Hexadecan-1-ol

Endpoint summary

Description of key information

 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/day. (Scientific Assoc, 1966a; rel. 2) In addition read-across from a reliable 28 day oral gavage study in rats using hexadecan-1-ol reported a NOAEL value of >1000 mg/kg bw/day (Henkel, 1985a; rel. 2). A 4-week reliable oral study in rats using octadecan-1-ol reported a NOAEL value of 1000 mg/kg bw/day, 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/day (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 bw/day (Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study.

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:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Report in German language, English summary page.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

(no neurobehavioural testing; limited range of endpoints assessed in other examinations)

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: M 84-98 g; F 81-93g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
- no data

VEHICLE
- Justification for use and choice of vehicle (if other than water): not stated
- Concentration in vehicle: 0, 2, 10 or 20%
- Amount of vehicle (if gavage): 5 ml/kg bw
- Lot/batch no. (if required): no data
- Purity: no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily, 5 days/week

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

500 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10 (main study) + 5 (satellite groups)

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: reversibility
- Post-exposure recovery period in satellite groups: 28 days
- Section schedule rationale (if not random): no data

Positive control:

none

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: clinical signs and mortality

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: Yes
- Time schedule for examinations: daily

FOOD EFFICIENCY: No data

WATER CONSUMPTION: Yes
- Time schedule for examinations: weekly

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: at end of study
- Dose groups that were examined: no data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 21/22 daily doses
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters examined.: Haematocrit, MCV, Hb, RBC, WBC, Thrombocytes, differential white count.

CLINICAL CHEMISTRY: Yes 
- Time schedule for collection of blood: After 21/22 daily doses
- Animals fasted: No data
- How many animals: No data
- Parameters examined: Serum urea, creatinine, Na, K, calcium, alkaline phosphatase, ALAT, ASAT, GT, bilirubin, chloride, albumin, total protein, cholesterol

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

ORGAN WEIGHTS: thyroid, adrenals, thymus, kidney, spleen, heart, brain, testes, liver

HISTOPATHOLOGY: Yes, all organs from the control and top dose animals were examined plus the animals from the reversibility study.

Statistics:

T-test. U-test for organ weights

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:

not specified

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

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

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:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No effects on mortality
Unremarkable other than top dose females appearing rather defensive when handled

BODY WEIGHT AND WEIGHT GAIN
No effects

FOOD CONSUMPTION
No effects

FOOD EFFICIENCY
No data

WATER CONSUMPTION
No effects

OPHTHALMOSCOPIC EXAMINATION
No effects

HAEMATOLOGY
No differences between treated and control animals other than an increase in neutrophils containing rodlike bodies observed in top dose females (confidence level 95%*). Values obtained (% rod like cells) were controls 2.5, low dose 3.3, mid dose 2.9, high dose 5.3*

CLINICAL CHEMISTRY
Statistically significant changes (*95% ** 99% confidence) in some clinical chemistry parameters were noted as follows:
- 500 mg/kg bw/day males increased potassium*,
- 500 mg/kg/day females increased GGT*, cholesterol** and chloride*
- glucose was elevated in top dose males (mmol/l): Control 6.03, Low  6.20, Mid 6.25, High 7.28**
These changes were not dose and/or sex related and not correlated with any histopathological findings and are therefore not considered of toxicological significance.

URINALYSIS
No effects

NEUROBEHAVIOUR
No data

ORGAN WEIGHTS
Both absolute and relative organ weights were essentially comparable in treated and control animals.
Sporadic changes were observed as follows (*95% ** 99% confidence):
- increase in absolute male kidney weight at 500 mg/kg/day*
- increase in absolute testis weight at 1000 mg/kg/day*; mean relative (absolute) testis weight: Control 0.856 (3.207), Low 0.839 (3.186), Mid 0.908 (3.455), High 0.893 (3.474*)
- the only change in relative organ weight was an increase in male adrenal weight at 1000 mg/kg/day*; mean relative (absolute) adrenal weight: Control 0.013 (0.050), Low  0.014 (0.054), Mid 0.014 (0.055), High 0.015* (0.058)

GROSS PATHOLOGY
No effects

HISTOPATHOLOGY: NON-NEOPLASTIC
No treatment related histopathological changes in test, control or reversibility groups.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Not applicable

HISTORICAL CONTROL DATA (if applicable)
No data

Key result

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, performed according to a protocol similar to OECD guideline 407, a 28-day oral NOAEL of 1000 mg/kg bw/day was determined in the rat. The study was performed in compliance with GLP.

Executive summary:

Using a protocol similar to OECD guideline 407, a GLP study, in which male and female rats were administered hexadecan-1-ol 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).

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

Data from the reliable 13-week repeat dose/reproductive oral feeding study in rats using hexadecan-1-ol (Scientific Associates, 1966a) will be considered as the basis for classification. The key study was selected because it was the most recent and reliable study available for hexadecan-1-ol. As no adverse systemic effects were observed for category members, the study using the highest dose from the available data was selected as key. The available repeated dose toxicity data 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).

A full discussion of the Category and considerations of RAAF Assessment Entities can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

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 bw/day (Scientific Assoc., 1966a).

A supporting study conducted with hexadecan-1-ol was also available, which supports the findings of the key study (Henkel, 1985).

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 bw/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 30 000 ppm equivalent to 2000 mg/kg bw/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., 2002a).

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 bw/day. 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., 2002a).

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.

Repeated dose toxicity data for the Category

	CAS	CHEMICAL NAME	Species/ Study type/ Duration 1	Route	NOAEL   (Ref)	Rel.
C5	123-51-3	Isoamyl alcohol (supporting)	Rat 17 wk	Gavage	500 mg/kg (Carpanini, 1973)	2
C6	111-27-3	Hexan-1-ol	Dog 13 wk	Diet	370 mg/kg (Sc.Assoc.’66b)	2
C6	111-27-3	Hexan-1-ol	Rat 13 wk	Diet	1127 mg/kg (Sc.Assoc.’66)	2
C6	111-27-3	Hexan-1-ol	Rat 3 wk	Diet	1000 mg/kg bw/day (Moody, 1978-1982)	2
C6	111-27-3	Hexan-1-ol	Rat subchronic 30 wk	Intraperit oneal	No peripheral neuropathy (Perbellini et al., 1978)	2
C8	111-87-5	Octan-1-ol	Rat  Dev. Tox.	gavage	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.	2
C9	143-08-8	Nonan-1-ol			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.
C10	112-30-1	Decan-1-ol			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.
C11	112-42-5	Undecan-1-ol			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.	2
C12	112-53-8	Dodecan-1-ol	Rat 5wk	Diet	2000 mg/kg (Hansen,1992a)	2
C13	112-70-9	1-Tridecan-1-ol (supporting)	Rat 2 wk	Gavage	184 mg/kg (Rhodes, 1984)	2
C14	112-72-1	Tetradecan-1-ol			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.	2
C15	629-76-5	Pentadecan-1-ol			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.	2
C16	36653-82-4	Hexadecan-1-ol	Rat 4 wk	Diet	>1000 mg/kg (Henkel, 1985a)	2
C16	36653-82-4	Hexadecan-1-ol	Dog 13 wk	Diet	>1054 mg/kg (Sc.Assoc,	2
C16	36653-82-4	Hexadecan-1-ol	Rat 13 wk	Diet	1966b)           >4257 mg/kg (Sc.Assoc, 1966a)	2
C18	112-92-5	Octadecan-1-ol	Rat 4 wk   Rat 5 wk	Gavage   Diet	>1000 mg/kg (Henkel, 1986a) 2000 mg/kg (Hansen, 1992b)	1   2
C18	143-28-2	9-Octadecen-1-ol, (9Z)-			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.	2
C20	629-96-9	Icosanan-1-ol			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.	2
C22	661-19-8	Docosan-1-ol	Rat 26 wk	Gavage	1000 mg/kg (Iglesias,2002a)	1
C22	661-19-8	Docosan-1-ol	Dog 26 wk	Gavage	2000 mg/kg (Iglesias,2002a)	1
C24	506-51-4	Tetracosan-1-ol			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.
C8	60435-70-3	2-methylheptan-1-ol
C9	68515-81-1	Nonan-1-ol, branched and linear			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.
C10	90342-32-8	Decan-1-ol, branched and linear			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.	2
C11	128973-77-3	Undecan-1-ol, branched and linear			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.
C13	90583-91-8	Tridecan-1-ol, branched and linear (supporting)			Low systemic toxicity expected	2
C15	90480-71-0	Pentadecan-1-ol, branched and linear			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.	2
C7-9		Alcohols, C7-9	Rat 1-wk   Rat 1 wk	Gavage   Gavage	4175 mg/kg (Brown, 1970) 128 mg/kg(Rhodes, 1984)	2   2
C8-10		Fatty Alcohol Blend	rat 90 day	dermal	1000 mg/kg bw/day (WIL, 1995)	2
C9-11		Alcohols, C9-11- branched and linear	Rat 9-day   Rat 2 wk	Inhalation   Gavage	>0.158 mg/L.(Darmer, 1982) <4150 mg/kg(Brown, 1970)	2   2
C11		Reaction mass of 2-methyldecan-1-ol and 2-propyloctan-1-ol and 2-ethylnonan-1-ol and 2-butylheptan-1-ol			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.
C12-13	75782-86-4	Alcohols, C12-13	Rat 4wk	Gavage	300 mg/kg; (Sasol, 1999	1
C12-13	740817-83-8	Alcohols, C12-13-branched and linear	Rat 4wk (read-across)	Gavage	300 mg/kg; (Sasol, 1999	1
C12-15	90604-40-3	Alcohols, C12-15-branched and linear	Rat 2 wk	Gavage	209 mg/kg(Rhodes, 1984)	2
C14-15	75782-87-5	Alcohols, C14-15	Rat 90 day	Diet	167 mg/kg; (Ito, 1978)	2
C14-15		Alcohols, C14-15-branched and linear	Rat 90 day (read-across)	Diet	167 mg/kg; (Ito, 1978)	2
C16-17		Alcohols, C16-17; Alcohols, C16-17 -branched and linear; Alcohols, C16-17-monobranched			No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested.

References:

PFA (2016). C6-24 Alcohols Category Report: Human Health. Version number:01. Peter Fisk Associates Ltd. February 2016.

Veenstra G, Webb C et al., (2009) Human health risk assessment of long chain alcohols. Ecotoxicology and environmental safety 71 1016-1030

Justification for classification or non-classification

Based on the available data for hexadecan-1-ol, no classification is required for specific target organ toxicity following repeated exposure according to Regulation (EC) No. 1272/2008.