Panthenol , DL-form

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

GLP and guideline study

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Short description of key information:
The assessment of toxicity to fertility was done by a read across approach from DL- Ethyl Panthenol. No adverse effects on spermatogenic endpoints (testicular and epididymal sperm numbers, sperm production rate, motility, and the percentage of morphological normal sperm), estrous cycle and reproductive organs could be observed in a subchronic 90- day oral toxicity study with DL- Ethyl Panthenol (see section 7.5.1). The close structural similarity between DL-Ethyl Panthenol and Panthenol strongly suggest that there are also no adverse effects on spermatogenic effects with DL- Panthenol.

Justification for selection of Effect on fertility via oral route:
In a oral repeated dose toxicity study with DL- Ethyl Panthenol spermatogenic endpoints were evaluated (see 7.5.1). For justification of read across please refer to the attachment in IUCLID5 section 13.

Effects on developmental toxicity

Description of key information

The assessment of developmental toxicity was done by a read across approach from DL- Ethyl Panthenol. No fetal malformations or developmental variations were attributed to DL- Ethyl Panthenol. In addition no test item-related clinical findings or effects on maternal body weight, body weight gains, or food consumption were observed at any dosage level.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Species:

rat

Quality of whole database:

GLP and guideline study

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Developmental toxicity (read across):

The objective of the study was to determine the potential of DL-Ethyl Panthenol to induce developmental toxicity after maternal exposure from implantation to 1 day prior to expected parturition, to characterize maternal toxicity at the exposure levels tested and to determine a no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity. The study was conducted in compliance with GLP regulations and in accordance with regulatory guidelines, including OECD 414.

The test item, DL- Ethyl Panthenol, in the vehicle (deionized water), was administered orally by gavage to 3 groups of 25 bred female Crl:CD(SD) rats once daily from gestation days 6 through 19. Dosage levels were 250, 500, and 1000 mg/kg/day administered at a dosage volume of 10 mL/kg. Dosages were selected following a range-finding study in which systemic exposure was demonstrated in the pregnant rat. A concurrent control group composed of 25 bred females received the vehicle on a comparable regimen. The females were approximately 14 weeks of age at the initiation of dose administration. All animals were observed twice daily for mortality and moribundity. Clinical observations, body weights, and food consumption were recorded at appropriate intervals. On gestation day 20, a laparohysterectomy was performed on each female. The uteri, placentae, and ovaries were examined, and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. Gravid uterine weights were recorded, and net body weights and net body weight changes were calculated. The fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations and developmental variations.

The analyzed dosing formulations were within the requested limits (85% to 115%), homogeneous, and stable after 10 days of refrigerated storage. All females survived to the scheduled necropsy on gestation day 20. There were no test article-related clinical observations noted at any dosage level. Additionally, there were no test article-related maternal macroscopic findings noted at the scheduled necropsy. There were no test article-related effects on body weights, body weight gains, net body weights, net body weight gains, or food consumption at any dosage level tested. Based on the parameters evaluated, including postimplantation loss, litter size, mean fetal body weights, and fetal sex ratios, intrauterine growth and survival were unaffected by test article administration at all dosage levels tested. There were no test article-related external, visceral, or skeletal malformations or developmental variations observed at any dosage level tested.

There were no test article-related clinical findings or effects on maternal body weight, body weight gains, or food consumption observed at any dosage level. In addition, there were no test article-related effects on embryo/fetal development at any dosage level. Based on the results of this study, a dosage level of 1000 mg/kg/day, the highest dosage level evaluated, was considered to be the no-observed-adverse-effect level (NOAEL) for maternal toxicity and embryo/fetal development when DL- Ethyl Panthenol was administered orally by gavage to bred Crl:CD(SD) rats. Based on these data it can be concluded that animals fed with DL-Ethyl Panthenol are concurrently exposed to Panthenol. Due to structure similarity and the absence of any effect in the developmental toxicity study with DL-Ethyl Panthenol in rats up to the highest tested dose of 1,000 mg/kg bw/d, it is highly likely that DL- Panthenol shows any developmental toxicity.

Justification for selection of Effect on developmental toxicity: via oral route:
In a developmental toxicity study with DL- Ethyl Panthenol no adverse effects on embryonic/fetal development occured. For justification of read across please refer to the attachment in IUCLID5 section 13.

Justification for classification or non-classification

Based on the results of the developmental toxicity/ teratogenicity study and the 90-days- oral repeated dose toxicity study (NOAEL = 1000 mg/kg bw/ d) with DL- Ethyl Panthenol, DL -Pantenol is not classified according to EU Directive 67/548/EEC or EU Regulation (EC) No 1272/2008. For justification of read across please refer to the attachment in IUCLID5 section 13.