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Description of key information

1, 6 Hexan diol is of low toxicity after repeated oral exposure.
- oral: NOEL = 1000 mg/kg bw (OECD 407), NOAEL = 400 mg/kg bw (OECD 408)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
400 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Subacute toxicity study (oral, 28 days):

Repeated dose toxicity of 1,6-hexanediol was assessed in a repeated dose 28-Day oral toxicity study conducted according OECD method 407 and EU method B.7 (BASF, 1995). Five male and five female Wistar rats per dose received doses of 100, 400 and 1000 mg/kg/d 1,6-hexanediol by stomach tube. The only observable effect was a statistical significant decrease in body weight in females of the 400 mg/kg bw group and decreased body weight gain in female rats at the 400 and 1000 mg/kg/d dose level toward the end of the study, respectively. However, since no dose-response relationship was found, these effects were regarded as incidental. In parallel, the values for food consumption were also reduced, but without showing statistical significance. Furthermore, all these changes were within ranges of historical controls. Thus, the NOEL was 1000 mg/kg bw/day under the condition of this study.

Subchronic toxicity study (oral, 90 days):

The effect of 1,6 -hexandiol on repeated toxicty was assessed in Wistar rats according to OECD 408 and GLP (BASF SE 2014). 1,6-Hexanediol was administered for 3 months daily by gavage to male and female Wistar animals at dose levels of 0, 100, 400 and 1000 mg/kg bw/d (test groups 0 - 3). Drinking water served as vehicle and vehicle control.

Regarding clinical examinations,the only effect observed was a treatment-related decrease of body weight in male animals of test group 3 (1000 mg/kg bw/d) on study days 77, 84 and 91 compared to the control group (up to -10.5%). Body weight gain decreases were in males of test group 3 on study days 56, 63, 70, 77, 84 and 91 (up to -18.7%). No changes in body weight parameters were observed for male animals of test groups 1 and 2 (100 and 400 mg/kg bw/d). Furthermore, no treatment-related effects on body weight/body weight gain were observed in female animals of test groups 1-3 (100, 400 and 1000 mg/kg bw/d).

No treatment-related effects were observed on food and water consumption, FOB, and motor activity measurement. 

Regarding clinical pathology, no treatment-related, adverse effects were observed up to a dose of the compound of 1000 mg/kg bw/d. Furthermore, there were no treatment-related effects in pathology as assessed by organ weight changes, gross lesions, and histopathological findings in male and female Wistar rats.

All findings occurred either individually or were biologically equally distributed over control and treatment groups. They were considered to be incidental or spontaneous in origin and without any relation to treatment.

The administration of 1,6 -Hexanediol by gavage to male and female Wistar rats for 3 months revealed a test substance-related decrease in body weight only in male animals at a dose level of 1000 mg/kg bw/d. No effects were noted in females receiving 1000 mg/kg bw/d, or at lower dose levels of either sex.

Therefore, under the conditions of the present study the no observed adverse effect level (NOAEL) was 400 mg/kg bw/d in male and 1000 mg/kg bw/d in female Wistar rats.

In another study, six Sprague-Dawley rats were treated with 0.5% 1,6-hexanediol in drinking water for 12 weeks to determine the molecular configuration of aliphatic hydrocarbons for the production of nervous system disease of a type characterized by central-peripheral distal axonopathy (Spencer, 1978). When tissues removed from the nervous system of the animals treated with 1,6-hexanediol, they were indistinguishable from those obtained from control rats. Thus, 1,6-Hexanediol produced no signs of neurotoxicity. As the study was concentrating on neurpathological effects it is not considered to be the key study but for additional,

supporting information only.

Conclusion

Taking all available information into consideration, it can be concluded that 1,6 -Hexandiol is of rather low systemic toxicity and does not induce adverse effects except of weight changes in high dose males (1000 mg/kg/d). Hence, classification is not warranted with respect to repeated dose toxicity.

 


Justification for classification or non-classification

Classification for repeated dose toxicity is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.