Alcohols, C12-13-branched

Endpoint summary

Description of key information

In a guideline 28-day study, an oral NOAEL of 300 mg/kg bw/day was determined for Safol 23 (Sasol 1999) but the effects seen in this study are not ascribed to a dose response effect but rather are associated with the method of dosing, and therefore are not suitable as a basis for DNEL. In studies on related materials, oral NOAELS were 2000 mg/kg bw/day for Dodecanol (Hansen 1992a) and 1440 mg/kg bw/day for Alcohols C7-11 branched and linear (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

723 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

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.

 

The key study was a 28-day oral toxicity assay, conducted to OECD guideline 407 and to GLP, in which the test material (Safol 23) was diluted in corn oil and administered to male and female rats by oral gavage. An NOAEL of 300 mg/kg bw/day was identified from this study, based on adverse effects at 1000 mg/kg bw/day (clinical signs, body weight, food consumption, food efficiency, haematology, clinical chemistry) (Sasol 1999). The effects seen in this study are not ascribed to a dose response effect but rather are associated with the method of dosing, and therefore are not suitable as a basis for DNEL.

 

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 C12-13-branched.

 

In a combined repeat dose and reproductive/developmental toxicity screening test performed to draft OECD guideline 422 and to GLP, an oral NOAEL of 2000 mg/kg bw/day (the highest dose tested) was established in rats for Dodecanol (Hansen 1992a). No maternal toxicity was seen in rats after oral gavage dosing with Alcohols C7-11 branched and linear at up to 1440 mg/kg bw/day on days 6 to 15 of gestation and this top dose was therefore the NOAEL (Hellwig & Jackh 1997). 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).

 

For Hexadecanol, oral NOAELs were 723 and 875 mg/kg bw/day in male and female rats respectively in a 90-day repeated dose toxicity test in which a somewhat limited range of endpoints was evaluated, based on adverse effects in males and females at 1822 and 2064 mg/kg bw/day and above, respectively, including reduced food consumption in both sexes and also reduced body weight gain and some organ weight changes in females (Scientific Associates 1966a). Using a protocol similar to OECD guideline 407, a GLP study, in which male and female rats were administered Hexadecanol by oral gavage on 5 days/week for 28 days, established an NOAEL of 1000 mg/kg bw/day, the highest dose tested (Henkel 1985a). In a limited study, conducted prior to the introduction of GLP, Alcohols C16-18 and C18 unsatd. was administered to male and female at a single dose level of 840 mg/kg bw/day by oral gavage and no toxicity was reported (Henkel 1973).

 

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.

Justification for classification or non-classification

Based on the available data, Alcohols C12-13 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.