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Title: Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK

Abstract

A diffusion model predicts that highly lipophilic toxicants penetrate the comparatively thick epithelium of the conducting airways much more slowly than less lipophilic toxicants. To validate this model, the tracheal walls of a Beagle dog were sprayed with very small quantities of tritiated, highly lipophilic benzo(a)pyrene (BaP), moderately lipophilic pyrene, or slightly lipophilic 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone-(NNK). The concentration of the hydrocarbons and their metabolites were measured in the circulating blood for up to 6 hr, and tissue retention was determined at the end of the experiment. Differences in absorption of these compounds into blood were manifested in several independent measurements. The highly lipophilic toxicant manifested: (1) a much slower penetration into azygous vein blood, the principal drainage system from the exposed area of the trachea; (2) a much slower appearance in the systemic circulation and (3) a much greater retention in the tracheal tissues at the end of the exposure. Increased retention mm in the airway mucosa allowed a grew fraction of lipophilic toxicants to be metabolized locally in the airway walls. This finding led us to conclude that, for example, if the carcinogens BaP and NNK are deposited at the same surface density on the airway mucosa, the highly lipophilicmore » BaP will reach a far higher concentration in the airway epithelium than will the less lipophilic NNK. Such sharp differences in local dosimetry should be considered in order to improve the accuracy of risk assessment models for inhalants.« less

Authors:
; ;  [1]
  1. Inhalation Toxicology Research Inst., Albuquerque, NM (United States); and others
Publication Date:
OSTI Identifier:
538963
Report Number(s):
CONF-960807-
TRN: 97:004029-0030
Resource Type:
Conference
Resource Relation:
Conference: 212. national meeting of the American Chemical Society (ACS), Orlando, FL (United States), 25-30 Aug 1996; Other Information: PBD: 1996; Related Information: Is Part Of 212th ACS national meeting; PB: 1830 p.
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; BENZOPYRENE; TOXICITY; BLOOD; CARCINOGENS; DOSIMETRY; EPITHELIUM; HYDROCARBONS; METABOLITES; RISK ASSESSMENT; TRACHEA; BEAGLES

Citation Formats

Dahl, A R, Muggenburg, B A, and Thornton-Manning, J R. Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK. United States: N. p., 1996. Web.
Dahl, A R, Muggenburg, B A, & Thornton-Manning, J R. Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK. United States.
Dahl, A R, Muggenburg, B A, and Thornton-Manning, J R. 1996. "Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK". United States.
@article{osti_538963,
title = {Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK},
author = {Dahl, A R and Muggenburg, B A and Thornton-Manning, J R},
abstractNote = {A diffusion model predicts that highly lipophilic toxicants penetrate the comparatively thick epithelium of the conducting airways much more slowly than less lipophilic toxicants. To validate this model, the tracheal walls of a Beagle dog were sprayed with very small quantities of tritiated, highly lipophilic benzo(a)pyrene (BaP), moderately lipophilic pyrene, or slightly lipophilic 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone-(NNK). The concentration of the hydrocarbons and their metabolites were measured in the circulating blood for up to 6 hr, and tissue retention was determined at the end of the experiment. Differences in absorption of these compounds into blood were manifested in several independent measurements. The highly lipophilic toxicant manifested: (1) a much slower penetration into azygous vein blood, the principal drainage system from the exposed area of the trachea; (2) a much slower appearance in the systemic circulation and (3) a much greater retention in the tracheal tissues at the end of the exposure. Increased retention mm in the airway mucosa allowed a grew fraction of lipophilic toxicants to be metabolized locally in the airway walls. This finding led us to conclude that, for example, if the carcinogens BaP and NNK are deposited at the same surface density on the airway mucosa, the highly lipophilic BaP will reach a far higher concentration in the airway epithelium than will the less lipophilic NNK. Such sharp differences in local dosimetry should be considered in order to improve the accuracy of risk assessment models for inhalants.},
doi = {},
url = {https://www.osti.gov/biblio/538963}, journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Dec 31 00:00:00 EST 1996},
month = {Tue Dec 31 00:00:00 EST 1996}
}

Conference:
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