Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
no data
Effect on fertility: via oral route
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Additional information

No studies on toxicity to reproduction performed to international guidelines were available on Alcohols C12-13 branched and linear by any route, but some limited relevant data are available from a repeated dose toxicity study.

 

A 28-day oral toxicity study in rats (to OECD guideline 407 and compliant with GLP) provided supporting data for male reproductive toxicity. The test material (Safol 23) was diluted in corn oil and administered by gavage with no effects on the absolute weight or microscopic appearance of the testes. An NOAEL of 1000 mg/kg bw/day (the highest dose tested) was identified (Sasol 1999).

 

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 results from reproductive toxicity studies on single- or multiple-constituent alcohols with appropriate chain lengths could be read across to Alcohols C12-13 branched and linear.

 

In two combined repeat dose and reproductive/developmental toxicity screening tests, performed in rats to draft OECD guideline 422 and to GLP, oral NOAELs of 2000 mg/kg bw/day (the highest dose tested) were determined for Dodecanol and Octadecanol for both the parental and F1 generations (Hansen 1992a, 1992b).

 

A one-generation study was carried out with Docosanol in rats, following a protocol equivalent to OECD guideline 415 and to GLP. The NOAEL for the parental and the F1 generations was 1000 mg/kg bw/day, the highest dose tested (Iglesias, 2000b).

A read-across feeding study reported a lack of effects on the reproductive organs of rats receiving Hexanol (NOAEL 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).

 

No studies on toxicity to reproduction were available on any of the long chain linear aliphatic alcohol family by the dermal or inhalation routes.

 

No two-generation reproductive toxicity studies were available for any of the long chain linear aliphatic alcohol family.

On the basis that no fertility effects were seen for Dodecanol or Octadecanol at 2000 mg/kg bw/day, it seems reasonable to assume that a screening test on Alcohols C12 -13 branched and linear would be likely to give a similar result. The fact that Alcohols C12 -13 branched and linear had no effect on the testes at up to 1000 mg/kg bw/day provides additional reassurance.

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 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.


Short description of key information:
There were no effects on the testes in a 28-day oral study in rats with Alcohols C12-13 branched and linear at up to 1000 mg/kg bw/day (Sasol 1999). Oral NOAELs of 2000 mg/kg bw/day were determined for parental and F1 rats in reproductive toxicity screening tests with Dodecanol and Octadecanol (Hansen 1992a, 1992b) and 1000 mg/kg bw/day in a one-generation study with Docosanol (Iglesias, 2000b). A read-across feeding study reported a lack of effects on the reproductive organs of rats receiving Hexanol (NOAEL 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).

Effects on developmental toxicity

Description of key information
Results from rat studies on related materials included an oral NOAEL of 1440 mg/kg bw/day for Alcohols C7-11 branched and linear in a guideline developmental toxicity study (Hellwig & Jackh 1997) and oral NOAELs of 2000 mg/kg bw/day in developmental toxicity screening tests with Dodecanol and Octadecanol (Hansen 1992a, 1992b).
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Additional information

The multi-constituent alcohol identified as ¿Alcohols C12-13 branched and linear¿ includes the following mixtures:

1. Alcohols C12-13: >80% linear; >95% C12/13 [range C11-C15]; even & odd (CAS 75782-86-4)

2. Alcohols C10-16 type C: 80-95% linear; >95% C12/C13 [range C11-15]; even & odd (CAS 67762-41-8)

3. Alcohols C10-16 type B: 5-50% linear; >=95% C12/13 [range C11-C14]; even & odd (CAS 67762-41-8).

 

No developmental toxicity/teratogenicity studies were available on Alcohols C12-13 branched and linear by any route.

 

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 developmental toxicity / teratogenicity studies on single- or multiple-constituent alcohols with appropriate chain lengths can be read across to Alcohols C12-13 branched and linear.

 

A prenatal developmental toxicity study, performed to OECD guideline 414 and to GLP, was performed in rats dosed orally by gavage on days 6 to 15 of gestation with Alcohols C7-11 branched and linear at up to 1440 mg/kg bw/day. No maternal or developmental toxicity was seen and the top dose was therefore the NOAEL (Hellwig & Jackh 1997).

 

In two combined repeat dose and reproductive/developmental toxicity screening test, performed in rats to draft OECD guideline 422 and to GLP, oral NOAELs of 2000 mg/kg bw/day (the highest dose tested) were determined for Dodecanol and Octadecanol for both maternal and developmental toxicity (Hansen 1992a, 1992b).

 

On the basis that no developmental effects were seen for Alcohols C7-11 branched and linear at 1440 mg/kg bw/day or for Dodecanol or Octadecanol at 2000 mg/kg bw/day, it is reasonable to assume that a screening test on Alcohols C14-15 branched and linear would be likely to give a similar result.

 

No reliable guideline studies on developmental toxicity/teratogenicity were available on any of the long chain linear aliphatic alcohol family by the dermal 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.

Toxicity to reproduction: other studies

Additional information

no data

Justification for classification or non-classification

Based on the available data, Alcohols C12-13 branched and linear would not be classified as toxic to reproduction under Regulation (EC) No. 1272/2008 (CLP) or Directive 67/548/EEC (DSD). Tests on similar substances included in this category are also supportive of these results, which do not warrant classification for toxicity to reproduction under DSD or GHS criteria.

Additional information