Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 211-546-6 | CAS number: 661-19-8
In the key study, no adverse effects were seen after dietary administration of a reliable 13 week oral feeding study in rats using hexadecan-1-ol, resulting in a NOAEL value of >4400 mg/kg bw. (Scientific Assoc, 1966a; rel. 2) In addition read across from a reliable 28 day oral gavage study in rats using octadecan-1-ol reported a NOAEL value of >1000 mg/kg bw (Henkel, 1985a; rel. 2). A four week reliable oral study in rats using octadecan-1-ol reported a NOAEL value of >1000 mg/kg bw, the highest dose tested (Henkel, 1986a; rel. 1). A reliable 26 week oral gavage study in rats using docosan-1-ol reported no adverse effects at the highest dose tested, 1000 mg/kg bw (Iglesias et al., 2002a). Further supporting data come from a 90 day feeding study in rats with of Alcohols, C14-15-branched and linear (Ito et al., 1978) which reported a NOAEL value of >3548 mg/kg bw/day. Read across data from a reliable 13 week dietary study in rats using hexan-1-ol reported a NOAEL of 1127 mg/kg (Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study.
For hexadecan-1-ol, oral NOAELs were > 4257 and > 4567 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 (Scientific Associates 1966a).
Read across data from the reliable 13 week repeat dose/reproductive oral feeding study in rats using structurally analogous hexadecan-1-ol (Scientific Associates 1966a) will be considered as the basis for classification for docosan-1-ol. The key study was selected from data for substances with similar human health classification and physicochemical properties and therefore absorption properties to the registration substance. As no adverse systemic effects were observed for category members, the study using the highest dose from the available data was selected as key. A full discussion of the Category can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016). The available repeated dose toxicity data for long chain alcohols have been reviewed and discussed, with the conclusion that the long chain alcohols are of low systemic toxicity (Veenstra G, Webb C et al., 2009).
In a 13-week study in rats hexadecan-1-ol (CAS 36653-82-4) was administered in the diet at concentrations of 0 (control), 1, 2.5 or 5- 10%; the level in the highest dose group being increased stepwise to 10% during the last 3 weeks of the study. Reductios in body weight gain (82-90% of control values) and food consumption (76 – 90% of control values) in the highest dose group and, occasionally, at the 2.5% level were the main findings of this study. Relative liver weights were increased in males at the top dose level (124% of control values) but in the absence of any microscopic findings the significance of this change is uncertain. A NOAEL was established to be equivalent to 4400 mg/kg/day (Scientific Assoc., 1966a).
A read across from a reliable 13 week dietary study in rats using hexan-1-ol reported a NOAEL of 1127 mg/kg. No adverse effects were noted at any of the dose levels administered during the study.
Supporting data are available from a 28 day repeated dose oral study in which octadecan-1-ol was administered by oral gavage to male and female rats at 0, 100, 500, 1000 mg/kg bw/day (Henkel, 1986). Statistically significant changes in some clinical chemical and haematological parameters and organ weights changes were not accompanied by histopathological changes and were either not dose related or appeared in only one sex. These effects are not considered of toxicological significance, so the NOAEL is considered to be >1000 mg/kg/day, the highest dose tested.
Further data for octadecan-1-ol comes from a combined repeated dose and reproductive/developmental screen feeding study in which octadecan-1-ol was tested in Wistar rats. Male animals were exposed for 37 days including the mating period, and no treatment-related histopathological changes were recorded. Clinical changes observed were without a dose response and are not considered to be adverse. The NOAEL was established to be 30 000ppm equivalent to 2000 mg/kg/day, the highest dose tested (Hansen, 1992b).
Docosan-1-ol (CAS 661-19-8) was administered daily to groups of rats at levels up to 1000 mg/kg for 26 weeks. Body weight and food consumption was not affected by treatment. Haematology, clinical chemistry and gross necropsy investigations showed no evidence of toxicity. There were no treatment related microscopic changes (Iglesias et al., 2002b).
In a 26-week oral gavage study docosan-1-ol (CAS 661-19-8; C22 alcohol) was administered daily to groups of dogs in levels up to 2000 mg/kg. Body weight and food consumption was not affected by treatment. Haematology, clinical chemistry and gross necropsy investigations showed no evidence of toxicity. There were no treatment related microscopic changes (Iglesias et al., 2002b).
Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:
In summary, the sub-category of the linear LCAAs is of a low order of toxicity upon repeated exposure. The LCAAs at lower end of this group caused local irritation at the site of first contact and induced signs of depression and respiratory effects when administered at very high dose levels and only as a bolus dose (C6, C8 alcohol) in the dog (C6 alcohol) and the rat (C8 alcohol). Other routes of exposure induced no apparent neurotoxicity either centrally or peripherally. Intermediate (>C8 to C12) and higher (>C12) linear LCAAs are non-irritant at the site of first contact and are without a neurotoxic potential. At high dose levels some of the higher LCAAs showed changes in clinical chemistry and liver weight but without further evidence of systemic toxicity; this finding may be indicative of mild, sub-clinical effects in the liver. There are no species differences observed for this sub-category, based on a comparison of the results of parallel studies in the rat and the dog.
In summary, the data for the essentially linear LCAAs, including the data from supporting substances, indicate a low order of toxicity upon repeated exposure. A consistent finding for this group is the effect on the liver: mild organ weight increases and/or slight clinical chemical changes but without evidence of significant histopathological effects. The clinical chemistry changes were generally of a slight grade but showed some inconsistencies, some of which relating to decreases in transferase activity, a change not normally associated with adverse hepatic effects. The (small) degree of the liver weight increases, the pattern of the clinical chemical changes and the absence of markers support the conclusion that this sub-category of LCAAs lacks a potential for the induction of peroxisomal proliferation. There is evidence of irritation at the first site of contact for the lower members of this group.
The repeat dose toxicity of the category of LCAAs with chain lengths ranging from C6 to C22 indicates a low order of toxicity upon repeated exposure. NOAELs recorded for this category range between approx. 200 mg/kg/day to >4000 mg/kg/day in the rat upon sub-chronic administration via the diet. No adverse systemic effects have been seen in reliable studies with members of the Category of C6-24 Alcohols, therefore the NOAELs represent the highest dose tested. At the lower end, members of this category induce local irritation at the site of first contact. Other notable findings observed for several members within this group suggest mild changes consistent with low-grade liver effects with the changes in essentially linear LCAAs being slightly more pronounced than in linear alcohols. Typical findings include: slightly increased liver weight, in some cases accompanied by clinical chemical changes but generally without concurrent histopathological effects. Special studies demonstrated that this category does not have a potential for peroxisome proliferation. A potential for depression as observed for short chain aliphatic alcohols (C1 to C4; not included in this category) was also identified for hexan-1-ol and octan-1-ol, however this effect was only expressed upon repeated administration of a bolus dose; effects were absent upon inhalation or dietary administration. Similarly, hexan-1-ol and octan-1-ol induced respiratory distress upon repeated administration of a bolus dose. LCAAs do not have a potential for peripheral neuropathy. Furthermore, the data from the substances supporting this category (i.e. isoamyl alcohol), demonstrate that the toxicological profile of the repeated dose toxicity of 100% branched alcohols is qualitatively similar to that of the corresponding essentially linear alcohols. Chronic and sub-chronic toxicity studies have shown that LCAAs 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. Where data gaps exist, the gap is filled by read-across from reliable evidence within the C6-24 Alcohols Category, where possible using interpolation between at least two reliable studies using higher and lower carbon number test substances.
Repeated dose toxicity data for the Category
Species/ Study type/
Isoamyl alcohol (supporting)
Rat 17 wk
500 mg/kg(Carpanini, 1973)
Dog 13 wk
Rat 13 wk
1127 mg/kg (Sc.Assoc.’66)
Rat 3 wk
1000 mg/kg bw/day (Moody, 1978-1982)
Rat subchronic 30 wk
No peripheral neuropathy (Perbellini et al., 1978)
Rat Dev. Tox.
130 mg/kg (Hellwig, 1997)
No systemic toxicity expected based on read across of a dermal study on Fatty Alcohol Blend of which octan-1-ol is a constituent, and on read-across from an oral study on hexan-1-ol. No adverse systemic effects were observed at the highest dose in either study.
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.
No systemic toxicity expected based on read across of a dermal study on Fatty Alcohol Blend of which decan-1-ol is a constituent, and on read-across from an oral study on hexan-1-ol. No adverse systemic effects were observed at the highest dose in either study.
2000 mg/kg (Hansen,1992a)
Rat 2 wk
184 mg/kg (Rhodes, 1984)
Rat 4 wk
>1000 mg/kg (Henkel, 1985a)
>1054 mg/kg (Sc.Assoc,
>4257 mg/kg(Sc.Assoc, 1966a)
Rat 5 wk
>1000 mg/kg (Henkel, 1986a)
2000 mg/kg (Hansen, 1992b)
Rat 26 wk
Dog 26 wk
Nonan-1-ol, branched and linear
Decan-1-ol, branched and linear
Undecan-1-ol, branched and linear
Tridecan-1-ol, branched and linear (supporting)
Low systemic toxicity expected
Pentadecan-1-ol, branched and linear
Rat 1 wk
4175 mg/kg(Brown, 1970)
128 mg/kg(Rhodes, 1984)
Fatty Alcohol Blend
rat 90 day
1000 mg/kg bw/day
Alcohols, C9-11- branched and linear
>0.158 mg/L.(Darmer, 1982)
<4150 mg/kg(Brown, 1970)
Reaction mass of 2-methyldecan-1-ol and 2-propyloctan-1-ol and 2-ethylnonan-1-ol and 2-butylheptan-1-ol
300 mg/kg; (Sasol, 1999
Alcohols, C12-13-branched and linear
Rat 4wk (read-across)
Alcohols, C12-15-branched and linear
209 mg/kg(Rhodes, 1984)
Rat 90 day
167 mg/kg;(Ito, 1978)
Alcohols, C14-15-branched and linear
Rat 90 day (read-across)
Alcohols, C16-17 -branched and linear;
Veenstra G, Webb C et al., (2009) Human health risk assessment of long chain alcohols. Ecotoxicology and environmental safety 71 1016-1030.
PFA (2016). C6-24 Alcohols Category Report: Human Health. Version number: 01. Peter Fisk Associates Ltd. February 2016
Based on the data from the 13 week repeat dose studies together with the absence of any treatment related effects in the various types of repeated dose studies that have been conducted within the category, it is concluded that there is no basis for classification and labelling of docosan-1-ol according to Regulation (EC) No 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again