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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Date of application: 21-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:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

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:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

Animal species / strain / quality: Rabbit / Himalayan / Chbb: HM (outbred strain)
Origin: Boehringer Ingelheim Pharma KG
Age of the animals: Young adult
Acclimatization period: Acclimatization for at least 1 week

Housing conditions
Room temperature / relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 – 24 °C for temperature and of 30 – 70 % for relative humidity. There were no deviations from these ranges, which influenced the results of 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 with grating, floor area: 3000 cm2.
No. of animals per cage: Single housing
Animal identification: Ear tattoo
Bedding: No bedding in the cages; wood shavings in the waste trays.
Drinking water: Tap water ad libitum
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.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

other: Untreated skin sites of the same animal.

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

Three

Details on study design:

Route of application: The test substance was applied in a single dose to the intact untreated skin. The test patch was secured in position with a semi-occlusive* dressing. The test substance was removed at the end of the exposure period with Lutrol®** and Lutrol®/water (1:1).

* The test substance has been covered with a test patch (Idealbinde, Pfaelzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull(R) stretch (adhesive fleece), Beiersdorf AG.
** Lutrol(R) E 400 = Polyethylenglycol DAB, BASF Aktiengesellschaft.

Clipping of the fur: At least 24 hours before the test, the fur was removed by clipping the dorsal part of the trunk of the animal(s). Only animals with healthy intact skin were used.

Application site: Upper third of the back or flanks.

Negative control: Untreated skin sites of the same animal.

Application volume: The test patch (2.5 cm x 2.5 cm) was moistened with a dose of 0.5 mL at about 50 °C heated test substance(before application it was cooled down to body temperature).

Exposure period: 4 h
Observation period: 14 d
Date of application: 21 June 1999
Body weight determination: Shortly before application of the test substance.
Readings: 1h, 24 h, 48 h, 72 h,7 d and 14 d after removal of the patch.
Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Erythema and edema were observed extending beyond the area of exposure. Under the test conditions chosen and considering the described findings, the test substance gives indication of an irritant property to the skin.

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 area-% by GC analysis.

The stability of the test substance was not determined by re-analysis, because the study and the characterisation were performed in the same time period.

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

 

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.

Tabulation of irritant response data for each individual animal at each observation time as well as calculation of the means.

Readings	Animal	Erythema	Edema	Symptoms
1 h	01	3	2	15, 16
	02	3	2	15, 16
	03	3	2	15, 16
24 h	01	3	1
	02	3	1	15, 16
	03	3	2	15, 16
48 h	01	3	1
	02	3	1	15, 16
	03	3	2	15, 16
72 h	01	3	1
	02	2	1	15, 16
	03	3	2	S, 15, 16
7 d	01	2	1	SS
	02	2	1	S
	03	2	1	S
14 d	01	1	0
	02	1	0	S
	03	1	0	S
Mean	01	3.0	1.0
	02	2.7	1.0
	03	3.0	2.0
Mean		2.9	1.3

S = Scaling

SS = Severe scaling

15 = Erythema extending beyond the area of exposure

16 = Edema extending beyond the area of exposure

 

Calculation of mean values

Calculation of the mean according to 93/21/EEC criteria of April 27^th1993 (for calculation of the means of erythema and edema only the readings of 24, 48 and 72 hours are used).

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the test conditions chosen and considering the described findings, the test substance gives indication of an irritant property to the skin.

Executive summary:

The skin irritation potential of the test substance was assessed according to OECD Test Guideline 404 and EU method B.4 using a single topical application of 0 .5 mL of the test substance to the intact skin of three Himalayan rabbits for four hours under semi-occlusive dressing.

The average score (24 to 72 hours) for irritation was calculated to be 2.9 for erythema and 1.3 for edema. The skin findings were not reversible in all animals within 14 days (study termination).

The mean value for erythema was ≥2.3 in all three rabbits and therefore the substance is classified as a skin irritant (Category 2).