Encephalopathic effect of phenol in rats.

The coma-inducing effect of phenol was studied in normal 300 +/- 50 gm Sprague-Dawley rats. Dose-response curves were developed which showed that one-half the animals became deeply comatose with 540 mumol of intraperitoneal phenol and 100% with 600 mumol. Five stages of encephalopathy were readily distinguished. In stage I, spontaneous activity was noticeably decreased, posture was upright, back-leg control normal, muscle tonus slightly increased, and response to stimuli normal. In Stage V, activity was gone, the rats were deeply unconscious, righting reflex and back-leg control were gone, muscles were completely relaxed, and there was no response to stimuli. With a coma-inducing dose of phenol, spontaneous activity decreased. After 1 min a body tremor developed interspersed with unpredictable jumping, and all four limbs began to shake. Leg control and then the righting reflex were lost by 2 min. Within 5 min rats were deeply unconscious and muscles completely relaxed while shaking of limbs continued until recovery 20 to 60 min later or death. With 480 mumol or less, none of the rats became comatose, but the shaking of limbs was present. The coma-inducing dose of phenol was reduced by 10% to 20% with simultaneous injection of subcoma doses of NH4+ or OA and by 20% to 30% with simultaneous DMDS leads to 2 methanethiol. Conversely, a subcoma dose of phenol reduced the coma-inducing doses of NH4+, OA, and DMDS by approximately 20% to 25%. Thus phenol, which accumulates in human hepatic failure, induces coma by itself in rats and acts synergistically with other hepatic failure toxins.