Registration Dossier

Administrative data

Description of key information

Bacillolysin (neutrase) has been tested for irritation in the eye and the skin.

- Under the conditions of this test and the criteria of the EEC, neutrase was classified as 'non-irritant' to skin. The formulation had a dry matter content of 23.4% and a total organic solids content of 16.1%.

- Under the conditions of this test and the criteria of the EEC, neutrase was classified as 'non-irritant' to the eye. The formulation had a dry matter content of 23.4% and a total organic solids content of 16.1%.

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07-07-1994 to 16-03-1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited
- Weight at study initiation: 3.17 - 3.67 kg
- Housing: Housed in suspended stainless steel cages mounted in mobile batteries.
- Diet (e.g. ad libitum): Standard pelleted rabbit diet STANRAB (P) SQC

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C (range 15°C - 23°C)
- Humidity (%): 55% (40% - 70%)

IN-LIFE DATES: From: 1994-11-15 To: 1994-11-18
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1 hour, 24 hours, 48 hours and 72 hours.
Number of animals:
6 (3 males and 3 females)
Details on study design:
TEST SITE
- Area of exposure: 3 x 2 cm
- Type of wrap if used: gauze patch held in place by strips of Blenderm. The control was covered by a similar semi-occlusive dressing but otherwise remained untreated.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified
- Time after start of exposure: 5 hours

OBSERVATION TIME POINTS
1 hour, 24 hours, 48 hours and 72 hours.

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 formations (injuries in the depth) ......................4

Edema formation
No edema ..........................................................................................................................................0
Very slight edema (barely perceptible) ............................................................................................1
Slight edema (edges of area well-defined by definite raising) .........................................................2
Moderate edema (raised approximately 1 mm) .................................................................................3
Severe edema (raised more than 1 mm and extending beyond the area of exposure) .................. 4
Irritation parameter:
erythema score
Remarks:
Intact skin
Basis:
animal: all animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
Intact skin
Basis:
animal: all animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Interpretation of results:
not irritating
Conclusions:
Under the conditions of this test and the criteria of the EEC, neutrase was classified as 'non-irritant' to skin. The formulation had a dry matter content of 23.4% and a total organic solids content of 16.1%.
Executive summary:

The potential of the retail concentration of neutrase PPA 4800, hereafter referred to as neutrase, to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 mL of the test material formulation to the closely-clipped dorsa of three New Zealand White rabbits for five hours. Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings. No dermal irritation response was observed at the test site of any rabbit at any time during the 72-hour observation period.

Under the conditions of this test and the criteria of the EEC, neutrase was classified as 'non-irritant' to skin. The formulation had a dry matter content of 23.4% and a total organic solids content of 16.1%.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31-08-1994 to 22-03-1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Section 4, sub-section 405, of the OECD Guidelines for Testing of Chemicals (1987)
Deviations:
no
GLP compliance:
yes
Remarks:
GLP equivalent at the time where the conduct of the study was subject to appropriate inspection by the quality assurance unit.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited
- Weight at study initiation: 2.80 - 3.59 kg
- Housing: Stainless steel cages mounted in mobile batteries.
- Diet (e.g. ad libitum): Standard pelleted rabbit diet (STANRAB (P) SQC)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C (15-23°C)
- Humidity (%): 55% (40%- 70%)

IN-LIFE DATES: From: 04-10-1994 To: 11-10-1994 for the sentinel animal. The remaining two rabbits From: 11-10-1994 To: 14-10-1994
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Test batch used as is:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL into the left eye
Duration of treatment / exposure:
Each animal was gently restrained. The dose was instilled into the right eye by pulling the lower eylid away from the eyeball to form a cup into which the formulation of the test material was dropped. The eyelids were gently held together for one second and then released. The left eye remained untreated.
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours after treatment.
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Not stated
SCORING SYSTEM: According to the Official Journal of the European Communities.
Irritation parameter:
cornea opacity score
Basis:
animal: 32TD 506M, 432M, 437M
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: 32TD 506M, 432M, 437M
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: 32TD 506M, 432M, 437M
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 32TD 506M, 437M
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 432M
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
Injection of the conjunctival blood vessels and very slight discharge were observed in all the rabbits during the first hour following instillation of the test material. At the 24 hour examination, injection of the conjunctival blood vessels were still apparent in the eye of one rabbit. The eyes of two rabbits were overtly normal at the 24 hour examination and the third at the 48 hour examinations. Instillation of the test material caused a very slight initial pain response in two rabbits and a moderate initial pain response in the third rabbit.
Interpretation of results:
not irritating
Remarks:
Not classified, Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this test and the criteria of the EEC, neutrase was classified as 'non-irritant' to the eye. The formulation had a dry matter content of 23.4% and a total organic solids content of 16.1%.
Executive summary:

The potential of the retail concentration of neutrase PPA 4800, hereafter referred to as neutrase, to cause damage to the conjunctivae, iris or cornea was assessed in three New Zealand white rabbits, each subjected to a single ocular instillation of 0.1 mL of the test material formulation. Ocular reactions were assessed 1, 24, 48 and 72 hours after instillation.

Injection of the conjunctival blood vessels and very slight discharge were observed in all the rabbits during the first hour following instillation. At the 24 hour examination, injection of the conjunctival blood vessels were still apparent in the eye of one rabbit. The eyes of the rabbits were overtly normal at the 24 or 48 hour examinations. Instillation of the test material caused a very slight to moderate initial pain response.

Under the conditions of this test and the criteria of the EEC, neutrase was classified as 'non-irritant' to the eye. The formulation had a dry matter content of 23.4% and a total organic solids content of 16.1%.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for classification or non-classification

Not classified.