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

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 Aug - 22 Aug 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Japanese test guidelines (12 Nousan, Notification No 8147, November 2000)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: 1407 - 1570 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 - 23.9
- Humidity (%): 46 - 89
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: 50 % (v/v) aqueous solution of ethanol

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g test substance moistened with 0.5 mL of the vehicle

Duration of treatment / exposure:

4 h

Observation period:

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

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on the dorsal area of one flank
- Type of wrap if used: The treated skin was covered with a metalline patch mounted on Micropore tape, that was wrapped around the abdomen and held in place with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test substance was removed with ethanol.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema 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

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean over 24,48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema 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

Irritant / corrosive response data:

At 1 and 24 h after the dermal application of the test substance, slight erythema formation (score 1) was observed in 1/3 animals. The observation was reversible within 48 h. No further erythema formation was observed at any other reading time point. The treatment with the test substance did not result in edema formation in any of the animals tested at any reading time point.

Other effects:

All animals survived and no symptoms of systemic toxicity were observed in the animals during the test period. No staining of the treated skin by the test substance was observed.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Japanese guidelines

GLP compliance:

yes

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

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

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

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

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

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

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

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

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

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.

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

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The skin irritating potential of UY-330 was investigated in a study performed according to OECD 404 and GLP (Hooiveld, 2003). The test substance moistened with 0.5 mL of an aqueous ethanol solution (50% v/v) was applied on the clipped skin of three male New Zealand White rabbits. The treated skin was covered semi-occlusive with a metalline patch mounted on Micropore tape and fixed with an elastic bandage. The dressing was removed after 4 h and the treated skin was cleaned with ethanol.

Edema and erythema formation were assessed 1, 24, 48 and 72 h after removal of the test substance using the Draize scoring system. At 1 and 24 h post application, slight erythema formation was observed in one animal. This reaction was reversible within 48 h. The other animals showed no erythema formation and no edema formation was observed in any animal at all. Under the test conditions, the test substance was not irritating to the skin.

The eye irritating potential of UY-330 was tested in a study performed by Hooiveld (2003) in accordance with OECD 405 and GLP. The unchanged powdery test substance was instilled in one eye of each of three male New Zealand White rabbits without washing afterwards. The other eye was not treated and served as control.

The grades of ocular reaction (conjunctivae redness, conjunctivae chemosis, cornea, iris) were assessed 1, 24, 48 and 72 h after instillation of the test substance.

At 1h post application, the iris of all animals showed very slight irritation and the conjunctivae of all animals showed slight redness and chemosis. The iris of all animals recovered within 24 h, the chemosis was fully reversible within 48 h and the redness resolved within 72 h in all animals.

No corneal opacity was observed at all. Under the test conditions, the test substance was not irritating to the eyes.

Justification for selection of skin irritation / corrosion endpoint:
Only one study is available.

Justification for selection of eye irritation endpoint:
Only one study is available.

Justification for classification or non-classification

The available data on skin irritation and eye irritation of the test substance does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.