Registration Dossier

Administrative data

Description of key information

Inhalation
NOAEC (systemic): 12470 mg/m³

Key value for chemical safety assessment

Mode of Action Analysis / Human Relevance Framework

Additional information

Inhalation

There are no inhalation repeated dose toxicity data available on isoheptane. However, there are reliable data available for another category member. Thus, read-across was conducted based on a category-approach.

In a comparative study designed to evaluate peripheral nerve toxicity of n-pentane, n-hexane and n-heptane male rats were exposed to 0 or 3000 ppm 12 hours/day, 7 days/week, for 16 weeks. The conduction velocity of tail nerves was measured to determine the functional status of the peripheral nerves. For animals exposed to n-heptane, the body weight gain was statistically significantly depressed (p<0.01) after 8 weeks of exposure compared to control animals but gradually increased throughout the experiment to body weight levels below control values but not statistically significantly lower. No abnormal behavioral changes were observed. There were no statistically significant differences in motor nerve conduction velocity, distal latency or mixed nerve conduction velocity in any region of the tail for n-heptane exposed rats. Peripheral nerves, muscles and neuromass junctions, examined microscopically were normal. Only n-hexane induced neuropathy. The NOAEC was determined to be > 3000 ppm corresponding to 12470 mg/m³ (Ono et al., 1979 and Takeuchi et al., 1980, 1981).

Rats were exposed to n-heptane via whole body inhalation at 0, 398 and 2970 ppm for 26 weeks with a subsequent 2-week recovery period conducted similar to OECD 413 (Shell, 1980). There were no treatment-related deaths during the study. The only treatment-related observations were labored breathing or rapid breathing and slight prostration during the first week of exposure and anogenital fur and dry rales during weekly observations. The in chamber signs were generally more numerous and severe at the higher concentration and appeared to abate by the second week of the study. No treatment-related effects were observed for body weight, hematology or urinalysis. Serum alkaline phosphatase was significantly elevated in high-concentration females and slightly elevated in low-concentration females. All other clinical chemistry values appeared normal with the exception of one high-concentration male whose serum glutamic pyruvic transaminase and serum alkaline phosphatase levels were markedly elevated when compared to all other exposed male rats. Proteinuria, elevated specific gravity and ketones were observed but were not considered related to treatment. Clinical pathology results had no correlate in histopathology. The NOAEC was 2970 ppm corresponding to 12200 mg/m³.

Justification for classification or non-classification

Based on read-across from a structurally related substance within a category-approach, no inhalation repeated dose toxicity is expected from the exposure to isoheptane. Therefore, iso-heptane need not be classified according to DSD and CLP criteria for classification and labelling.