Registration Dossier

Administrative data

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. This value is supported by data from a 13 week from a reliable oral feeding study in rats using hexadecan-1-ol. This study reports a NOAEL value of > 4400 mg/kg bw. (Scientific Associates 1966a). In addition a read across 28 day study using octadecan-1-ol (rat, oral gavage), reported a NOAEL >1000 mg/kg bw [Henkel, 1985a; rel. 2]). 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.

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:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity 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 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

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

The key study was selected from data for substances with similar human health classification and physicochemical properties and therefore absorption properties to the registration substance. As no adverse systemic effects were observed for category members, the study using the highest dose from the available data was selected as key. 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). A full discussion of the Category can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

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).

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).

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 (Institute of toxicology,1992a)

2

C13

112-70-9

1-Tridecan-1-ol (supporting)

Rat 2 wk

Gavage

184 mg/kg (Central Toxicology Laboratory, 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 (Institute of toxicology, 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
(Shell, 1970)

128 mg/kg(Central Toxicology Laboratory, 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.(Shell, 1982)

<4150 mg/kg(Shell, 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(Central Toxicology Laboratory, 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.



The selected study was conducted according to a protocol similar to an appropriate OECD guideline using structural analogue Alcohols, C14-15, branched and linear.

Justification for classification or non-classification

Based on the read across data from the 13 week rat oral feeding studies using Alcohols, C14-15-branched and linear and (NOAELs > 3548 mg/kg/bw/d, Ito et al., 1978) and the absence of any repeat dose study treatment related effects from within the category, it is concluded that there is no basis for classification and labelling of tetradecan-1-ol in accordance with Regulation (EC) No 1272/2008.