An ultrastructural evaluation of toluene toxicity using cultured mammalian cells.

Animal cells were cultured in media containing toluene and then examined by electron microscopy to determine changes in subcellular architecture. Cellular viability and cloning studies indicated toluene toxicity at concentrations of 50-500 ppm. At all dosage levels, toluene accelerated cell death compared to comparable control cells that had not been exposed to toluene. However, media composition and, particularly, the presence or absence of fetal bovine serum (FBS), markedly affected toluene toxicity. In media without FBS reversible changes in filopodia and cell shape were identified after 15 min of exposure to as little as 50 ppm toluene, and cell death occurred within 5 min at concentrations of 500 ppm toluene. In media with FBS, no filopodial changes were observed at 50 ppm toluene, and cell death, although accelerated, was clearly evident only after 24-48 h of exposure to 200-500 ppm toluene. Except for the cell-surface changes, chronic toluene exposures (50-100 ppm without FBS or 200-500 ppm with FBS in the growth medium) produced no unusual intracellular changes until 24-48 h of toluene exposure. With toluene exposures of 24 h or longer, cellular changes included condensation of heterochromatin in nuclei, formation of bulbous protuberances at the cell surface, loss of polyribosomes (but not ribosomes) and, ultimately, degeneration of organelles. These late changes were irreversible and the prelude to cell death.