Alcohols C13-15 (branched and linear, odd numbered), reaction product with 1-chloro-2,3-epoxypropane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

A prenatal developmental toxicity test (OECD test guideline 414) has been conducted on test substance (WIL Research Laboratories, Inc., 1997). This test was designed to provide information on the possible effects of test substance on reproduction and/or development by dermal in the rats at concentrations of 0, 10, 50, 100 and 200mg/kg/day.

All maternal animals survived to the scheduled necropsy on gestation day 20. The only treatment-related clinical sign observed was vocalization at the time of dosing in the 50, 100 and 200 mg/kg/day groups between gestation days 7 and 15.

Dermal irritation at the application site was observed in the 50, 100 and 200 mg/kg/day groups. Erythema, oedema and desquamation occurred in all animals in these groups (with the exception of no oedema for one 50 mg/kg/day group animal). The severity and/or time of onset for these findings were dose-related. More severe signs of dermal irritation were noted only at dose levels of 100 and 200 mg/kg/day. These included fissuring, eschar formation and atonia in two to five 100 mg/kg/day group animals and in all 200 mg/kg/day group animals. The severity of erythema and oedema and the frequency of fissuring, eschar formation and atonia tended to decrease during the post-treatment period. No test article-related dermal irritation was noted at the application site in the 1 and 10 mg/kg/day groups. Findings at the application site were limited to scabbing in two and six animals in the 100 and 200 mg/kg/day groups, respectively, and thickening in two of these high dose group animals.

Parameters evaluated included post implantation loss, mean fetal body weight, viable litter size, fetal sex ratios and the mean numbers of corpora, lutea and implantation sites. One control group fetus had macroglossia. No other external malformations and no external developmental variations were observed in fetuses in this study.

In conclusion, localized dermal irritation was observed in a dose-related manner at dose levels of 50, 100 and 200 mg/kg/day. No maternal toxicity or developmental toxicity was apparent at any dose level. Based on the results of this study, the no-effect level for dermal irritation was considered to be 10 mg/kg/day and the no-effect level for maternal toxicity and developmental toxicity was considered to be 200 mg/kg/day.

Short description of key information: Only localized dermal irritation was observed in a dose-related manner at dose levels of 50, 100 and 200 mg/kg/day. No maternal toxicity or developmental toxicity was apparent at any dose level. Based on the results of this study, the no-effect level for dermal irritation was considered to be 10 mg/kg/day and the no-effect level for maternal toxicity and developmental toxicity was considered to be 200 mg/kg/day.

Justification for selection of Effect on fertility via oral route: Since the most likely route is considered to be via dermal, the test via oral can be waived.

Justification for selection of Effect on fertility via inhalation route: Since the most likely route is considered to be via dermal, the test via inhalation can be waived.

Effects on developmental toxicity

Description of key information

The only treatment-related clinical sign observed was vocalization at the time of dosing in the 50, 100 and 200 mg/kg/day groups.
No external fetal malformations were observed in the treated groups, and no external developmental variations were noted in fetuses in this study.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

A potential maternal toxicity and developmental toxicity of test substance was available by dermal route. The test article in acetone was administered as a single daily application to six groups of eight bred Crl:CD@(SD)BR rats, from gestation days 6 through 15. The test article was applied to the clipped intact dorsal skin (10% area) of each rat. The application sites were not occluded. Dosage levels were 1, 10, 50, 100 and 200 mg/kg/day administered at a dose volume of 1 ml/kg. A concurrent control group, composed of eight bred females, received the vehicle, acetone, on a comparable regimen at 1 ml/kg.

On day 20 of gestation, all females were euthanized and scheduled laparohysterectomies were performed. The uteri and ovaries were examined and the numbers of fetuses, early and late resorptions, total implantations and corpora lutea were recorded. Mean gravid uterine weights and net body weight changes were calculated for each group. Fetuses were weighed, sexed and examined for external malformations and developmental variations.

 

All maternal animals survived to the scheduled necropsy on gestation day 20; no test article-related internal findings were observed. The only treatment-related clinical sign observed was vocalization at the time of dosing in the 50, 100 and 200 mg/kg/day groups. Body weight gain and food consumption in the treated groups were unaffected by test article administration. Intrauterine growth and survival were also unaffected at all dose levels. No external fetal malformations were observed in the treated groups, and no external developmental variations were noted in fetuses in this study.

Justification for selection of Effect on developmental toxicity: via oral route: Since the most likely route is considered to be via dermal, the test via oral can be waived.

Justification for selection of Effect on developmental toxicity: via inhalation route: Since the most likely route is considered to be via dermal, the test via inhalation can be waived.

Justification for classification or non-classification

Only localized dermal irritation was observed in a dose-related manner at dose levels of 50, 100 and 200 mg/kg/day. No maternal toxicity or developmental toxicity was apparent at any dose level. Based on the results of this study, the no-effect level for dermal irritation was considered to be 10 mg/kg/day and the no-effect level for maternal toxicity and developmental toxicity was considered to be 200 mg/kg/day. Therefore, test substance is not classified under CLP (Regulation EC No.1272/2008).