4-(2-chlorophenyl)-N-cyclohexyl-N-ethyl-5-oxo-4,5-dihydro-1H-tetrazole-1-carboxamide

Endpoint summary

Description of key information

Skin irritation (OECD 404, GLP), rabbit: not irritating

 

Eye irritation (OECD 405, GLP), rabbit: 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:

29 Nov - 13 Dec 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 17 July 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: HC:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult
- Weight at study initiation: 3.4 kg, 3.9 kg, 3.7 kg
- Housing: individual housed in stainless steel cages with flat rod bases or plastic cages with perforated bases, under standardized conventional conditions
- Diet: Standard diet (Ssniff K4, Ssniff Spezialdiaten GmbH,Soest), approx. 100 - 120 g per animal/day; once per day in the morning
- Water: tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1.5
- Humidity (%): 20 - 60
- Air changes (per hr): 12 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: ununchanged, pulverized test substance was applied moistened with deionized water

Controls:

not required

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 500 mg (pulverized test substance, moistened with deionized water)

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h and 7 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorso-lateral area of the trunk, 6 cm²
- Type of wrap if used: semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed with water without altering the existing response, or the integrity of the epidermis.
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h and 7 days

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

No local reactions indicative for skin irritation have been observed except very slight erythema which have been observed 1 h after patch removal in one animal which was fully reversible within 24 h. No other skin reactions were determined.

Table 1; Test for Irritant Effects on the Skin (Expos.: 4 h, DRAIZE grade)

animal number	1 h		24 h		48 h		72 h		7 day
	erythema	oedema	erythema	oedema	erythema	oedema	erythema	oedema	erythema	oedema
1	1	0	0	0	0	0	0	0	0	0
2	0	0	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0	0	0

 

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Conclusions:

A reliable study conducted in accordance with OECD 404 and GLP, determined the test material to be non- irritating to the skin of rabbits. Very slight erythema observed in one animal 1 h after patch removal were fully reversible within 24 h and no oedema were reported at any time point. CLP: 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:

29 Nov - 13 Dec 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 February 1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: HC:NZW

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult
- Weight at study initiation: 3.9 kg, 4kg, 3.7 kg
- Housing: individual housed in stainless steel cages with flat rod bases or plastic cages with perforated bases, under standardized conventional conditions
- Diet: Standard diet (Ssniff K4, Ssniff Spezialdiaten GmbH,Soest), approx. 100 - 120 g per animal/day; once per day in the morning
- Water: tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1.5
- Humidity (%): 20 - 60
- Air changes (per hr): 12 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 µl pulverized test substance, corresponding to approximately 31 mg

Duration of treatment / exposure:

24 h

Observation period (in vivo):

1, 24, 48 and 72 h and 7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: the treated eye was rinsed with saline
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system, the aqueos humour (opacity) as described by Mc Donald and Shadduck

TOOL USED TO ASSESS SCORE: hand-slit lamp, fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Only in one rabbit mild irritation (score 1) of the conjuctivae was observed at the 1 h reading time point. No further reactions have been observed in any animal., which was fully reversible within 48 h.

Table 2: Test for Irritant Effects on the Eye (Expos. 24 h, DRAIZE grade)

Animal number	Tissue	Sign	1 h	24 h	48 h	72 h	7 day
1	cornea	opacity	0	0	0	0	0
		redness	0	0	0	0	0
	fluorescein	intensity	-	0	-	-	-
		area	-	0	-	-	-
	iris		0	0	0	0	0
	conjunctivae	redness	1	1	0	0	0
		swelling	0	0	0	0	0
	aqueous humour		0	0	0	0	0
	discharge		0	0	0	0	0
2	cornea	opacity	0	0	0	0	0
		redness	0	0	0	0	0
	fluorescein	intensity	-	0	-	--	-
		area	-	0	-	-	-
	iris		0	0	0	0	0
	conjunctivae	redness	0	0	0	0	0
		swelling	0	0	0	0	0
	aqueous humour		0	0	0	0	0
	discharge		0	0	0	0	0
3	cornea	opacity	0	0	0	0	0
		redness	0	0	0	0	0
	fluorescein	intensity	-	0	-	-	-
		area	-	0	-	-	-
	iris		0	0	0	0	0
	conjunctivae	redness	0	0	0	0	0
		swelling	0	0	0	0	0
	aqueous humour		0	0	0	0	0
	discharge		0	0	0	0	0

 

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

Under the conditions of the acute eye irritation/corrosion test, the test substance did not show irritant properties.
CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

In the available skin irritation study performed according to OECD TG 404 and in compliance with GLP three albino rabbits were exposed to 500 mg test substance onto clipped skin for 4 h under semi-occlusive conditions (1995c). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48 and 72 h and 7 days post-application. One rabbit revealed erythema scored with 1, which was fully reversible within 24 h. The remaining animals revealed no erythema. No edema formation or further local or systemic effects were apparent in any animal during the study period. Based on the study results the test substance is not considered to be irritating to the skin.

 

Eye irritation

In the available eye irritation study performed with the test substance according to OECD TG 405 and in compliance with GLP (1995c) 0.1 mL of the pulverized test substance was instilled in the eye of three albino rabbits. After an exposure period of 24 h the treated eye was rinsed with saline. The untreated eye served as control. Local reactions in the eyes were evaluated according to the Draize scoring system 1, 24, 48, 72 h and 7 days after application. Further, opacity as described by Mc Donald and Shadduck was evaluated. No effects on corneal opacity and iris were noted at any time point in any animal. However, mild conjunctival redness was observed in 1/3 animals at the 1 h and 24 h reading time point (scored with grade 1), which was fully reversible within 48 h. No chemosis was observed during the study period in any animal. No further local or systemic effects were observed in any animal during the study period. Based on the obtained results, the test substance is not considered eye irritating.

 

Conclusion on skin and eye irritation properties

Skin and eye irritation properties of the test substance have been investigated in vivo indicating no irritating properties towards the skin or eyes.

Justification for classification or non-classification

The available data on skin and eye irritatin/corrosion of the target substance do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). Data are therefore conclusive but not sufficient for classification.