Docosan-1-ol

Endpoint summary

Description of key information

A reliable 90-days dietary study in rats, using hexadecan-1-ol and reporting a NOAEL value greater than 4400 mg/kg bw/day based on no observed adverse effects is read-across (Scientific Assoc, 1966a; rel. 2)

There is also a reliable 26-week oral gavage study available on the registered substance docosan-1-ol that reported no adverse effects at the highest dose tested, 1000 mg/kg bw/day (Iglesias et al., 2002a).

Both studies are used as weight of evidence but as no adverse systemic effects were observed for category members, the study using the highest dose from the available data was considered as the basis for classification. Therefore, the 90-day dietary study conducted with the structurally analogous substance hexadecan-1-ol is used to derive the NOAEL for docosan-1-ol.

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test is commissioned with the registered substance and will be conducted according to OECD Test Guideline 422 and in compliance with GLP.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Valid with restrictions including lack of biochemical investigations and limited reporting of statistical findings

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rats treated via the diet for 90 days with limited evaluation

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc.
- Age at study initiation: no data but "young"
- Weight at study initiation: males 104.1 g, females 90.5 g
- Fasting period before study: no data
- Housing: individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data but "controlled within narrow limits"
- Humidity (%): no data but "controlled within narrow limits"
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): basal laboratory diet (Purina Laboratory Chow)
- Storage temperature of food: no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

continuous in diet

Dose / conc.:

1 other: %

Remarks:

nominal in diet

Dose / conc.:

2.5 other: %

Remarks:

nominal in diet

Dose / conc.:

5 other: %

Remarks:

nominal in diet

Dose / conc.:

7.5 other: %

Remarks:

nominal in diet

Dose / conc.:

10 other: %

Remarks:

nominal in diet

No. of animals per sex per dose:

10 (treated), 20 (controls)

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: no satellite groups

Positive control:

none

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 5 days/week
- Cage side observations included: general physical appearance, gross signs of systemic toxicity and/or pharmacological effect, behaviour, mortality

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as mg/kg bw/day: Yes

FOOD EFFICIENCY: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: days 30 and 90
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 5/sex per group
- Parameters examined: microhaematocrit, haemoglobin, total and differential leukocyte count

CLINICAL CHEMISTRY: No

URINALYSIS: Yes
- Time schedule for collection of urine: days 30 and 90
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- How many animals: 5/sex per group (samples pooled)
- Parameters examined: albumin, acetone, bilirubin, colour, occult blood, sugar, pH, appearance, microscopic examination of sediment

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

ORGAN WEIGHTS: brain, thyroid, heart, liver, spleen, kidneys, adrenals, gonads (testes or ovaries)

HISTOPATHOLOGY: Yes
- brain, thyroid, parathyroid, heart, lung, liver, spleen, stomach, small intestine, large intestine, pancreas, kidney, urinary bladder, adrenal, gonad, lymph node, bone, bone marrow
- all listed tissues from 5/sex from high dose and controls examined

Other examinations:

none

Statistics:

Chi-squared test for comparing relative organ weights. Original organ weight analyses using the Chi square test were supplemented by Tukey tests carried out by the Weinberg group (see 'Any other information on materials and methods')

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
- all animals survived the 13 week treatment  period.
- all surviving animals appeared normal

BODY WEIGHT AND WEIGHT GAIN
- significantly reduced (84.7 - 89.8% of controls) in top dose males for most study weeks, in mid dose females at weeks 4-13 and high dose females (81.7-89.7%) throughout the study
- changes were attributed at least in part to reduced food consumption and the high content of test material in the diet.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
- significantly reduced (76.4 - 89.2% of controls) in  top dose males at weeks 1 and 12, in mid dose males at week 13, in mid dose females at week 1 and high dose females weeks 1 and 12 (79.1 - 89.9%  of controls).

FOOD EFFICIENCY
- no data

WATER CONSUMPTION
- not examined

OPHTHALMOSCOPIC EXAMINATION
- not examined

HAEMATOLOGY
- no effects

CLINICAL CHEMISTRY
- not examined

URINALYSIS
- no effects

NEUROBEHAVIOUR
- not examined

ORGAN WEIGHTS
- the original report indicated that there were significant differences in some relative organ weights from treated groups compared to controls. These were reanalysed by the Weinberg Group using the Tukey test (see 'Remarks on results' section)

GROSS PATHOLOGY
- unremarkable

HISTOPATHOLOGY: NON-NEOPLASTIC
- there were no treatment related histopathological changes in the control and top dose animals examined (including testes & ovaries). 

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- not applicable

HISTORICAL CONTROL DATA (if applicable)
- no data

Key result

Dose descriptor:

NOAEL

Effect level:

> 4 257 other: mg/kg (bw) based on highest dose tested.

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No adverse effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

> 4 567 other: mg/kg (bw) based on highest dose tested.

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No adverse effects observed

Critical effects observed:

no

Conclusions:

In a reliable study, in which rats were treated with Alfol 16 via the diet for 13 weeks, an NOAEL of >4400 mg/kg bw/day (highest dose tested) was determined. Reduced weight gain, food consumption and organ weight changes were deemed to be secondary to the high dose administered but not specific to the test substance.

Executive summary:

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).

Reference 2

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

no

Principles of method if other than guideline:

Well-conducted study according to a protocol very similar to OECD guideline 408, but with a treatment duration of 26 weeks

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: ~21-28 days at purchase
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 5/cage in stainless steel cages, containing absorbent paper
- Diet (e.g. ad libitum): expanded rodent diet (Special Diets Services, UK), ad libitum
- Water (e.g. ad libitum): public supply (Suffolk Water Company, UK), ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: no data

Route of administration:

oral: gavage

Vehicle:

other: 1% aqueous Tween 80

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
- test material heated to approx. 80 deg C
- vehicle heated to approx. 75 deg C
- vehicle added to test material while being magnetically stirred at high speed
- resulting 20% (w/w) suspension homogenized and slowly cooled to below 60 deg C
- when cooled to 30 deg C, suspension slowly homogenized again for >=2 min
- cooled to room temp.
- stored at 13 deg C
- prepared once weekly
- 20% suspension used for top dose; for low and mid doses, suspension magnetically stirred and aliquots taken for dilution on day of use; constant dose volume of 5 ml/kg bw per dose
- dilutions mixed by hand swirling followed by magnetic stirring

VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: 1%
- Amount of vehicle (if gavage): 5 ml/kg bw per dose
- Lot/batch no. (if required): no data
- Purity: no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

26 weeks

Frequency of treatment:

daily, 7 days/week

Dose / conc.:

10 mg/kg bw/day (nominal)

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

20

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: additional 10/sex per treatment group for toxicokinetic study, 6/sex controls
- Post-exposure recovery period in satellite groups: none
- Section schedule rationale (if not random): random

Positive control:

none

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS (including mortality): Yes
- Time schedule: >=twice daily
- Cage side observations included: evidence of reaction to treatment or moribund condition, evidence of ill health such as blood or loose faeces

DETAILED CLINICAL OBSERVATIONS: Yes, individual observations
- Time schedule: once daily during week 1, twice weekly during weeks 2 to 4, once weekly during weeks 5 to 13, once every 2 weeks from week 14 onwards

BODY WEIGHT: Yes
- Time schedule for examinations: pre-study, weekly during the study or more frequently if appropriate (for animals in moribund condition), at necropsy

FOOD CONSUMPTION:
- Food consumption for each cage determined: Yes

FOOD EFFICIENCY:
- Weekly group mean food conversion efficiencies calculated from the consumption and body weight gain data: Yes, for the first 14 weeks of treatment

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: Yes, prestudy and at weeks 12 and 25

HAEMATOLOGY: Yes
- Time schedule for collection of blood: weeks 14 and 26
- Anaesthetic used for blood collection: Yes - halothane/nitrous oxide
- Animals fasted: Yes
- How many animals: 10/sex per dose level
- Parameters examined: packed cell volume, haemoglobin concentration, erythrocyte count, total and differential leukocyte count, platelet count, mean cell haemoglobin concentration, mean cell haemoglobin, mean cell volume; blood film samples examined for abnormal morphologhy and unusual cell types including normoblasts; prothrombin time

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: weeks 14 and 26
- Animals fasted: Yes
- How many animals: 10/sex per dose level
- Parameters examined: alkaline phosphatase activity, alanine amino transferase, aspartate amino transferase, gamma-glutamyl transpeptidase, glucose, total bilirubin, total cholesterol, urea, total triglyceride, total protein, electrolyte levels (Na, Cl, Ca), inorganic phosphorus, electrophorectic protein, creatine concentration

URINALYSIS: Yes
- Time schedule for collection of urine: weeks 12 and 25
- Metabolism cages used for collection of urine: No data
- Animals fasted: No, but water deprived
- Parameters examined: pH, protein, glucose, ketones, bilirubin, urobilinogen, blood, specific gravity, appearance, volume

NEUROBEHAVIOURAL EXAMINATION: No

OTHER:
- Bone marrow samples from femur: myeloid:erythroid ratio, cellularity and composition of marrow

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

ORGAN WEIGHTS: adrenals, brain, kidneys, liver, lungs (with main stem bronchi), ovaries, pituitary, prostate, spleen, testes, thymus, thyroid (with parathyroids), uterus (with cervix)

HISTOPATHOLOGY: Yes - adrenals, brain, eyes, optic nerve, femur, heart, kidneys, liver, lungs, seminal vesicles, spinal cord, stomach, thyroid, uterus

Other examinations:

Satellite group for toxicokinetic study:
- Blood taken from satellite groups (3M+3F) non-fasted  on days 1, during weeks 13 and 26 at 0.5, 1, 2, 4, 8 and 24 hours after  dosing.

Statistics:

Bartlett's test for homogeneity of variance (organ weights, body weight changes); if significant, Behrens-Fisher test, otherwise Dunnett's test.
Two-tailed Fisher's exact test (macroscopic/microscopic pathological findings).
Student's t-test (haematology, clinical chemistry, urinalysis).

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
- one male in the mid-dose group died at week 25 (examination suggested aspiration of test material through mis-dosing; not considered to be treatment-related)
- no other clinical signs of systemic toxicity or mortality

BODY WEIGHT AND WEIGHT GAIN
- no effects

FOOD CONSUMPTION
- presumably no effects

FOOD EFFICIENCY
- no effects

WATER CONSUMPTION
- not examined

OPHTHALMOSCOPIC EXAMINATION
- no effects

HAEMATOLOGY
- no effects
- no effects seen in bone marrow smears

CLINICAL CHEMISTRY
- no effects

URINALYSIS
- no effects

NEUROBEHAVIOUR
- not examined

ORGAN WEIGHTS
- no effects

GROSS PATHOLOGY
- no effects

HISTOPATHOLOGY: NON-NEOPLASTIC
- no effects

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- no effects

HISTORICAL CONTROL DATA (if applicable)
- no data

OTHER FINDINGS
- toxicokinetic study: concentrations of behenyl alcohol in the blood were measured on  day 1 and in weeks 13 and 26; maximum mean plasma concentration (Cmax) of behenyl alcohol occurred 1 hour after dosing in all males and most females; 24 hours after dosing plasma concentrations were below the limit of quantification  (<10ng/ml) at the 10 and 100 mg/kg dose levels while levels following  administration of 1000 mg/kg/day remained quantifiable on each sampling  day; Cmax in the top dose group ranged from 203.68 to 528.82 ng/ml throughout the duration of the study; statistically significant differences in area under the curve  (AUC24) were observed between males and females treated with 10 and 1000  mg/kg/day on day 1 and during week 13; the rate and extent of systemic  exposure to rats as shown by AUC24 and Cmax on day 1 and in weeks 13 and 26 increased with increasing dose level; increases were less than the proportionate dose increment and there was statistically significant evidence of non-proportionality on each sampling day.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed

Critical effects observed:

no

Conclusions:

In a reliable study conducted according to a protocol very similar to OECD guideline 408, a repeated oral dose (26-week) NOAEL of 1000 mg/kg bw/day was determined in the rat. The study was performed in compliance with GLP.

Executive summary:

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

4 400 mg/kg bw/day

Study duration:

subchronic

Species:

rat

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

There is a reliable 26-week oral gavage study available on the registered substance docosan-1-ol that reported no adverse effects at the highest dose tested, 1000 mg/kg bw (Iglesias et al., 2002a).

Read across data from the reliable 13-week repeat dose/reproductive oral feeding study in rats using the structurally analogous hexadecan-1-ol (Scientific Associates 1966a) will be considered as the basis for classification for docosan-1-ol as using the highest dose.

A full discussion of the Category can be found in the Human Health Alcohols C6-24 Category report (PFA, 2022). 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. Reductions 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).

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).

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.

Further supporting data coming from a 90-day feeding study in rats with Alcohols, C14-15-branched and linear (Ito et al., 1978), reported a NOAEL value of >3548 mg/kg bw/day.

Supporting data are also 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).

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.

Conclusion:

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.

Justification for classification or non-classification

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 for specific target organ toxicity following repeated exposure of docosan-1-ol according to Regulation (EC) No 1272/2008.