Registration Dossier

Administrative data

Description of key information

Oral LD50 (OECD guideline 401), rat = 7500 mg/kg bw
RA: CAS 7695-91-2, LD50 (OECD guideline 401), rat > 10000 mg/kg bw
Dermal LD50 (OECD guideline 402), rabbit > 1000 mg/kg bw
Read-across CAS: 59-02-9: 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 VIII, 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:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliable study comparable to guideline, but limited documentation.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
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: Charles River Breeding Laboratories, Inc., Wilmington, MA
- Weight at study initiation: 200 to 300 g
- Fasting period before study: overnight (approximately 18 hours
- Housing: individually housed in wire mesh bottom cages in environmental 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
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
- Necropsy of survivors performed: no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 15 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Two animals showed diarrhea on day 2.
Body weight:
No abnormalities observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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 databse is conclusive and of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

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

Additional information

Acute oral toxicity

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.

The supporting study was performed with D,L-alpha-tocopheryl acetate similar to the OECD guideline 401 (limit test) in Sprague-Dawley rats. The test material was applied as a 50% solution in olive oil. The animals received a single application of 10000 mg/kg bw (50% a.i.) by gavage. The median lethal dose (LD50) of the a.i. was caculated to be >5000 mg/kg bw for males and females.

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).

It is concluded that the median lethal dose (LD50) of "RRR-(alpha-, beta-, gamma-, delta)-Tocopherol is ≥ 5000mg/kg.

Acute dermal toxicity

There is one reliable study available concerning acute oral toxicity of the test item itself. The evaluation is based on the results of this study and a study which is performed with the close homolog "RRR-alpha-Tocopherol".

The acute dermal toxicity study was performed with the test item "RRR-(alpha, beta-, gamma-, delta)-Tocopherol". The acute dermal toxicity of the test item was investigated in five female and 5 male New Zealand White rabbits. No mortality occurred. Some animals showed decreased acitivity, loss of appetite and diarrhea. All signs vanished until day 14. One animal showed weight loss.

The acute dermal median lethal dose (LD50) of the test item (50% a.i.) in the rabbit was estimated to be greater than 2000 mg/kg body weight. The LD50 of the a.i. was calculated to be greater than 1000 mg/kg bw.

Another study was performed with the structural homolog "RRR-alpha-tocopherol". The acute dermal toxicity of the test item was investigated in five female and 5 male New Zealand White rabbits. 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.

As no mortalities and only some minor treatment-related effects (diarrhea, loss of apetite, decreased activity, nasal discharge) occurred in some animals dosed with the test item "RRR-(alpha, beta-, gamma-, delta)-Tocopherol" (50% a.i.) and additionally the LD50 of a very close homolog "RRR-alpha-tocopherol" was estimated to be greater than 5000 mg/kg bw. Therefore

it is concluded that the median lethal dose (LD50) of "RRR-(alpha-, bea-, gamma-, delta)-Tocopherol" is 2000mg/kg.

Justification for selection of acute toxicity – oral 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.