Esterase, aryl

Eye irritation

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

Test material information

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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

3

Results 9

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 10

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

other: discharge

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 13

Irritation parameter:

other: discharge

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

3

Results 14

Irritation parameter:

other: discharge

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

3

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 16

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

3

Results 17

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

Results 18

Irritation parameter:

other: discharge

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 19

Irritation parameter:

other: discharge

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

3

Results 20

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.