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Neurotoxicity

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Description of key information

Four studies were identified that examined neurotoxicity endpoints.  These studies were comprised of 90-day inhalation toxicity studies (n-pentane; 2-methylbutane; cyclopentane) and a test on nerve conduction velocity and distal latency (n-pentane).  

Key value for chemical safety assessment

Additional information

Potential neurotoxic effects of pentanes were evaluated in three select subchronic repeated dose studies via inhalation, each of which contained a neurotoxicity screening component (Takeuchi et al., 1981; Schreiner, 1998; Gamer, 1998). No treatment-related effects related to neurotoxicity were reported in any of these studies. Additionally,nerve conduction velocity and distal latency was measured in rats exposed to n-pentane for 16 weeks via inhalation (Takeuchi et al., 1980). N-pentane did not prolong distal latency or disturb the conduction velocity of the motor nerve and mixed nerve in the rat's tail. No changes were observed in the peripheral nerve, the neuromuscular junction, and muscle fibre of rats exposed to n-pentane at 3000 ppm for 16 weeks. No changes in body weight or behaviour were observed in n-pentane exposed rats when compared with control animals. 

Additionally, a relevant and useful supporting study also was available for n-pentane (Stoughton, 1936). This information is also presented in the Acute Toxicity section under inhalation. In this study, the anaesthetic activity of n-pentane on mice. In the first test series, referred to as the "light anesthesia" test, two mice were placed in a 2 liter bottle containing the n-pentane gas mixture. During this test, mice were dosed at concentrations of 3.0, 3.5, and 4.2 mmol/L. If animals were unable to maintain their upright posture after spinning the bottle then they were said to be lightly anaesthetized. For the three concentration levels tested, the time it took for mice to become lightly anaesthetized ranged from 1.3 to 10 minutes. No mice died during the first test series. In the second test series, referred to as the "complete anaesthesia" test, five mice were placed in a 20 liter bottle containing the n-pentane gas mixture. During this test, mice were dosed at concentrations of 4.2, 4.5, and 4.9 mmol/L. If animals were unable to regain their upright positioning after shaking then they were said to be anaesthetized. After two hours, the mice were removed from the bottle and the number of mortalities was noted. No mortalities occurred at 4.2 mmol/L, 8 mortalities occurred at 4.5 mmol/L, and 7 mortalities occurred at 4.9 mmol/L. The average recovery time for the survivor test mice ranged from 4 to 8 minutes. The LC50 was not calculated. Based on this study, it can be inferred that 2 -methylbutane should be classified and labelled for drowsiness and dizziness under Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008.

Justification for classification or non-classification

Based on the information presented in the study on anaesthetic activity of n-pentane, 2 -methylbutane is classified as R67, Vapours may cause drowsiness and dizziness in accordance with Dangerous Substances Directive 67/584/EEC and as STOT Single Exp. 3 (H336: May cause drowsiness or dizziness) in accordance with CLP EU Regulation 1272/2008.