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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 iso-octane is unlikely to present a hazard as neurotoxicant.

Key value for chemical safety assessment

Additional information

No data are available on neurotoxic effects of iso-octane. However, data are available for a structurally related substance, allowing read-across based on a category approach.

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) of iso-octane (Alkanes, C7-10-iso-, CAS No. 90622-56-3), 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. The exposure levels used were sufficiently high to induce very mild signs of general toxicity (slightly decreased body weights). No significant neurobehavioural effects were observed up to the highest dose, therefore the NOAEC was considered to be greater than 14000 mg/m³ (CEFIC, 2001).

Several other members of the category have also been tested, namely n-heptane; n-octane; hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane; hydrocarbons, C7 -C9, isoalkanes and naphtha (petroleum), light alkylate (analogue substance for hydrocarbons, C7-C9, isoalkanes). 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, 2000; 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:

 

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.

 

CEFIC,(2000). The Effects of Short-term Inhalatory Exposure to n-octane on Behaviour in the Rat. Unpublished. Testing laboratory: TNO Nutrition and Food Research Institute. Report no.: V99.429 Final. Owner company: CEFIC,. Study number: 40.144/01.04. Report date: 2000-01-12.

 

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.

 

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.

 

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.

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