Reaction mass of 1,3-diacetoxypropan-2-yl 12-acetoxyoctadecanoate and 2,3-diacetoxypropyl 12-acetoxyoctadecanoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 2003-08-19 and 2003-10-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline and GLP study with no deviations.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

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

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-530-8

EC Name:

-

Cas Number:

736150-63-3

Molecular formula:

Not applicable

IUPAC Name:

1,3-bis(acetyloxy)propan-2-yl 12-(carboxyoxy)octadecanoate; 2,3-bis(acetyloxy)propyl 12-(acetyloxy)octadecanoate

Details on test material:

Name of test material (as cited in study report): TS-ED 532
- Lot/batch No.: batch 10102
- Expiration date of the lot/batch: 2003-11-23

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: rabbit
- Age at study initiation: 10-11 weeks (male) and 12 weeks (female)
- Weight at study initiation: 2276 g (male), 2309 g and 2185 g (both female)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes per h
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other:

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 h

Observation period:

The scoring of skin reactions was performed at 1, 24, 48 and 72 h, as well as 7 days after removal of the dressing. Observations of viability/mortality and clinical signs were performed daily from acclimatization to termination. The bodyweight was measured at start of acclimatization, on the days of application and at termination.

Number of animals:

3 (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: ca. 4x4 cm on a clipped area of 10x10 cm.
- % coverage: in accordance with guideline.
- Type of wrap if used: semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 h

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the EEC Commision Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48, 72 h, as well as 7 days after the removal of the dressing, gauze patch and test item.

Grading of Skin Reactions:

ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema: 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema) reading: 4

OEDEMA FORMATION
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (edges raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure): 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean score 1

Time point:

other: overall at 24, 48 and 72 h

Score:

1.33

Max. score:

2

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score 2

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Max. score:

2

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean score 3

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Max. score:

1

Results 4

Irritation parameter:

erythema score

Max. score:

2

Remarks on result:

other: max. duration: 3 days; max. value at end of observation period: 0 (related to all animals)

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean score 1

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Max. score:

1

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean score 2

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Max. score:

1

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean score 3

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

0

Results 8

Irritation parameter:

edema score

Max. score:

1

Remarks on result:

other: max. duration: 1 d; max. value at end of observation period: 0 (related to all animals)

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 7 days
Overall assessment of skin irritation scores for erythema: Not irritating
Overall assessment of skin irritation scores for oedema: Not irritating

Other effects:

No staining of the treated skin was observed. Neither alterations of the treated skin were observed nor were corrosive effects evident.

Any other information on results incl. tables

Table 1 Skin irritation scores – individual scores

Animal Number	Sex	Evaluation interval	Erythema	Oedema
82 83 84	M F F	1 hour	2 1 1	0 0 0
82 83 84	M F F	24 hours	2 2 1	1 1 0
82 83 84	M F F	48 hours	1 1 1	0 0 0
82 83 84	M F F	72 hours	1 0 1	0 0 0
82 83 84	M F F	7 days	0 0 0	0 0 0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The primary skin irritation potential of TS-ED 532 was tested in 3 rabbits by topical semi-occlusive application.
Based on the results, it is concluded that TS-ED 532 is not irritating.

Executive summary:

The primary skin irritation potential of TS-ED 532 was tested in 3 rabbits by topical semi-occlusive application of 0.5 mL TS-ED 532 to clipped skin using a patch. The duration of treatment was 4 h. The scoring of skin reaction was performed at 1, 24, 48 and 72 h, as well as 7 days after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 h after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

The mean erythema/eschar score of the 3 animals was 1.33, 1.00 and 1.00 respectively and the mean oedema score was 0.33, 0.33 and 0.00, respectively. 

The application of TS-ED 532 resulted in moderate signs of irritation which included erythema and oedema. These effects were reversible and were no longer evident 7 days after treatment. TS-ED 532 caused no staining of the treated skin and no corrosive effects were observed. No clinical signs of TS-ED 532 related effects were observed.

Overall, TS-ED 532 did not induce significant or irreversible damage to the skin. Hence, TS-ED 532 is considered to be “not irritating” to rabbit skin.