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Inhaled particles and lung cancer, part B: Paradigms and risk assessment
Author(s) -
Borm Paul J.A.,
Schins Roel P.F.,
Albrecht Catrin
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20064
Subject(s) - lung cancer , carcinogen , medicine , lung , toxicity , inhalation exposure , inhalation , inflammation , fibrosis , pathology , immunology , physiology , toxicology , chemistry , biology , biochemistry , anesthesia
Abstract Poorly soluble particles of low toxicity (PSP), such as CB, TiO 2 and coal mine dust, have been demonstrated to cause lung cancer in rodents, being most pronounced in rats. Adequate epidemiologic studies do not clearly indicate increased lung cancer rates in humans exposed to such particles. This has caused controversial positions in regulatory decisions on PSP on different levels. The present review discusses the current paradigms in rodent particle carcinogenicity, i.e., ( i ) role of particle overload and of persistent inflammation and ( ii ) fibrosis as an intermediate step in particle‐induced lung cancer with regard to human risk assessment. Fibrosis, which is usually considered a precursor of lung cancer in humans, was not related to lung tumors in an animal study using 6 different particles, each at 3 dosages. Lung tumors after both inhalation and intratracheal instillation of PSP are related to particle surface dose, which forwards hazard assessment at surface‐based nonoverload concentrations and a standard setting using surface as an exposure metric. The scarce data available on humans do not support the overload concept but suggest a role for persistent lung inflammation. Differences in antioxidant protection between different rodent species correlate with susceptibility to PSP‐induced carcinogenicity and support the need for detailed studies on antioxidant response in humans. Apart from such bridging studies, further focus is also needed on surface chemistry and modifications in relation to their adverse biologic effects. © 2004 Wiley‐Liss, Inc.