Annals of Occupational Hygiene Advance Access originally published online on March 24, 2005
Annals of Occupational Hygiene 2005 49(6):461-472; doi:10.1093/annhyg/mei012
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© 2005 British Occupational Hygiene Society Published by Oxford University Press
Original Article |
Titanium Dioxide: Inhalation Toxicology and Epidemiology
1 Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK; 2 ICI Group Headquarters North West Group Safety, Security, Health and Environment, PO Box 13, The Heath Runcorn, Cheshire WA7 4QF, UK; 3 Environmental Management Services, Bushey Flatt Farm, Newlandside, Stanhope, Co Durham DL13 2PP, UK
* Author to whom correspondence should be addressed. Tel: +44 1625 514559; fax: +44 1625 590249; e-mail: paul.hext{at}syngenta.com
Titanium dioxide (TiO2) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO2, but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO2 and a similarly limited amount of epidemiological information with respect to TiO2 exposure in the workplace, a consortium of TiO2 manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO2 and to conduct detailed epidemiological surveys of the major manufacturing sites. The toxicology studies exposed rats, mice and hamsters to pigment-grade TiO2 (PG-TiO2, 0, 10, 50 and 250 mg m–3) or ultrafine TiO2 (UF-TiO2, 0, 0.5, 2 and 10 mg m–3) for 90 days and the lung burdens and tissue responses were evaluated at the end of the exposure period and for up to 1 year after exposure. Results demonstrated clear species differences. Rats and mice had similar lung burdens and clearance rates while hamsters showed high clearance rates. At high lung particle burdens, rats showed a marked progression of histopathological lesions throughout the post-exposure period while mice and hamsters showed minimal initial lesions with recovery apparent during the post-exposure period. Lung neutrophil responses, a sensitive marker of inflammatory changes, reflected the development or recovery of the histopathological lesions. The use of surface area rather than gravimetric lung burden provided closer correlates of the burden to the biological effect across both TiO2 types. The epidemiological investigations evaluated the mortality statistics at 11 European and 4 US TiO2 manufacturing plants. They concluded that there was no suggestion of any carcinogenic effect associated with workplace exposure to TiO2.
Keywords: epidemiology • inhalation • titanium dioxide • toxicology
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