Alcohols, C11-14-iso-, C13-rich

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data available.

Additional information

Based on the available data it can be concluded that isotridecanol is not a reproductive agent.

A one-generation study in rats (Hansen, 1992) was performed with the analog substance 1-dodecanol (CAS RN 112-53-8) using the Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test protocol. Male and female rats were administered 1-dodecanol orally via the feed at doses of 100, 500 and 2000 mg/kg/day for a period of 14 days. No effects were seen on reproductive or developmental parameters up to doses of 2000 mg/kg/day. 1-Dodecanol at the dose administered had no influence on body weight, weight gain, food consumption and reproductive efficiency in the parental generation. Pregnancy rates were not statistically altered and there were no differences in the lengths of the gestation periods. No organ toxicity was observed in the females, and there was no effect on the number of pups per litter, weight, sex ratio, or mortality rate from Days 1 to 5 after birth.

Short description of key information:
Low potential for reproductive toxicity.

Effects on developmental toxicity

Description of key information

Low potential for developmental toxicity.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

500 mg/kg bw/day

Additional information

Read across following an analogue approach is used to fill the developmental toxicity information requirement for the registered substance (Exxal 13), based on a hypothesis that the source (Exxal 11) and target substance (Exxal 13) elicit the same types of effects in biological systems due to their similarity in structure, metabolism to similar compounds through oxidation and Phase II conjugation reactions mediated by the constitutive androstane receptor (CAR), and similarity in effects observed in repeated dose studies (ie., effects in the liver with compensatory thyroid response).

In a PNDT study on Exxal 11, pregnant female rats were administered Exxal 11 by oral gavage at 0 (vehicle control), 100, 500, or 1000 mg/kg/day once daily from Gestation Day (GD) 6 through 20 (25 rats/group). The animals were sacrificed on GD 21 and the following parameters were evaluated: viability, maternal clinical signs, maternal body weight and body weight gain, maternal food consumption, maternal thyroid hormone evaluation, gross necropsy findings, maternal thyroid weight and histopathology, ovarian and uterine examination, fetal sex ration, fetal body weight, fetal anogenital distance, and fetal abnormalities (external, visceral, and skeletal). Maternal toxicity occurred consistent with the liver effects described in Table 4: at 500 and 1000 mg/kg/day, adult female livers were 30% and 93% enlarged, respectively. At the highest dose, a significant reduction in maternal body weight, maternal body weight gain and maternal food consumption occurred. The only fetal effects occurred at the highest dose: a 16% reduction in fetal body weights. No malformations occurred in any fetus at any dose. Thus, the reduction in fetal body weight is a non-specific secondary mechanism to maternal stress and disruption of homeostasis, due to the compromised systemic nutrition of the rat fetuses resulting from the disruption to homeostasis (adaptive liver changes and decreased food consumption). See detailed justification for this analogue-based read across hypothesis in the Section 13 assessment report titled: "Analogue-based read across approach Oxo alcohols.pdf".

Based on the Exxal 11 data, qualitatively similar effects are expected for the reproductive and developmental endpoint: maternal toxicity consisting of liver effects and compensatory thyroid response, reduced body weight gain, and reduced food consumption resulting in compromised fetal nutrition resulting in non-specific effects secondary to maternal stress. Reduced fetal body weight gain is observed at the highest dose and is the basis of the effect level. However, it should be noted that this effect is considered an non-specific secondary response to maternal toxicity. An absence of test-substance related primary effects on the fetus are expected at non-maternally toxic doses (500 mg/kg/day). The maternal NOAEL and developmental NOAEL are considered 500 mg/kg/day.

 

Justification for classification or non-classification

No classification for reproductive or developmental toxicity is indicated according to the general classification and labeling requirements for dangerous substances and preparations (Directive 67-548-EEC) or the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.

.