Registration Dossier

Administrative data

Description of key information

Read-across CAS: 1406-66-2: Oral LD50 (OECD guideline 401), rat = 7500 mg/kg bw
Dermal LD50 (OECD guideline 402), rabbit = 5000 mg/kg bw
Acute toxicity by inhalation was not tested according to Regulation (EC) No 1907/2006, Annex VII, Section 8.5, Column 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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliable study with limited data on material and method, please refer to IUCLID section 13 for read across justification.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
only one dose
GLP compliance:
yes
Test type:
fixed dose procedure
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA
- Weight at study initiation: approximately 200 to 300 g
- Fasting period before study: overnight (approximately 18 hours)
- Housing: individually housed in wire mesh bottom cages in environmenta controlled rooms
- Acclimation period: 3-5 days

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
15000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were weighed prior to dosing and at termination. They were observed frequently on the day of dosing and daily for a total of 15 days. All gross and visible toxic or pharmacological effects were recorded.
- Necropsy of survivors performed: yes (all animals that died during the study)
- Other examinations performed: body weight
Sex:
male/female
Dose descriptor:
LD0
Effect level:
15 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 7 500 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred.
Clinical signs:
In 2 animals diarrhea occurred on day 2 after administration which lasted one day.
Body weight:
no abnormalities
Gross pathology:
no data
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the rat was estimated to be greater than 15000 mg/kg bw. According to the a.i. concentration the LD50 of the a.i. (CAS: 1406-66-2) is calculated to be greater than 7500 mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was investigated in five Sprague-Dawley rats of each sex similar to the OECD guidelines for acute oral toxicity studies (limit test). The rats received a single oral dose of 15000 mg/kg bw. No mortality occurred. Two animals showed diarrhea on day 2.

The acute oral median lethal dose (LD50) of the test item in the rat was estimated to be greater than 15000 mg/kg body weight. The a.i. content was 50% and thus the LD50 of the a.i. (CAS: 1406 -66 -2) was calculated to be greater than 7500 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The whole database is conclusive.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited information on test item.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: H.A.R.E. - Rabbits for research, Hewitt, N.J.
- Weight at study initiation: 2 - 4 kg
- Housing: housed individually in wire mesh bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- clipped with electric clippers
- prior to administration abrasion of the skin was performed on the exposure sites of 3 males and 2 females. The skin of the remaining 2 male and 3 female rabbits was left intact. Abrasions were made with the point of a 22 gauge disposable hypodermic needle. The abrasions were minor incisions through the stratum corneum that were not sufficiently deep to disturb the derma or to produce bleeding.
- Area of exposure:
- % coverage: occlusive
- Type of wrap if used: layer of plastic wrap, a protective cloth and stockinette binder, all securely held in place with masking tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gently wipped with clean gauze to remove as mucg non-absorbed test article as possible
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approximately 5ml
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes constant concentration
Duration of exposure:
24 h
Doses:
5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality, local reactions, and toxicological findings were recorded for a total of 14 days. Body weights were recorded on the initial day of testing and at the study termination or day of death.
- Necropsy of survivors performed: no
- Other examinations performed: body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal was found dead on day 14.
Clinical signs:
Some animals showed decreased acitivity, loss of appetite, nasal discharge and diarrhea.
Body weight:
3 animals showed weight loss.
Gross pathology:
Left lung almost totally dark red in color. Stomach and intestines are gas filled. Both kidneys pale yellow. Urinary bladder full of urine.
Other findings:
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal mediam lethal dose (LD50) of the test item in the rabbit was estimated to be greater than 5000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of the test item was investigated in five female and 5 male New Zealand White rabbits.

Prior to administration abrasion of the skin was performed on the exposure sites of 3 males and 2 females. The skin of the remaining 2 male and 3 female rabbits was left intact. Abrasions were made with the point of a 22 gauge disposable hypodermic needle. The abrasions were minor incisions through the stratum corneum that were not sufficiently deep to disturb the derma or to produce bleeding.

One animal was found dead on day 14. Some animals showed decreased acitivity, loss of appetite, nasal discharge and diarrhea. Three animals showed weight loss.

The acute dermal median lethal dose (LD50) of the test item in the rabbit was estimated to be greater than 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000

Additional information

Acute oral toxicity

No reliable data concerning acute oral toxicity of the test item itself is available. The evaluation is based on data from two very close structutal homologs.

The key study was performed with "Mixed Tocopherols". The acute oral toxicity of "Mixed Tocopherols" was investigated in five Sprague-Dawley rats of each sex. The study revealed no significant treatment-related findings except diarrhea in two animals on day 2 after administration. The acute oral median lethal dose (LD50) of the test item (50% a.i.) in the rat was estimated to be greater than 15000 mg/kg body weight and thus the LD50 of the a.i. was calculated to be greater than 7500 mg/kg bw.

Another study was performed with the close homolog "DL-alpha-Tocopherol". The acute oral toxicity of "DL-alpha-Tocopherol" was investigated in Wistar rats equivalent or similar to the OECD guideline 401 for acute oral toxicity studies (limit test).

The acute oral median lethal dose (LD50) of the test item in the rat was estimated to be greater than 4000 mg/kg body weight (see ECHA dissiminated dossier CAS: 10191 -41 -0).

As no mortalities and no relevant treatment-related effects, besides diarrhea in two animals dosed with 7500 mg/kg bw of "Mixed tocopherols" occurred, it is concluded that the median lethal dose (LD50) of "D-alpha-Tocopherol" is ≥ 5000mg/kg.

Acute dermal toxicity

The acute dermal toxicity of D-alpha-tocopherol was investigated in five male and five female New Zealand White rabbits. One of the animals was found dead on day 14. Some animals showed decreased activity, loss of appetite, nasal discharge and diarrhea. Three animals showed weight loss. Thus, the acute dermal toxicity of the target substance is low, the median lethal dose was estimated in rabbits to be greater than 5000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Reliable guideline study which is the basis for classification, please refer to IUCLID section 13 for read across justification.

Justification for selection of acute toxicity – dermal endpoint
Reliable guideline study which is the basis for classification.

Justification for classification or non-classification

The available data on acute toxicity does not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.