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Citation
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HERO ID
1290666
Reference Type
Journal Article
Subtype
Review
Title
Review of the toxicity of chemical mixtures: Theory, policy, and regulatory practice
Author(s)
Mccarty, LS; Borgert, CJ
Year
2006
Is Peer Reviewed?
1
Journal
Regulatory Toxicology and Pharmacology
ISSN:
0273-2300
EISSN:
1096-0295
Volume
45
Issue
2
Page Numbers
119-143
Language
English
PMID
16701933
DOI
10.1016/j.yrtph.2006.03.004
Abstract
An analysis of current mixture theory, policy, and practice was conducted by examining standard reference texts, regulatory guidance documents, and journal articles. Although this literature contains useful theoretical concepts, clear definitions of most terminology, and well developed protocols for study design and statistical analysis, no general theoretical basis for the mechanisms and interactions of mixture toxicity could be discerned. There is also a poor understanding of the relationship between exposure-based and internal received dose metrics. This confounds data interpretation and limits reliable determinations of the nature and extent of additivity. The absence of any generally accepted classification scheme for either modes/mechanisms of toxic action or of mechanisms of toxicity interactions is problematic as it produces a cycle in which research and policy are interdependent and mutually limiting. Current regulatory guidance depends heavily on determination of toxicological similarity concluded from the presence of a few prominent constituents, assumed from a common toxicological effect, or presumed from an alleged similar toxic mode/mechanism. Additivity, or the lack of it, is largely based on extrapolation of existing knowledge for single chemicals in this context. Thus, regulatory risk assessment protocols lack authoritative theoretical underpinnings, creating substantial uncertainty. Development of comprehensive classification schemes for modes/mechanisms of toxic action and mechanisms of interaction is needed to ensure a sound theoretical foundation for mixture-related regulatory activity and provide a firm basis for iterative hypothesis development and experimental testing.
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IRIS
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Methylmercury
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