2-[2-(3-butoxypropyl)-1,1-dioxo-1,2,4-benzothiadiazin-3-yl]-5'-tert-butyl-2-(5,5-dimethyl-2,4-dioxo-1,3-oxazolidin-3-yl)-2'-[(2-ethylhexyl)thio]acetanilide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Aug - 23 Aug 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Japanese guidelines

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): UY-330
- Physical state: solid
- Appearance: white powder
- Batch No.: CE-201
- Expiration date of the lot/batch: 01 Jan 2005
- Storage condition of test material: at room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 6 - 9 weeks
- Weight at study initiation: 1546 - 2032 g
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: approximately 100 g/d Charles River Breeding and Maintenance Diet for Rabbits (Altromin) and pressed hay (twice a week)
- Water: tap water, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.4 - 23.2
- Humidity (%): 40 - 96
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 34.8 - 38.3 mg, what corresponds to a volume of approximately 0.1 mL

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

72 h
reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 males

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

other: mean out of all 3 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Results 2

Irritation parameter:

iris score

Basis:

other: mean out of all 3 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 h

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Instillation of the test substance into one eye of each of the three rabbits resulted in effects on the iris and conjunctivae. The iris of all animals showed slight irritation at the 1 h reading timepoint. This effect was reversible within 24 h. On the conjunctivae of all animals, slight redness (score 2) and chemosis (score 2) was observed at the 1 h reading timepoint. Within 24 h, the conjunctivae of all animals recovered and showed slight redness (score 1) and chemosis (score 1). The chemosis was fully reversible within 48 h, whereas the slight redness of the conjunctivae (score 1) resolved within 72 h in all animals.
No corneal opacity was observed and treatment of the eyes with 2% fluorescein 24 h after test substance instillation revealed no corneal epithelial damage in any of the animals.

Other effects:

All animals survived and no symptoms of systemic toxicity were observed in the animals during the test period. No staining of ocular and peri-ocular tissues by the test substance was observed.

Any other information on results incl. tables

Table 1. Results of eye irritation study.

Rabbit #	Time [h]	conjunctivae		iris	cornea			conjunctivae		iris	cornea
		redness	swelling					redness	swelling
1	1	2	2	1	0
	24	1	1	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	0.67	0.33	0	0		Time to reversion	72	48	24	0
2	1	2	2	1	0
	24	1	1	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	0.67	0.33	0		0	Time to reversion	72	48	24	0
3	1	2	2	1		0
	24	1	1	0		0
	48	1	0	0		0
	72	0	0	0		0
	average	0.67	0.33	0		0	Time to reversion	72	48	24	0
	Time [h]	conjunctivae		iris	cornea
		redness	swelling				avg. time to reversion	72	48	24	0
average score	1	2	2	1	0
	24	1	1	0	0
	48	1	0	0	0
	72	0	0	0	0
	24+48+72	0.67	0.33	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified