Hydrocarbons, C7-8

Endpoint summary

Description of key information

Inhalation
NOAEC: 8117 mg/m³

Additional information

Inhalation

There are no inhalation repeated dose toxicity data available on hydrocarbons, C7-C8, cyclics. However, 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 after 13 weeks. 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 a less reliable supporting study by Treon et al. (1943) rabbits (4/group) were exposed to methylcyclohexane over a maximum exposure period of 10 weeks at concentrations of 0.95 and 4.57 mg/L (10 weeks), 11.35 mg/L (3 weeks), 21.90 mg/L (4 weeks), 28.75 and 39.55 (2 weeks), and 59.95 mg/L (70 min) (241, 1162, 2886, 5567, 7308, 10054, and 15227 ppm, respectively). Death reportedly occurred in rabbits exposed repeatedly to 28.75 mg/L (7308 ppm) or higher for 60 hours, 6 hr/day, 5 d/wk; light narcosis and severe convulsions were reported. Similar exposure to 11.35 mg/L (2886 ppm) for 90 hours produced barely discernable microscopic evidence of cellular injury in the liver and kidneys. Exposure to 4.57 mg/L (1162 ppm) for 10 weeks was reported to be innocuous. No adverse effects were observed in hematology, erythrocyte, or leukocyte counts evaluated weekly. The NOAEL was reported as 4.57 mg/L (1162 ppm).

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, C7-C8, cyclics. No need for classification according to the DSD and CLP criteria for classification and labelling.