Propanoic acid, 2-hydroxy-2-methyl-, 2-propen-1-yl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Principles of method if other than guideline:

The intial weight of animal (no. 041) was above the preferrred range specified in the General Study Plan (2.0 - 3.0kg). This deviation has no impact on the integrity of the test.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

prop-2-en-1-yl 2-hydroxy-2-methylpropanoate

EC Number:

700-908-3

Cas Number:

19444-21-4

Molecular formula:

C7H12O3

IUPAC Name:

prop-2-en-1-yl 2-hydroxy-2-methylpropanoate

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elvage Scientifique des Dombes 01400 Chatillon sur Chalaronne, France
- Age at study initiation: Approximately 2 - 4 months
- Weight at study initiation: 2380 - 3060 g
- Housing: Individual
- Diet (e.g. ad libitum): NAFAG No. 814 (NAFAG, Gossau/SG, Switzerland) available ad libitum
- Water (e.g. ad libitum): Available ad libitum from automatic dispensers; source is municiple water supply.
- Acclimation period: 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50% ± 20%
- Air changes (per hr): 13-14/hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

3 days in 1 rabbit
7 days in 2 rabbits

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 10 cm
- % coverage:
- Type of wrap if used: Gauze patches, 2cm x 3cm (Rhena Gaze Kompresse, IVF, Neuhausen, Switzerland). Standard household aluminium foil wrap. Isocomfort self-adhesive wrap (soplast AG, Brugg, Switzerland)

Approximately 42 houts before treatment, an area approximately 10 cm wide from one flank to the other (across the back) of each anmimal was shaved with an electric clipper.
The test article was appliied to the shaved skin on one flank by means of a guaze patch. A control patch was applied to the other flank. The patches were loosly covered with aluminium foil and held in place with adhesive tape. Control patches were moistened with distilled water to improce contact.
Checked daily.

REMOVAL OF TEST SUBSTANCE
4 hours after treatment, the dressings were removed and the area washed with lukewarm water to remove any remaining test article.

SCORING SYSTEM: OECD (Draize Scale)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: for full results see table below

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

ca. 0

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: for full results see table below

Irritant / corrosive response data:

Very slightly erythema (score of 1) was observed in two animals (no. 060 and 055) from 1 hour through to 72 hours after patch removal. Very slight up to well defined erythema (scores of 1-2) was observed in one animal (no. 041) from 1 hour through to 24 hours after patch removal. Very slight edema (score of 1) was observed in one animal (no. 041) after 1 hour examination. All sin reactions were fully reversed within 7 days after patch removal. The results of the sin examinations for individual animals are presented in Table 1. Calculated skin irritation indices and scores according to OECD/EEC guidelines are presented in Table 2.

Other effects:

There was no mortality in the test.
There were no remarkable clinical observations.
A slight loss of body weight was reported in one rabbit (no. 060) between study start and day 3. Individual body weights are presented in Table 3.

Any other information on results incl. tables

Table1: Individual Dermal Irritation Scores (Draize)

ANIMAL NO.	FEMALES
	041		060		055
	ERYTHMA AND ESCHAR
	CF	TF	CF	TF	CF	TF
AFTER 1 HOUR AFTER 24 HOURS AFTER 48 HOURS AFTER 72 HOURS* AFTER 7 DAYS**	0 0 0 0 -	1 2 0 0 -	0 0 0 0 0	1 1 1 1 0	0 0 0 0 0	1 1 1 1 0
	EDEMA
AFTER 1 HOUR AFTER 24 HOURS AFTER 48 HOURS AFTER 72 HOURS* AFTER 7 DAYS**	0 0 0 0 -	1 0 0 0 -	0 0 0 0 0	0 0 0 0 0	0 0 0 0 0	0 0 0 0 0
CF: CONTROL FLANK    TF: TEST FLANK

*Study end for no. 041

**Study end for no. 050 and 055

Table 2: Summary Dermal Irritation Scores (OCED/EC)

ANIMAL NO.	FEMALES
	041	060		055
	ERTHYEMA AND ESCHAR
MEAN SCORE 24 – 72 HOURS	0.67		1		1
OVERALL MEAN SCORE 24 – 72 HOURS	0.89
	EDEMA
MEAN SCORE 24 – 72 HOURS	0		0		0
OVERALL MEAN SCORE 24 – 72 HOURS	0

 

 

Table 3: Body Weights (g)

ANIMAL NO.	FEMALES
	041		041
AT TEST START AFTER 3 DAYS* AFTER 7 DAYS**	3060 3080 -	2380 2320 2440	2860 2870 2970

*Study end for no. 041

**Study end for no. 050 and 055

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to Commission Directive 93/21/EEC, issued May 4, 1993, the results of this test indicate that CA 225 A (IntermedIate of CGA 276854) is not required to be classified for skin irritation.

Executive summary:

A dermal irritation/corrosion was conducted with test article CA 2215 A (Intermediate of CGA 276854) (batch P.608005). The test article (0.5 ml) was applied to the shaved skin of 3 rabbits for 4 hours under occlusive conditions. The test sites were examined for skin irritation at 1, 24, 48 and 72 hours after patch removal in all rabbits, and a 7 day after patch removal in two rabbits. 

The test article caused skin irritation in all animals. Very slight erythema was observed in two animals form 1 hour to 72 hours after patch removal. Very slight up to well defined erythema was observed I one animal from 1 hour through to 24 hours after patch removal. Very slight edema was observed in one animal examination. All skin reactions were fully reversed within 7 days after patch removal. There was no mortality, and there were no remarkable clinical observations. A slight loss of body weight was recorded in one rabbit between study start and day 3. 

Calculation of mean scores for individual animals (EEC method, 24 – 72 hours) for erythema and eschar resulted in scores from 0.67 to 1, with an overall mean of 0.89. All scores for edema were 0. According to the test results, CA 225 A (Intermediate of CGA 276854) is not required to be classified according to Commission Directive 93/21/EEC, issued May 4, 1993.