Carbon tetrachloride

Neurotoxicity

Description of key information

Acute toxicity studies in humans and animals reported neurotoxic effects of carbon tetrachloride at high-doses.

Additional information

Like many volatile halocarbons, inhalation of carbon tetrachloride leads to rapid depression of the central nervous system. Depending on exposure levels, common signs of central nervous system effects include headache, giddiness, weakness, lethargy, and stupor. Effects on vision (restricted peripheral vision, amblyopia) have been observed in some cases, but not in others. Sudden severe epileptiform seizure and coma occurred in a subsequently fatal case following weekly combined inhalation/dermal exposure over a period of 3 months. In several fatal cases, microscopic examination of brain tissue taken at autopsy revealed focal areas of fatty degeneration and necrosis, usually associated with congestion of cerebral blood vessels. Exposure levels leading to effects on the central nervous systems of humans are not precisely defined. No symptoms of lightheadedness or nausea were experienced by humans exposed to 50 ppm for 70 minutes or 10 ppm for 3 hours, but nausea, headache, and giddiness were found to be common symptoms in workers exposed to carbon tetrachloride for 8 hours/day at concentrations of 20–125 ppm. Dizziness has also been reported in humans following short-term exposure (15 minutes) at a higher concentration (250 ppm). This suggests that the threshold for central nervous system effects in humans is, as a conservative estimate, probably in the range of 20–50 ppm for an 8-hour work day.

 

Central nervous system depression is also observed in animals exposed to carbon tetrachloride vapors. Drowsiness or stupor occurred in rats exposed for 0.1–8.0 hours to 4,600 ppm, with ataxia and unconsciousness at 12,000 ppm, and death (from respiratory failure) at 19,000 ppm. Similarly, dogs exposed for 2–10 hours to 15,000 ppm experienced profound depression of the autonomic system, as evidenced by decreases in respiration, reflex activit, body temperature, heart rate, and blood pressure (the latter due to marked vasodilation). Exposure of rats, monkeys, or guinea pigs to concentrations of carbon tetrachloride up to 400 ppm, 8 hours/day, 5 days/week for over 10 months did not cause any observable effects on activity, alertness, or appetite, indicating that this level did not cause obvious central nervous system depression in animals. However, histological examination of sciatic and optic nerves revealed degenerative changes in a number of animals exposed to 200–400 ppm, and in a few animals (rats) after exposure to levels as low as 50 ppm under the same exposure schedule. The changes were apparently not severe enough to impair movement or vision. Exposure to ≥5 ppm carbon tetrachloride vapor for 6 hours/day, 5 days/week for 2 years resulted in decreased absolute brain weights in male, but not female, rats, however, this effect was attributed to the overall depression in body weight, since brain weights relative to body weight were increased. Furthermore, no histopathology was detected in the brain in either sex at any concentration.

Justification for classification or non-classification

As effects on the central nervous system are reported only at high-dose levels, no classification is warranted for this endpoint, according to EU Regulation (EC) N0. 1272/2008 (CLP).