Registration Dossier

Administrative data

Description of key information

Lipase is neither a skin nor an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 March 2009 - 05 August 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Lipase is also used in animal feed. Thus, in vivo skin irritation study were required to assess worker safety according to the provisions of Regulation EC 429/2008. Also, the findings from these studies were used for product classification and labelling in the US (OSHA, HSC).
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
- Substance type: UVCB
- Physical state: translucent tan liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA.
- Age at study initiation: Approximately 19 weeks
- Weight at study initiation: 2.8-3.3 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 March 2009 To: 28 March 2009
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL of test item/site under a 2.5 x 2.5 cm, 4 ply surgical gauze patch.
Duration of treatment / exposure:
The test article was kept in contact with the skin for 4 hours.
Observation period:
Test sites were examined for evidence of primary irritation approximately 1, 24, 48 and 72 hours later.
Number of animals:
Three
Details on study design:
A site of approximately 10 x 10 cm on the dorsal area of each animal was clipped free of hair. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm, 4 ply surgical gauze patch. The patch was secured with non-irritation tape. The torso was covered with a piece of porous dressing (semi-occlusive) large enough to cover the dose site with at least 5 cm square to spare on all sides of the gauze patch. Porous, non-irritation tape was used to encircle the trunk of the animal. The test article was kept in contact with the skin for 4 hours, at with time the wrappings were removed. Residual test article was removed from the test site by gently washing with distilled water at the end of the exposure period, prior to scoring for dermal reactions.
The test sites were scored for dermal irritation at 60 minutes and at 24, 48 and 72 hours following patch removal.
Erythema and oedema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction.

Irritation parameter:
erythema score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
No evidence of skin irritation was observed at any time follwoing the 4 hour exposure period. The substance is not classified as a skin irritant under GHS and CLP criteria.
Other effects:
No corrosive effects were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
Lipase is classified as "Non Dermal Irritant".
Executive summary:

The objective of this study was to assess the local irritant effect of Lipase when applied topically as a single dose. The study was conducted according to the method recommended in the OECD Guideline No 404, “Acute Dermal Irritation/Corrosion” and the study complied with all GLP standards.

The test article (0.5 mL) was applied to one intact site/rabbit and covered with semi-occlusive dressing. Three rabbits were used. The test article was kept in contact with the skin for 4 hours, at which time the wrappings were removed and residual test article removed by gently washing. Dermal reactions were scored at 1, 24, 48 and 72 hours after patch removal. There were no erythema or edema noted at any of the scoring periods. The dermal irritation score was 0. There were no overt signs of systemic toxicity.  

GHS Classification: Not classified.

Endpoint:
skin irritation: 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
Justification for type of information:
Lipase is also used in animal feed. Thus, in vivo skin irritation study were required to assess worker safety according to the provisions of Regulation EC 429/2008. Also, the findings from these studies were used for product classification and labelling in the US (OSHA, HSC).
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:
20 March 2009 - 05 August 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Lipase is also used in animal feed. Thus, in vivo eye irritation study were required to assess worker safety according to the provisions of Regulation EC 429/2008. Also, the findings from these studies were used for product classification and labelling in the US (OSHA, HSC).
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA.
- Age at study initiation: Approximately 19 weeks
- Weight at study initiation: 2.8 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 March 2009 To: 28 March 2009
Vehicle:
unchanged (no vehicle)
Controls:
other: Contralateral eye served as control.
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Eyelids were held together for about one second and then released.
Observation period (in vivo):
Assessment of ocular damage/irriation was made at 1, 24, 48 and 72 hours post dose.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Calculated from the weighted Draize scale
TOOL USED TO ASSESS SCORE: Mini-Maglite® flashlight; fluorescein at the 24 hr observation interval with ultraviolet light source.
Irritation parameter:
cornea opacity score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
animal: 1, 3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
animal #2
Time point:
other: 1 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
0
Remarks on result:
other: No ocular effects were noted during the study
Irritant / corrosive response data:
There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted as discharge at the 1-hour reading in 1/3 eyes, cleared by 24 hours.
No other ocular effects were observed in any of the three animals at any time during the study. The substance is not classified as an eye irritant under GHS criteria based on the results of this study.
Interpretation of results:
GHS criteria not met
Conclusions:
Lipase should be classified as "Non Irritant".
Executive summary:

The study was conducted according to OECD Guideline No. 405 and complied with all GLP standards.

Three New Zealand rabbits (1 female; 2 males) were used. The test article (0.1 mL) was instilled in one eye/rabbit. The eyes were scored at 1, 24, 48 and 72 hours post dosing. Sodium fluorescein dye procedures were used at the 24-hour observation interval. The untreated eye served as control.

There were no effects on cornea or iris at any scoring time. Conjunctival irritation, noted as discharge at the 1-hour reading in one animal only, cleared by 24 hours. The eye irritation score based on the 24, 48 and 72 hrs scoring was 0. There were no overt signs of systemic toxicity. Lipase is judged to be a non-irritant to the eye.

GHS Classification: Not classified

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
Justification for type of information:
Lipase is also used in animal feed. Thus, in vivo skin irritation study were required to assess worker safety according to the provisions of Regulation EC 429/2008. Also, the findings from these studies were used for product classification and labelling in the US (OSHA, HSC).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The skin and eye irritation potential of lipase has been tested according to OECD guidelines, in compliance with GLP. There were no signs of irritation, and both dermal irritation- and eye irritation score were 0.

The conclusion was that lipase is neither a skin nor an eye irritant.

Justification for classification or non-classification

The skin and eye irritation potential of lipase has been tested according to OECD guidelines and in compliance with GLP. The conclusion was that lipase did not exert any skin and eye irritation and should not be classified.