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Neurotoxicity

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Description of key information

Key value for chemical safety assessment

Additional information

Data on this endpoint are presented in Section 4.1.2.10 of the EU RAR (2001; page 54ff).

No key studies were selected. However, result of EU RAR is presented here.

It was concluded in the EU RAR that neurotoxicity effects are limited to unspecific CNS depression at high dose levels (500 ppm). They are readily reversible. Exposure to cumene vapour was neither neurotoxic nor ototoxic in Fischer 344 rats.

 

In addition,Cumene was one of six alkylbenzenes tested at 0, 2,000, 4,000, or 8,000 ppm that all produced a short-lived profile of neurobehavioral effects in mice, indicating CNS depressant activity (Tegeris and Balster, 1994). Effects noted from brief (20-min) exposures to cumene included those on CNS activity (decreased arousal and rearing at >=2,000 ppm) muscle tone/equilibrium (changes in grip strength and mobility >=4,000 ppm), and sensorimotor activity (including decreased tail pinch and touch response >=4,000 ppm).

 

 

Studies in EU RAR

Tham et al. (1984; cited in EU RAR) studied the influence of a variety of industrial solvents on the vestibulo ocular reflex (VOR) in rats. Female Sprague Dawley rats were used. The compounds investigated were administered by continuous intravenous infusion during 60 min. They were dissolved in an emulsion of lipids used for human parenteral nutrition (Intralipid). The concentration of the tested compound varied between 0.1 and 10%. The infusion rate of the Intralipid solution was 32μl/min. Threshold limit for excitatory effect of cumene on the vestibulo-oculomotor reflex in rats was 144 mg/l blood, this level was caused by an intravenous infusion at a rate of 4.8 mg cumene/kg/min during 60 min.

In the 90 day subchronic inhalation study of cumene in rats (15 rats per sex per group) including an evaluation of potential neurotoxicity and ototoxicity (Cushman et al., 1995; cited in EU RAR). At exposure concentration up to 1200 ppm for 6 h per day, 5 days per week, cumene did not cause peripheral auditory dysfunction as indicated by the auditory brain stem response. Minor motor activity decreases were seen only in male rats at 500 and 1200 ppm. This result was not replicated in a second study. Following a single, 6 h inhalation exposure to cumene at 500 or 1200 ppm some parameters of the FOB were affected at 1 and 6 h, but not at 24 h.

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