Title
A mode-of-action ontology model for safety evaluation of chemicals: Outcome of a series of workshops on repeated dose toxicity
Author
Desprez, B.
Birk, B.
Blaauboer, B.
Boobis, A.
Carmichael, P.
Cronin, M.T.D.
Curie, R.
Daston, G.
Hubesch, B.
Jennings, P.
Klaric, M.
Kroese, D.
Mahony, C.
Ouédraogo, G.
Piersma, A.
Richarz, A.N.
Schwarz, M.
van Benthem, J.
van de Water, B.
Vinken, M.
Publication year
2019
Abstract
Repeated dose toxicity evaluation aims at assessing the occurrence of adverse effects following chronic or repeated exposure to chemicals. Non-animal approaches have gained importance in the last decades because of ethical considerations as well as due to scientific reasons calling for more human-based strategies. A critical aspect of this challenge is linked to the capacity to cover a comprehensive set of interdependent mechanisms of action, link them to adverse effects and interpret their probability to be triggered in the light of the exposure at the (sub)cellular level. Inherent to its structured nature, an ontology addressing repeated dose toxicity could be a scientific and transparent way to achieve this goal. Additionally, repeated dose toxicity evaluation through the use of a harmonized ontology should be performed in a reproducible and consistent manner, while mimicking as accurately as possible human physiology and adaptivity. In this paper, the outcome of a series of workshops organized by Cosmetics Europe on this topic is reported. As such, this manuscript shows how experts set critical elements and ways of establishing a mode-of-action ontology model as a support to risk assessors aiming to perform animal-free safety evaluation of chemicals based on repeated dose toxicity data. © 2019
Subject
Adverse outcome pathway
Mode-of-action
Ontology model
Repeated dose toxicity
Cosmetic
Adverse outcome
Biotransformation
Chemical parameters
Chemical structure
Cytotoxicity
Exposure
Human
Kinetics
Metabolism
Mode of action
Nonhuman
Note
Ontology
Organ distribution
Physical chemistry
Repeated dose toxicity
Safety
Toxicity testing
Toxicology
Workflow
To reference this document use:
http://resolver.tudelft.nl/uuid:fdd36fee-f5b2-4ab3-93cf-903c1fa866b4
DOI
https://doi.org/10.1016/j.tiv.2019.04.005
TNO identifier
866701
ISSN
8872-333
Document type
article