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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 12, 1981 - January 15, 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure was according to the Code of Federal Regulations 1979, title 16, § 1500.41

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Code of Federal Regulations 1979, title 16, § 1500.41
Deviations:
no
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular
Details on test material:
Porcine concentrate of Pancrease Trypsin NOVO
- Physical state: Brown powder
- Name of test material (as cited in study report): Porcine concentrate of Pancras Trypsin NOVO
- Lot/batch No.: FTTE 193
- Storage condition of test material: Stability was kept by placing the test substance in refrigerator
- Expiration date of the lot/batch: At storage of 25°C, the product maintain declared activity for at least 3 months. At 5°C, the declared activity is maintained for at least a year.

Bovine concentrate of Pancrease Trypsin NOVO
- Physical state: Brown powder
- Name of test material (as cited in study report): Bovine concentrate of Pancras Trypsin NOVO
- Lot/batch No.: FTTE 056
- Storage condition of test material: Stability was kept by placing the test substance in refrigerator
Specific details on test material used for the study:
Porcine concentrate of Pancrease Trypsin NOVO
- Physical state: Brown powder
- Name of test material (as cited in study report): Porcine concentrate of Pancras Trypsin NOVO
- Lot/batch No.: FTTE 193
- Storage condition of test material: Stability was kept by placing the test substance in refrigerator

Bovine concentrate of Pancrease Trypsin NOVO
- Physical state: Brown powder
- Name of test material (as cited in study report): Bovine concentrate of Pancras Trypsin NOVO
- Lot/batch No.: FTTE 056
- Storage condition of test material: Stability was kept by placing the test substance in refrigerator

Test animals

Species:
rabbit
Strain:
other: Albino rabbits, Danish Landstrain
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bred by Novo Industry A/S
- Weight at study initiation: 2 - 3 kg
- Housing: Individually in galvanized steel cages with mesh floors.
- Diet (e.g. ad libitum): Standard diet (Ewos Brood Stock Feed for Rabbits and Guinea Pigs)
- Water (e.g. ad libitum): Automatic, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 40-60%

IN-LIFE DATES: From: 1981-11-17 To: 1981-11-20

Test system

Type of coverage:
occlusive
Preparation of test site:
other: Abraded and non-abraded
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test material (Porcine and Bovine Trypsin concentrate) moistened with 0.4 mL physiological saline.
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
The test compounds, Porcine and Bovine Trypsin concentrate were assessed by occlusive application of 0.5 g of the test material moistened with 0.4 mL physiological saline to an areal of 1 inch x 1 inch (2.5 x 2.5 cm) on the closely-clipped intact and abraded skin on the back of three male and three female albino rabbits for 24 hrs.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Remarks:
bovine trypsin
Basis:
mean
Time point:
24/48/72 h
Score:
3.6
Reversibility:
not specified
Irritation parameter:
overall irritation score
Remarks:
porcine trypsin
Basis:
mean
Time point:
24/48/72 h
Score:
2.8
Reversibility:
not specified
Irritation parameter:
erythema score
Remarks:
porcine trypsin
Basis:
mean
Remarks:
intact skin
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
porcine trypsin
Basis:
mean
Remarks:
abraded skin
Time point:
24 h
Score:
2.67
Reversibility:
not reversible
Irritation parameter:
erythema score
Remarks:
porcine trypsin
Basis:
mean
Remarks:
abraded skin
Time point:
72 h
Score:
3.67
Reversibility:
not specified
Irritation parameter:
edema score
Remarks:
porcine trypsin
Basis:
mean
Remarks:
Intact skin
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Remarks:
porcine trypsin
Basis:
mean
Remarks:
intact skin
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Remarks:
porcine trypsin
Basis:
mean
Remarks:
abraded skin
Time point:
24 h
Score:
3.83
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Remarks:
porcine trypsin
Basis:
mean
Remarks:
abraded skin
Time point:
72 h
Score:
0.83
Reversibility:
not specified
Irritation parameter:
erythema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
intact skin
Time point:
24 h
Score:
1.33
Reversibility:
not reversible
Irritation parameter:
erythema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
intact skin
Time point:
72 h
Score:
1.67
Reversibility:
not specified
Irritation parameter:
erythema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
abraded skin
Time point:
24 h
Score:
2.17
Reversibility:
not reversible
Irritation parameter:
erythema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
abraded skin
Time point:
72 h
Score:
3.67
Reversibility:
not specified
Irritation parameter:
edema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
intact skin
Time point:
24 h
Score:
0.83
Reversibility:
fully reversible
Irritation parameter:
edema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
intact skin
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
abraded skin
Time point:
24 h
Score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Remarks:
bovine trypsin
Basis:
mean
Remarks:
adraded skin
Time point:
72 h
Score:
0.67
Reversibility:
not specified
Irritant / corrosive response data:
Porcine Trypsin 24 hours reading:
In 6/6 rabbits, intact skin sites applicated Porcine Typsin concentrate showed no reaction, while abraded skin sites showed well-defined to moderate erythema (score 2-3) and moderate to severe edema (score 3-4).

Porcine Trypsin 72 hours reading:
In 6/6 rabbits, intact skin sites applicated Porcine Typsin concentrate showed no reaction, while the main part of abraded skin sites showed a slight superficial eschar formation (score 4) but no chemosis.

Bovine Trypsin 24 hours reading:
In 4/6 rabbits, intact skin sites applicated Bovine Trypsin concentrate showed very slight to moderate erythema and edema (score 1-3), while intact skin sites in 2/6 rabbits showed no reactions. Abraded skin sites showed almost the same reaction as described for Procine Trypsin.

Bovine Trypsin 72 hours reading:
In 3/6 rabbits, intact skin applicated Bovine Trypsin concentrate showed well-defined erythema to slight superficial eschar formation (score 2-4) while intact skin sites in 3/6 rabbits showed no reactions. Abraded skin sites showed almost the same reaction as described for Porcine Trypsin.

Calculation of a primary irritation score for Porcine and Bovine Trypsin concentrate yielded 2.8 and 3.6, respectively

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the test conditions employed Porcine and Bovine concentrate of Pancreas Trypsin Novo had primary irritation scores of 2.8 and 3.6, respectivly. In the current GHS classification criteria it corresponds to Category 2 (irritant).
Executive summary:

An in vivo skin irritation test was conducted to assess the potential of the test substances, Porcine (batch FTTE 193) and Bovine (batch FTTE 056) Trypsin concentrate to cause skin irritation. The Code of Federal regulations 1979, title 16, § 1500.41 was followed.

0.5 g of each test substance moistened with 0.4 mL physiological saline was applied under occlusive conditions on clipped intact and abraded skin on 6 rabbits (Danish Landstrain) for 24 hours. After 24 hours the patches were removed from the rabbits and resulting reactions evaluated. Readings were again made 72 hours after exposure.

The primary irritation score for Porcine Trypsin concentrate (24 and 72 hours reading on intact and abraded skin) was 2.8.

The primary irritation score for Bovine Trypsin concentrate (24 and 72 hours reading on intact and abraded skin) was 3.6.

Both test substances were found to be significant more irritating on abraded skin then on intact skin. The test substances were both classified as "moderate irritant" to skin.

Under the test conditions employed Porcine and Bovine concentrate of Pancreas Trypsin Novo had primary irritation scores of 2 .8 and 3.6, respectivly, and were both classified as "moderate irritant" to skin. In the current GHS classification criteria it corresponds to Category 2.