Decreased pain sensitivity due to trimethylbenzene exposure: case study on quantitative approaches for hazard identification
Citation:
Davis, Allen AND A. Kraft. Decreased pain sensitivity due to trimethylbenzene exposure: case study on quantitative approaches for hazard identification. 4th International Symposium on Systematic Review and Meta-Analysis of Laboratory Animal Studies, Research Triangle Park, North Carolina, August 24 - 25, 2017.
Impact/Purpose:
Abstract for poster describing quantitative meta-analysis and meta-regression methods for hazard identification
Description:
Traditionally, human health risk assessments have relied on qualitative approaches for hazard identification, often using the Hill criteria and weight of evidence determinations to integrate data from multiple studies. Recently, the National Research Council has recommended the development of quantitative approaches for evidence integration, including the application of meta-analyses. The following hazard identification case study applies qualitative as well as meta-analytic approaches to trimethylbenzene (TMB) isomers exposure and the potential neurotoxic effects on pain sensitivity. In the meta-analytic approach, a pooled effect size is calculated, after consideration of multiple confounding factors, in order to determine whether the entire database under consideration indicates that TMBs are likely to be a neurotoxic hazard. The pain sensitivity studies included in the present analyses initially seem discordant in their results: effects on pain sensitivity are seen immediately after termination of exposure, appear to resolve 24 hours after exposure, and then reappear 50 days later following foot-shock. Qualitative consideration of toxicological and toxicokinetic characteristics of the TMB isomers suggests that the observed differences between studies are due to testing time and can be explained through a complete consideration of the underlying biology of the effect and the nervous system as a whole. Meta-analyses and –regressions support this conclusion: when all studies are included and possible confounders (isomer, testing time, laboratory, etc.) are accounted for, the pooled effect sizes are ≥ 0, thus indicating that TMBs are a possible neurotoxic hazard to human health. This case study demonstrates how traditional, qualitative hazard identification methods can be combined with quantitative methods to provide a more robust consideration of all relevant information for the purpose of hazard identification.