Alcohols, C8-10-iso-, C9-rich

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Based on the available data for an analog substance, isononanol will not be a reproductive toxicant. 

 

Briefly, the read-across hypothesis is that the 5 Exxal alcohols elicit qualitatively similar effects in biological systems (i.e., effects on the liver with compensatory thyroid response) due to their similarity in structure and subsequent metabolism to similar compounds via oxidation and Phase II conjugation reactions mediated by the constitutive androstane receptor (CAR). Quantitatively, the strength of the primary effect (activation of CAR and enzyme induction) increases as the carbon-chain length distribution increases. See assessment reports in section 13 on the read-across approach for Oxo alcohols for human health endpoints for details on substance similarity, toxicological similarity, and read-across hypothesis. 

 

Please see the Chapter 13 assessment report (Part 2: Read across approach for HH endpoints) for an overview of the planned approach to fill the reproductive and developmental toxicity endpoints across the 5 Exxal substances. Fertility effects will be assessed n extended one-generation studies currently planned (on isooctanol) or in progress (on isoundecanol), in response to compliance checks. This information will be submitted later based on ECHA communication/decision number TPE/CCH-D/xxxxxxxxxx-xx-xx/x (draft decision letter on isooctanol dated 26 April 2022). In response to a compliance check on isononanol (draft decision letter dated 25 April 2022), it is proposed that the results of planned and in progress extended one-generation and prenatal developmental studies in rats and in rabbits (on isooctanol and isoundecanol) be completed prior to a decision on whether the read across hypothesis is valid to predict reproductive/developmental endpoints or if additional animal testing on isononanol is warranted.

 

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

1 000 mg/kg bw/day

Additional information

The potential for developmental effects is low based on available studies. Based on read across to structurally and toxicologically similar substances, two prenatal development studies in which isooctanol was administered to rats at doses up to 1000 mg/kg bw/day showed no evidence of litter-based, statistically significant adverse effects on uterine implantation parameters, mean fetal body weight, or fetal variation/malformations (developmental NOAEL=1000 mg/kg bw/day).  A prenatal development study in which isoundecanol was administered to rats at doses up to 1000 mg/kg bw/day identified no fetal effects in the absence of maternal toxicity. The developmental NOAEL is 500 mg/kg bw/day, based on reduced fetal body weight that occurred concurrently with maternal morbidity, mean body weight losses, lower mean body weight gains, and reduced food consumption (at 1000 mg/kg bw/day).

 

Please see the Chapter 13 assessment report (Part 2: Read across approach for HH endpoints) for an overview of the planned approach to fill the reproductive and developmental toxicity endpoints across the 5 Exxal substances. A prenatal developmental study in rabbits on isooctanol is planned in response to a  compliance check, this information will be submitted later based on ECHA communication/decision number TPE/CCH-D/xxxxxxxxxx-xx-xx/x (draft decision letter on isooctanol dated 26 April 2022). In response to a compliance check on isononanol (draft decision letter dated 25 April 2022), it is proposed that the results of planned and in progress extended one-generation and prenatal developmental studies in rats and in rabbits (on isooctanol and isoundecanol) be completed prior to a decision on whether the read across hypothesis is valid to predict reproductive/developmental endpoints or if additional animal testing on isononanol is warranted.

 

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

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.

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