Coumarin

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:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Coumarin

EC Number:

202-086-7

EC Name:

Coumarin

Cas Number:

91-64-5

Molecular formula:

C9H6O2

IUPAC Name:

2H-chromen-2-one

Test material form:

solid: crystalline

Details on test material:

-Name of test material: coumarin
-Substance type: pure active substance
-Physical state:crystal
-Analytical purity:100%
-Lot/batch No.: not metioned

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

10 New Zealand White rabbits, aged 9-12 weeks are used for each test. The whole dorsal surface is clipped 3-4 days before the test is due to start, and animals in the telogen phase of hair growth are selected.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

yes

Amount / concentration applied:

Amount applied: 0.2g solid

Duration of treatment / exposure:

The test material and appropriate standards are applied to the clipped dorsum of rabbits for 4 hours under individual semi-occlusive patches,
the treated areas are wiped and examined for evidence of irritation.

Observation period:

72h

Number of animals:

8

Details on study design:

Occlusive patches are prepared by heat-sealing 1”*1” 24 ply gauze pads on to 1.25”*1.25” squares of polythene sheeting which is then attached to 3.5”*1” strips of adhesive tape. Test solids (0.2g) are applied to a moistened patch. Aerosol preparations are applied directly to the skin with two 1-second bursts and the patches are saturated with spray which acts as a reservoir.

The patches are firmly attached to ensure good contact between the skin and test substance. The animals are immobilized in a canvas body sleeve for 4 hours after application of the patch. When the patches are removed, the treatments sites are wiped clean of excess material. The positions of treatment sites are randomized. Experimental detail for this test are in Table I.
Scoring system:
er-erythema
oe-oedema
cr-cracking
sc-scaling
Reaction Grades and Scores
a marginal/very slight =1
b slight=2
c fairly distinct =3
d quite distinct =4
e becoming well developed =6
f well developed =8
g becoming severe =10
h severe =12

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24h, 48h, 72h

Score:

0

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24h, 48h, 72h

Score:

0.33

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24h, 48h, 72h

Score:

0

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24h, 48h, 72h

Score:

0

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24h, 48h, 72h

Score:

0

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24h, 48h, 72h

Score:

1.33

Results 7

Irritation parameter:

erythema score

Basis:

animal: #7

Time point:

other: 24h, 48h, 72h

Score:

3

Results 8

Irritation parameter:

erythema score

Basis:

animal: #8

Time point:

other: 24h, 48h, 72h

Score:

0.33

Results 9

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24h, 48h, 72h

Score:

0

Results 10

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24h, 48h, 72h

Score:

0.33

Results 11

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24h, 48h, 72h

Score:

0

Results 12

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24h, 48h, 72h

Score:

0

Results 13

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24h, 48h, 72h

Score:

0

Results 14

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24h, 48h, 72h

Score:

0.67

Results 15

Irritation parameter:

edema score

Basis:

animal: #7

Time point:

other: 24h, 48h, 72h

Score:

2.67

Results 16

Irritation parameter:

edema score

Basis:

animal: #8

Time point:

other: 24h, 48h, 72h

Score:

0

Irritant / corrosive response data:

See talbe I in "any other information on results incl. tables

Other effects:

None

Any other information on results incl. tables

Treatment Site No.

4 Hours

24 Hours

48 Hours

72 Hours

Totals

Total

Score(T)

er

oe

cr

sc

er

oe

cr

sc

er

oe

cr

sc

er

oe

cr

sc

er

oe

cr

sc

2

a

_

_

_

_

1

_

1

3

a

a

a

a

_

_

2

2

4

4

a

a

_

_

_

1

1

2

5

_

_

_

_

_

_

6

_

_

_

_

_

_

1

c

5

c

5

a

_

_

7

4

11

3

c

c

d

d

d

d

d

c

15

14

29

4

a

a

a

_

_

_

2

1

3

er-erythema oe-oedema cr-cracking sc-scaling

Reaction Grades and Scores

a marginal/very slight =1 b slight=2 c fairly distinct =3 d quite distinct =4

e becoming well developed =6 f well developed =8 g becoming severe =10 h severe =12

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Only one animal shows mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema. According to GHS criterion, at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal. Therefore, it's not classified as irritating.

Executive summary:

Methods and Results.

Occlusive patches are prepared by heat-sealing 1”*1” 24 ply gauze pads on to 1.25”*1.25” squares of polythene sheeting which is then attached to 3.5”*1” strips of adhesive tape. Test solids (0.2g) are applied to a moistened patch. Aerosol preparations are applied directly to the skin with two 1-second bursts and the patches are saturated with spray which acts as a reservoir.

The patches are firmly attached to ensure good contact between the skin and test substance. The animals are immobilized in a canvas body sleeve for 4 hours after application of the patch. When the patches are removed, the treatments sites are wiped clean of excess material. The positions of treatment sites are randomized. Experimental detail for this test are in Table I. Only one animal shows mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema.

Conclusion. The test substance when administered to rabbits by dermal route, under the experimental conditions adopted, has to be considered as non irritant for the skin.