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Citation
Tags
HERO ID
4452957
Reference Type
Journal Article
Title
An updated analysis of respiratory tract cells at risk for formaldehyde carcinogenesis
Author(s)
Miller, FJ; Conolly, RB; Kimbell, JS
Year
2017
Is Peer Reviewed?
Yes
Journal
Inhalation Toxicology
ISSN:
0895-8378
EISSN:
1091-7691
Volume
29
Issue
12-14
Page Numbers
586-597
Language
English
PMID
29405084
DOI
10.1080/08958378.2018.1430191
Web of Science Id
WOS:000425698700008
Abstract
Study 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 previous assessment, predicted additional risks were up to 87% greater at exposure levels ≤1 ppm, but up to about 130% lower at high exposure levels (2-5 ppm). While this work should not be considered an update to MOA-based risk assessments for formaldehyde described previously, it illustrates the sensitivity of parameter estimates and risk predictions to the quantitative specification of cells at risk of carcinogenic transformation and, therefore, the motivation for describing the relevant biology as accurately as possible.
Keywords
Formaldehyde carcinogenesis; humans; dosimetry; progenitor cells
Tags
IRIS
•
Formaldehyde
HAWC
Asthma
Excluded
Human cancer
Excluded
Respiratory tract cancer animal
Excluded
Respiratory tract cancer mechanistic
Met PECO
Possibly impactful
Search Update 2016-2017
Animal UR Cancer Studies
WoS
Asthma and Immune effects Immune Section
PubMed
Exposure
WoS
Search Update 2018-2021
Human cancer studies
PubMed
UR Cancer MOA
PubMed
2017-2018 LitSearch
Animal UR Cancer Studies
Search Update
WOS
Exposure
Search Update
WOS
Immune Section
Pubmed
Search Update
UR Cancer MOA
Pubmed
Search Update
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