Registration Dossier

Administrative data

Description of key information

Repeated dose toxicity:
- oral: NOAEL = 1000 mg/kg bw/day (OECD 407; analogue 1,6-hexanediol  CAS 629-11-8)
- oral: NOAEL = 400 mg/kg bw/day (OECD 408; analogue 1,6-hexanediol CAS 629-11-8)
- oral: NOAEL (systemic parental toxicity) = 1000 mg/kg bw/d (OECD 422; metabolite d-valerolactone CAS 542-28-9)

- oral: NOAEL (local parental toxicity)=  300 mg/kg bw/d (OECD 422; metabolite d-valerolactone CAS 542-28-9)

 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
400 mg/kg bw/day

Additional information

The evaluation of the endpoint repeated dose toxicity of 1,5-pentanediol (CAS 111-29-5) is based on a weight of evidence approach using the toxicological data of the chemical analogue 1,6-hexanediol (CAS 629-11-8) and main metabolite of 1,5-pentanediol d-valerolactone (CAS 542-28-9) (for WoE information, see chapter 13.2).

 

1,6-Hexanediol:

Subacute toxicity study (oral, 28 days):

A repeated dose 28 -day oral toxicity study was conducted according OECD method 407 and EU method B.7. Five male and five female Wistar rats per dose received doses of 100, 400 and 1000 mg/kg/d 1,6-hexanediol (BASF, 1995). The only observable effects was a statistical significant decrease in body weight in females of the 400 mg/kg bw group and decreased body weight gain in female r.ats at the 400 and 1000 mg/kg/d dose level towards the end of the study, r)espectively. 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 reported 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 dose toxicity 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 inmale 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.

 

 

d-Valerolactone:

OECD 422, oral

d-Valerolactone was tested in a repeated dose/reproductive toxicity screening test (BASF SE, 2013, OECD 422). One local finding in the forestomach noted at 1000 mg/kg bw/d in a single female rat was the only local adverse effect observed after oral application. Therefore, a NOAEL for local parental toxicity of 300 mg/kg bw/d and a NOAEL for systemic parental toxicity of 1000 mg/kg bw/d was derived from this study.

 

 

Conclusion

Taking all available information into consideration, it can be concluded that 1,6 -hexanediol and d-valerolactone are of rather low systemic toxicity and do not induce excessive adverse effects at high doses (1000 mg/kg/d). Hence, classification is not warranted with respect to repeated dose toxicity. Considering the structural similarity of 1,5 -pentanediol and 1,6 -hexanediol and the in vivo metabolization to d-valerolactone, it can be concluded that 1,5 -pentanediol does also not pose any risk to human health and does hence not require classification with respect to repeated dose toxicity.

 

 

 

 

 

 

Justification for classification or non-classification

The available information do not warrant classification of 1,5 -pentanediol with respect to repeated dose toxicity according to Directive 67 /548/EEC and according to Regulation EC1272/2008 (CLP), respectively.