2-ISOPROPYL-1,3-DIOXANE-5,5-DICARBOXYLIC ACID DIETHYL ESTER

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-ISOPROPYL-1,3-DIOXANE-5,5-DICARBOXYLIC ACID DIETHYL ESTER

EC Number:

609-063-4

Cas Number:

35113-48-5

Molecular formula:

C13H22O6

IUPAC Name:

2-ISOPROPYL-1,3-DIOXANE-5,5-DICARBOXYLIC ACID DIETHYL ESTER

Test material form:

other: Liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK. At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and were twelve to sixteen weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (Certified Rabbit Diet (Code 5322) supplied by PMI Nutrition International, Nottingham, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml of the test material

Duration of treatment / exposure:

4h

Observation period:

1, 24, 48, 72h and 7d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure:2.5*2.5
- Type of wrap if used: surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing : cotton wool soaked in 74% industrial methylated spirits
- Time after start of exposure:

SCORING SYSTEM:
EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 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 (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1h

Score:

ca. 0.66

Max. score:

1

Reversibility:

not fully reversible within: 7d

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h

Score:

ca. 0.33

Max. score:

1

Reversibility:

not fully reversible within: 7d

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48h

Score:

ca. 0.33

Max. score:

1

Reversibility:

not fully reversible within: 7d

Remarks on result:

other: loss of skin elasticity

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72h

Score:

ca. 0.33

Max. score:

1

Reversibility:

not fully reversible within: 7d

Remarks on result:

other: loss of skin elasticity

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 7d

Score:

ca. 0

Max. score:

0

Remarks on result:

other: slight desquamation

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1h

Score:

ca. 0.66

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 7

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h

Score:

ca. 0.33

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48h

Score:

ca. 0.33

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 9

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72h

Score:

ca. 0.33

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 10

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 7d

Score:

ca. 0

Max. score:

0

Irritant / corrosive response data:

Very slight erythema was noted at two treated skin sites one hour after patch removal and persisted at one treated skin site at the 24, 48 and 72-hour observations.
Very slight oedema was noted at two treated skin sites one hour after patch removal and persisted at one treated skin site at the 24, 48 and 72-hour observations.
Loss of skin elasticity was noted at one treated skin site at the 48 and 72-hour observations with slight desquamation at this treated skin site at the 7-day observation.
One treated skin site appeared normal throughout the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 0.7 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 93/21/EEC.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§ OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 17 July 1992)

§ Commission Directive 92/69/EEC Method B4 Acute Toxicity (Skin Irritation)

Results. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema and very slight oedema. Other reactions noted were loss of skin elasticity and slight desquamation. One treated skin site appeared normal throughout the study.

Conclusion. The test material produced a primary irritation index of 0.7 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 93/21/EEC.