Hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, >5% n-hexane

Endpoint summary

Description of key information

Inhalation
NOAEC (systemic): 8117 mg/m³ 

Additional information

Inhalation

There are no inhalation repeated dose toxicity data available on hydrocarbons, C6-C7, n-alkanes, iso-alkanes, cyclics, > 5% n-hexane. However, there are reliable data available for structurally related substances. Thus, read-across was conducted based on structural analogues.

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 week 13. 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.

Another inhalation study was conducted with commercial hexane. Similar to OECD 413, groups of male/female rats and mice were exposed by whole body inhalation to 0, 904, 2984, 8992 ppm(analytical conc.) commercial hexane (40-55% n-hexane, > 10% methylcyclopentane) for 6 hours/day, 5 days/week for 13 weeks (Anonymous,1990).

Rats exposed to hexane: No rats died during the study. Transient excess lacrimation was observed in the female rats. No other effects attributable to exposure were noted. In high exposed males, increased platelets and mean corpuscular volume was observed. Clinical chemistry examinations showed increased creatinine, total protein, and albumin levels and decreased serum chloride contents for males at the high dose level. Increased relative spleen and liver weights were noted for high exposed males. The liver effects appeared to be treatment related. Females at the high dose level showed increased relative spleen weights. Histopathological examinations revealed hemorrhage and inflammation in the liver of the high exposed males. There was also inflammation in the kidneys of males in the high and middle exposure groups. Based on liver and kidney effects, the NOAEC for male rats was determined to be 5500 mg/m³ corresponding to 2984 ppm. The NOAEC for female rats was 16500 mg/m³ corresponding to 8992 ppm.

Mice exposed to hexane: Seven mice died during the study, 3 from drawing blood, and 4 others died accidently. None of these deaths were attributed to treatment. There was sporadic excessive lacrimation due to exposure, no other clinical signs were considered treatment related. Males at the high dose level showed increased mean corpuscular volume. No other treatment related effects were observed in male or female mice. The NOAEC for male and female rats was determined to be 16500 mg/m³ corresponding to 8992 ppm.

The fact, that inflammation in the liver and in the kidneys was limited to male rats at the high exposure group and that the test substance belongs to a category of substances which are known for their ability to induce nephropathy in male rats, the observed effects in the liver and in the kidneys have to be regarded as species-specific and are not relevant for risk assessment in humans. Therefore, 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, C6-C7, n-alkanes, iso-alkanes, cyclics, > 5% n-hexane.

Justification for classification or non-classification

Based on the read-across from the structurally related substance light alkylate naphtha distillate, no inhalation repeated dose toxicity is expected from the exposure to hydrocarbons, C6-C7, n-alkanes, iso-alkanes, cyclics, > 5% n-hexane. No need for classification according to the DSD and CLP criteria for classification and labelling.

However, considering n-hexane concentrations ≥ 5%, the substance hydrocarbons, C6 -C10, n-alkanes, iso-alkanes, > 5% n-hexane needs to be classified.

DSD: R48/20

CLP: STOT repeated exposure category 2