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Description of key information

The key study for acute oral toxicity in rat reports an LD50 value of >2000mg/kg (Safepharm Laboratories, 1996; rel 1). The key study for acute inhalation in rat reports a 1 hour LC50 value of >1.5mg/l, which is the equivalent of 0.375 mg/l for a 4 hour exposure (Scientific Association, 1977; rel2). The key study for acute dermal toxicity in rabbit reports a 24 hour occluded LD50 value of ca. 8000 mg/kg (Scientific Associates, 1977; rel 2).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04/09/1996-03/10/1996
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 -8 weeks

- Weight at study initiation: male rats weighed 161 to 169g, and the females 128 to 151

- Fasting period before study: overnight

- Housing: the animals were housed in groups of up to 5 by sex in solid floor polypropylene cages furnished with woodflakes

- Diet:ad libitum, except overnight fast immediately before and two hours immediately after dosing

- Water: ad libitum, except overnight fast immediately before and two hours immediately after dosing

- Acclimation period: minimum of 5 days




ENVIRONMENTAL CONDITIONS

- Temperature (°C): 20-22

- Humidity (%): 49-61

- Air changes (per hr): ca.15

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


IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10ml/kg


DOSAGE PREPARATION (if unusual): The test material was freshly prepared, as required, as a solution at the appropriate concentration in arachis oil BP. A warming bath was used to aid preparation.


Doses:
2000mg/kg bw
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: Animals were weighed on days 0,7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Red/brown staining around the snout were noted in the male at 0.5, 1 and 2 hour observations.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of >2000mg/kg was determined in a reliable study conducted according to the appropriate guideline. The study was compliant with GLP.
Executive summary:

In the acute oral toxicity study, 2000 mg/kg bw of test material in arachis oil was administered orally to 5 male and 5 female rats. During the 14 -day study period, the animals were weighed on days 0, 7 and 14 and any clinical and bihavioural signs were noted regularly. Necropsy was performed at the end of the study period.

There were no deaths during the 14 -day study period. No signs of systemic toxicity were noted and all animals showed the expected body weight gain during the study period. No abnormalities were noted at nectorpsy.

An LD50 value of > 2000 was reported. The study was conducted according to an appropriate OECD test guideline and in compliance with GLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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: In house protocol
GLP compliance:
not specified
Test type:
fixed concentration procedure
Limit test:
no
Species:
rat
Strain:
other: COX-SD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS


- Weight at study initiation: 238-338g

- Housing: A 57 litre capacity glass chamber


ENVIRONMENTAL CONDITIONS

- Air changes (per hr): Air flow rate of 600 litres per hour



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


- Exposure chamber volume: 57 litres

- Method of holding animals in test chamber: Animals were contained in a glass chamber.

- Source and rate of air: ALFOL 14 alcohol was introduced by passing an air flow over the test material as it was heated in a 60C at an ambient chambre concentration of approximately 1.5mg per litre of air at a flow rate of ten litres per minute for a period of one hour.


TEST ATMOSPHERE


- Samples taken from breathing zone: Prior to the actual test period, the test material was introduced into the chambre for six minutes, in order that the test atmospheric concentration could reach theoretical equilibrium.


VEHICLE

- Lot/batch no. (if required): 8714J



CLASS METHOD (if applicable)

- Rationale for the selection of the starting concentration: The 1.5mg/litre test concentration was chosen since the level does not exceed any to which man could be subjected to in any foreseeable use of the material.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 h
Concentrations:
1.5 mg/l
No. of animals per sex per dose:
5 female, 5 male
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: Final body weight records of the ten animals at termination (14 days) showed weight gains within expected limits of that expected in all ten animals. The animals were observed frequently on the day of exposure and daily thereafter. Survivors were weighed and necropsied at the end of  the exposure period.

Statistics:
No statistical test was performed.
Sex:
male/female
Dose descriptor:
other: Inhalation
Effect level:
> 1.5 mg/L air
Exp. duration:
1 h
Mortality:
There were no mortalities during the exposure itself or in the 14 day observation period.
Clinical signs:
other: There were no clinical signs of toxicity present at any point of the study.
Body weight:
Body weight gain remained within expected limits for all ten animals.
Gross pathology:
Gross necropsy of the animals sacrificed at termination (14 days) showed no remarkable findings.
Other findings:
There were no other observations.

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

Nominal

Conc. (mg/L)

MMAD

µm

GSD

 

Number with evident toxicity (#/total)

Males

Females

Combined

 1.5mg/L

 

 

0 /5

0/5

0/10

 

Interpretation of results:
GHS criteria not met
Conclusions:
The rat 1 hour inhalational LC50 for tetradecan-1-ol is >1.5 mg/l. There were no signs of toxicity and findings at gross necropsy were unremarkable.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1.5 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
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 conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
8 000 mg/kg bw

Additional information

The acute oral toxicity key study was chosen as key since it was the most recent and high reliability source available (Safepharm Laboratories, 1996; rel1). However, another high reliability oral toxicity study was also available supporting the key study with an LD50 value of >20000 mg/kg bw (Scientific Associates, 1977; rel 2). The remaining low reliability supporting studies are in accordance with the key information. The study for acute inhalation toxicity was selected as it was the most recent and high reliability available study. The LC50 value for the study is below the concentration necessary for classification purposes. Furthermore, the saturated vapour concentration (calculated by the reviewer using the ideal gas equation on the basis of the physicocemical properties of tetradecan-1-ol) demonstrates that the highest theoretically achievable vapour concentration would have been reached or exceeded in this study (4h LC50 value of 0.375 mg/l). Therefore the recorded concentration in the key study represents the highest possible exposure concentration and can be considered for classification purposes.

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 study reports an LD50 value of 8000 mg/kg bw (Scientific Assoc., 1977). The available supporting studies support the finding of the key study.

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. 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.


Justification for classification or non-classification

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