Esterification product of castor oil fatty acids and pentaerythritol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Remarks:

skin irritation/corrosion in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 December 1999-4 January 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Likely performed under GLP but not sufficiently documented

Justification for type of information:

Guideline method conducted in a reliable laboratory but without sufficient GLP documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: US Dept. of Transporation (DOT) 49 CFR 173.136-7, 1994

Principles of method if other than guideline:

Occlusive exposure of rabbits to test material for 3 m, 60 m or 4 h.

GLP compliance:

yes

Remarks:

signature of QA officer but no statement available.

Test material

Test material information

Constituent 1

Reference substance name:

3-hydroxy-2,2-bis(hydroxymethyl)propyl (R)-12-hydroxyoleate

EC Number:

201-095-3

EC Name:

3-hydroxy-2,2-bis(hydroxymethyl)propyl (R)-12-hydroxyoleate

Cas Number:

78-22-8

Molecular formula:

C23H44O6

IUPAC Name:

3-hydroxy-2,2-bis(hydroxymethyl)propyl 12-hydroxyoctadec-9-enoate

Constituent 2

Reference substance name:

Castor oil

EC Number:

232-293-8

EC Name:

Castor oil

Cas Number:

8001-79-4

Test material form:

liquid

Details on test material:

Contains an additive (identifier redacted, CBI) having the following characteristics: Skin Corr Category 1C, Eye Damage Category 1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm
- Age at study initiation:
- Weight at study initiation:
- Housing:singly in suspended stainless steel cages with mesh floors.
- Diet (e.g. ad libitum): ad libitum, Purina Rabbit Chow 5326
- Water (e.g. ad libitum): ad libitum, municiple tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: December 1999 To: January 21, 2000

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

Oster A5-small

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

0-3 minutes, from 3 - 60 minutes, from 60 minutes to 4 hours.

Observation period:

1 h after patch removal. For the 4 hour time point, subsequent evaluations were performed approximately 24, 48 and 72 h after removal of the 4 h patch.

Number of animals:

3 per time point

Details on study design:

The dorsal area of each rabbit's trunk was clipped free of fur; each was examined for evidence of pre-test skin irritation. Three test sites, each approximately 6 cm2, were delineated on each rabbit. Five-tenths of a ml of the test stubstance was applied to each of the sites on each animal and covered with a 1 in x 1 in 4-ply gauze pad. The torso of each was wrapped with 3-in Micropore tape and Elizabethan collars were placed on each rabbit and they were returned to their cages. The collars were removed after 4 h.

The patches were removed at the appropriate intervals (3 minutes, 1 hour and 4 hours). The sites were gently wiped with water and a clean towel to remove any residual test substance. All sites were evaluated for corrosion 1 h after patch removal. Subsequent evaluations were performed approximately 24, 48 and 72 h after removal of the 4 h patch.

Corrosion was considered to have resulted if the test substance caused full-thickness necrosis (or ulceration) at the test site in at least 1 animal. Full-thickness necrosis is defined as moderate to severe tissue destruction with well-defined dark brown or black discoloration and/or stiffened texture, covering a substantial area. Epidermal sloughing, erythema edema or fissuring were not considered tissue destruction. The test sites were also evaluated for skin irritation according to the Draize score system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: corrosion

Basis:

mean

Time point:

other: 3 minutes, 60 minutes, 4 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: not corrosive

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of moderate irritation

Results 3

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of moderate irritation

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

10 d

Score:

0.3

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

10 d

Score:

0

Max. score:

8

Reversibility:

fully reversible within: 10 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No sign of dermal corrosion was noted at any of the treated sites. The test substance is considered non-corrosive as applied.
Some irritation was noted in all animals, persisting through day 10. By day 14, the irritation was reversed. The conclusion is moderate irritation.

Other effects:

3-minute exposure: One hour after patch removal, very slight edema and/or erythema were observed in 2 of 3 animals. By the 24-h evaluation mark, very slight and/or very slight to well-defined erythema were noted at all 3 sites. The incidence and severity decreased with time and cleared by day 7. Desquamation was evident in one animal between days 7-10, when the site cleared.
1-hour exposure: One hour after patch removal, very slight edema and/or erythema were observed in all 3 animals. By the 24-h evaluation mark, very slight to well-defined edema and erythema were noted at all 3 sites. The incidence and severity decreased with time and cleared by day 7. Desquamation was evident in one animal between days 7-10, when the site cleared.
4-hour exposure: One hour after patch removal, very slight edema and/or erythema were observed in all 3 animals. By the 24-h evaluation mark, very slight to well-defined edema and well-defined erythema were noted at all 3 sites. The incidence and severity decreased with time and desquamation was evident in one animal between days 7-14, when the site cleared.

The highest value for erythema and edema were observed in the group having the 4 hour exposure, where the PDII was 3.7 of 8, considered by the study directors to be moderately irritating.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The skin corrosion and irritation potential of the test substance was examined in rabbits in a guideline skin corrosion study in rabbits. The neat substance is not corrosive to the skin at exposure times up to 4 hours. A 4-hour exposure was found to be moderately irritating to the skin, likely due to the contribution of an additive known to cause skin corrosion (Category 1C) and severe eye damage (Category 1) These effects resolved within 10-14 days after exposure.