Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 Oct 1986 - 18 Nov 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
according to GLP, no characterization data on test substance available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Adopted 12 May 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Adopted 25 April 1984
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
α-chloro-o-xylene
EC Number:
209-013-8
EC Name:
α-chloro-o-xylene
Cas Number:
552-45-4
Molecular formula:
C8H9Cl
IUPAC Name:
1-(chloromethyl)-2-methylbenzene
Test material form:
liquid
Specific details on test material used for the study:
clear yellow fluid
purity ca. 99% (no analytical information available)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, conventional breeding
- Age at study initiation: ca. 3-5 months
- Weight at study initiation: 2.1 - 3.4 kg
- Housing: single
- Diet (e.g. ad libitum): Altromin 2123 diet, ad libitum
- Water (e.g. ad libitum): deionized, chlorinated water, ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light):12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
in the dorsal area of the rump, a ca. 25 cm2 area was shaved with electric clippers.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted

VEHICLE
- Amount(s) applied (volume or weight with unit): none
Duration of treatment / exposure:
3 min or 4 hours
Observation period:
14 days post application
Number of animals:
3 animals (3 min), 3 animals (4 hours)
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage:
- Type of wrap if used: cellulose patch, coverd with semiocclusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: at the end of exposure period (3 min / 4 hrs)

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 30-60 min, 24 hours, 48 hours, 72 hours, 7 days, 14 days

SCORING SYSTEM: Similar to OECD Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
4 hours exposure
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
4 hours exposure
Basis:
mean
Time point:
24/48/72 h
Score:
3.8
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3 min exposure
Basis:
mean
Time point:
other: 30 - 60 min
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3 min exposure
Basis:
mean
Time point:
other: 30 - 60 min
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
not reversible
Remarks:
in 1/3 animals, effects were not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3 min exposure
Basis:
mean
Time point:
24/48/72 h
Score:
2.2
Max. score:
4
Reversibility:
not reversible
Remarks:
in 1/3 animals, the effects were not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
other: scar formation
Basis:
animal #3
Time point:
14 d
Remarks on result:
positive indication of irritation
Remarks:
scar formation was observed in 1/3 animals at 14 days post exposure

Any other information on results incl. tables

3 min exposure time

Time after removal of dressing

30-60’

24 h

48 h

72 h

7 d

14 d

Animal #

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

Erythema formation

2

2

2

3

2

4

4

4

4

2

2

4

1

1

4

0

0

4

Edema formation

1

1

1

2

0

4

2

2

4

1

1

4

0

0

4

0

0

4

Skin surface

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

- Dry, chapped

 

 

 

 

 

 

 

 

 

 

 

 

X

X

X

X

 

x

Eschar formation

 

 

 

 

 

X

 

X

X

 

X

X

 

 

X

 

 

x

Open wound

 

 

 

 

 

 

 

 

 

 

 

 

 

 

X

 

 

 

Skin detachment

 

 

 

 

 

 

 

 

 

 

 

 

 

 

X

 

 

 

Scar

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

X

Hematoma

 

 

 

 

 

X

 

 

X

 

 

X

 

 

X

 

 

 

 

 

4 hour exposure time

Time after removal of dressing

30-60’

24 h

48 h

72 h

7 d

Animal #

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

Erythema formation

4

4

4

4

4

4

4

4

4

4

4

4

4

4

4

Edema formation

4

4

4

4

4

4

4

3

4

4

3

4

4

4

4

Skin surface

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

- Dry, chapped

 

 

 

 

 

 

 

 

 

 

 

 

X

X

X

Eschar formation

 

 

 

 

 

 

 

 

 

 

 

 

X

X

X

Open wound

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Skin detachment

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Scar

 

 

 

 

 

 

 

 

 

 

 

 

 

X

X

Beige skin discoloration

 

 

 

 

 

 

 

 

 

 

 

 

 

X

X

Hematoma

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Based on the effects observed and according to the criteria specified in Regulation (EC) 1272/2008 (CLP), classification as "causes severe skin burns and eye damage" (H314) is warranted.
Executive summary:

The test substance was applied to skin of rabbits for either 3 min or 4 hours under semi-occlusive dressing. Following exposure, the remaining test substance was washed off. Animals exposed for 3 min showed clear edema and very slight erythema within 1 hour, which became severe erythema and slight to severe edema within 48 hours following exposure. Two of three animals recovered within 7 days, however one animal showed severe erythema, edema and scar formation until the end of the observation period (14 days). In accordance with the criteria laid down in Regulation (EC) 1272/2008, substances causing corrosive damage to skin after 3 min incubation are to be classified in Cat. 1 for skin corrosion. Since the test substance did not show corrosive effects within 60 min following exposure, classification as Cat. 1B is warranted.