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KMID : 1034820160120030313
Molecular & Cellular Toxicology
2016 Volume.12 No. 3 p.313 ~ p.325
Subchronic inhalation toxicity study of 3R4F reference cigarette smoke in rats
Choi Seong-Jin

Lee Sang-Hyub
Lee Sang-Jin
Yang Mi-Jin
Lee Kyu-Hong
Abstract
This study aimed to investigate the subchronic exposure toxicity of smoke from 3R4F reference cigarettes. Male and female Sprague-Dawley rats were exposed to cigarette smoke at total particulate matter (TPM) concentrations of 50, 100, or 200 ¥ìg/L for a period of 13 weeks. Body weight gain of male rats significantly decreased upon exposure to 200 ¥ìg TPM/L of smoke. All smoke-exposed groups showed increase in blood carboxyhemoglobin, urinary nicotine and its metabolites, and inflammatory cytokines relative to the control group. Increased alveolar macrophages, pigmented and thickened alveolar walls, and hypertrophy/hyperplasia were observed in the lungs at concentrations above 50 ¥ìg TPM/L. These changes were related to the increase in absolute or relative lung weights. Histopathological examination revealed cigarette smoke-related changes in the nasal cavity, larynx, and trachea. The respiratory tract was adversely affected by inhalation of cigarette smoke. We identified that blood carboxyhemoglobin, urinary nicotine and its metabolites were tobacco-specific biomarkers, and suggested that CXCL1, CCL2, IL-1¥â, IL-10, TIMP-1, TIMP-2 were useful biomarkers for cigarette smoke. These results may serve as reference data to compare toxicity of tobacco products.
KEYWORD
Cigarette smoke, 3R4F reference cigarette, Inhalation toxicity, Carboxyhemoglobin, Nicotine, Nicotine metabolites, Inflammatory cytokines, ISO, GLP, OECD
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