Toxicology of Industrial Compounds

fiber exposure. While the IARC review (IARC, 1988) concluded that there
is ‘limited evidence’ for carcinogenicity in humans, reports subsequent to
the IARC review have further clarified potential confounding factors and,
if anything, shown weaker evidence of a relationship between exposure and
lung cancer.
Experimental studies
Toxicologic studies of MMVFs have been conducted in both in vitro and in
vivo systems. In addition, the physical and chemical characteristics thought
to correlate with toxicity have been examined. The in vitro studies have
been conducted using cells from the lungs of animals as well as bacterial
and cell lines. Two categories of whole-animal studies have been reported:
studies using artificial methods to implant high concentrations of fibers in
the abdomen, pleura or trachea of animals; and inhalation studies of
maximum tolerated doses and multiple dose levels of fibers.
Cell culture studies
T.W.HESTERBERG ET AL. 95
The use of cell culture systems for studying the toxic effects of fibers has
been recently reviewed (Hesterberg et al., 1993a). A number of studies
have shown that fiber length and diameter are important in determining
the toxicity of mineral fibers of various chemical compositions to cells
grown in culture (Chamberlain et al., 1979, Tilkes and Beck, 1980;
Hesterberg and Barrett, 1984; Hesterberg et al., 1993a; Hart et al., 1994).
Chemical composition has also been shown to be critical to the toxicity of
fibers to rat tracheal epithelial cells (Ririe et al., 1985) and human
bronchial epithelial cells grown in culture (Kodama et al., 1993). MMVFs
have also been shown to induce neoplastic transformation (Hesterberg and
Barrett, 1984; Poole et al., 1986) and genetic damage to cells in culture
(Sincock and Seabright, 1975; Oshimura et al., 1984). Cell culture models
are important for understanding the mechanisms of fiber toxicity and, with
further development, have potential for use as part of a battery of shortterm
screening tests to assess the toxic and tumorigenic potential of
mineral fibers. However, it was recently shown that cytotoxicity of different
compositions MMVFs to Chinese hamster ovary (CHO) cells in culture did
not correlate with the in vivo toxicity of theses MMVFs (Hart et al., 1994).
This may be related to CHO cells being aneuploid, preneoplastic and not a
normal target cell for fiber toxicity in vivo. Future in vitro studies of MMVF
toxicity should focus on the use of cell types that represent the relevant
target tissues, and cells should be as close to normal as possible.