Characterization and reclassification of titanium dioxide-related pulmonary lesions.
OBJECTIVE
Using current diagnostic criteria, this work summarizes the microscopic review of 16 proliferative squamous lesions, previously diagnosed as cystic keratinizing squamous cell carcinoma, in the lungs of rats from a 2-year inhalation study with pigment-grade titanium dioxide particles.


METHODS
In the aftermath of two international pathology workshops designed, in part, to establish histological criteria for classifying pulmonary keratin lesions, these lesions were evaluated by four pathologists using current diagnostic criteria.


RESULTS
Unanimous agreement was reached as to the diagnosis of each of the lesions. Two of the lesions were diagnosed as squamous metaplasia and one as a poorly keratinizing squamous cell carcinoma. The remaining 13 lesions were diagnosed as non-neoplastic pulmonary keratin cysts.


CONCLUSIONS
These keratin cysts are a species-specific lesion that is unique to the rat lung under conditions of particle overload exposure.
Warheit
David B
DB
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714-0050, USA. david.b.warheit@usa.dupont.com
Frame
Steven R
SR
D000818:Animals; D003560:Cysts / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004391:Dust; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D019570:Inhalation Exposure; D007633:Keratins; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D018307:Neoplasms, Squamous Cell / Q000139:chemically induced / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D013045:Species Specificity; D014025:Titanium / Q000009:adverse effects*
D004391:Dust; C009495:titanium dioxide; D007633:Keratins; D014025:Titanium