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Association of adrenal pheochromocytoma and lung pathology in inhalation studies with particulate compounds in the male F344 rat--the National Toxicology Program experience.

Abstract：

:Systemic hypoxemia, occurring in space-occupying lung pathologies such as inflammation and neoplasms. reduces the gas exchange area and stimulates catecholamine secretion from the adrenal medulla where chronic endocrine hyperactivity may lead to hyperplasia and neoplasia. We investigated the possible correlation between nonneoplastic chronic pulmonary lesions and adrenal pheochromocytoma in 9 recent, NTP, 2-year particulate inhalation studies in male F344 rats. Re-evaluation for chronic active inflammation, interstitial fibrosis, alveolar epithelial hyperplasia, squamous metaplasia, proteinosis, and histiocytosis revealed significant associations of pheochromocytoma only with the severity of inflammation and fibrosis. Nickel oxide, cobalt sulfate, indium phosphide, talc, and nickel subsulfide studies showed chemical-related incidences of adrenal pheochromocytoma and significant (p < 0.01) associations with inflammation and fibrosis. Gallium arsenide, vanadium pentoxide, molybdenum trioxide, and nickel sulfate hexahydrate studies revealed an increased incidence and/or severity of nonneoplastic lung lesions, but no increased incidence of pheochromocytoma. Although gallium arsenide and molybdenum trioxide showed no dose-related increase in pheochromocvtoma, a significant (p < 0.01) correlation of the latter with the severity of fibrosis and inflammation occurred. In the vanadium pentoxide and nickel sulfate hexahydrate studies, no relationship between nonneoplastic lung lesions and pheochromocytoma was manifested. Our investigation assessed the strength of these various associations and supports the possible roles of 2 chronic pulmonary lesions-fibrosis and inflammation-and hypoxemia in the induction of pheochromocytoma in the F344 male rat.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Ozaki K,Haseman JK,Hailey JR,Maronpot RR,Nyska A

doi

10.1080/019262302753559605

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

263-70

issue

eissn

0192-6233

issn

1533-1601

journal_volume

pub_type

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Association of adrenal pheochromocytoma and lung pathology in inhalation studies with particulate compounds in the male F344 rat--the National Toxicology Program experience.