Registration Dossier

Administrative data

Description of key information

The key data is from a reliable (Klimisch 2) 26 week oral gavage study using docosan-1-ol in rats. In this study a NOAEL > 1000 mg/kg was reported. A read across from a reliable 13 week dietary study in rats using hexan-1-ol reported a NOAEL of 1127 mg/kg for males and 1243 mg/kg bw/day for females (Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 243 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
This study examined male nad female albino rats for 13 weeks. Exposure to hexan-1-ol was through the diet. There were no clinical signs of toxicity or mortality and no changes in body weight or food consumption. Hematological, gross, and histopathological examinations showed no adverse signs. The NOAEL was 1127 mg/kg bw/day for males and 1243 mg/kg bw/day for females (highest doses tested).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

 

Alcohols, C20-30 (even numbered), is a UVCB substance that comprises several linear long chain alcohols, predominantly tetracosan-1-ol (C24), hexacosan-1-ol (C26), and octacosan-1-ol (C28). Together, these substances make up approximately 70% of the composition of Alcohols, C20-30 (even numbered). Other constituents include, to a much lesser extent, secondary long chain alcohols and complex mixtures of long chain carboxylate esters. On this basis, study data, where available, for each of the long chain alcohol constituents has been evaluated and considered together; this is consistent with the Category approach applied for Long Chain Alcohols (LCA) under REACH. 

 

Available data for D-002, a defined mixture of higher aliphatic alcohols (triacontanol, octacosanol, dotriacontrianol, hexacosanol, tetracosanol) isolated from beeswax, and policosanol, a mixture of long-chain primary aliphatic alcohols isolated and purified from sugar cane wax (octacosanol, triacontanol, hexacosanol, tetracosanol, heptacosanol, nonacosanol, dotriacontanol and tetratriacontanol) have also been considered in this evaluation.

 

In a conservative approach the most sensitive study result from the constituents of the LCA category have been identified and used to address the endpoint in question.

 

Data from a reliable (Klimisch 2) 26 week oral gavage study using docosan-1-ol in rats reported a NOAEL > 1000 mg/kg. In addition a 26 week oral study in dogs reported a NOAEL >2000 mg/kg. In a reliable study, the NOAEL for hexan-1-ol in rats following 13 weeks dietary exposure was 1127 mg/kg bw/day for males and 1243 mg/kg bw/day for females (highest doses tested). A subchronic study on D-002 in mice lead to the conclusion that D-002 is non-toxic with a NOAEL of 625 mg/kg/day and a chronic study on beagles also reported no toxic effects in doses up to 250 mg/kg/day. Two 12-month studies on policosanol, one on beagles and one on rats, elicited no drug-related toxic effects in the highest dose groups. Additionally a 54-week study in monkeys revealed no toxic effects at the highest does administered, 25 mg/kg/day. Policosanol results were similar in a 6 month study in mice, with no drug-related toxic effects seen in the highest does group, concluding NOAEL of >5000 mg/kg/day. 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. Consequently in line with the read-across justification included, Alcohols, C20-30 (even numbered), is considered to be of low toxicity with a NOAEL established at 1000mg/kg (for sub-chronic exposures).

 


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
This reliable Klimisch 2 study meets the generally accepted scientific principles and is acceptable for assessment.

Justification for classification or non-classification

These findings do not warrant the classification of Alcohols, C20-30 (even numbered),as repeated dose toxicant under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) and under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.