Benchmark dose modeling for epidemiological dose-response assessment using case-control studies.

Abstract

Following a previous article that focused on integrating epidemiological data from prospective cohort studies into toxicological risk assessment, this paper shifts the focus to case-control studies. Specifically, it utilizes the odds ratio (OR) as the main epidemiological measure, aligning it with the benchmark dose (BMD) methodology as the standard dose-response modeling approach to determine chemical toxicity values for regulatory risk assessment. A standardized BMD analysis framework has been established for toxicological data, including input data requirements, dose-response models, definitions of benchmark response, and consideration of model uncertainty. This framework has been enhanced by recent methods capable of handling both cohort and case-control studies using summary data that have been adjusted for confounders. The present study aims to investigate and compare the "effective count" based BMD modeling approach, merged with an algorithm used for converting odds ratio to relative risk in cohort studies with partial data information (i.e., the Wang algorithm), with the adjusted OR-based BMD analysis approach. The goal is to develop an adequate BMD modeling framework that can be generalized for analyzing published case-control study data. As in the previous study, these methods were applied to a database examining the association between bladder and lung cancer and inorganic arsenic exposure. The results indicate that estimated BMDs and BMDLs are relatively consistent across both methods. However, modeling adjusted OR values as continuous data for BMD estimation aligns better with established practices in toxicological BMD analysis, making it a more generalizable approach.