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Description of key information

Inhalation
NOAEC (systemic): 8117 mg/m³

Key value for chemical safety assessment

Additional information

Inhalation

In a short-term inhalation study, male rats were exposed to 0, 300, 900 or 3000 ppm iso-octane via whole body inhalation for 8 hours/day for 3 consecutive days (CEFIC, 2001). No remarkable clinical signs were observed. In the high exposure group, body weights were slightly decreased during exposure. Under the test conditions, short-term exposure to iso-octane did not induce any toxicologically significant effects. Thus, the NOAEC was determined to be 14000 mg/m³.

Since only basic data were given in this study and the study was limited to 3 days, additional experimental data were used to evaluate repeated dose toxicity via inhalation.

There are reliable data available for the structurally related substance light alkylate naphtha distillate. Thus, read-across was conducted based on a structuralanalogue.

A 13-week inhalation toxicity study was conducted using wholly vaporized light alkylate naphtha distillate (LAND-2) generated in nitrogen (Schreiner et al., 1998). Male and female rats were exposed by inhalation in whole-body exposure cages 6 hours/day, 5 days/week for 13 weeks at analytical concentrations of 0, 668, 2220, and 6646 ppm. All animals survived the treatment period and were sacrificed according to study design at the end of week 13 or 18 (recovery group). No test-related observations were noted in the exposure chambers during any exposure period for any treatment groups or during non-exposure periods. From weekly clinical observations, the only apparent treatment-related finding was an increased incidence of red facial staining in both male and female rats in the high dose group. At week 13, there were statistically significant dose-related increases in absolute and relative kidney weights in males of all 3 treatment groups. The kidney weights of high-dose males remained elevated after the recovery period. These increases correlated with microscopic observations of hyaline droplet formation in the proximal convoluted tubules considered to contain an alpha2-microglobulin-hydrocarbon complex as well as an increase in incidence and severity of nephropathy and dilated tubules at the corticomedullary junction. These microscopic finding are characteristic of ‘light hydrocarbon nephropathy” also known as hyaline droplet nephropathy and are male rat specific. Therefore these effects are not considered to be relevant to humans. Statistically significant increases in absolute and relative liver weights were observed in high-dose male and female rats at week 13 after sacrifice. Differences were not present after the recovery period and had no microscopic correlate. Thus, the NOAEC for systemic toxicity was 8117 mg/m³ corresponding to 2200 ppm.

There are also reliable data available for another category member. Thus, read-across was conducted based on a category-approach.

In a study conducted similar to OECD 413, groups of male rats were exposed by whole body inhalation to 0, 360, 590, or 1600 ppm n-nonane for 6 hours/day, 5 days/week, for 13 weeks (Carpenter et al., 1978). Clinical signs included salivation, mild loss of coordination and fine tremors throughout the first 4 days of exposure in the high dose group. Salivation and lacrimation were observed during the remaining exposure periods. Mean body weights or mean body weight changes of rats at 1600 ppm were statistically significantly lower than controls throughout the study. Histopathological evaluation conducted on weeks 4, 8, and 13 revealed only common sporadic lesions that were not considered to be treatment-related. No effects were noted in the 360 or 590 ppm dose groups throughout the study. The NOAEC for this study was determined to be 8400 mg/m³ corresponding to 1600 ppm.

 Since the inhalation study of Schreiner et al. (1998) conducted with light alkylate naphtha distillate revealed the more sensitive endpoint compared to the studies which tested iso-octane or n-nonane, the NOAEC of 8117 mg/m³ was taken forward to evaluate the risk potential of iso-octane.

Justification for classification or non-classification

Based on read-across from a structurally related substance (light alkylate naphtha distillate), no inhalation repeated dose toxicity is expected from the exposure to iso-octane. Therefore, iso-octane need not be classified according to DSD and CLP criteria for classification and labelling.

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