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Administrative data

Description of key information

The stomach and liver were the target organs for toxicity in a 7-day rat study with the Alcohols C9-11 linear and branched at 4150 mg/kg bw/day (Brown et al. 1970). In a guideline developmental toxicity study, maternal toxicity (clinical signs) was seen with Octanol at 130 mg/kg bw/day (Hellwig & Jackh 1997). A read-across from a reliable 13-week dietary study in rats using Hexanol reported a NOAEL of 1127 mg/kg bw/day and no adverse effects were noted at any of the dose levels administered during the study (Scientific Associates Inc. 1966).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
130 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

No repeated dose toxicity studies performed to international guidelines were available on Alcohols, C9-11 (odd numbered) branched and linear by any route, but a limited oral study has been reported.

 

The key study was a screening assay in which the test material (Linevol 911) was administered undiluted to male and female rats by oral gavage at 4150 mg/kg bw/day for 7 days. Evaluation comprised histopathological examination of major areas of the digestive tract and revealed adverse effects in the stomach and liver. An LOAEL of 4150 mg/kg bw/day was identified from this limited study (Brown et al. 1970).

 

The Category hypothesis is that the long chain linear aliphatic alcohol family has at its centre an homologous series of increasing carbon chain length, which is associated with a consistency and predictability in the property data across the group, for the physicochemical, environmental and toxicological property data sets. In view of the structural and chemical similarities, it is considered that the results from a number of reliable repeated dose toxicity studies on single- or multiple-constituent alcohols with appropriate chain lengths can be read across to Alcohols, C9-11 (odd numbered) branched and linear.

 

A developmental toxicity study was performed on two alcohols, to OECD guideline 414 and to GLP, in rats dosed orally on days 6 to 15 of gestation. With Octanol clinical signs were seen at 130 mg/kg bw/day, the lowest dose tested. There was no maternal toxicity with Alcohols C7-11 branched and linear at up to 1440 mg/kg bw/day and this top dose was therefore the NOAEL (Hellwig & Jackh 1997).

 

An oral NOAEL of 2000 mg/kg bw/day (the highest dose tested) was established in rats for Dodecanol, in a combined repeat dose and reproductive/developmental toxicity screening test performed to draft OECD guideline 422 and to GLP (Hansen 1992a).

For Hexanol, oral NOAELs were 1127 and 1243 mg/kg bw/day (the highest doses tested) in male and female rats respectively in a 90-day repeated dose toxicity test in which a somewhat limited range of endpoints was evaluated (Scientific Associates 1966a).

 

No repeated dose toxicity studies were available on any of the long chain linear aliphatic alcohol family by the dermal route.

No reliable guideline repeated dose toxicity studies were available on any of the long chain linear aliphatic alcohol family by the inhalation route.

Chronic and sub-chronic toxicity studies have shown that long chain alcohols (LCA) are of low toxicity. Furthermore, combined repeated-dose studies with developmental endpoints, as well as reproductive and developmental studies showed no effects at the highest dose tested. Rather than having separate values for the three endpoints, one endpoint “systemic effects” has been used instead. Since the NOAELs do not vary greatly across the category, one key study has been chosen as being representative of the whole category.

 

C6, Hexanol has been chosen as the category representative because shorter chain molecules are usually regarded as more toxic when compared to structural analogues with longer carbon chain lengths.

In some cases the CAS and chemical identity stated refer to the SDA nomenclature for this substance. In REACH substance identification it is necessary to be more specific as to the chain lengths present. Full details may be found in the CSR.


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; digestive: stomach

Justification for classification or non-classification

Based on the available data, Alcohols, C9-11 (odd numbered) branched and linear would not be classified for specific target organ toxicity-repeated exposure under Regulation (EC) No. 1272/2008 (CLP) since no adverse effects occurred at <100 mg/kg bw/day, or for danger of serious damage to health by prolonged exposure under Directive 67/548/EEC (DSD) since no adverse effects occurred at <50 mg/kg bw/day. Tests on similar substances included in this category are also supportive of these results, which do not warrant classification under DSD or GHS criteria.