3,7,11,15-tetramethylhexadecane-1,2,3-triol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted in June 1999.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,7,11,15-tetramethylhexadecane-1,2,3-triol

EC Number:

277-923-2

EC Name:

3,7,11,15-tetramethylhexadecane-1,2,3-triol

Cas Number:

74563-64-7

Molecular formula:

C20H42O3

IUPAC Name:

3,7,11,15-tetramethylhexadecane-1,2,3-triol

Test material form:

other: Solid

Details on test material:

Name of test substance: Phytantriol
Substance number: 99/98-1
Batch number: Lot. Nr. 08-0388
Degree of purity/content: 98.8 area % (GC)
Date of manufacturing: 25-Sep-1998
Physical state/appearance:
Solid, colorless - milky at about 8 degrees centigrade;
Liquid, colorless after heating at about 50 degrees centigrade
Storage conditions: Refrigerator, exclusion of light and oxygen (under nitrogen)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Origin : Boehringer Ingelheim Pharma KG
Age of the animals :Young adult animals .
Animal weights at start of the study :Animals of comparable weight ; (150g - 300g) (+/- 20 % of the mean weight).
Acclimatization period : Acclimatization for at least 1 week .

Room temperature/relative humidity :The animals were housed in fully air-conditioned rooms . Central air-conditioning guaranteed a
range of 20 - 24 degrees centigrade for temperature and of 30 - 70 Z for relative humidity . There were no deviations from these ranges, which influenced the results of the study .

Day/night rhythm: 12 h/12 h (6 .00 a .m . - 6 .00 p .m./6 .00 p .m . - 6 .00 a .m. )
Type of cage :Stainless steel wire mesh cages, type DK-III (Becker & Co ., Castrop-Rauxel, FRG )
No . of animals per cage :Single housing .
Animal identification :Individual identification using cage cards and group identification by tail marking .
Bedding :No bedding in the cages ; wood shavings in the waste trays .
Drinking water :Tap water ad libitum per day .
Diet :Kliba-Labordiaet, Provimi Kliba SA, Kaiseraugst, Switzerland, ad libitum
Analysis of drinking water :The drinking water is regularly assayed for
chemical contaminants by the municipal authorities
of Frankenthal and the technical services
of BASF Aktiengesellschaft as well as for the
presence of germs by a contract laboratory .

Analysis of feed :The feed used in the study was assayed for
chemical and microbiological contaminants .

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

Selection of doses
Based on the physical and chemical characteristics of the test substance and the composition no pronounced acute oral toxicity was expected. Therefore a dose of 2000 mg/kg body weight has been chosen in a first step with 3 male animals.
Because no mortality occurred, 2000 mg/kg body weight have been tested in a second step with animals of the other sex (3 female animals).

2000 mg/kg was administered at 40 mg/100mL in olive oil. 5 mL/kg was administered.

Doses:

2000 mg/kg

No. of animals per sex per dose:

Three males and three females

Control animals:

no

Details on study design:

Route of administration: Single oral administration by gavage.
Fasting period: The animals were given no feed at least 16 hours before administration, but water was available ad libitum.
Form of administration: Solution. Before application it was cooled down to body temperature.
Test substance formulation with: Olive oil
Reason for the vehicle: Good solubility of the test substance in olive oil
Time of administration: In the morning
Observation period: 14 days
Date of first administration: 23 June 1999
Date of last administration: 30 June 1999

Body weight determination: Individual body weights shortly before application (Day 0), weekly thereafter and at the end of the study (before fasting period); additionally animals that died or were sacrificed moribund.

Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals; these records were maintained with the raw data.

Mortality: A check for any dead or moribund animal was made twice each workday and once of Saturdays, Sundays and on public holidays.

Pathology: Necropsy at the last day of the observation period. Withdrawal of food at least 16 hours before killing with CO2; then necropsy with gross pathology examination. Necropsy of all animals that died before as early as possible.

Statistics:

None specified

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality of the male animals (cumulative): No mortality
Mortality of the female animals (cumulative): No mortality

Clinical signs:

Symptoms
Male animal symptoms cage-side observations: No abnormality

Female animal symptoms cage-side observations
Impaired general state: h3 – h5 (1 animal)
Dyspoea: h3 – h5 (1 animal)
Diarrhea: h3 – h5 (1 animal)
h = hour

Body weight:

Mean body weight of the male animals (g)
Day 0: 177
Day 7: 243
Day 13: 283

Mean body weight of the female animals (g)
Day 0: 194
Day 7: 266
Day 13: 237

Gross pathology:

There were no particular organ findings in any animal.

Any other information on results incl. tables

Analysis of the test substance

The degree of purity of the test substance was found to be 98.8 % by GC analysis.

The stability of the test substance has not been determined by reanalysis, because the study and the characterisation were performed in the same time period.

After heating at about 50°C the test substance was homogenous by visual inspection.

 

Analysis of test substance preparations

The stability of the test substance in olive oil for a time period of 4 hours was confirmed by analysis.

The test substance is soluble in olive oil after heating the test substance preparation at about 50°C and simultaneous homogenizing in an ultrasonic bath.

 

Analysis of Feed

In view of the aim and duration of the study the contaminants occurring in commercial feed should not influence the results.

 

Analysis of drinking water

In view of the aim and duration of the study there are no special requirements exceeding the specification of drinking water.

Individual bodyweight of the male animals (g)

Cage	Day 0	Day 7	Day 13
957	177	242	284
958	177	242	285
959	177	244	281

 

Individual bodyweight of the female animals (g)

Cage	Day 0	Day 7	Day 13
988	193	226	242
989	194	224	236
990	196	227	233

 

Pathology

	Male	Female
Total Number	3	3
Organs without particular findings	3	3

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the median lethal dose of the test substance after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals.

Executive summary:

The acute oral toxicity of the test substance was assessed according to OECD Test Guideline 423 (acute toxic class method), EU Method B.1 tris and EPA OPPTS 870.1100 using a single oral dose of the test material preparation in olive oil at a dose level of 2000 mg/kg body weight.

No mortality occurred. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals. The test substance is therefore not classified for acute oral toxicity.