Registration Dossier

Toxicological information

Neurotoxicity

Currently viewing:

Administrative data

Description of key information

The weight of evidence based on a category approach indicates that Normal-Heptane is unlikely to present a hazard as neurotoxicant.

Key value for chemical safety assessment

Additional information

Inhibition of propagation and maintenance of electrically evoked seizure discharge was tested as a parameter for the acute neurotropic effect of heptane in rodents. Groups of 4 male rats and 8 female mice per dose were exposed by inhalation to ambient air or 3 concentrations selected in the linear part of an effect-concentration curve (between 25 and 75% of the maximum effect), which had been determined in preliminary experiments. Following exposure, measurements of biological effects were conducted. After a short electrical impulse applied through ear electrodes, the duration of tonic extension of hindlimbs (rats) and the velocity of tonic extension (mice) was measured. Data were processed by linear regression and the effect in the lower third of the dose-response curve (linear part) was chosen as the critical level. Isoeffective concentrations, corresponding to the critical level of effect (ECC), were interpolated and the 90% confidence intervals were calculated. The lowest effective concentration EC10was determined as well. The interpolated estimates of concentrations evoking a 30% of the maximum possible effect were 2740 ppm (corresponding to ca. 12000 mg/m³) for rats and 4740 ppm (ca. 21000 mg/m³) for mice, with a width of a one-sided 90% confidence interval of 730 and 1590 ppm, respectively. The isoeffective concentration of Normal-Heptane (ECC and EC10, mean of the value in rats and mice) expressed as percentage of the concentration of saturated vapours (CSV) at 37 °C were 3.4 and 0.9 %. Under the conditions of the test, Normal-Heptane was capable of blocking electrically evoked seizures, underlining the effects on behaviour (Frantik et al. 1994).

Several other members of the category have also been tested, namely octane; 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 (CEFIC, 2000, 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 (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.

 

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.

 

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

The available data on neurotoxicity of heptane and structurally related substances within a category approach are conclusive but not sufficient for classification.