Undecan-1-ol

Endpoint summary

Description of key information

In the key study, no adverse effects were seen after dietary administration of Alcohols, C14-15-branched and linear for 90 days to rats (Ito et al., 1978) which reported a NOAEL value of >3548 mg/kg bw/day. A read across 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.

The results are also supported by a reliable three week feeding study in rats using hexan-1-ol which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody 1978 ). 

In addition a 90 day repeated dose dermal study (Wil Research 1995) in rats where a multi-constituent solution containing circa 50% decan-1-ol and circa 45% octan-1-ol (semi-occluded conditions) reported no systemic effects at the highest dose tested. The study did however give rise to marked dermal irritative effect. It is however important to take in to account the different test protocol that was used, that is a 90 day repeated dose dermal study (6 hours/day for 5 days/week) compared to a standard 4 hour dermal irritation study and the different species (rats instead of rabbit) and test duration (90 days vs. 4 hours).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

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:

yes

Remarks:

(no ophthalmology or neurobehavioural testing; slightly limited pathology examination; some details missing from report)

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: Wistar-SLC

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 5 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: "cages" (no further details given)
- Diet (e.g. ad libitum): CE-2, made by Nihon Kurea, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): CE-2 solid food, made by Nihon Kurea
- Storage temperature of food: no data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

90 days

Frequency of treatment:

continuously

Dose / conc.:

0.2 other: %

Remarks:

Nominal in diet

Dose / conc.:

1 other: %

Remarks:

Nominal in diet

Dose / conc.:

5 other: %

Remarks:

Nominal in diet

Dose / conc.:

169 mg/kg bw/day (actual dose received)

Dose / conc.:

702 mg/kg bw/day (actual dose received)

Dose / conc.:

3 548 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

11

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: none

Positive control:

none

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: no data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: Twice weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):  Evaluated twice 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 time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY: Evaluated  twice weekly
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: Weekly

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at 90 days
- Anaesthetic used for blood collection: Yes (pentabarbital) (except blood sugar sample, which was taken from the tail vein, apparently without anaesthetic)
- Animals fasted: No data
- How many animals: all
- Parameters checked: sugar, RBC and WBC (by microcell counter), Hb (by cyanomethaemaglobin method), Haemocrit (by capillary centrifugal separation method), platelet count (by platelet counter) and differential  count (i.e. % of WBC; by ointment sample: GIEMSA dye).

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at 90 days
- Animals fasted: No data
- How many animals: all
- Parameters checked: Alkaline phosphatase activity, ALAT and ASAT (alanine and aspartate transaminase activities), total protein, albumin/globulin ratio, total cholesterol, urea nitrogen, sodium and potassium (using a Greiner electronic selective analyser II); glucose (using enzyme method: Tokyo Zoki Kagaku reagent).

URINALYSIS: Yes, in all animals
- Time schedule for collection of urine: at 90 days
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked: pH, protein, sugar, ketone bodies, occult blood (using Labstix by Nihon Emusu)

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC)
Macroscopic: general examination
Organ weights: brain, hypophysis, thyroid, thymus, heart, liver,  kidney, spleen, adrenal, testes or ovaries.
Microscopic: the above mentioned organs plus stomach, pancreas, small &  large intestine, lymph gland, bone marrow.

Other examinations:

none

Statistics:

STATISTICAL METHODS: Student  t test.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Reduced at 1% and 5%

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Reduced at 1% and 5%

Food efficiency:

effects observed, treatment-related

Description (incidence and severity):

Increased at 1% and 5%

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Increased relative weight of several organs in males and females at 5%

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No significant dose-related effects

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No animals died during the study and clinical signs were unremarkable.

BODY WEIGHT AND WEIGHT GAIN
Reduced at 1% and 5%

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Reduced at 1% and 5% (water consumption was also reduced at these dietary levels). Food loss due to spillage was frequently reported in these groups.

FOOD EFFICIENCY
Increased at 1% and 5%

HAEMATOLOGY
Haemoglobin was significantly reduced in top dose males (15.2 g/dl (SD +-0.5) compared to 15.9 g/dl (SD +-0.4) for controls). 
Eosinophils were significantly reduced at all dose levels in males but  this was not dose related (control 1.5%; low dose 0.6%; mid dose 0.2%;  high dose 0.6%).
White blood cell count was significantly increased in high-dose females (100/mm3: control 47 (SD +- 12.2); top dose 73.2 (SD +-16.2)). This was not accompanied by any significant changes in the  differential leucocyte count. There was no increase in WBC at the low and mid dose (mean values 45.2 and 45.5 respectively).

CLINICAL CHEMISTRY
See Table 1, below.
Alkaline phosophatase (AP) activity increased from 1%; Total protein increased at 1% and 5% in males and at 5% in females. At 5%, alanine aminotransferase activity increased (ALAT), albumin/globulin ratio (AG) increased, (in females) total cholesterol reduced and (in males) potassium increased.

URINALYSIS
No treatment-related changes

ORGAN WEIGHTS
See Table 2, below.
The most significant effects on organ weights were:
Increased relative weight of thyroid, liver and kidney in males and females at 5%.
Decreased absolute weight of brain in males and females at 5%.

At 5%:
Absolute brain & heart weights were decreased in males and females. 
Absolute lung, thymus and hypophysis weights were decreased in males. 
Absolute kidney and spleen  weights were decreased in males (this effect was seen in the mid-dose males as well). 
Absolute liver, kidney and thyroid weights were increased in females.
Relative lung and heart weights were increased in males. 
Relative liver, kidney, adrenal, thyroid and hypophysis weights increased in males (adrenal and thyroid effect also seen in mid-dose males).
Relative thyroid, kidney and liver weights increased in high-dose females (the liver and kidney were also significantly affected in mid-dose females).

No biologically signficant changes in either absolute or relative organ weights were observed at the low-dose level (0.2%).

GROSS PATHOLOGY
No treatment-related effects.
Blood was observed in the stomach of 1 female in each of the mid- and high-dose groups.  There were no other remarkable changes.

HISTOPATHOLOGY: NON-NEOPLASTIC
No significant treatment-related effects.  
Slight kidney changes such as hyaline casts, calculi and increased medullary connective  tissue were observed but these were not dose related. 
In the liver slight focal necrosis was observed in 1/5 low-dose females examined; there  were no histopathological changes in mid- or high-dose groups. 
No  abnormalites were observed in any other organs including the gonads.

Key result

Dose descriptor:

NOAEL

Effect level:

3 548 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Average dose. Effects observed on body weight, food consumption and food efficiency were considered to be attributable to lower food consumption as a result of lack of palatability. Effects noted on clinical chemistry were not considered adverse.

Critical effects observed:

no

ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: The dose levels were based on  the results of a 14 day preliminary study in which 

groups of rats  received 0.5, 1, 3 and 10% Dobanol 45 in the diet. As only the 10% level  showed any fatalities or signs of intoxiciation the 

dose levels for the  90 day study were set at 0.2, 1 and 5% in the diet. These are equivalent  to mean intakes (in mg/kg bw/day) of: 

males 171 (101 -317), females 167 108 -271 (0.2%); 

males 759  (488 -1301), females 736 (523 -1040) (1%); 

males 3626 (2660 -5659), females 3491 (2529 -4802) (5%)


Table 1 - Clinical chemistry: Significant changes from control are as shown below:

Dose          AP          ALAT          T-P          A/G         T-chol          K-
Males         (KA-U)       (K-U)          (g/dl)                    mg/dl          mEq l
Control         13.0         37.7          5.79          1.12          39.5          4.45
0.2%          13.7         46.0          5.93          1.09          40.5          4.66
1%           15.6**        36.5          5.94*          1.14          43.0          4.66
5%           16.4**        71.6**         5.52*          1.25**         42.2          4.93**
Females                                                
Control         12.9         35.3          5.78          1.12          52.1          4.45
0.2%          12.4         36.7          5.83         1.12         52.8           4.36
1%           15.5**        35.8          5.75          1.13        52.6           4.27
5%          19.8**        99.4**         5.55*          1.28**         42.7**          4.38

Table 2 - Organ weights: The more significant changes (either seen in both sexes or dose related) in relative organ weights

expressed in mg/100g (thyroid  & adrenal) or g/100g are shown in the table below. 

Dose         Brain         Thyroid     Testes     Liver       Kidney      Adrenal
Males        
Control        0.57         4.55         0.91         3.14         0.61         11.6
0.2%         0.57         4.72         0.90         3.09         0.59         12.3
1%         0.61**       5.07*       0.98*        3.30         0.62         13.0*
5%         0.71**       5.53**      1.12**      4.08**     0.71*        15.4**

Females                          Ovary                        
Control      0.93        6.05         31.8         2.89         0.61         26.1
0.2%         0.92        6.52         31.0         2.98         0.64         24.8
1%         0.96        6.79         32.0         3.12*        0.65**      26.0
5%         0.96        7.60**      36.8**      3.97**       0.70**      25.9

Conclusions:

In a reliable study, conducted using a protocol similar to OECD guideline 408, male and female rats were fed diets containing 0, 0.2%, 1% or 5% Dobanol-45 (providing average intakes of 169, 747 or 3548 mg/kg bw/day, respectively) for 90 days. Effects seen at doses higher than 0.2% included increased liver enzyme activity (alkaline phosphatase and alanine aminotransferase) and increased relative weights of a number of organs, which is attributable to the reduced body weight due to lower food consumption as a result of lack of palatability. It is considered that the increases in hepatic enzymes are not adverse as there was no associated pathology. It is therefore concluded that the NOAEL is 3548 mg/kg bw/day, the highest dose tested.

Executive summary:

The key study was performed using a protocol similar to OECD guideline 408 but prior to the introduction of GLP. The test material Alcohols, C14-15 branched and linear was administered to rats via the diet for 90 days at concentrations of 0, 0.2, 1 and 5% (providing average intakes of 169, 747 or 3548 mg/kg bw/day, respectively). The top and intermediate dose level (5 and 1%, respectively) had limited palatability and induced a considerable reduction in growth (>30% and approx. 15% reduction in body weight in high and mid dose males, respectively). Biochemistry showed increased liver enzyme activity (alkaline phosphatase and alanine aminotransferase) at the 1 and/or 5% level. It is considered that the increases in hepatic enzymes are not adverse as there was no associated pathology. The increase in relative weights of a number of organs is attributable to the reduced body weight due to lower food consumption as a result of lack of palatability. No treatment-related microscopic changes were observed, including both the testis and ovaries at this same dose level. Based on the effect on body weight a NOAEL was established at the 5% dietary incorporation level (approx. 3548 mg/kg/day) (Ito et al., 1978).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3 548 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Reliable (2) repeated dose feeding study.

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

Link to relevant study records

Reference

Endpoint:

chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

15 March to 15 June 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)

Deviations:

no

GLP compliance:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Inc., USA
- Age at study initiation: males approximately 43 days and females approximately 64 days
- Weight at study initiation: 225 - 299g males; 214 - 246g females
- Fasting period before study: no
- Housing: individually in wire mesh cages
- Diet (ad libitum): Purina Certified Rodent Chow #5002
- Water (ad libitum): municpal water supplied to Test Facility
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71.3 - 75.2
- Humidity (%): 41.6 - 77.7
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15 March 1994 To: 15 June 1994

Type of coverage:

semiocclusive

Vehicle:

other: 0.9% Sodium chloride (this was dosed to the control group at a dose volume of 1.2 ml/kg.

Details on exposure:

TEST SITE
- Area of exposure: dorsal skin

- Type of wrap: gauze binder, secured with tape

REMOVAL OF TEST SUBSTANCE
- Washing: test article was removed from the application site with a wet paper towel

- Time after start of exposure: six hours

TEST MATERIAL - Control group
- Amount(s) applied: 1.2 ml/kg (Control and high dose), 0.12 ml/kg (low dose), 0.36 ml/kg (intermediate dose)

- Concentration (if solution): 0.9% saline

- Constant volume or concentration used: yes

TEST MATERIAL - Test groups(2-4)
- Amount applied: 100, 300 and 1000 mg/kg/day respectively

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

The application sites were wrapped for six hours with a gauze binder, secured with tape.

The range of areas exposed averaged approximately 8, 2, 4 or 9% of total body surface area for the Control, 100, 300 or 1000 mg/kg/day groups respectively.

Frequency of treatment:

Application for five days a week over thirteen consecutive weeks to the shaved intact dorsal skin of each rat for a minimum of 65 applications.

Dose / conc.:

100 mg/kg bw/day

Dose / conc.:

300 mg/kg bw/day

Dose / conc.:

1 000 mg/kg bw/day

No. of animals per sex per dose:

Control group: 20 rats (10 male and 10 female) which received 0.9% saline on a comparable regimen at a dose volume of 1.2 ml/kg.

Three test groups: 20 rats (10 males and 10 females) administered dosage levels of 100, 300 and 1000 mg/kg/day respectively.

Control animals:

yes

Details on study design:

- Dose selection rationale: not stated

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once weekly

DERMAL IRRITATION: Yes
- Time schedule for examinations: once weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/animal/day: Yes
- Time schedule for examinations: weekly

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to start of dosing and Week 12
- Dose groups that were examined: all

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Week 13 at scheduled necropsy
- Anaesthetic used for blood collection: not stated
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table No.1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Week 13 at scheduled necropsy
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table No.2 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

ORGAN WEIGHTS: Yes (see table 3)
GROSS PATHOLOGY: Yes (see table 4)
HISTOPATHOLOGY: Yes (see table 4)

Other examinations:

Selected organs were weighed and a microscopic examination was conducted on selected tissues from all animals at the scheduled necropsy.

Statistics:

All analyses were conducted using two-tailed tests for significance levels of 5% and 1% comapring the treated groups to the vehicle control group by sex. Body weight, body weight change, food consumption, clinical laboratory and absolute and relative organ weight data were subjected to a one-way analysis of variance follwoed by Dunnett's Test. Clinical laboratory values for cell types that occur at low incidence (i.e. monocytes, eosinophils, basophils and unsegmented neutrophils) were not subjected to statistical analysis.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Vocalisation, struggling during exposure and hypersensitivity to touch.

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.

Mortality:

mortality observed, treatment-related

Description (incidence):

Vocalisation, struggling during exposure and hypersensitivity to touch.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The mean body weights were lower in the middle and high dose groups compared to the control group.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Mean food consumption (evaluated as g/animal/day) was slightly but consistently decreased in the high dose group (males) during the first two thirds of the study period but was comparable with Controls thereafter.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

no effects observed

Description (incidence and severity):

No test related ophthalmic lesions were present at the week 12 opthalmologic examinations.

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Mean white blood cell counts were increased in a non dose related manner in all the test groups (not the control). This was attributed to the acute dermal inflammation that was observed.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

In the serum chemistry parameters albumin means were decreased and globulin means were increased (resulting in decreased A/G ratios). Again this was attributed to the acute dermal inflammation that was observed.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The adrenals, brain, kidneys, liver, ovaries and testes were weighed at necropsy. No remarkable statistically significant changes in organ weight were note for any of the organs, except increaed absolute and relative adrenal weights.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Scabbing and thickening of the skin was noted in all dose groups.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Squamous cell hyperplasia, hyperkeratosis and suppurative inflammation were noted at teh application site in all treated groups.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

No effect of treatment.

Details on results:

CLINICAL SIGNS AND MORTALITY
Vocalisation (due to pain) was the predominant sign observed in the high dose group (females) generally on one to three days most often during the second week of test article administration. Excessive struggling was also reported during exposure on single occasions for one male in the low dose group and two female in the high dose group. Hypersensitivity to touch was also reported on two separate occasions for a single high dose male.
                                                                                                          
Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.

BODY WEIGHT AND WEIGHT GAIN
Group mean body weights were lower than Control during the study for males at 300 mg/kg/day and both sexes at 1000 mg/kg/day by up to 19% at the end of the treatment period. A simialr, but less marked effect on body weight was recorded for both sexes at 100 mg/kg/day and 300 mg/kg/day females with group mean body weight up to 6% lower than Control at the end of the treatment period.

FOOD CONSUMPTION
Group mean food consumption was slightly lower than Control for males at 1000 mg/kg/day up to Week 9 of the treatment period. Slightly lower group mean food consumption was also noted for females at the same dose during the first week of treatment. For both males and females food consumption was comparable to Controls thereafter.

OPHTHALMOSCOPIC EXAMINATION
No effect of treatment.

HAEMATOLOGY
Group mean white blood cell count and neutrophil counts were increased in treated groups compared to Control. The magnitude of the increases was not dose-related. The effect on white cell counts was considered to be attributable to the acute dermal inflammatory response.

CLINICAL CHEMISTRY
Group mean albumin was increased and group mean globulin and A/G ratio were decreased in a non dose-related manner in all treatment groups. These changes were considered to be indicative of the acute dermal inflammatory response.

A dose-related decrease in group mean glucose levels was noted in all treated groups. Group mean calcium was decreased in 1000 mg/kg/day males and females. Increases in group mean urea nitrogen, alkaline phosphatase, aspartate aminotransferse and/or alanine aminotransferase were also noted at 1000 mg/kg/day.

ORGAN WEIGHTS
Group mean absolute and relative adrenal weights were increased in all treated groups.

GROSS PATHOLOGY
The only test article related gross lesions observed included scabbing and thickening of the skin at the test site. (Irritant related effects). There were no other test article related gross findings at the scheduled necropsy.

HISTOPATHOLOGY: NON-NEOPLASTIC
Squamous cell hyperplasia, hyperkeratosis and suppurative inflammation in the skin of the application site was noted in males and females of all treated groups.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: NOAEL for systemic effects

Dose descriptor:

LOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: NOAEL for local effects, based on severe dermal irritation recorded at all doses.

Critical effects observed:

not specified

Conclusions:

Based on the data that was reported the No-Observed-Effect-Level (NOEL) following dermal administration of fatty alcohol blend for a minimum of 90 days was stated to be less than 100 mg/kg/day. This is based primarily on the local irritation (and related) effects.

The local irritation effects are considered adverse and therefore the local, dermal Lowest-Observed-Adverse-Effect-Level (LOAEL) is 100 mg/kg/day (2.8 mg/cm3 based on test substance applied to 2% body surface area at this dose). It should be noted that the test substance was repeatedly applied to already damaged skin, which may have exacerbated the effects noted. Furthermore the dermal effects noted were variable in terms of the relationship of severity with duration of administration. The clinical signs and effects on body weight and food consumption are considered to be a consequence of the local irritant effect and the effects on white blood cell counts and albumin and globulin levels attributable to the acute dermal inflammatory response. The increased adrenal weights (with no associated pathological changes) were attributed to a stress response, also as a result of the dermal irritation. Therefore these effects are secondary to the local irritant effect of fatty alcohol blend.

There were also changes to some clinical chemistry parameters noted (decreased glucose and calcium, increased urea nitrogen, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase). The magnitude of change was generally not marked and/or was without pathological correlate in all cases and so they were considered not be adverse. Therefore, as there were no systemic effects noted that could not be attributed to the local irritant response, or were considered to be adverse, the systemic No-Observed-Adverse-Effect-Level following dermal administration of fatty alcohol blend for a minimum of 90 days was considered to be 1000 mg/kg/day (the highest dose tested).

Executive summary:

Intermediate (>C8 to C12) and higher (>C12) linear LCAAs are non-irritant at the site of first contact and are without a neurotoxic potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

15 March to 15 June 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)

Deviations:

no

GLP compliance:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Inc., USA
- Age at study initiation: males approximately 43 days and females approximately 64 days
- Weight at study initiation: 225 - 299g males; 214 - 246g females
- Fasting period before study: no
- Housing: individually in wire mesh cages
- Diet (ad libitum): Purina Certified Rodent Chow #5002
- Water (ad libitum): municpal water supplied to Test Facility
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71.3 - 75.2
- Humidity (%): 41.6 - 77.7
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15 March 1994 To: 15 June 1994

Type of coverage:

semiocclusive

Vehicle:

other: 0.9% Sodium chloride (this was dosed to the control group at a dose volume of 1.2 ml/kg.

Details on exposure:

TEST SITE
- Area of exposure: dorsal skin

- Type of wrap: gauze binder, secured with tape

REMOVAL OF TEST SUBSTANCE
- Washing: test article was removed from the application site with a wet paper towel

- Time after start of exposure: six hours

TEST MATERIAL - Control group
- Amount(s) applied: 1.2 ml/kg (Control and high dose), 0.12 ml/kg (low dose), 0.36 ml/kg (intermediate dose)

- Concentration (if solution): 0.9% saline

- Constant volume or concentration used: yes

TEST MATERIAL - Test groups(2-4)
- Amount applied: 100, 300 and 1000 mg/kg/day respectively

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

The application sites were wrapped for six hours with a gauze binder, secured with tape.

The range of areas exposed averaged approximately 8, 2, 4 or 9% of total body surface area for the Control, 100, 300 or 1000 mg/kg/day groups respectively.

Frequency of treatment:

Application for five days a week over thirteen consecutive weeks to the shaved intact dorsal skin of each rat for a minimum of 65 applications.

Dose / conc.:

100 mg/kg bw/day

Dose / conc.:

300 mg/kg bw/day

Dose / conc.:

1 000 mg/kg bw/day

No. of animals per sex per dose:

Control group: 20 rats (10 male and 10 female) which received 0.9% saline on a comparable regimen at a dose volume of 1.2 ml/kg.

Three test groups: 20 rats (10 males and 10 females) administered dosage levels of 100, 300 and 1000 mg/kg/day respectively.

Control animals:

yes

Details on study design:

- Dose selection rationale: not stated

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once weekly

DERMAL IRRITATION: Yes
- Time schedule for examinations: once weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/animal/day: Yes
- Time schedule for examinations: weekly

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to start of dosing and Week 12
- Dose groups that were examined: all

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Week 13 at scheduled necropsy
- Anaesthetic used for blood collection: not stated
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table No.1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Week 13 at scheduled necropsy
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table No.2 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

ORGAN WEIGHTS: Yes (see table 3)
GROSS PATHOLOGY: Yes (see table 4)
HISTOPATHOLOGY: Yes (see table 4)

Other examinations:

Selected organs were weighed and a microscopic examination was conducted on selected tissues from all animals at the scheduled necropsy.

Statistics:

All analyses were conducted using two-tailed tests for significance levels of 5% and 1% comapring the treated groups to the vehicle control group by sex. Body weight, body weight change, food consumption, clinical laboratory and absolute and relative organ weight data were subjected to a one-way analysis of variance follwoed by Dunnett's Test. Clinical laboratory values for cell types that occur at low incidence (i.e. monocytes, eosinophils, basophils and unsegmented neutrophils) were not subjected to statistical analysis.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Vocalisation, struggling during exposure and hypersensitivity to touch.

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.

Mortality:

mortality observed, treatment-related

Description (incidence):

Vocalisation, struggling during exposure and hypersensitivity to touch.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The mean body weights were lower in the middle and high dose groups compared to the control group.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Mean food consumption (evaluated as g/animal/day) was slightly but consistently decreased in the high dose group (males) during the first two thirds of the study period but was comparable with Controls thereafter.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

no effects observed

Description (incidence and severity):

No test related ophthalmic lesions were present at the week 12 opthalmologic examinations.

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Mean white blood cell counts were increased in a non dose related manner in all the test groups (not the control). This was attributed to the acute dermal inflammation that was observed.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

In the serum chemistry parameters albumin means were decreased and globulin means were increased (resulting in decreased A/G ratios). Again this was attributed to the acute dermal inflammation that was observed.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The adrenals, brain, kidneys, liver, ovaries and testes were weighed at necropsy. No remarkable statistically significant changes in organ weight were note for any of the organs, except increaed absolute and relative adrenal weights.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Scabbing and thickening of the skin was noted in all dose groups.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Squamous cell hyperplasia, hyperkeratosis and suppurative inflammation were noted at teh application site in all treated groups.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

No effect of treatment.

Details on results:

CLINICAL SIGNS AND MORTALITY
Vocalisation (due to pain) was the predominant sign observed in the high dose group (females) generally on one to three days most often during the second week of test article administration. Excessive struggling was also reported during exposure on single occasions for one male in the low dose group and two female in the high dose group. Hypersensitivity to touch was also reported on two separate occasions for a single high dose male.
                                                                                                          
Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.

BODY WEIGHT AND WEIGHT GAIN
Group mean body weights were lower than Control during the study for males at 300 mg/kg/day and both sexes at 1000 mg/kg/day by up to 19% at the end of the treatment period. A simialr, but less marked effect on body weight was recorded for both sexes at 100 mg/kg/day and 300 mg/kg/day females with group mean body weight up to 6% lower than Control at the end of the treatment period.

FOOD CONSUMPTION
Group mean food consumption was slightly lower than Control for males at 1000 mg/kg/day up to Week 9 of the treatment period. Slightly lower group mean food consumption was also noted for females at the same dose during the first week of treatment. For both males and females food consumption was comparable to Controls thereafter.

OPHTHALMOSCOPIC EXAMINATION
No effect of treatment.

HAEMATOLOGY
Group mean white blood cell count and neutrophil counts were increased in treated groups compared to Control. The magnitude of the increases was not dose-related. The effect on white cell counts was considered to be attributable to the acute dermal inflammatory response.

CLINICAL CHEMISTRY
Group mean albumin was increased and group mean globulin and A/G ratio were decreased in a non dose-related manner in all treatment groups. These changes were considered to be indicative of the acute dermal inflammatory response.

A dose-related decrease in group mean glucose levels was noted in all treated groups. Group mean calcium was decreased in 1000 mg/kg/day males and females. Increases in group mean urea nitrogen, alkaline phosphatase, aspartate aminotransferse and/or alanine aminotransferase were also noted at 1000 mg/kg/day.

ORGAN WEIGHTS
Group mean absolute and relative adrenal weights were increased in all treated groups.

GROSS PATHOLOGY
The only test article related gross lesions observed included scabbing and thickening of the skin at the test site. (Irritant related effects). There were no other test article related gross findings at the scheduled necropsy.

HISTOPATHOLOGY: NON-NEOPLASTIC
Squamous cell hyperplasia, hyperkeratosis and suppurative inflammation in the skin of the application site was noted in males and females of all treated groups.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: NOAEL for systemic effects

Dose descriptor:

LOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: NOAEL for local effects, based on severe dermal irritation recorded at all doses.

Critical effects observed:

not specified

Conclusions:

Based on the data that was reported the No-Observed-Effect-Level (NOEL) following dermal administration of fatty alcohol blend for a minimum of 90 days was stated to be less than 100 mg/kg/day. This is based primarily on the local irritation (and related) effects.

The local irritation effects are considered adverse and therefore the local, dermal Lowest-Observed-Adverse-Effect-Level (LOAEL) is 100 mg/kg/day (2.8 mg/cm3 based on test substance applied to 2% body surface area at this dose). It should be noted that the test substance was repeatedly applied to already damaged skin, which may have exacerbated the effects noted. Furthermore the dermal effects noted were variable in terms of the relationship of severity with duration of administration. The clinical signs and effects on body weight and food consumption are considered to be a consequence of the local irritant effect and the effects on white blood cell counts and albumin and globulin levels attributable to the acute dermal inflammatory response. The increased adrenal weights (with no associated pathological changes) were attributed to a stress response, also as a result of the dermal irritation. Therefore these effects are secondary to the local irritant effect of fatty alcohol blend.

There were also changes to some clinical chemistry parameters noted (decreased glucose and calcium, increased urea nitrogen, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase). The magnitude of change was generally not marked and/or was without pathological correlate in all cases and so they were considered not be adverse. Therefore, as there were no systemic effects noted that could not be attributed to the local irritant response, or were considered to be adverse, the systemic No-Observed-Adverse-Effect-Level following dermal administration of fatty alcohol blend for a minimum of 90 days was considered to be 1000 mg/kg/day (the highest dose tested).

Executive summary:

Intermediate (>C8 to C12) and higher (>C12) linear LCAAs are non-irritant at the site of first contact and are without a neurotoxic potential.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

2.8 mg/cm²

Study duration:

subchronic

Species:

rat

Additional information

No repeated dose toxicity studies performed to international guidelines were available on undecan-1 -ol.

The read across 13 week feeding study using hexan-1-ol (Scientific Associates Inc., 1966) is chosen as the basis for classification because it is of longer study duration than the other available study (Moody 1978). The key oral study was selected from data for substances with similar 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. 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). The key dermal study was the only available study. A full discussion of the Category can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

Rats exposed to hexan-1-ol via the diet for 13 weeks showed no signs of significant toxicity when administered at nominal concentrations up to 1% (with staged increases at concentrations up to 6% during the last phase of the exposure period). There were no microscopic alterations recorded in the animals receiving concentrations of 6% (equivalent to 1127 mg/kg/day). Examination of testes and the ovaries did not show any abnormalities (Scientific Associates, 1966a).

Exposure of male rats to high dietary concentrations (up to 8%) of hexan-1-ol for 2 weeks did not produce evidence of peroxisome proliferation (Moody and Reddy, 1978, 1982).

In a developmental toxicity study administration of octan-1-ol by daily gavage of doses in the range 130 - 1300 mg/kg bw to pregnant rats caused dose-related clinical signs of toxicity, including nasal discharge, pneumonia, and signs consistent with slight, transient CNS depression at levels of 650, 975 and 1300 mg/kg/day. Slight decreases in body weight gain and food consumption were observed. The severity of these effects may have been exacerbated by the pregnancy of the test animals, therefore this study was not selected as key. No detailed assessment of the maternal toxicity was included in the design of this study (Hellwig and Jäckh, 1997).

In a supporting screening assay in which the test material was administered undiluted to male and female rats by oral gavage at 4150 mg/kg bw/day for 7 days. Evaluation comprised histopathological examination of major areas of the digestive tract and revealed adverse effects in the stomach and liver. An LOAEL of 4150 mg/kg bw/day was identified from this limited study (Brown et al. 1970).

In a 90 day repeated dose dermal study (WIL, 1995) in rats where a multi-constituent solution containing circa 50% decan-1-ol and circa 45% octan-1-ol (semi-occluded conditions) there were no systemic effects at the highest dose tested. The study did however gave rise to marked dermal irritative effect. However, the test substance was repeatedly applied to already damaged skin, which may have exacerbated the effects noted. Furthermore the dermal effects noted were variable in terms of the relationship of severity with duration of administration. The clinical signs and reductions in body weight and food consumption noted are considered to be a consequence of the local irritant effect and the effects on white blood cell counts and albumin and globulin levels attributable to the acute dermal inflammatory response. The increased adrenal weights (with no associated pathological changes) were attributed to a stress response also as a result of the dermal irritation. Therefore these effects are secondary to the local irritant effect of fatty alcohol blend.

There were also changes to some clinical chemistry parameters noted (decreased glucose and calcium, increased urea nitrogen, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase). The magnitude of change was generally not marked and/or was without pathological correlate in all cases and so they were considered not be adverse. Therefore, as there were no systemic effects noted that could not be attributed to the local irritant response, or were considered to be adverse, the systemic No-Observed-Adverse-Effect-Level following dermal administration of fatty alcohol blend for a minimum of 90 days was considered to be 1000 mg/kg/day (the highest dose tested) and the LOAEL for local effects was 100 mg/kg/day (2.8 mg/cm²) (the lowest dose tested).

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:

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.

 

Justification for classification or non-classification

Based on the available data, undecan-1 -ol does not require classification in accordance with Regulation (EC) No 1272/2008.