Two-week inhalation study in rats with cellulose fibers

This study was conducted to assess the pulmonary toxicity of inhaled cellulose fibers. Male rats were exposed to an aerosol of Thermocell mechanical wood pulp (Laxa Bruks AB, Rofors, Sweden) cellulose fibers for 2 weeks at target concentrations of 300 and 575 fibers/cc. Following exposures, the lungs of rats were evaluated 3 and 10 days, as well as 1 and 3 months postexposure by bronchoalveolar lavage (BAL); and immediately after, as well as 10 days, 1 and 3 months for biopersistence/clearance studies. The parameters that were evaluated were pulmonary clearance, retention and durability of inhaled cellulose fibers, pulmonary inflammation, as measured by bronchoalveolar lavage indices (cell differentials, acid LDH, protein, N-acetyl-glucosaminidase and alkaline phosphatase), and a BrdU method for cellular proliferation of airway and alveolar cells. The study is currently ongoing and has not been completed past the 3-month postexposure period. Two-week high-dose inhalation exposures to cellulose fibers produced lung burdens in the range of 3 x 10 E7 fibers. Clearance of cellulose fibers was moderate to slow with mean values in the high dose group of 2.84 x 10 E7 reduced to 1.55 x 10 E7 after 3 months postexposure. Preliminary data indicate that the median lengths of fibers recovered from digested lungs of exposed rats were the following: 13 mu m (2 week/0); 10 mu m(2 week/10D); 11 mu m (2 week/1M); and 10 mu m (2 week/3M). Using bronchoalveolar lavage techniques, it was demonstrated that inhaled cellulose fibers produced a mild but transient pulmonary inflammatory response, and this returned to control levels within 10 days postexposure. The interim results suggest that inhaled cellulose fibers have a slow clearance pattern but do not produce sustained pulmonary inflammatory effects.