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:
2000-05-01 to 2000-09-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted: 17th July 1992
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Phthalaldehyde
EC Number:
211-402-2
EC Name:
Phthalaldehyde
Cas Number:
643-79-8
Molecular formula:
C8H6O2
IUPAC Name:
phthalaldehyde
Specific details on test material used for the study:
- Name in the study report: "o-PHTHALALDEHYDE"
- Chemical name: 1,2-Benzenedicarboxaldehyde
- Trade name: OPA
- CAS No.: 643-79-8
- Batch No.: FKGP908
- Appearance: Slight yellow solid with scaly appearance
- Conditions of storage: Room temperature, in the dark
- Date of expiry: December 2000

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, D-97633
- Weight at study initiation: Animal No. 1: 2.2 kg, Animal No. 2: 2.3 kg and Animal No.3: 2.3 kg
- Housing: Individual caging in metal wire cages
- Diet (e.g. ad libitum): ad libitum, Altromin 2023 diet for rabbits
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 58
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 1.0 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3 female rabbits
Details on study design:
TEST SITE
- Area of exposure: Dorsal area
- coverage: 2.5 cm x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period the dressings, the tapes with the patches and the collars were removed, residual test substance was wiped off with wet Kleenex-tissues, if necessary
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
The treated areas and the surrounding untreated skin (control area) of the animals were examined for erythema/eschar and oedema as well as for other local alterations approximately 1, 24, 48 and 72 hours after patch removal. Additional examinations were performed 6, 8, 10 and 14 days after the patch removal.

SCORING SYSTEM:
- Method of calculation: Dermal alterations were scored and recorded using the scores given in Table 1 in box “Any other information on materials and methods incl. tables”

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
A dark green or partly green staining of the skin at the application site was seen in all animals from 1 h onwards until 10 d p.a., but did not impede the examination of the skin for erythema.
Erythema/eschar: In all animals changes were seen already 1 h p.a. until the end of the observation period. Eschar formation was noted from 6 d p.a. onwards. Wounds and scars were notable under the eschar 10 d and 14 d p.a.
Edema: In all animals severe edema were noted already 1 h after the patch removal. Lesions were still present 14 d after the exposure.

Any other information on results incl. tables

Table 2: Scores of the application sites

Time after the end of the exposure

Erythema/Eschar

Animal No.

Oedema

 

1

2

3

1

2

3

1 h(c)

3

3

3

4

4

4

24 h(c)

2

2

2

4

3

3

48 h(c)

1

2

2

3

2

3

72 h(c)

1

2

2

3

2

3

Mean (24 – 72h)

1.3

2.0

2.0

3.3

2.3

3.0

 14 days  4(a)(b)  4 (a)(b)  4 (a)(b)  4  3  3

(a) Eschar formation

(b) Wounds/scars

(c) Dark green staining

Applicant's summary and conclusion

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
In conclusion, in an acute dermal irritation/corrosion study according to OECD 404, the test item is considered to be skin corrosive.
Executive summary:

In a primary dermal irritation study conducted according to guideline OECD 404, 3 female New Zealand White rabbits were dermally exposed to 0.5 g of ortho-Phthalaldehyde, moistened with 1.0 mL deionised water to the closely-clipped dorsal site (2.5 cm x 2.5 cm). Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 14 days. A dark green or partly green staining of the skin at the application site was seen in all animals from 1 h onwards until 10 d p.a., but did not impede the examination of the skin for erythema. In all animals, erythema changes were seen already 1 h p.a. until the end of the observation period. Eschar formation was noted from 6 d p.a. onwards. Wounds and scars were notable under the eschar 10 d and 14 d p.a. Severe oedema were noted already 1 h after the patch removal. Lesions were still present 14 d after the exposure.

Based on these results, the test item has to be classified as Category 1 for skin corrosion/irritation.