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Administrative data

Description of key information

 The key study for acute oral toxicity reports an LD50 value of >2000 mg/kg in rat (Safepharm Laboratory, 1996; rel 1). The key information for acute inhalation is read across from decan-1-ol (CAS 112-30-1), which reports an LC50 value of >71 mg/L air in rat (Scientific Associates, 1977; rel 2) and from tetradecan-1-ol (CAS 112-72-1), which reports an LC50 value of >1.5 mg/L air in rat (Scientific Associates, 1977; rel 2). The result of the key study for acute dermal toxicity was LD50 8000-12000 mg/kg in rabbit (Scientific Associates 1977; rel 2).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Charles River (UK)

- Age at study initiation: 5 to 8 weeks

- Weight at study initiation: males 166-191g, females 131-158g

- Fasting period before study: overnight

- Housing: in groups of 5 by sex in solid floor polypropylene cages furnished with woodflakes.

- Diet: ad libitum

- Water: ad libitum

- Acclimation period: minimum 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19 to 23

- Humidity (%): 49 to 55

- Air changes (per hr): ca. 15

- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:
2000 mg/kg
No. of animals per sex per dose:
5M, 5F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:The animals were observed for deaths and overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing on day 0 and on day 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macrosopic abnormalities was recorded. No tissues were retained.
Preliminary study:
There were no deaths or clinical signs of toxicity. Based on this information a dose level of 2000 mg/kg bw was selected for the main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected body weight gain during the study.
Gross pathology:
No abnormalities detected.
Other findings:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of >2000 mg/kg bw is reported in a reliable study conducted according to the appropriate guideline. The study was compliant with GLP.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Method: other: standard in house procedure
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
other: Holzman albino
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: undiluted
Doses:
4.72, 6.66, 9.42, 13.30, 18.78 and 26.53 g/kg
No. of animals per sex per dose:
10
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 26 530 mg/kg bw

MORTALITY: There were no mortalities at any dose level.

CLINICAL SIGNS: No signs of toxicity or pharmacological effects were observed at any dose level on the day of dosing. Within 24 hours, diuresis 

was evident at all test levels. Weakness and bloody nasal discharge were exhibited by most of the animals at the top dose level (26.53 g/kg) at this 

time. These effects persisted for less than 72 hours. Hair loss of the posterior ventral surface of the body occurred in most of the animals at the two

highest dosage levels at varying times  throughout the observation period. Final weight records showed normal gain in all animals.

NECROPSY FINDINGS: Gross necropsy revealed no visceral abnormalities.

POTENTIAL TARGET ORGANS: None identified

SEX-SPECIFIC DIFFERENCES: None obvious from the report.

Interpretation of results:
GHS criteria not met
Conclusions:
The rat oral LD50 for Alfol 12 was >26.53 g/kg with no obvious target organ identified.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: other: contract laboratory protocol
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: COX-CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 216 to 253 grams

- Housing: Glass chamber for the duration of exposure to the test substance which after the animals were placed in individual wire-bottomed cages elevated above droppings.

- Diet: Purina laboratory Chow, pelletized (ad libitum)

- Water: ad libitum



IN-LIFE DATES: Not stated.
Route of administration:
other: mist
Type of inhalation exposure:
whole body
Vehicle:
other: atmosphere generated as a mist
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: DeVilbiss Nebulizer

- Exposure chamber volume: 57 litres

- Method of holding animals in test chamber: shared glass chamber

- Source and rate of air: six litres per minute


TEST ATMOSPHERE

- Brief description of analytical method used: non specified

- Samples taken from breathing zone: not specified



CLASS METHOD (if applicable)

- Rationale for the selection of the starting concentration:
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
71 mg/l
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The animals were observed for gross effects at regular intervals on the day of exposure and daily thereafter for fourteen days. All animals were weighed at the beginning and end of the test period.
Statistics:
No statistical analysis performed.
Preliminary study:
No preliminary study.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 71 mg/L air
Exp. duration:
1 h
Mortality:
All rats survived the 1 hour exposure and subsequent 14 day  observation period.
Clinical signs:
other: During exposure, all animals displayed hypoactivity and/or ataxia, salivation and gasping. Generalised weakness was also evident when the animals were removed from the chamber at the end of the exposure. At the 24 hour observation period, all animals show
Body weight:
Final bodyweight records of the animals at termination (14 days) showed gains within expected limits, in all animals.
Gross pathology:
Gross necropsy of the animals at fourteen days showed slight to moderate pulmonary (all animals) and adrenal (two animals) congestion; otherwise findings were unremarkable.
Other findings:
The lungs were affected in all rats.

Table 1: Concentrations, exposure conditions and number of evident toxicity per animals treated.

Nominal

Conc. (mg/L)

Number with evident toxicity (#/total)

Males

Females

Combined

 71

 0/5

0/5

0/10

 

Interpretation of results:
GHS criteria not met
Conclusions:
The result was read across from 1-decanol. The rat 1 hour LC50 for Alfol 10 (mist) was >71 mg/l. Signs of intoxication during exposure included lethargy,and/or ataxia, salivation and gasping. Gross necropsy revealed congestion of the lungs in all animals.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
71 mg/m³
Quality of whole database:
The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP. This study is read across from decan-1-ol (CAS 112-30-1).

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: other: Contract laboratory protocol
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 2.3 to 2.9 kg

- Housing: The rabbits were individually housed in metal cages elevated above the droppings.

- Diet: Purina rabbit Chow (ad libitum)

- Water: Tap water (ad libitum)


IN-LIFE DATES: Not stated.
Type of coverage:
occlusive
Vehicle:
other: 50% w/w dilution tetradecanol in 1 % w/w gum tragacanth
Details on dermal exposure:
TEST SITE

- Area of exposure: The skin of the trunk which was clipped free of hair.

- Type of wrap if used: plastic binder


REMOVAL OF TEST SUBSTANCE

- Washing (if done): The binder was removed and the amount of unabsorbed substance estimated. The animals were then washed and the carefully blotted dry with absorbent hand towels.

- Time after start of exposure: The test compound was removed after 24 hours of exposure.


TEST MATERIAL


- Amount(s) applied (volume or weight with unit): The animals were distributed evenly as to sex in each of three dosage groups as follows: 2M+2F (1M+1F each intact and abraded) and dosed 2.0, 4.0 and 8.0 g/kg of the test substance.


- Concentration (if solution): A 50% w/w dilution of ALFOL 14 alcohol in 1% w/w gum tragacanth.



VEHICLE

- Amount(s) applied (volume or weight with unit): 1% w/w gum tragacanth.



Duration of exposure:
24 hours
Doses:
2, 4 and 8 g/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for fourteen days.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Body weights were recorded prior to dosing and on observation day 14.
Statistics:
No statistical analysis was carried out.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
8 000 mg/kg bw
Based on:
test mat.
Mortality:
100% of the animals with abraded skin died between 8 and 10 days of the exposure period. The animals with intact skin survived.
Clinical signs:
At twenty-four hours following test application, all animals showed slight to moderate erythema, desquamation, wrinkling and dryness of the skin at the treatment site. In all surviving animals, desquamation and wrinkling of the skin occurred and persisted in varying degrees through determination (14 days). At the highest dosage level (8 g/kg body weight, two of the surviving animals showed signs of weakness, emaciation and pallor; however all appeared systematically normal within 96h following exposure. One animal showed signs of moribundity.
Body weight:
Final body weight records of the surviving animals at termination (fourteen days), showed a slight loss in one animal, a constant weight in one animal and gains within expected limits in the eight remaining animals.
Gross pathology:
Gross necropsy of animals which succumbed showed depletion of visceral fatty tissue (one animal), moderate dermal irritation and desquamation at the treatment site (two animals). Gross necropsy of the animals which survived the 14 day observation period and were sacrificed, showed one animal with slight accumulation of clear viscous fluid within the peritoneal cavity and crazing over cortex of both kidneys. Eight animals showed no signs of gross systemic abnormalities.

Table 1: Number of animals dead within the 14 day observation period.

Dose
(g/kg
bw)

Mortality (# dead/total)

Time range of deaths (day)

Male

Female

Combined

2.0

 0/2

0/2

0/4 

 -

4.0

 0/2

0/2

0/4 

 -

8.0

 1/2

1/2 

2/4 *

 9 and 11

*thedead animals were from the group with skin prepared with abrasion.

 

Interpretation of results:
GHS criteria not met
Conclusions:
The rabbit dermal LD50 (24 hour occluded) for Alfol 14 was approx. 8000 mg/kg. All survivors showed skin irritation at the application site throughout the observation period. Signs of intoxication included weakness, emaciation and pallor. The result is read across from tetradecan-1-ol (CAS 112-72-1).
Executive summary:

In the acute dermal toxicity study, 2, 4 and 8 g/kg of test material was applied to the flanks of 2 male and 2 female rabbits per dose, kept in contact to the skin under occlusive dressing for 24 hours. The experiement was performed on intact and abrated skin. Body weight changes and clinical signs of toxicity were noted regularly. Necropsy was performed at the end of the 14 -day study period.

100% of the animals with abraded skin died between 8 and 10 days of the exposure period. The animals with intact skin survived. At twenty-four hours following test application, all animals showed slight to moderate erythema, desquamation, wrinkling and dryness of the skin at the treatment site. In all surviving animals, desquamation and wrinkling of the skin occurred and persisted in varying degrees throughout the 14 -day study period. At the highest dosage level (8 g/kg body weight, two of the surviving animals showed signs of weakness, emaciation and pallor; however all appeared systematically normal within 96 hours following exposure. Final body weight records of the surviving animals at termination, showed a slight loss in one animal, a constant weight in one animal and gains within expected limits in the eight remaining animals. At necropsy, there was one animal with slight accumulation of clear viscous fluid within the peritoneal cavity and crazing over cortex of both kidneys. Eight animals showed no signs of gross systemic abnormalities.

An LD50 value of 8000 mg/kg bw was reported. The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The humidity was below the targeted lower limit of 30% during the study. A portable humidifier was used to increase the humidity levels during this time.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace animals Inc., Boyertown, PA
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 221-236g males, 182-200g females
- Housing: singly housed in suspended stainless steel caging with mesh floors
- Diet: Purina rodent chow, ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 19-52
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: 10
- Type of wrap if used: the gauze pad under which the test material resided was wrapped with tape to avoid dislocation of the pad and to minimize loss of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test sites were gently cleansed with a 3% soap solution followed by ethanol then tap water using a clean paper towel to remove any residual test substance
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): individual doses were calculated based on the initial body weights, taking into account the specific gravity of the test substance.

Duration of exposure:
24 hours
Doses:
5000mg/kg
No. of animals per sex per dose:
5M, 5F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Individual body weights were recorded prior to test substance application (initial) and again on days 7 and 14. The animals were observed for mortality, signs of gross toxicity, and behavioural changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Tissues and organs of the thoracic and abdominal cavities were examined.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities.
Clinical signs:
Other than the dermal irritation noted at all dose sites between days 1 and 12, there were no other clinical findings recorded for any animal over the course of the study.
Body weight:
All animals gained body weight during the study.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14 day observation period.

Erythema, desquamation and hyperkeratosis were present at the dose site.

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of >5000 mg/kg is reported in a reliable study conducted according to an appropriate guideline. The study was compliant with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The C10 study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP. LD50 8000-12000 mg/kg bw in rabbit. The C14 study was conducted according to EPA OPPTS 870.1200 (Acute Dermal Toxicity) and in compliance with GLP. LD50 LD50 >2000 mg/kg bw in rat.

Additional information

The key study for acute oral toxicity reports an LD50 value of >2000 mg/kg in rat (Safepharm Laboratory, 1996; rel 1). The key information for acute inhalation is read across from decan-1-ol (CAS 112-30-1), which reports an LC50 value of >71 mg/L air in rat (Scientific Associates, 1977; rel 2) and from tetradecan-1-ol (CAS  112-72-1), which reports an LC50 value of >1.5 mg/L air in rat (Scientific Associates, 1977; rel 2). The result of the key studies for acute dermal toxicity were LD50 8000-12000 mg/kg bw in rabbit (Scientific Associates 1977; rel 2) and LD50 >2000 mg/kg bw in rat (Eurofins, 2009). No adverse effects were observed in any of the key studies. The supporting studies for all endpoints were in accordance with the key studies. The key studies were selected on the basis of most recent result and highest reliability available. The category of similar chain length alcohols supports the low acute toxicity of these substances.


Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:

Acute toxicity tests of the linear and essentially linear alcohols do not indicate any potential hazard for acute, dermal or inhalation toxicity. The available data for the Category have been reviewed with the conclusion that the long chain alcohols are of a low order of acute oral and dermal toxicity, and the inhalation LC50 is expected to be greater than the substantially saturated vapour concentration (Veenstra G, Webb C et al., 2009). Tests on various substances included in this category are all supportive of these results and do not warrant classification for most of the acute toxicity endpoints under GHS criteria. The majority of the substances are therefore not classified for acute toxicity in accordance with Regulation (EC) No 1272/2008. The only exception to this is hexan-1-ol, which finds that the acute dermal data for the test substance are consistent with Acute dermal tox category 4 and Acute oral tox 4 H302/R22, in line with the Annex VI entry. A full discussion of the Category can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

Justification for classification or non-classification

Based on the available data, dodecan-1-ol does not require classification for acute toxicity according to Regulation (EC) No 1272/2008.