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Neurotoxicity

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Description of key information

NOAEC (rat) > 14000 mg/m³
The weight of evidence based on a category approach indicates that octane is unlikely to present a hazard as neurotoxicant.

Key value for chemical safety assessment

Additional information

Groups of male rats (8/dose level) were exposed by inhalation to 0, 1400, 4200 or 14000 mg/m³ (corresponding to ca. 300, 900 and 3000 ppm) octane, 8 h per day, for 3 consecutive days. Animals were tested daily for effects on motor activity, functional observation measures and learned performance of a visual discrimination task. No clear signs of general intoxication and no significant effects on any of these parameters were observed up to and including the highest dose, therefore the NOAEC was considered to be greater than 14000 mg/m³ (CEFIC, 2000).

Several other members of the category have also been tested, namely normal-heptane; hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane; hydrocarbons, C7-C9, isoalkanes; naphtha (petroleum), light alkylate (analogue substance for hydrocarbons, C7-C9, isoalkanes) and alkanes, C7-10-iso- (analogue substance for iso-octane). Studies on neurotoxic effects were performed in rodents upon single and/or repeated dose inhalation exposure to the test substances. In the majority of cases, measurement of various parameters of neurobehavioral response showed minimal to no adverse effects. In some cases, however, reversible neurobehavioural effects occurred at the higher dose levels. NOAEC values for neurobehavioural effects were ≥ 1000 ppm (ca. 3500-5200 mg/m³ depending on composition), mice being much more sensitive than rats (Frantik et al., 1994; CEFIC, 2001; Lammers, 2001; Balster et al., 1997; Bowen and Balster, 1997; Schreiner et al. 1998).

Therefore, the substances in this category are unlikely to present a hazard as neurotoxicants.

 

 

References:

 

Balster, R. L. et al. (1997). Evaluation of the acute behavioral effects and abuse potential of a C8-C9 isoparaffin solvent. Drug and Alcohol Dependence 46: 125-135.

Bowen, S. E. and Balster, R. L. (1998). The Effects of Inhaled Isoparaffins on Locomotor Activity and Operant Performance in Mice. Pharmacology Biochemistry and Behavior, 61(3): 271-280.

CEFIC (2001). The Effects of Short-term Inhalatory Exposure to Iso-octane on Behaviour in the Rat. Unpublished. Testing laboratory: TNO Nutrition and Food Research Institute. Report no.: V99.430 Final. Owner company: CEFIC. Study number: 40.144/01.09. Report date: 2001-02-15.

Frantik, E. et al.(1994). Relative Acute Neurotoxicity of Solvents: Isoeffective Air Concentrations of 48 Compounds Evaluated in Rats and Mice. Environmental Research 66: 173-185.

Lammers, J. H. C. M. (2001). The Effects of Short-term Inhalatory Exposure to Cypar 7 on Behaviour in the Rat. Unpublished. Testing laboratory: TNO Nutrition and Food Research Institute. Report no.: V99.1115 Final. Owner company: CEFIC. Study number: 40.144/01.10. Report date: 2001-02-15.

Schreiner, C. et al. (1998). Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats. Journal of Toxicology and Environmental Health (Part A) 55:277-296.

Justification for classification or non-classification