Alkanes, C8-9-iso-

Endpoint summary

Description of key information

Inhalation
NOAEC (systemic): 8117 mg/m³

Additional information

Inhalation

Systemic toxicity of hydrocarbons, C7-C9, isoalkanes, belonging to the same category as the test substance, was assessed in a 12-week inhalation toxicity study in rats (ExxonMobil Chemical,1979). In this study, repeated exposure to 400 or 1200 ppm of the test substance for 6 hours/day, 5 days/week, for 12 weeks resulted in male rat kidney effects consistent with the alpha-2µ-globulin-induced nephropathy in male rats. There was no treatment-related mortality and clinical findings were unremarkable. Under the test conditions, the NOAEC (excluding male rat nephropathy) was determined to be >1200ppm.

The fact, that alpha-2µ-globulin-induced nephropathy was strictly limited to male rats and that the test substance belongs to a category of substances which are known for their ability to induce nephropathy in male rats due to their exclusive expression of alpha-2µ -globulin, the protein known to play the crucial role in the onset of this disease, the observed effects in the kidney have to be regarded as species-specific and are not relevant for risk assessment in humans. Therefore, 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.

In another study of Schreiner et al. (2000) conducted according to OECD 413, rats were exposed to light catalytic reformed naphtha distillate via whole body inhalation at 0, 750, 2490 or 7480 ppm (analytical conc.). Male and female rats were exposed for 6 hours/day, 5 days/week, for 13 weeks. All animals survived to study termination. The increased relative kidney weights and microscopically observed hyaline droplet formation and renal tubule dilation in high dose males reflected the occurrence of alpha-2µ-globulin-induced nephropathy, effects in male rats which have been determined to have no relevance to humans. The increased spleen weights and hematological changes had no microscopic correlate and appeared reversible with 4 weeks of recovery. There were no neurobehavioral effects observed during the study and the increased motor activity in recovery high dose males were not supported by other behavior changes or microscopic abnormalities in neural tissues, suggesting the observation may have been fortuitous. Therefore, the NOAEC was 2510 ppm .

The NOAEC of the inhalation study of Schreiner et al. (1998) conducted with light alkylate naphtha distillate was taken forward to evaluate the risk potential of hydrocarbons, C8-C9, isoalkanes.

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 hydrocarbons, C8-C9, isoalkanes. No need for classification according to the DSD and CLP criteria for classification and labelling.