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Evaluation of toluene and acetone inhalant abuse II. Model development and toxicology*1

1981; Elsevier BV; Volume: 61; Issue: 3 Linguagem: Inglês

10.1016/0041-008x(81)90351-3

1096-0333

James V. Bruckner,

Animal testing and alternatives

The capacity of toluene and of acetone to cause toxic injury was evaluated under conditions approximating solvent abuse. Exposure of male mice to 4000 ppm toluene 3 hr/day, five times weekly for up to 8 weeks produced no manifestations of toxicity other than minor, transient elevations in SGOT. In order to develop exposure protocols which mimicked typical episodes of solvent “sniffing,” male mice and rats were exposed by inhalation to toluene vapor levels ranging from 4000 to 12,000 ppm for as long as 3 hr. Although toluene is a potent and rapidly acting narcotic, the animals quickly recovered from its CNS depressant effects and had to be administered the solvent repeatedly to be maintained in an inebriated state. On the basis of pilot studies, an intermittent exposure protocol was adopted in which groups of mice and rats were subjected on a daily basis to seven consecutive inhalation cycles, each cycle consisting of a 10-min exposure to 12,000 ppm toluene followed by a 20-min, solvent-free recovery interval. Additional groups of rats were exposed 3 hr daily to 19,000 ppm acetone. These toluene and acetone regimens were repeated 5 days per week for 8 weeks. Groups of each species were sacrificed after 2, 4, and 8 weeks and 2 weeks postexposure. Clinical chemistry indices (i.e., SGOT, LDH, BUN, liver triglyceride content, lung fluid content) and histopathological examination of tissues (i.e., lung, liver, brain, kidney, and heart) failed to reveal manifestations of acute injury or residual organ damage at any sacrifice time. Body weight gain and absolute organ weights of solvent-exposed mice and rats were generally depressed during and in some cases 2 weeks after the 8-week exposure regimens. Our studies indicate that toluene and acetone are relatively nontoxic, even under the extreme exposure conditions of solvent abuse.