CELLULAR BIOLOGICAL EFFECTS AND A SINGLE TRANSTRACHEAL INJECTION TESTIN 3 TYPES OF WHISKER FIBERS

Recently, various kinds of asbestos substitutes have been used over a wide range of industrial applications. The dimensions of whisker fiber s are similar to some forms of asbestos, thus raising the concern of p otential health effects for workers exposed in occupational environmen ts. In this experiment, we compared the in vitro activity in cellular assays and the in vivo activity, hocusing on lung inflammatory and fib rotic effects by a single transtracheal injection test among three wel l-characterized whisker fibers. The geometrical mean and SD of length (mu m) and width (mu m) and the numbers of fibers per microgram are: s ilicon carbide whisker (SC1), 6.4 +/- 2.45, 0.30 +/- 1.58, 0.3 x 10(6) ; titanium oxide whisker (TO1), 2.1 +/- 2.0, 0.14 +/- 1.5, 0.63 x 10(6 ); potassium titanate whisker (PT1), 6.0 +/- 2.0, 0.35 +/- 1.51, 0.51 x 10(6)). The RAW 264.7 murine macrophage-like cell line was used for target cells. UICC crocidolite and TiO2 (rutile) particles were used a s a positive and a negative control, respectively. Although the 3 type s of whiskers caused an increase in lactic dehydrogenase (LDH) transud ation and a decrease of cell viability at 24 h of incubation in a dose -dependent manner, there was no significant difference found among the 3 kinds of whiskers. Tumor necrosis factor alpha (TNF-alpha) in the c ulture medium showed a plateau at 12 h in a dose-dependent manner up t o 0.1 mg/ml concentration of whiskers, and TO1 induced about double th e TNF-alpha of other whiskers, crocidolite, and TiO2 particles. AN of the whiskers and the TiO2 particles did not cause a marked increase of intracellular interleukin-1 beta (IL-1 beta), whereas crocidolite ind uced a significant increase at 12 h. In pathological findings, at 2 mo after a single intratracheal injection at high dose into rats, whiske rs caused a substantial amount of inflammatory cell aggregation around the resident fibers, causing very slight fibrous reactions without ma rked difference among three kinds of whiskers. Obvious differences of biological effects in vitro and in vivo among the three kinds of whisk ers were not observed except for TNF-alpha. When compared on the basis of number per unit mass, the three kinds of whiskers showed very simi lar concentration in TNF-alpha production, whereas TO1 showed lesser v alues than SCI and PT1 in IL-1 beta. We conclude that whisker-induced biological effects may be caused by shape and size and not chemical co mposition (SiC vs. K2TiO8O17, TO1 vs. TiO2 particles), and TNF-alpha p roduction may relate to whisker numbers, whereas IL-1 beta production may relate to whisker size in macrophagelike cells. However. the diffe rences of size and numbers per unit mass among the three types of whis kers did not reflect the degree of inflammation and fibrosis in the lu ngs of whisker-inhaling rats.