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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Arylesterase 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).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
Remarks:
Test article characterization, provided by Sponsor, was not conducted according to GLP; however, it was conducted under Good Manufacturing Practices.
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Active enzyme protein of Esterase, aryl (EC no. 232-884-0, CAS no. 9032-73-9, EC name: arylesterase, Enzyme Class no. 3.1.1.2)
Molecular formula:
Not applicable, see remarks
IUPAC Name:
Active enzyme protein of Esterase, aryl (EC no. 232-884-0, CAS no. 9032-73-9, EC name: arylesterase, Enzyme Class no. 3.1.1.2)
Constituent 2
Reference substance name:
Protein as a constituent of enzyme deriving from the fermentation or extraction process
Molecular formula:
Not available
IUPAC Name:
Protein as a constituent of enzyme deriving from the fermentation or extraction process
Constituent 3
Reference substance name:
Inorganic salts as a constituent of enzyme deriving from the fermentation or extraction process
Molecular formula:
Not available. See remarks.
IUPAC Name:
Inorganic salts as a constituent of enzyme deriving from the fermentation or extraction process
Constituent 4
Reference substance name:
Carbohydrates constituent of enzyme deriving from the fermentation or extraction process
Molecular formula:
Not available. See remarks.
IUPAC Name:
Carbohydrates constituent of enzyme deriving from the fermentation or extraction process
Constituent 5
Reference substance name:
Lipids as a constituent of enzyme deriving from the fermentation or extraction process
Molecular formula:
Not available. See remarks.
IUPAC Name:
Lipids as a constituent of enzyme deriving from the fermentation or extraction process
Test material form:
solid: granular
Details on test material:
- Substance type: UVCB
- Physical state: Granular

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Corvance Research Products, Inc. Denver, PA
- Age at study initiation: about 16 weeks
- Weight at study initiation: 2.7 - 3.4 kg
- Housing: Individually housed in suspended cages with paper bedding placed beneath the cages that was changed at least 3x a week.
- Diet (e.g. ad libitum): provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled room; specific temperature range not reported
- Photoperiod (hrs dark / hrs light): 12 hr ligh/dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
Amount applied: 60.4 mg (0.1 mL equivalent)
Duration of treatment / exposure:
Single dose
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
2 males, 1 female
Details on study design:
SCORING SYSTEM: Draize technique

TOOL USED TO ASSESS SCORE: A Mini-Maglite® flashlight equipped with a high intensity bulb was used to aid scoring. Sodium fluorescein dye procedures were used at the 24-hour observation interval in the treated eyes. The eyes were examined with the aid of an ultraviolet light source.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
other: all
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
other: all
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: some redness was oberved at 1 h but it was cleared within 24 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: some chemosis was oberved at 1h but it was cleared within 24h
Irritation parameter:
other: discharge
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: some discharge was oberved at 1h but it was cleared within 24h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
other: discharge
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
other: discharge
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
3
Irritation parameter:
other: discharge
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: some chemosis was oberved at 1h but it was cleared within 24h
Irritation parameter:
other: discharge
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
other: discharge
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
3
Irritation parameter:
other: discharge
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
3
Irritant / corrosive response data:
There was no corneal opacity or iritis noted at any observation period. conjunctival irritation, noted in 3/3 eyes was cleared by 72 hours. Fluorescein stain examination of the treated eye was negative for corneal injury at 24 hours after instillation of the test substance.
Other effects:
There were no abnormal physical signs noted during the observation period.

Any other information on results incl. tables

 

Ocular Findings

Animal

Tissue

Reading

1 Hour

24 Hour

48 Hour

72 Hour

1

Cornea

Opacity

0

0

0

0

Area

0

0

0

0

Iris

 

0

0

0

0

Conjunctiva

Redness

2

0

0

0

Chemosis

2

0

0

0

Discharge

2

0

0

0

Sodium Fluorscein

N/A

0

N/A

N/A

2

Cornea

Opacity

0

0

0

0

Area

0

0

0

0

Iris

 

0

0

0

0

Conjunctiva

Redness

2a

2

1

0

Chemosis

2

1

0

0

Discharge

2

1

0

0

Sodium Fluorscein

N/A

0

N/A

N/A

3

Cornea

Opacity

0

0

0

0

Area

0

0

0

0

Iris

 

0

0

0

0

Conjunctiva

Redness

1

1

1

0

Chemosis

2

0

0

0

Discharge

2

1

0

0

Sodium Fluorscein

N/A

0

N/A

N/A

a Test article remaining in eye

N/A = not applicable

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance produced irritation which cleared in 72 hours.
Executive summary:

This study was carried out in accordance with OPPTS 870.2400 to determine if the test substance had irritant or corrosive effects when  instilled into the rabbit eye. Three rabbits were dosed in one eye with the test substance (60.4 mg, 0.1 mL equivalent) and the contralateral eye served as the control. Observations for mortality, toxicity and pharmalogical effects were recorded at 1, 24, 48, and 72 hours. Sodium fluorescein dye procedures were used at the 24-hour observation interval. Body weights were recorded pre-test.

All animals were negative for corneal opacity and iritis at all observations periods. Fluorescein stain examination of the treated eye was negative for corneal injury at 24 hours after instillation of the test substance. There were no abnormal physical signs noted during the observation period. Conjunctival irritation was observed in all three animals and was cleared within 72 hours.