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Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL (maternal and reproduction) = 1000 mg/kg/g (OECD 421, BASF AG (1995), analogue substance 1,6-hexanediol CAS 629-11-8 and OECD 422, BASF SE (2013), metabolite d-valerolactone CAS 542-28-9)

Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

The evaluation of th endpoint toxicity to reproduction 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

The Reproduction / Developmental Toxicity Screening Test with 1,6-hexanediol was conducted under GLP according to OECD Guideline 421 to evaluate toxicity to reproduction and development (BASF, 1995).

Thereby, ten male and ten female Wistar rats per dose received 1,6-hexanediol at doses of 100, 400 and 1000 mg/kg/d by gavage. The application period was about four weeks for males and about six weeks for the females starting at least 14 day before mating. After the mating period, the male animals were sacrificed while the females were allowed to litter and rear their pups until day 4 post partum. Thereafter, the pups (F1-generation) and the F0-females were sacrificed. It was found, that the food consumption of F0 males at the 1000 mg/kg bw/day dose level was statistically significantly reduced during study weeks 0 - 1 and 3 – 4 resulting in a statistically significantly reduced mean body weights at the end of the study. The body weight gains of the high dose F0 males were also statistically significantly lower compared to the control F0 males between test weeks 2 - 3 and over the total study period. However, no substance-related effects on organ weights and no gross- and histopathological findings were observed in F0 males and females. As there is no corresponding effects to organ weight nor any histopathologically effect in this study, the observed effect is not considered to be advese. No signs for general toxicity were present in males and in females at 1000, 400 and 100 mg/kg bw/day. In addition, no signs for impairment of reproductive function and no signs of developmental toxicity in the offspring were apparent. Therefore, the NOAEL for parental and F0 toxicity was found to be 1000 mg/kg bw/day for females and for males; the NOAEL for reproductive function and for developmental toxicity was 1000 mg/kg/ bw/day.

 

d-Valerolactone

Furthermore the data of d-valerolactone from a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (according to OECD 422) did not indicate adverse effects on reproductive organs, tissues or behaviour up to the limit dose of 1000 mg/kg bw/day.

 

Short description of key information:
According to the results of the reproductive toxicity screening studies with 1,6 hexanediol and d-valerolactone, 1,5-pentanediol is not considered to be a reproductive toxicant. There was no effect at the limit dose of 1000 mg/kg bw/day.

 


Toxicity to reproduction:
- NOAEL = 1000 mg/kg bw/day (OECD 421; 1,6-hexanediol CAS 629-11-8, OECD 422; d-valerolactone 542-28-9)

 

Effects on developmental toxicity

Description of key information

NOAEL (maternal and developmental) = 1000 mg/kg/g (OECD414, BASF SE (2014), analogue substance 1,6-hexanediol CAS 629-11-8 and OECD 414, BASF SE (2016), metabolite d-valerolactone CAS 542-28-9)

Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

Developmental Toxicity:

There is no data available with the test substance 1,5 -pentanediol. However, the potential of the test substance to indcue developmental toxicity can be assessed through the toxicity data of its structural analogue 1,6 -hexandiol and its metaolite d-valerolatone in a weight of evidence approach (for WoE information, see chapter 13.2).

The potential of 1,6 -hexanediol to induce developmental toxicity was assessed in an OECD 414 guideline study (BASF SE, 2014). In this prenatal developmental toxicity study the test compound 1,6 -hexanediol was administered to pregnant Wistar rats daily by gavage from implantation to one day prior to the expected day of parturition (GD 6-19) to evaluate its potential maternal and prenatal developmental toxicity.

Analyses confirmed the correctness of the prepared concentrations and the stability of the test substance in the vehicle. Generally, clinical observations revealed no toxicologically relevant findings in the animals receiving 100, 400 or 1000 mg/kg bw/d 1,6 -hexanediol. No differences of toxicological relevance between the control and the treated groups (100, 400 or 1000 mg/kg bw/d) were observed for any reproductive parameters, such as conception rate, mean number of corpora lutea, mean number of implantations, as well as pre- and postimplantation loss. Similarly, no influence of the test compound on fetal weight and sex distribution of the fetuses was noted at any dose.

Overall, there was no evidence for any toxicologically relevant adverse effect of the test item on fetal morphology at any dose.

 

Furthermore, the metabolite d-valerolactone was tested in a recent OECD 414 study and no treatment-related adverse systemic effect or developmental toxicity/teratogenicity was observed after oral application up to the limit dose.

 

Short description of key information:
According to the results of the developmental toxicity studies with 1,6 hexanediol and d-valerolactone, 1,5-pentanediol is not considered to be a reproductive toxicant. There was no effect at the limit dose of 1000 mg/kg bw/day.

 

Developmental toxicity:
- NOAEL = 1000 mg/kg bw/day (OECD 414; 1,6-hexanediol CAS 629-11-8, OECD 414; d-valerolactone 542-28-9)

Justification for classification or non-classification

Due to the results of guideline studies with the structural analogue 1,6-hexanediol and the metabolite d-valerolactone no classification for reproductive/developmental toxicity is necessary for 1,5 -pentanediol according to Directive 67/548/EEC and Regulation 1272/2008 (CLP).

Additional information