Reaction mass of 1-(2,3-epoxypropoxy)-2,2-bis ((2,3-epoxypropoxy)methyl) butane and 1-(2,3-epoxypropoxy)-2-((2,3-epoxypropoxy)methyl)-2-hydroxymethyl butane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

study report dated 12 Nov 1976 (no additional details)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

GLP compliance:

no

Remarks:

prior to GLP

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 1-(2,3-epoxypropoxy)-2,2-bis ((2,3-epoxypropoxy)methyl) butane and 1-(2,3-epoxypropoxy)-2-((2,3-epoxypropoxy)methyl)-2-hydroxymethyl butane

EC Number:

701-135-4

Cas Number:

30499-70-8

Molecular formula:

C15H26O6;C15H22O5

IUPAC Name:

Reaction mass of 1-(2,3-epoxypropoxy)-2,2-bis ((2,3-epoxypropoxy)methyl) butane and 1-(2,3-epoxypropoxy)-2-((2,3-epoxypropoxy)methyl)-2-hydroxymethyl butane

Test material form:

other: liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Healthy New Zealand White rabbits (Porton strain) aged ·13 - 17 weeks with average body weights of 3.04 kg. (males) and 2.46 kg (females), bred on the premises and maintained under a semi-barrier system. Six rabbits (3 of each sex) were acclimatized in the test area for one week prior to the start of the trial. The rabbits were caged singly in an experimental room maintained at a temperature of 20degrees C (+/-1°) and a relative humidity of 50-70%. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shaved with one area intact and one area abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

6

Details on study design:

Twenty-four hours prior to the dermal application, the backs of the rabhits were shaved over an area consisting of at least 10% of the total body surface. Two test sites lateral to the mid line "of the back were used on each rabbit. lmmediately before the application of the test compound, the right hand site was abraded with the point of a sterile hypodermic needle. The abrasions were sufficiently deep to penetrate the stratum corneum but not to damage the dermis. The left hand site remained intact.
0.5ml of the test compound was applied to each test site on a 2.5cm square gauze pad. These were covered with aluminium foil secured with adhesive tape. The test sites were then covered by a 6 inch wide self adhesive bandage in order to retain the test substance in close contace with the skin.
After 24 hours the dressing was removed and· the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 hours and for any further period considered necessary up to 14 .

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24-72 hrs

Score:

7.17

Max. score:

8

Reversibility:

not fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not specified

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not specified

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

24 hours: Well defined erythema was present on 2/6 intact sites and all the remaining sites were showing evidence of necrosis. Moderate to severe oedema was also seen on all sites.
72 hours: Eschar formation involving dermal layers was ssen on 4/6 intact and 6/6 abraded sites. The remaining 2 intact sites were showing slight to well defined erythema. Slight to severe oedema was present on all sites.
6 days: Eschar formation was seen on 4/6 intact and 6/6 abraded sites with the remaining 2 intact sites showing well defined-erythema. Slight ·to moderate oedema was also present on all sites. 3 rabbits were sacrificed at this time.
10 days: The 3 remaining rabbits showed eschar formation and very slight to slight oedema on all sites.
14 days: (Termination of study) Eschar formation was still present on all sites and very slight to slight oedema on 2/3 intact and 3/3 abraded sites.
"If sufficient time had been allowed to elapse all sites would have eventually healed with some residual scarring.

Generally, there was very little difference seen in the reactions between intact and abraded sites.
The primary irritation score was 7.2.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test material is corrosive to skin in the albino rabbit.

Executive summary:

Healthy New Zealand White rabbits (Porton strain) were tested for skin irritation with the test material. Reactions of 4+ (according to Draize scoring) for erythema and oedema was seem on abraded and intact sites on all animals at 72 hours and was still seen at 14 days on 3/6 animals. The test material is considered corrosive to skin in the albino rabbit.