,17,40], as well as the influence of pesticide mixtures on the predicted toxicity [41]. Huang et al [40], for example, demonstrated that females of the aquatic sowbug Asellus aquaticus were less sensitive to imidacloprid than males.…”

“…For example, TKTD models from the family of General Unified Threshold models of Survival (GUTS) enable estimating survival probabilities for any time-variable exposure profile [15,16]. GUTS modeling results are species-and compound-specific and explicitly describe the internal exposure dynamics in an organism (toxicokinetics) and the related damage and effect dynamics (toxicodynamics), thereby connecting the external exposure concentration dynamics with the simulated mortality or immobility over time [17].…”

“…Indeed, Focks et al [9] reported that GUTS predictions based on acute exposure to the neonicotinoids thiacloprid and thiamethoxam were underpredicting the actual effects of the pulsed exposure of these pesticides on the survival of macroinvertebrates. This thus warrants additional validation studies of the GUTS for a representative number of substances differing in exposure dynamics and toxic modes of action, with special emphasis on compounds with the potential to show increased toxicity under long-term exposure, such as neonicotinoids [9,[17][18][19]. Neonicotinoids also receive special attention because they have been reported to affect the mobility and survival of aquatic mayfly nymphs already at low concentrations [20][21][22][23].…”

A meta-analysis of ecotoxicological models used for plant protection product risk assessment before their placing on the market

“…In our collection, issues regarding model reliability were pointed out for one case of population and community model. While being more recently developed (Jager et al, 2011;Kooijman, 2009), TKTD models such as GUTS and DEBtox models are of high interest for ERA (Brock et al, 2021;EFSA PPR Panel, 2018a). They are ready to use in practice in a regulatory context for few organisms like aquatic macroinvertebrates, fish and macrophytes, and their potential is mentioned for other organisms like non-target arthropods (EFSA PPR Panel, 2015a).…”

Taking full advantage of modelling to better assess environmental risk due to xenobiotics—the all-in-one facility MOSAIC

“…The TD part makes the link between damages suffered by organisms due to internal bioaccumulated concentrations with observable effects on life history traits such as an increased mortality or a reduced growth. Combined TKTD models are recommended by EFSA to refine Tier-2 risk assessment, especially for plant protection products acting on aquatic organisms when exposed to time-variable exposure profiles (European Commission, 2013;Ockleford et al, 2018;Brock et al, 2020). In particular, the EFSA already considers ready-to-use for ERA the TKTD models dedicated to the prediction of survival over time, and the EFSA encourages more research for the other types of TKTD models, namely those based on the Dynamic Energy Budget (DEB) theory for growth and reproduction of ec-totherm species and those for macrophytes.…”