An updated analysis of respiratory tract cells at risk for formaldehyde carcinogenesis

AbstractStudy of the mode of action (MOA) relating exposure to a given chemical with an associated adverse outcome is an iterative process with each iteration driven by new understandings of the relevant biology. Here, we revisit a previously described, MOA-based clonal growth model of the human respiratory tract cancer risk associated with formaldehyde inhalation. Changes reflect a better understanding of populations of cells at risk of carcinogenic transformation in the pharynx, larynx and respiratory bronchiolar portions of the human respiratory tract and inclusion of basal cells in the pool of cells at risk. The focus of this report is not on cancer risk per se, but rather on the sensitivity of model parameters and predicted risks to alternative descriptions of the fraction of cells at risk for carcinogenic transformation. For a population of formaldehyde-exposed nonsmokers, revised specification of cells at risk resulted in changes in both parameter estimates and in predicted risks. Compared to our p...