Citation:

Farrar, D., T. Blessinger, Allen Davis, Jeff Gift, M. Wheeler, AND Lily Wang. BMD Analysis of Multiple Endpoints in Human Health Risk Assessment: Chloroprene Case Study. Society of Environmental Toxicology and Chemistry Europe Annual Meeting, Dublin, IRELAND, April 30 - May 04, 2023.

Impact/Purpose:

 Due to the challenges in utilizing current BMD methods to analyze and interpret toxicity data with multiple outcomes and complex relationships for risk assessment, such as wide ranges and high variability resulting from analysis of a single endpoint at a time, there is an increasing interest and need for the development of advanced BMD for integrated analysis of multiple outcomes simultaneously in a single analysis. To promote scientific exchanges and communications on BMD method development and application, 2023 European SETAC has organized a session focusing on “Advanced Multivariate Benchmark Dose (BMD) Approach for the Application of High-throughput Toxicology Data to Chemical Risk Assessment”, and I have been selected as the primary chair to host session and present as well. The major goal of this session is to present advanced and effective multivariate BMDs that can simultaneously model all the dose-response data obtained from an in vivo traditional animal study or in vitro high throughput toxicity screening in a single analysis for more robust data analysis results and valuable biological and toxicological information to support risk assessment decision-making. As a professional in the fields of environmental toxicity data analysis and human health risk assessment, I would like to take this great opportunity to learn new techniques and methods and advances in the fields to expand my knowledge and skills and find solutions to the problems we are facing in the current research, such as HERA for advanced multivariate BMD modeling approach I am currently leading. The conference will also give me the opportunity to talk to conference scientist one-on-one for their advice on how to enhance our own work. I will have the opportunity to ask presenters and session participants questions about their work and the rationale behind it, which I can’t do when reading journal articles  

Description:

Human health risk assessment often evaluates multiple endpoint variables in order to form a comprehensive picture of the toxicity effects of an environmental chemical or toxicant. Benchmark dose (BMD) modeling is a flexible method that takes the shape of the dose-response curve and important measures of uncertainty and variability in the data into account. While BMD modeling is an improvement over previous (e.g., NOAEL) methods, existing BMD models are designed to evaluate single or independent endpoints, not multiple related endpoints simultaneously. Therefore, development of an advanced BMD approach for efficient analysis of multiple related endpoints could be beneficial to risk assessment. This presentation will present our research in univariate, ordinal and multivariate analysis of multiple endpoints including simultaneous analysis of multiple correlated endpoints using environmental chemical toxicity data. Our results demonstrate that multivariate BMD approaches produced comparable and stable BMDLs in a single analysis, with less variability and more robust estimation of adverse health outcomes. In addition, this presentation will also include the major approaches that are currently used in multivariate modeling of multiple endpoints for human health risk assessment, and the challenges in applying these models, such as model choice and model averaging, clustered, Bayesian versus likelihood or frequentist methods, and the analysis of aggregate versus individual data.    (The information in this Abstract has been subjected to review by the Center for Public Health and Environmental Assessment and approved for presentation.  Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.)

Record Details: