PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 14649752

An air quality data analysis system for interrelating effects, standards, and needed source reductions: Part 13--Applying the EPA Proposed Guidelines for Carcinogen Risk Assessment to a set of asbestos lung cancer mortality data.

Ralph I Larsen
View original source ↗Export metadata ↓

Abstract

The Clean Air Act Amendments of 1990 (CAAA-90) list 189 hazardous air pollutants (HAPs) for which "safe" ambient concentrations are to be determined. The primary purpose of this paper is to develop two mathematical models, lognormal and logarithmic, that effectively express excess lung cancer mortality as a function of asbestos concentration for an example set of data and also to suggest using these two models for additional HAPs. The secondary purpose of this paper is to calculate a "safe" asbestos concentration by first assuming a default linear extrapolation (to one excess death per million people, as specified for carcinogenic HAPs). The resulting "safe" concentration is an impossible-to-achieve 1/1000 of present background asbestos concentrations. A letter to the editor and a response in this Journal issue use additional asbestos data that suggest that the "safe" concentration should be about 730 times higher than first calculated here and that a default nonlinear extrapolation should be used instead, with the "safe" concentration proportional to the desired mortality level raised to the 0.39 power. These results suggest that the most important problem in setting a "safe" concentration for each carcinogenic HAP is to determine the correct nonlinear extrapolation to use for each HAP.

Explore related subjects

AsbestosEnvironmentEnvironmental ExposureEnvironmental MonitoringEnvironmental PollutionGuidelines as TopicHumansLung NeoplasmsModels, TheoreticalPublic HealthRisk AssessmentSafetyUnited StatesUnited States Environmental Protection AgencyJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ralph I Larsen. 2003. An air quality data analysis system for interrelating effects, standards, and needed source reductions: Part 13--Applying the EPA Proposed Guidelines for Carcinogen Risk Assessment to a set of asbestos lung cancer mortality data.. https://doi.org/10.1080/10473289.2003.10466308

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Assessing the combined effect of asbestos exposure and smoking on lung cancer: a Bayesian approach.

We review the literature on the combined association between lung cancer and two environmental exposures, asbestos exposure and smoking, and explore a Bayesian approach to assess evidence of interaction between the exposures. The meta-analysis combines separate indices of additive and multiplicative relationships and multivariate relative risk estimates. By making inferences on posterior probabilities we can explore both the form and strength of interaction. This analysis may be more informative than providing evidence to support one relation over another on the basis of statistical significance. Overall, we find evidence for a more than additive and less than multiplicative relation.

Asbestos↗
PubMed2007

Comparison of validity of assessment methods using indices of adjusted agreement.

For comparing the validity of rating methods, the adjusted kappa (S coefficient) and Yule's Y index are better than Cohen's kappa which is affected by marginal probabilities. We consider a validity study in which a subject is assessed as exposed or not-exposed by two competing rating methods and the gold standard. We are interested in one of the methods, which is closer in agreement with the gold standard. We present statistical methods taking correlations into account for comparing the validity of the rating methods using S coefficient and Y index. We show how the S coefficient and Yule's Y index are related to sensitivity and specificity. In comparing the two rating methods, the preference is clear when the inference is the same for both S and Y. If the inference using S differs from that using Y, then it is not obvious how to decide a preference. This may occur when one rating method is better than the other in sensitivity but not in specificity. Numerical examples for comparing asbestos-exposure assessment methods are illustrated.

Asbestos↗
PubMed2006

TNF-alpha inhibits asbestos-induced cytotoxicity via a NF-kappaB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis.

Asbestos is the main cause of human malignant mesothelioma (MM). In vivo, macrophages phagocytize asbestos and, in response, release TNF-alpha and other cytokines that contribute to carcinogenesis through unknown mechanisms. In vitro, asbestos does not induce transformation of primary human mesothelial cells (HM); instead, asbestos is very cytotoxic to HM, causing extensive cell death. This finding raised an apparent paradox: How can asbestos cause MM if HM exposed to asbestos die? We found that asbestos induced the secretion of TNF-alpha and the expression of TNF-alpha receptor I in HM. Treatment of HM with TNF-alpha significantly reduced asbestos cytotoxicity. Through numerous technical approaches, including chemical inhibitors and small interfering RNA strategies, we demonstrate that, in HM, TNF-alpha activates NF-kappaB and that NF-kappaB activation leads to HM survival and resistance to the cytotoxic effects of asbestos. Our data show a critical role for TNF-alpha and NF-kappaB signaling in mediating HM responses to asbestos. TNF-alpha signaling through NF-kappaB-dependent mechanisms increases the percent of HM that survives asbestos exposure, thus increasing the pool of asbestos-damaged HM that are susceptible to malignant transformation. Cytogenetics supported this hypothesis, showing only rare, aberrant metaphases in HM exposed to asbestos and an increased mitotic rate with fewer irregular metaphases in HM exposed to both TNF-alpha and asbestos. Our findings provide a mechanistic rationale for the paradoxical inability of asbestos to transform HM in vitro, elucidate and underscore the role of TNF-alpha in asbestos pathogenesis in humans, and identify potential molecular targets for anti-MM prevention and therapy.

Asbestos↗