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Neurotoxicity

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Description of key information

NOAEC (rat) > 4200-<14000 mg/m³
The weight of evidence based on a category approach indicates that hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane are unlikely to present a hazard as neurotoxicant.

Key value for chemical safety assessment

Additional information

Hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane were tested for neurobehavioural effects in a sub-acute inhalation exposure study. Groups of male rats (8/dose level) were exposed by inhalation to 0, 1400, 4200 or 14000 mg/m³ (corresponding to ca. 302, 915 and 3050 ppm), 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 signs of general toxicity. At 14000 mg/m³, slightly decreased body weight after the 3-day exposure and a decrease in body temperature after both the first and the third exposure were observed.

Results of the behavioural tests indicated no effects on functional observational measures and motor activity attributable to exposure to the test substance.

Mild effects were noted on measures of learned performance: increased latencies to make a correct choice and increased variability in the speed of performance. The effects were most clearly observed after the first 8-h exposure period.

Exposure-related effects occurred at 14000 mg/m³, while at the lower dose levels no neurobehavioural effects were observed. On this basis, the NOAEC was considered to be in the range of 4200 to 14000 mg/m³, corresponding to ca. 915 to 3050 ppm (Lammers, 2001). Several other members of the category have also been tested, namely heptane; n-octane; 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, 2000, 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.

 

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.

 

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.

Justification for classification or non-classification

The available data on neurotoxicity ofhydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexaneand structurally related substances within a category approach are conclusive but not sufficient for classification.