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Titolo:
Human interindividual variability in susceptibility to airborne particles
Autore:
Hattis, D; Russ, A; Goble, R; Banati, P; Chu, M;
Indirizzi:
Clark Univ, Marsh Inst, Worcester, MA 01610 USA Clark Univ Worcester MA USA 01610 iv, Marsh Inst, Worcester, MA 01610 USA US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA US EPA Washington DC USA 20460 ironm Assessment, Washington, DC 20460 USA
Titolo Testata:
RISK ANALYSIS
fascicolo: 4, volume: 21, anno: 2001,
pagine: 585 - 599
SICI:
0272-4332(200108)21:4<585:HIVIST>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
AIR-POLLUTION; BRONCHIAL RESPONSIVENESS; INHALED PARTICLES; DAILY MORTALITY; RESPIRATORY-TRACT; LUNG-FUNCTION; DEPOSITION; POPULATION; ASTHMA; DISTRIBUTIONS;
Keywords:
interindividual variability; particles; pharmacokinetics; pharmacodynamics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Social & Behavioral Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Hattis, D Clark Univ, Marsh Inst, 950 Main St, Worcester, MA 01610 USA Clark Univ 950 Main St Worcester MA USA 01610 ster, MA 01610 USA
Citazione:
D. Hattis et al., "Human interindividual variability in susceptibility to airborne particles", RISK ANAL, 21(4), 2001, pp. 585-599

Abstract

Part of the explanation for the persistent epidemiological findings of associations between mortality and morbidity with relatively modest ambient exposures to airborne particles may be that some people are much more susceptible to particle-induced responses than others. This study assembled a database of quantitative observations of interindividual variability in pharmacokinetic and pharmacodynamic parameters likely to affect particle response. The pharmacodynamic responses studied included data drawn from epidemiologic studies of doses of methacholine, flour dust, and other agents that induce acute changes in lung function. In general, the amount of interindividual variability in several of these pharmacodynamic response parameters was greater than the variability in pharmacokinetic (breathing rate, deposition,and clearance) parameters. Quantitatively the results indicated that humaninterindividual variability of breathing rates and major pharmacokinetic parameters-total deposition and tracheobronchial clearance-were in the region of Log(GSD) = 0.1 to 0.2 (corresponding to geometric standard deviations of 10(1)-10(2) or 1.26-1.58). Deposition to the deep lung (alveolar region)appeared to be somewhat more variable: Log(GSD) of about 0.3 (GSD of about2). Among pharmacodynamic parameters, changes in FEV1 in response to ozoneand metabisulfite (an agent that is said to act primarily on neural receptors in the lung) were in the region of Log(GSD) of 0.2 to 0.4. However, similar responses to methacholine, an agent that acts on smooth muscle, seemedto have still more variability (0.4 to somewhat over 1.0, depending on thetype of population studied). Similarly high values were suggested for particulate allergens. Central estimates of this kind of variability, and the close correspondence of the data to lognormal distributions, indicate that 99.9th percentile individuals are likely to respond at doses that are 150 to450-fold less than would be needed in median individuals. It seems plausible that acute responses with this amount of variability could form part of the mechanistic basis for epidemiological observations of enhanced mortality in relation to ambient exposures to fine particles.

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Documento generato il 29/02/20 alle ore 07:51:32