A protocol to evaluate the fibrogenic potential of inhaled materials.
A protocol to provide a more rapid assessment of the fibrogenic potential of an inhaled particulate has been developed. Young rats are exposed nose-only for 6 h/day, 7 days a week for 28 days to a respirable aerosol of the test compound. After exposure the rats are kept for up to 1 year, followed by histopathological assessment of the lung. Interim sacrifices could allow an estimate of the rate and severity of the development of any fibrogenic lesion. The protocol has been evaluated for chrysotile asbestos, alpha-quartz and titanium dioxide using rats of both sexes and two different ages at first exposure. The results indicate that there are no significant differences in either the rate, type or extent of lesion provoked by a 28-day exposure period when compared with the more conventional 1-year exposure period studies. It can be concluded that neither sex nor age at first exposure cause any biologically significant differences in response, although young rats would be used in practice. Only one sex need be investigated. The protocol offers considerable benefits over conventional inhalation studies for fibrogenicity (where a 1-year exposure period followed by a further 1-year holding period is usual) by virtue of time, specificity (in the absence of continued exposure the development of any lesion can be studied free from initial inflammatory response) and cost, and could be incorporated into a standard subacute inhalation study design. The results obtained are also of more physiological relevance than studies based on intratracheal instillation.
Bennett
I P
IP
ICI PLC, Central Toxicology Laboratory, Macclesfield, UK.
Pigott
G H
GH
Isaacs
K
K
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001194:Asbestos / Q000633:toxicity; D017632:Asbestos, Serpentine; D001835:Body Weight / Q000187:drug effects; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000473:pathology; D011791:Quartz / Q000633:toxicity; D051381:Rats; D012137:Respiratory System / Q000473:pathology; D012822:Silicon Dioxide / Q000633:toxicity; D014025:Titanium / Q000633:toxicity
D000393:Air Pollutants; D017632:Asbestos, Serpentine; D001194:Asbestos; D011791:Quartz; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium