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An Approach to Mechanism-based Cancer Risk Assessment for Formaldehyde

The established carcinogenicity of formaldehyde in the rat and suggestive epidemiological evidence that formaldehyde may be a human carcinogen have led to its regulation by U.S. Federal agencies as a probable human carcinogen. These risk assessments have typically been based on tumor data in F344 ra... Full description

Journal Title: Environmental Health Perspectives 1 December 1993, Vol.101, pp.169-176
Main Author: Conolly, Rory B.
Other Authors: Andersen, Melvin E.
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: JSTOR Sustainability
ID: ISSN: 00916765
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recordid: jstor_sus_journals4640371
title: An Approach to Mechanism-based Cancer Risk Assessment for Formaldehyde
format: Article
creator:
  • Conolly, Rory B.
  • Andersen, Melvin E.
subjects:
  • Health Effects of Selected Materials
ispartof: Environmental Health Perspectives, 1 December 1993, Vol.101, pp.169-176
description: The established carcinogenicity of formaldehyde in the rat and suggestive epidemiological evidence that formaldehyde may be a human carcinogen have led to its regulation by U.S. Federal agencies as a probable human carcinogen. These risk assessments have typically been based on tumor data in F344 rats exposed chronically to formaldehyde by inhalation and used the inhaled concentration as a measure of dose and the linearized multistage model (LMS) for dose-response characterization. Low-dose risks estimated with the LMS are thought to be conservative but are also generally acknowledged to be highly uncertain. In this manuscript, we first consider in generic terms how use of chemical-specific data on mechanisms of target tissue dosimetry and the series of tissue responses to the chemical that culminate in tumor formation can lead to more accurate dose-response characterization. A planned mechanism-based risk assessment for formaldehyde is then described. This risk assessment uses data on target tissue dosimetry, size of the target cell population in the rat nasal epithelium, number and size of putative preneoplastic lesions, and tumor incidence. These data establish parameter values for a biologically based, multistage cancer model that is then used to predict cancer risk at low exposure levels. Such work provides insights into the relative roles of formaldehydestimulated cell replication and procarcinogenic mutation in tumor formation. Finally, future directions are outlined for research on tissue dosimetry and scaling of the mechanism-based formaldehyde risk model from rats to people.
language: eng
source: JSTOR Sustainability
identifier: ISSN: 00916765
fulltext: fulltext_linktorsrc
issn:
  • 0091-6765
  • 00916765
url: Link


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titleAn Approach to Mechanism-based Cancer Risk Assessment for Formaldehyde
creatorConolly, Rory B. ; Andersen, Melvin E.
ispartofEnvironmental Health Perspectives, 1 December 1993, Vol.101, pp.169-176
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subjectHealth Effects of Selected Materials
descriptionThe established carcinogenicity of formaldehyde in the rat and suggestive epidemiological evidence that formaldehyde may be a human carcinogen have led to its regulation by U.S. Federal agencies as a probable human carcinogen. These risk assessments have typically been based on tumor data in F344 rats exposed chronically to formaldehyde by inhalation and used the inhaled concentration as a measure of dose and the linearized multistage model (LMS) for dose-response characterization. Low-dose risks estimated with the LMS are thought to be conservative but are also generally acknowledged to be highly uncertain. In this manuscript, we first consider in generic terms how use of chemical-specific data on mechanisms of target tissue dosimetry and the series of tissue responses to the chemical that culminate in tumor formation can lead to more accurate dose-response characterization. A planned mechanism-based risk assessment for formaldehyde is then described. This risk assessment uses data on target tissue dosimetry, size of the target cell population in the rat nasal epithelium, number and size of putative preneoplastic lesions, and tumor incidence. These data establish parameter values for a biologically based, multistage cancer model that is then used to predict cancer risk at low exposure levels. Such work provides insights into the relative roles of formaldehydestimulated cell replication and procarcinogenic mutation in tumor formation. Finally, future directions are outlined for research on tissue dosimetry and scaling of the mechanism-based formaldehyde risk model from rats to people.
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abstractThe established carcinogenicity of formaldehyde in the rat and suggestive epidemiological evidence that formaldehyde may be a human carcinogen have led to its regulation by U.S. Federal agencies as a probable human carcinogen. These risk assessments have typically been based on tumor data in F344 rats exposed chronically to formaldehyde by inhalation and used the inhaled concentration as a measure of dose and the linearized multistage model (LMS) for dose-response characterization. Low-dose risks estimated with the LMS are thought to be conservative but are also generally acknowledged to be highly uncertain. In this manuscript, we first consider in generic terms how use of chemical-specific data on mechanisms of target tissue dosimetry and the series of tissue responses to the chemical that culminate in tumor formation can lead to more accurate dose-response characterization. A planned mechanism-based risk assessment for formaldehyde is then described. This risk assessment uses data on target tissue dosimetry, size of the target cell population in the rat nasal epithelium, number and size of putative preneoplastic lesions, and tumor incidence. These data establish parameter values for a biologically based, multistage cancer model that is then used to predict cancer risk at low exposure levels. Such work provides insights into the relative roles of formaldehydestimulated cell replication and procarcinogenic mutation in tumor formation. Finally, future directions are outlined for research on tissue dosimetry and scaling of the mechanism-based formaldehyde risk model from rats to people.
pubNational Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare
date1993-12-01