Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
31 680 mg/m³
Additional information

In a key reproduction toxicity study (Daughtrey et al., 1994), the effect of inhalation of commercial hexane (~52% n-hexane) on reproduction in rats was determined (Daughtrey, 1994; Klimisch score =1). Groups of 25 male and 25 female rats were exposed to nominal concentrations of 0, 900, 3000, or 9000 ppm of test substance for 10 weeks pre-breeding. Reproductive parameters were similar in exposure groups and control groups. There was reduced body weight in the F1 and F2 generation in both sexes in the 9000 ppm exposure group in both adults and offspring. The NOAEC is therefore 3000 ppm (10560 mg/m3), and the LOAEC is 9000 ppm (31680 mg/m3). Since there were no adverse effects in offspring without adverse maternal effects, the NOAEC for reproduction is 9000 ppm (31680 mg/m3). This study directly informs the DNEL.


Short description of key information:
One key toxicity to reproduction study was identified for inhalation exposure.

The toxicity to reproduction NOAEC for both male and female rats (adults and offspring) was 3000 ppm (10560 mg/m3). The LOAEC for these groups was 9000 ppm based on reduced body weight. There were no adverse effects to reproduction therefore the NOAEC for reproduction is 9000 ppm
(31680 mg/m3).

Effects on developmental toxicity

Description of key information
Two key studies were identified to examine the developmental toxicity. In a developmental toxicity study of commercial hexane in mice, the maternal 
NOAEC was 900 ppm, and the maternal LOAEC was 3000 ppm (10560 mg/m3) based on color changes in the lungs. The developmental NOAEC was 3000 ppm and the LOAEC was 9000 ppm(31680 mg/m3) in mice.
In rats, the maternal NOAEC was 3000 ppm (10560 mg/m3), and the maternal LOAEC was 9000 ppm (31680 mg/m3) based on color changes in the
lungs, reduced body weight gain, and reduced food consumption. The developmental NOAEC 9000 ppm (31680 mg/m3) in rats.
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
31 680 mg/m³
Additional information

In a key developmental toxicity study groups of 30 pregnant female mice were exposed to commercial hexane (52.19% n-hexane) at concentrations of 0, 900, 3000, or 9000 ppm for 6 hrs/day during gestational days 6 -15 (API, 1989; Klimisch score =1). The animals were then sacrificed on GD 18. During the study, the animals were examined for clinical signs, mortality, food and water consumption, and body weights taken. After sacrifice, the internal organs were examined, and the uterus was examined for viable fetuses, number of resorptions, and number of corpora lutea. Fetuses were examined for malformations. Necropsy revealed color changes in the lungs of females in the 3000 and 9000 ppm groups. Fetuses in from dams in the 9000 ppm group had a statistically significant increase in some skeletal abnormalities. The maternal NOAEC in mice was 900 ppm (3168 mg/m3), and the LOAEC 3000 ppm based on lung color changes. The developmental NOAEC in mice was 3000 ppm (10560 mg/m3) and the LOAEC 9000 ppm (31680 mg/m3) based on skeletal abnormalities.

In a developmental toxicity study of commercial hexane in rats, groups of 25 pregnant female rats were exposed to concentrations of 0, 900, 3000, or 9000 ppm for 6 hrs/day during gestational days 6 -15 (API, 1989; Klimisch score = 1). The animals were then sacrificed on GD 21. During the study, the animals were examined for clinical signs, mortality, food and water consumption, and body weights taken. After sacrifice, the internal organs were examined, and the uterus was examined for viable fetuses, number of resorptions, and number of corpora lutea. Fetuses were examined for malformations. Necropsy revealed color changes in the lungs of females in the 9000 ppm groups along with reduced body weight gain, and reduced food consumption. No treatment related abnormalities was seen in the fetuses. The maternal NOAEC in rats was 3000 ppm (10560 mg/m3), and the LOAEC 9000 ppm based on lung color changes, reduced body weight gain, and reduced food consumption. The developmental NOAEC in rats was 9000 ppm (31680 mg/m3).

Justification for classification or non-classification

This substance is classified as a Category 2 reproductive toxicant.