Animal models, health risk characterization

See also Ames Test Analytical Toxicology Animal Models Biomarkers, Human Health Epidemiology Good Laboratory Practices (GLP) In Vitro Test In Vivo Test Risk Assessment, Human Health Risk Characterization Toxicity, Acute Toxicity, Chronic Toxicity, Subchronic. 

Advances in the understanding of the immunobiology of skin sensitization have led to the establishment of predictive in vivo tests which not only identify sensitizing hazards but also characterize their potency. Recently, appreciation of the underlying biology has also resulted in the development of mechanistically based in vitro alternatives which offer the prospect of the replacement of current in vivo methods. Assays under active validation include the Direct Peptide Reactivity Assay (DPRA), the human Cell Line Activation Test (h-CLAT), and KeratinoSens. None of the methods have a sufficient level of accuracy or freedom from applicability domain limitations to allow them to act as a standalone replacement. Consequently, it will be necessary to consider how to deploy these assays, perhaps in combination and/or in a structured assessment of skin sensitization hazard, to ensure at least the same level of predictive accuracy as the in vivo methods. However, a challenge remains the capacity of these methods to provide potency information on skin-sensitizing chemicals has yet to be assessed. This is an essential requirement for future risk assessment without use of animal models if we are to retain the same level of human health protection that is currently delivered. 

Even the most sophisticated risk assessment has limitations. It involves numerous assumptions about both exposure and hazard. Exposure assessments typically reflect modeled concentrations or extrapolations from measured data. The degree of exposure by different individuals may vary, and their response can depend on factors such as general health, genetic predisposition, or other factors. Dose-response factors are typically extrapolated from animal studies and thus inherently introduce the imcertainty of relating the response of laboratory animals to that of humans or one of the many species in an ecosystem. The endpoints characterized may not include all of the potential effects for example, the potential for endocrine disruption has not been considered in many risk assessments and in fact standardized testing methods were not published until approximately 2007 or later [90]. And risk assessment tools only model relatively simple scenarios. They rarely account for exposure to multiple chemicals, or fully accoimt for the effects on a complex web of organisms in an ecosystem. 

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