How to evaluate the quality of toxicokinetic-Toxicodynamic models in the context of environmental risk assessment

TY - JOUR

T1 - How to evaluate the quality of toxicokinetic-Toxicodynamic models in the context of environmental risk assessment

AU - Jager, Tjalling

AU - Ashauer, Roman

N1 - ©2018 SETAC. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2018/9

Y1 - 2018/9

N2 - Environmental risk assessment (ERA) of chemicals relies on the combination of exposure and effects assessment. Exposure concentrations are commonly estimated using mechanistic fate models, but the effects side is restricted to descriptive statistical treatment of toxicity data. Mechanistic effect models are gaining interest in a regulatory context, which has also sparked discussions on model quality and good modeling practice. Proposals for good modeling practice of effect models currently focus very much on population and community models, whereas effects models also exist at the individual level, falling into the category of toxicokinetic-toxicodynamic (TKTD) models. In contrast to the higher-level models, TKTD models are usually completely parameterized by fitting them to experimental data. In fact, one of their explicit aims is to replace descriptive methods for data analysis. Furthermore, the construction of these models does not fit into an orderly modeling cycle, given that most TKTD models have been under continuous development for decades and are being applied by many different research groups, for many different purposes. These aspects have considerable consequences for the application of frameworks for model evaluation. For example, classical sensitivity analysis becomes rather meaningless when all model parameters are fitted to a data set. We illustrate these issues with the General Unified Threshold model for Survival (GUTS), relate them to the quality issues for currently used models in ERA, and provide recommendations for the evaluation of TKTD models and their analyses. Integr Environ Assess Manag 2018;00:000-000. ©2018 SETAC.

AB - Environmental risk assessment (ERA) of chemicals relies on the combination of exposure and effects assessment. Exposure concentrations are commonly estimated using mechanistic fate models, but the effects side is restricted to descriptive statistical treatment of toxicity data. Mechanistic effect models are gaining interest in a regulatory context, which has also sparked discussions on model quality and good modeling practice. Proposals for good modeling practice of effect models currently focus very much on population and community models, whereas effects models also exist at the individual level, falling into the category of toxicokinetic-toxicodynamic (TKTD) models. In contrast to the higher-level models, TKTD models are usually completely parameterized by fitting them to experimental data. In fact, one of their explicit aims is to replace descriptive methods for data analysis. Furthermore, the construction of these models does not fit into an orderly modeling cycle, given that most TKTD models have been under continuous development for decades and are being applied by many different research groups, for many different purposes. These aspects have considerable consequences for the application of frameworks for model evaluation. For example, classical sensitivity analysis becomes rather meaningless when all model parameters are fitted to a data set. We illustrate these issues with the General Unified Threshold model for Survival (GUTS), relate them to the quality issues for currently used models in ERA, and provide recommendations for the evaluation of TKTD models and their analyses. Integr Environ Assess Manag 2018;00:000-000. ©2018 SETAC.

KW - Journal Article

KW - TKTD

KW - Risk assessment

KW - Good modeling practice

KW - GUTS

KW - Model quality

KW - Environmental Monitoring/methods

KW - Toxicokinetics

KW - Ecotoxicology

KW - Models, Chemical

KW - Risk Assessment

KW - Environmental Pollutants/toxicity

UR - http://www.scopus.com/inward/record.url?scp=85051805570&partnerID=8YFLogxK

U2 - 10.1002/ieam.2026

DO - 10.1002/ieam.2026

M3 - Article

C2 - 29573552

SN - 1551-3777

VL - 14

SP - 604

EP - 614

JO - Integrated Environmental Assessment and Management

JF - Integrated Environmental Assessment and Management

IS - 5

ER -