Risk assessment future prospects

It is well recognised that the faecal bile acid content of random stool samples is highly variable with marked daily variation.Therefore, studies testing the association between luminal bile acid exposure and the presence of colorectal neoplasia have usually measured serum bile acid levels, which demonstrate less variability and are believed to reflect the total bile acid pool more accurately. Serum DCA levels have been shown to be higher in individuals with a colorectal adenoma compared with individuals without a neoplasm. Only one study has assessed future risk of CRC in a prospective study of serum bile-acid levels. The study was hampered by the small sample size (46 CRC cases). There were no significant differences in the absolute concentrations of primary and secondary bile acids or DCA/CA ratio between cases and controls although there was a trend towards increased CRC risk for those with a DCA/ CA ratio in the top third of values (relative risk 3.9 [95% confidence interval 0.9-17.0 = 0.1]). It will be important to test the possible utility of the DCA/ CA ratio as a CRC risk biomarker in larger, adequately powered studies. A recent study has demonstrated increased levels of allo-DCA and allo-LCA metabolites in the stool of CRC patients compared with healthy controls. ... 

Assessors should base their selection of methods on clearly defined decision criteria, and they need to communicate the results using clear and transparent language. This includes statements on the extrapolation issues that were considered but not addressed, and the magnitude and direction of the bias that may have been introduced by the extrapolation or lack thereof. In lower tiers and prospective risk assessment, this should lead to setting more appropriate UFs and ensure that lower tier approaches are more conservative than higher tier approaches. All this helps assessors to make informed decisions, on one hand, but it also allows the identification of future research needs, on the other hand, especially when methods are not available. 

Worth AP and Balls M (eds.) (2002) Alternative (non-animal) methods for chemicals testing Current status and future prospects. Chapter 3 The scientific basis of chemical risk assessment. Alternatives to Laboratory Animals ATLA 30(Suppl. 1) 21-25. 

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. 

Science policy issues and controversies underlie almost every aspect of cancer risk assessment. These policy issues are primarily a function of the scientific uncertainties inherent in risk assessment. As new scientific methods and data begin to fill in some of the data gaps and uncertainties in risk assessment, the role of policy will gradually recede, although there is no prospect of policy issues being mooted entirely in the foreseeable future. Moreover, the extent to which we substitute novel scientific data and models for preexisting policy inferences is itself an ongoing policy debate, as is the appropriate role of precaution and conservatism in risk assessment. 

As an alternative, the current paper presents an approach for analysis of aviation incidents that takes a multi-agent perspective, and is based on formal methods. The approach is an extension of the approach introduced in the work of Bosse and Mogles [4], which was in turn inspired by Blom, Bakker, Blanker, Daams, Everdij and Klompstra [1]. Whereas this approach mainly focuses on the analysis of existing accidents (also called accident analysis or retrospective analysis), the current paper also addresses analysis of potential future accidents (called risk analysis or prospective analysis). This is done by means of a multi-agent simulation framework that addresses both the behaviour of individual agents (operators, pilots) as well as their mutual communication, and interaction with technical systems. By manipulating various parameters in the model, different scenarios can be explored. Moreover, by means of automated checks of dynamic properties, these scenarios can be assessed with respect to their likelihood of the occurrence of accidents. The approach is illustrated by a case study on a runway incursion incident at a large European airport in 1995. 

There has been a welcome shift from the retrospective black spot engineering approach—where treatments are applied to sites (or lengths of road) with high casualty crash numbers—to the prospective approach of undertaking traffic safety risk assessments to identify sections with design, construction, or traffic management issues that may increase future crash probabilities. 

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