Registration Dossier

Administrative data

Description of key information

One key study (Kimura et al., 1971) was identified for acute oral toxicity.  Two key studies were identified for acute inhalation toxicity (DeMartino et al., 1987 and Hine et al., 1970).  One key study was identified for acute dermal toxicity (Hine et al., 1970).  The study by Hine et al., 1970 was read-across from C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
16 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
259 354 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
3 350 mg/kg bw

Additional information

In a key acute oral toxicity study (Kimura et al., 1971; Klimisch score=2), groups of 6-12 rats were given doses of n-hexane by oral gavage. Rats of Four different ages were tested: newborns, 14 -days old, young adult, and older adults. Due to difficulty in administering small doses, the LD50 for newborn rats could not be determined, but was assumed to be <1.0 ml/kg. The LD50 for 14-day old rats was 24 ml/kg, which was significantly lower than the LD50 for young adult rats, 49 ml/kg, and older adult rats, 43.5 ml/kg. Since the LD50s for rats older than newborns were 24 ml/kg (~16 g/kg) or above, the test substance is not classifiable under EU guidelines.

In a key read-across acute dermal toxicity study from C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane. (Hine et al., 1970 Klimisch=2), 5.0 ml/kg of test substance was placed on the shaved skin of 3 male rabbits. The test area was then covered with a saran wrap sleeve for 4 hrs. After the exposure period, the test substance washed off, and the animals observed for toxicity and mortality over the next 14 days. No animals died; however, they did show signs of discomfort and uncoordination after the exposure. The LD50 for dermal exposure is > 5.0 ml/kg (3350 mg/kg). Therefore, the test substance is not classified under EU criteria.

Two key acute inhalation studies (Klimisch scores=2) were identified (DeMartino et al., 1987; Hine et al., 1970). DeMartino et al. (1987) examined the effects of exposure to n-hexane via inhalation for 24 hrs to male rats. A group of 17 male rats were exposed to a concentration of 5000 ppm of test substance vapors for 24 hrs. The animals were observed for clinical signs and body weights. The animals were sacrificed at different time points after exposure: immediately after exposure, and on days 2, 7, 14, and 30 post-exposure. The testes and epididymis were examined for lesions and histopathological changes. Lesions to the epididymis were seen in 4 of 6 animals sacrificed immediately after exposure. 3 of these animals also had lesions to the testis. Lesions in these areas continued to be seen in animals sacrificed up to 14 days after exposure, however, the severity of the lesions lessened. The animals sacrificed at 30 days post-exposure had no lesions in these areas, suggesting complete recovery. The LOAEC for a single 24 -hr exposure is 5000 ppm (17600 mg/m3) based on effects to the epididymis and testes. No animals died from the exposure, therefore the LC50 is > 5000 ppm (17600 mg/m3). The second key study for acute inhalation toxicity was read-across from commercial hexane. Hine et al. (1970) exposed groups of 10 male rats exposed to concentrations of hexane vapor for 4 hours. Animals were then observed for clinical signs and mortality for at least 6 days post-exposure. Several animals died during the exposure period. Surviving animals experienced severe toxicological effects during the exposure. One animal experienced convulsions during and after exposure and died on day 6 post-exposure. The LC50 was determined to be 73,680 ppm (259354 mg/m3).

Justification for classification or non-classification

n-Hexane is classified as a Category 1 aspiration hazard.