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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Male and female Sprague Dawley rats were chosen for a one-generation reproductive toxicity study. Reproduction function in the male and female was examined as well as reproductive performance, both which had no changes due to treatment. Parental animals had no changes in body weight, histopathological or gross pathological parameters. Offpsring also had no effects seen for viability or gross pathology.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
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. 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.

The conclusion that the members of the aliphatic long chain alcohol category (C6 to C22) are not expected to impair dertility is based on a weight of evidence approach using data from reproductive screening studies for docosonol (C22), icosanol (C20), hexanol (C6), D002, and policosanol and fertility studies for docosanol (C22),icosanol (C20) , D002 and policosanol together with a lack of effect on the reproductive organs in repeat dose studies over the range of linear and essentially linear alcohols. In addition there have been no other treatment related effects reported in any of the other studies using long chain alcohols.

 

On the basis of this reproductive toxicity information included as part of this submission and in line with the read-across justification it is concluded that Alcohols, C20-30 (even numbered), is not likely to impair fertility.


Short description of key information:
A reliable one-generation reproduction study using docosan-1-ol in rats reported a NOAEL of 1000 mg/kg.

A read across feeding study reported a lack of effects on the reproductive organs of rats receiving hexan-1-ol (Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study.

A study on male and female NMRI mice over a 6 or 8 week period reported doses of D-002 up to 625 mg/kg-day that showed no sign of reproductive toxicity.

Justification for selection of Effect on fertility via oral route:
In a reliable (Klimisch 2) generational study, conducted to a protocol similar to OECD guideline 415 and performed in compliance with GLP. The appropriate species, doses groups, animals per dose and time period was selected.

Effects on developmental toxicity

Description of key information
A reliable developmental toxicity study using docosan-1-ol in rabbits reported a NOAEL for developmental and maternal effects of > 2000 mg/kg. 
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subchronic
Species:
rabbit
Quality of whole database:
Female New Zealand white rabbits were treated on days 6-19 of gestation to examine maternal and embryotoxic effects. Three dose groups were chosen and 22 rabbits were placed in each group. Both maternal and fetal examinations were made. There were no maternal effects except for pale faces in the highest dose group and there were no embryotoxic or teratogenic effects.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
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. 

 

A reliable (Klimish 2) study examining the developmental and teratogenicity of D-002, a defined mixture of higher aliphatic alcohols (triacontanol, octacosanol, dotriacontrianol, hexacosanol, tetracosanol) isolated from beeswax, has also been considered. Both Sprague Dawley rats and New Zealand White rabbits showed no maternal or fetal adverse effects due to gestational exposure to doses of D-002 up to 1000 mg/kg bw/day. A reliable (Klimisch 2) study on policosanol administered the test substance to Sprague Dawley rats on gestation days 6-15 and New Zealand White rabbits on gestation days 6-18 at doses up to 500 and 1000 mg/kg/day, respectively. Administration to both species revealed no drug related developmental toxicity. 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.

 

Based on the weight of evidence from other alcohols across the category it is concluded that tetracosan-1-ol, hexacosan-1-ol, and octacosan-1-ol are unlikely to be a developmental toxicant in the absence of maternal toxicity. Consequently on the basis of this information Alcohols, C20-30 (even numbered), is also unlikely to be developmental toxicant in the absence of maternal toxicity.


Justification for selection of Effect on developmental toxicity: via oral route:
Comparable to guideline study without detailed documentation and in GLP compliance.

Justification for classification or non-classification

These findings do not warrant the classification of Alcohols, C20-30 (even numbered), as reproductive/developmental 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.

Additional information