Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 16, 2015 to July 31, 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Guidance document on acute oral toxicity testing, OECD series on testing and assessment no 24, 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Guidance document on the recognition, assessment and use of clinical signs as human endpoints for experimental animals used in safety evaluation. Environmental health and safety publications series on testing and assessment no 19, 2000.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
2-hydroxy-3-[(2,2,3,5-tetramethylhexanoyl)oxy]propyl (9Z)-octadec-9-enoate; 2-hydroxy-3-[(2,2,3,5-tetramethylhexanoyl)oxy]propyl (9Z,12Z)-octadeca-9,12-dienoate; 2-hydroxy-3-[(2,2,3,5-tetramethylhexanoyl)oxy]propyl octadecanoate
EC Number:
617-001-2
Cas Number:
80207-00-7
Molecular formula:
not applicable
IUPAC Name:
2-hydroxy-3-[(2,2,3,5-tetramethylhexanoyl)oxy]propyl (9Z)-octadec-9-enoate; 2-hydroxy-3-[(2,2,3,5-tetramethylhexanoyl)oxy]propyl (9Z,12Z)-octadeca-9,12-dienoate; 2-hydroxy-3-[(2,2,3,5-tetramethylhexanoyl)oxy]propyl octadecanoate
Test material form:
liquid
Remarks:
Brown

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Velaz Prague, Czech Republic.
- Body weight at study initiation: 175±15 g.
- Fasting period before study: 16 h.
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central air conditioning.
- Diet: A laboratory food Altromin (Altromin Speziallfutter GmbH, Germany) was offered in recommended doses each day approximately at the same time.
- Water: Tap water ad libitum.
- Acclimation period: 5 d.

ENVIRONMENTAL CONDITIONS
- Temperature: 22±2°C.
- Humidity: 55±10%.
- Photoperiod: 12 h light and 12 h dark cycle.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
- Dose preparation: The required amount of the test substance (according to body weight) was mixed with vehicle (olive oil) shortly before administration.
- Dose administration: The test substance was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following the period of fasting, the animals were weighed and the test substance administered. After the test substance had been administered, food was withheld for further 3-4 h.
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
6 females
Details on study design:
- Duration of observation period following administration: 14 d.
- Frequency of observations: The onset, type and duration of all symptoms of poisoning, and the time of death, were noted immediately after the administration of the test substance and then 0.5, 1, 2, and 4 h later. Then each animal was inspected daily for the next 14 d.
- Body weights: Individual weights of animals were determined shortly before the test substance was administered and at weekly thereafter.
- Clinical observation: Animals were observed individually immediately after the administration of the test substance and then 0.5, 1, 2, and 4 h later. Then each animal was inspected daily for the next 14 d. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: All test animals were subjected to gross necropsy. Full, detailed gross necropsy included careful examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents. All gross pathological changes were recorded for each animal.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in the treated animals.
Clinical signs:
other: Animals lived through observation period without important visible signs of intoxication. Neither change of health nor negative reactions were registered.
Gross pathology:
During necropsy, no macroscopic changes were noticed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of the test substancein rats was determined to be >2000 mg/kg bw.
Executive summary:

A study was conducted to assess the acute toxicity of the test substance to Wistar rats according to OECD Guideline 423, in compliance with GLP. The test substance was administered by gavage to 6 fasted females at the limit dose of 2000 mg/kg bw. Animals were observed individually immediately after dosing, at 0.5, 1, 2 and 4 h, then daily for 14 d. Bodyweights were recorded before treatment, then 7 and 14 d after treatment. All animals were sacrificed at the end of the study and subjected to gross examination. There was no mortality and no bodyweight loss between one and two week after administration of the test substance. No significant signs of toxicity were observed during the first 4 h or in the course of the 14 d observation period. At necropsy, no macroscopic changes were noted. Based on the results of the study, the oral LD50 of the test substance was determined to be >2000 mg/kg bw (Hozova, 2015).