Triglycerides, C16-C18 (even numbered) and C18 (unsaturated), maleated

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-11-18 to 2015-01-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Triglycerides, C16-C18 (even numbered) and C18 (unsaturated), maleated

EC Number:

941-396-3

Molecular formula:

A molecular formula cannot be provided due to a complex mixture of reaction products.

IUPAC Name:

Triglycerides, C16-C18 (even numbered) and C18 (unsaturated), maleated

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): MSOHO
- Chemical Name: High oleic sunflower oil, maleated
- Batch No.: PROD 240614
- Physical State at RT: liquid
- Colour: turbid yellow
- Density: 1.0127 g/mL
- Purity: 100%, UVCB
- Storage Conditions: at room temperature, protected from light
- Expiry Date: 24 December 2015

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 153 - 202 g
- Fasting period before study: 16 to 19 hours
- Housing: in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102140831)
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1239)
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10; Full barrier in an air-conditioned room
- Photoperiod (hrs dark / hrs light): 12/ 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:

2000 mg/kg bw (starting dose)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days for general clinical signs, morbidity and mortality.
- Other examinations performed: Animals were weighed on day 1 (prior to the administration) and on days 8 and 15.

- Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor,
convulsions, salivation, diarrhoea, lethargy, sleep and coma.

- Pathology
At the end of the observation period the all animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally
(Narcoren®, Merial; lot no.: 236014; expiry date: 31 January 2017) at a dosage of 250-400 mg/kg bw.
All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In absence of gross pathological
changes no tissues were preserved for a possible histopathological evaluation.

Statistics:

According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation
of the results is not regarded as necessary.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: cut-off value

Mortality:

All animals survived until the end of the study.

Clinical signs:

All animals did not show any test-item related signs of toxicity.

Body weight:

Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain.

Gross pathology:

At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Under the conditions of the present study, a single oral application of the test item MSOHO to rats at a dose of 2000 mg/kg body weight
was associated with no signs of toxicity or mortality.
The median lethal dose of MSOHO after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): > 5000 mg/ kg bw
In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item MSOHO has no obligatory labelling
requirement for toxicity.
According to Annex I of Regulation (EC) 1272/2008 the test item MSOHO has no obligatory labelling requirement for toxicity and is not classified.
According to GHS (Globally Harmonized Classification System) the test item MSOHO has no obligatory labelling requirement for toxicity
and is not classified.

Executive summary:

Summary Results

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of

2000 mg/kg body weight. The test item was suspended with with the vehicle Polyethylenglycol at a concentration of 0.2 g/mL and

administered at a dose volume of 10 mL/kg.

All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days.

The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs.

All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period.

Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and

examined macroscopically.

All animals survived until the end of the study without showing any test-item related signs of toxicity.

Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain.

At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC,

the substance should be:

classified asvery toxic
classified astoxic
classified as harmful
not classified	X
limit test	X

On the basis of the test results given below and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008,

the substance should be:

classified into category 1
classified into category 2
classified into category 3
classified into category 4
not classified	X

 

 

On the basis of the test results given below and in conformity with the criteria given in GHS (Globally Harmonized System of Classification and Labelling of Chemicals), the substance should be:

classified into category 1
classified into category 2
classified into category 3
classified into category 4
classified into category 5
not classified	X

LD₅₀:  > 5000 mg/kg bw

Species/strain: WISTAR Crl: WI(Han) rats

Vehicle: Polyethylenglycol

Number of animals: 3 per step / 2 steps performed

Method: OECD 423, EC 440/2008, Method B.1 tris, OPPTS 870.1100

Conclusion

Under the conditions of the present study, a single oral application of the test itemMSOHOto rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

The median lethal dose of MSOHO after a single oral administration to female rats, observed over a period of 14 days is:

LD₅₀cut-off (rat): > 5000 mg/ kg bw

In conformity with the criteria given inAnnex VI to Commission Directive 2001/59/EC the test itemMSOHOhas no obligatory labelling

requirement for toxicity.

According to Annex I of Regulation (EC) 1272/2008 the test itemMSOHOhas no obligatory labelling requirement for toxicity and is not classified.

According to GHS (Globally Harmonized Classification System)[11]the test itemMSOHOhas no obligatory labelling requirement for toxicity

and is not classified.