Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Skin Corrosion and Irritation

,

doi:10.1787/9789264274693-en

Cited by 9 publications

(2 citation statements)

References 47 publications

(92 reference statements)

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“…We selected three diverse and most commonly applied k 1 models for parametrizing the general IVIVE-BCF model in this study: (i) from Arnot and Gobas 2003 which is based on fish mass and K OW and is used as the default calculation in the Nichols et al IVIVE-BCF model; (ii) from Arnot et al 2008 which is a function of fish weight, water temperature, and K OW ; and (iii) the k 1 model from Sijm et al − which is a function of fish weight. The model (ii) from Arnot et al 2008 is a modification of “method 5” cited in Brooke et al and was recently applied successfully to derive BCFs from a dietary study by Chen et al The simple k 1 model from Sijm et al is described in the guidance document to OECD TG 305 to derive BCFs from dietary studies and is therefore used frequently.…”

Section: Methodsmentioning

confidence: 99%

Examining Uncertainty in In Vitro–In Vivo Extrapolation Applied in Fish Bioconcentration Models

Laue

Hostettler

Badertscher

et al. 2020

Environ. Sci. Technol.

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In vitro biotransformation rates were determined for 30 chemicals, mostly fragrance ingredients, using trout liver S9 fractions (RT-S9) and incorporated into in vitro–in vivo extrapolation (IVIVE) models to predict bioconcentration factors (BCFs). Predicted BCFs were compared against empirical BCFs to explore potential major uncertainties involved in the in vitro methods and IVIVE models: (i) in vitro chemical test concentrations; (ii) different gill uptake rate constant calculations (k 1); (iii) protein binding (different calculations and measurement of the fraction of unbound chemical, f U); (iv) species differences; and (v) extrahepatic biotransformation. Predicted BCFs were within 0.5 log units for 44% of the chemicals compared to empirical BCFs, whereas 56% were overpredicted by >0.5 log units. This trend of overprediction was reduced by alternative k 1 calculations to 32% of chemicals being overpredicted. Moreover, hepatic in vitro rates scaled to whole body biotransformation rates (k B) were compared against in vivo k B estimates. In vivo k B was underestimated for 79% of the chemicals. Neither lowering the test concentration, nor incorporation of new measured f U values, nor species matching avoided the tendency to overpredict BCFs indicating that further improvements to the IVIVE models are needed or extrahepatic biotransformation plays an underestimated role.

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Section: Methodsmentioning

confidence: 99%

Examining Uncertainty in In Vitro–In Vivo Extrapolation Applied in Fish Bioconcentration Models

Laue

Hostettler

Badertscher

et al. 2020

Environ. Sci. Technol.

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“…27 Moreover, OECD strives toward integration of knowledge into Integrated Approaches for Testing and Assessment (IATA), providing practical approaches for combining mechanistic assays to predict toxic effects. 28,29 The AOP paradigm has its merits and limitations. It rightly focuses attention to mode of action and mechanistic aspects of chemical toxicity, facilitating judgment about the relevance of findings for the human situation.…”

Section: Applications Of Ontologiesmentioning

confidence: 99%

Advanced Toxicological Risk Assessment by Implementation of Ontologies Operationalized in Computational Models

StaalYvonne

PenningsJeroen

HesselEllen

et al. 2017

Applied In Vitro Toxicology

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Given tremendous progress in biology, toxicology, and chemistry knowledge in recent decades, the time is right for serious consideration of options to move away from animal experimentation in chemical hazard and risk assessment. Individual alternative and animal-free assays as a replacement of individual animal studies have met with understandable reluctance in the scientific and regulatory arenas. An integrated conceptual approach based on mechanistic information built from all available information on biology, chemistry, and mechanisms of toxicity, might allow sufficient coverage of the biological system to provide the basis for reliable animal-free chemical hazard and risk assessment for man. We describe construction of an ontology, which can be considered a network of adverse outcome pathways, including feedback loops representing homeostasis. Basic elements in the ontology are subjects (such as enzymes, receptors, and cell types) and their quantitative relationships (response-response relationships), together forming a multidimensional network of biological interactions. This network can be modeled in silico, providing an integrated system toxicology computational model with which toxicity predictions can be made at the level of adverse outcomes in the intact individual. The model will indicate critical rate-determining steps in the network that can be monitored in a battery of dedicated in vitro assays, providing a testing strategy to collect data feeding into the systems model. Connecting this integrated dynamic model with exposure models allows quantitative hazard and risk assessment for man, avoiding animal experiments.

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Towards a tiered test strategy for plant protection products to address mixture toxicity by alternative approaches in human health assessment

Bloch

Marx‐Stoelting

Martin

2020

Pest Management Science

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Plant protection products (PPPs) consist of pesticide active substances and co‐formulants. Generally, active substance effects are assumed to dominate in PPP toxicity. Nevertheless, co‐formulants may well affect the toxicity of PPPs via toxicodynamic and toxicokinetic interaction. To account for potential mixture effects and improve PPP data requirements for application in risk assessment, a tiered test strategy is proposed. The strategy is based on a comparison of PPP and active substance toxicity, which enables the prioritisation of PPPs for further testing, adaptation of the toxicological threshold value or removal of toxic co‐formulants from the PPP. Moreover, it focuses on the integrative assessment of existing information and newly generated data using alternative test methods. The proposed strategy will improve PPP toxicological assessment by accounting for mixture toxicity, providing a set of regulatory options for risk assessment and the necessary data for hazard assessment. The predictivity of alternative methods for PPPs will improve by evaluation of their reliability and uncertainty. © 2020 The Authors. Pest Management Science published by JohnWiley & Sons Ltd on behalf of Society of Chemical Industry.

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Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Skin Corrosion and Irritation

Cited by 9 publications

References 47 publications

Examining Uncertainty in In Vitro–In Vivo Extrapolation Applied in Fish Bioconcentration Models

Examining Uncertainty in In Vitro–In Vivo Extrapolation Applied in Fish Bioconcentration Models

Advanced Toxicological Risk Assessment by Implementation of Ontologies Operationalized in Computational Models

Towards a tiered test strategy for plant protection products to address mixture toxicity by alternative approaches in human health assessment

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