6-glycidyloxynapht-1-yl oxymethyloxirane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08.04.1986 to 21.04.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study performed under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-960-2

EC Name:

-

Cas Number:

27610-48-6

Molecular formula:

C16H16O4

IUPAC Name:

2-[({6-[(oxiran-2-yl)methoxy]naphthalen-1-yl}oxy)methyl]oxirane

Test material form:

liquid: viscous

Details on test material:

-Appearance: Brown viscous liquid.
The sample was received on 15 January 1986 and was stored at ambient temperature.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

-New Zealand White strain rabbits in the weight range 2.3 to 2.8 kg, prior to treatement on Day 1 and approximately 10 to 12 weeks of age were obtained fromFroxfield rabbits, Petersfield, Hamshire, England.
-The rabbits selected for the study were all acclimated to the laboratory environment.
-Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This number was unique within the HRC Industrial Toxicology Departmentthroughout the duration of the study.
-The rabbits were individually housed in metal cages with perforated floors in Building R14 Room1. They had free access to tap water and SDS Standard Rabbit Diet.
-Animal room temperature was maintained at approximately 19°C and relative humidity at 30-70%.
-Air exchange was maintained at approximately 19 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900) hours in each 24 hour period.
-All animals were observed daily for signs of ill health or toxic signs.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated flank

Amount / concentration applied:

no data

Duration of treatment / exposure:

Exposure duration: 4 hours

Observation period:

-Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Day 2, 3 and 4. Additional observations were made on Days 5 through 14.

Number of animals:

-Six New Zealand White strain males rabbits.

Details on study design:

TEST SITE
- Area of exposure: The dorso-lumbar region of each rabbit.
- % coverage: 10 cm square
- Type of wrap if used: Gauze pad and each treatment site was occluded with "Elastoplast" elastic adhesive.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Done using distilled water in an attempt to remove any residual test substance.
- Time after start of exposure: after 4 hours period.

SCORING SYSTEM:
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 aera 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:

animal #1

Time point:

other: day 1 to 14

Score:

>= 1 - <= 4

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: day 1 to 14

Score:

>= 1 - <= 4

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 12 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: day 1 to 14

Score:

>= 2 - <= 3

Max. score:

3

Reversibility:

not reversible

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: day 1 to 14

Score:

>= 1 - <= 3

Max. score:

3

Reversibility:

not reversible

Results 7

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Results 8

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Results 9

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Results 10

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: day 4 to 14

Score:

ca. 1

Max. score:

1

Reversibility:

not reversible

Results 11

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 12 days

Results 12

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: day 1 to 14

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not reversible

Irritant / corrosive response data:

There was no initial response to the four hours exposure to Epiclon EXA 4032, however, by Day 2 slight to well-defined reactions had developed. These increased in severity and by Day 4 necrotic lesions were observed in 2 rabbits and well-defined erythema with very slight to slight oedema in the four remaining animals. Ar this time whiote "blanched" arears also saterted to develop and by Day 7 were present in four rabbits.
Slight to well-defined or moderate reactions accompanied by desquamation of the stratum corneum were still present on Day 14.
Considerable difficulty had been experienced in trying to remove the test substance at the end.

Applicant's summary and conclusion

Conclusions:

In conclusion, a single semi-occlusive application of EPICLON EXA 4032 to intact rabbit skin for four hours elicited well-defined to severe dermal irritation.

Executive summary:

This study was designed to assess skin irritation potential in the rabbit.The study was performed according Guidelines as described in the Federal Register, Vol. 50, N° 188, Part II of 27 September 1985, Section 798.4470_Primary Dermal Irritation.

For the experiment, six New Zealand White starin rabbits were used.

A 0.5 ml aliquot of EPICLON EXA 4032 was applied under a 2.5 cm square gauze pad to one intact skin site on each animal during four hours (semi-occlusive application).

Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Day 2, 3 and 4. Additional observations were made on Days 5 through 14.

In conclusion, a single semi-occlusive application of EPICLON EXA 4032 to intact rabbit skin for four hours elicited well-defined to severe dermal irritation.