Dose-response analysis of growth curves for rodents exposed to inorganic mercury salts
In toxicology, dose-response analysis seeks the calculation of a benchmark dose (BMD) and benchmark dose lower (BMDL) bound as a point-of-departure (POD) where statistically significant exposure-related change would be observed. While dose-response analysis of single or multivariate endpoints have been well-studied, little exploration has been done on functional responses, such as growth curves. Paradigm analysis involves analysis of endpoints from the final timepoint, but this approach ignores information and reduces power. We developed a novel approach based on functional data analysis, treating the growth curves as exposure-related responses. We derive BMDs and BMDLs for this approach using linear dose-response of growth rates. We compared approaches using an example dataset on developmental body weights in Wistar rats exposed to mercuric chloride. Our analysis yielded a lower BMDL than the paradigm analysis, emphasizing greater sensitivity to detect endpoint POD.