The role of fiber length in crocidolite (12001284) toxicity was studied in-vitro and in-vivo. Thioglycollate elicited C57B1/6-mouse peritoneal macrophages were incubated with crocidolite in preparations having at least 60% of the fibers longer than 2 microns (long fiber preparation) or 90% of the fibers shorter than 2 microns (short fiber preparation). In some experiments the fibers had been coated with deferoxamine or catalase or superoxide-dismutase (SOD) was added to the incubation mixture. Cytotoxicity was assessed by measuring loss of viability and release of hydrogen-peroxide and superoxide-ion. C57B1/6-mice were injected intraperitoneally with 200 micrograms (microg) short, long, or mixed length crocidolite fibers or titanium-dioxide (13463677). Some fibers had been presoaked with deferoxamine. Some mice were also injected with catalase or SOD. Peritoneal macrophages were recovered by lavage 3 days after dosing. Cytotoxicity was assessed by the trypan-blue dye exclusion test and release of lactate-dehydrogenase. Spontaneous release of hydrogen-peroxide and reactive oxygen metabolites was also evaluated. Other mice were injected with 200microg per milliliter (ml) long or mixed crocidolite fibers or 120microg/ml short crocidolite fibers weekly for 22 to 60 weeks. The animals were killed when they showed signs of ascites or intestinal blockage and examined for peritoneal mesotheliomas. In-vitro, both long and short crocidolite fibers were cytotoxic. Precoating the fibers with deferoxamine or adding catalase or SOD to the incubation mixture decreased the toxicity of long and short fibers. In-vivo, crocidolite was cytotoxic to peritoneal macrophages. The extent of cellular injury was greater with long fibers. The fiber preparations induced release of hydrogen-peroxide and reactive oxygen metabolites. Catalase, SOD, and deferoxamine protected against crocidolite toxicity. Titanium-dioxide was not cytotoxic. The mixed, long, and short crocidolite fiber preparations induced peritoneal mesotheliomas in 37.5, 23.5, and 50.0% of the animals, respectively. The authors conclude that short as well as long crocidolite fibers are cytotoxic and carcinogenic.