Martin, Olwenn V;
Martin, Scholze;
Andreas, Kortenkamp;
(2013)
Dispelling urban myths about default uncertainty factors in chemical risk assessment – sufficient protection against mixture effects?
Environmental Health
, 12
, Article 53. 10.1186/1476-069X-12-53.
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Abstract
Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment.
| Type: | Article |
|---|---|
| Title: | Dispelling urban myths about default uncertainty factors in chemical risk assessment – sufficient protection against mixture effects? |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/1476-069X-12-53 |
| Publisher version: | https://doi.org/10.1186/1476-069X-12-53 |
| Language: | English |
| Additional information: | © The Author(s), 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Acceptable daily intake, Extrapolation, Hazard assessment, Mixture, Risk assessment, |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL SLASH UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities > Arts and Sciences (BASc) |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10197305 |
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