The use of surrogate endpoints to assess potential toxicity in humans
The use of surrogate endpoints to assess potential toxicity in humans
Data on toxic effects in humans may come from epidemiology studies, accidental poisonings, surveillance schemes or following intentional exposures. In many cases, a surrogate endpoint related to the adverse effect is investigated. Effects produced following intentional exposures are usually restricted to readily reversible, mild surrogate endpoints of the adverse effect of concern. Not all initial interactions within the target organ are related to the toxic effect, and many measurements are biomarkers of exposure not response. Biomarkers of response represent surrogate endpoints of response only if they are critical to the mode of action. The use of biomarkers and the possible problems with using surrogate endpoints are illustrated with data on aniline, cadmium, carbon monoxide, erythrosine, paracetamol (acetaminophen) and styrene. In vivo surrogate endpoints are normally used in risk assessment directly, whereas in vitro surrogate endpoints can be incorporated by the development of a biologically based dose–response model, or used to replace a default uncertainty factor by a chemical-specific adjustment factor.
toxicokinetics, toxicodynamics, risk assessment, biomarkers, uncertainty factor, cadmium, carbon monoxide, erythrosine, styrene
97-110
Renwick, Andrew G.
3a210ca8-de23-4dae-aa6c-c853a1651d19
Walton, Kim
b6e22017-f234-449b-a6f8-84a88fc05242
2001
Renwick, Andrew G.
3a210ca8-de23-4dae-aa6c-c853a1651d19
Walton, Kim
b6e22017-f234-449b-a6f8-84a88fc05242
Renwick, Andrew G. and Walton, Kim
(2001)
The use of surrogate endpoints to assess potential toxicity in humans.
Toxicology Letters, 120 (1-3), .
(doi:10.1016/S0378-4274(01)00288-0).
Abstract
Data on toxic effects in humans may come from epidemiology studies, accidental poisonings, surveillance schemes or following intentional exposures. In many cases, a surrogate endpoint related to the adverse effect is investigated. Effects produced following intentional exposures are usually restricted to readily reversible, mild surrogate endpoints of the adverse effect of concern. Not all initial interactions within the target organ are related to the toxic effect, and many measurements are biomarkers of exposure not response. Biomarkers of response represent surrogate endpoints of response only if they are critical to the mode of action. The use of biomarkers and the possible problems with using surrogate endpoints are illustrated with data on aniline, cadmium, carbon monoxide, erythrosine, paracetamol (acetaminophen) and styrene. In vivo surrogate endpoints are normally used in risk assessment directly, whereas in vitro surrogate endpoints can be incorporated by the development of a biologically based dose–response model, or used to replace a default uncertainty factor by a chemical-specific adjustment factor.
This record has no associated files available for download.
More information
Published date: 2001
Keywords:
toxicokinetics, toxicodynamics, risk assessment, biomarkers, uncertainty factor, cadmium, carbon monoxide, erythrosine, styrene
Identifiers
Local EPrints ID: 27352
URI: http://eprints.soton.ac.uk/id/eprint/27352
ISSN: 0378-4274
PURE UUID: 3a34cf02-65de-42bc-ad27-fcba4342db46
Catalogue record
Date deposited: 27 Apr 2006
Last modified: 15 Mar 2024 07:18
Export record
Altmetrics
Contributors
Author:
Andrew G. Renwick
Author:
Kim Walton
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics