p-[4,5-dihydro-4-[[2-methoxy-5-methyl-4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulphonic acid, sodium salt

Endpoint summary

Description of key information

Both skin and eye irritation assessments are based on studies performed with rabbits (in vivo) according to FDA guidelines (patch test and mucuous membrane test). No irritating effect that would be relevant for a classification was observed in any of the test systems. Both test systems include 1 treatment with the pure substance, an exposure time of 24 h and an observation time until 72 h after application. The test item was found to have no adverse effects (not irritating).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977-05-09 to 1977-05-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FDA Patch Test

GLP compliance:

yes

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

- Test animal weight: 1.5 - 2.0 kg
- One cage per animal
- Feeding: standard food ERKA 8300, ad libitum
- Water: tap drinking water, ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg powder

Duration of treatment / exposure:

1 treatment at 0 h

Observation period:

72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm²
- Type of wrap if used: gaze and PVC sheet (coverage)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

OBSERVATION TIME POINTS: 24 h, 48 h, 72 h

SCORING SYSTEM:
- Method of calculation: erythema (scoring 0-4) and oedema (scoring 0-4)
- The erythema and oedema scores were calculated for each individual animal after 25 and 72 h. The sum of the scores for all rabbits was divided by 6 (number of test animals) and then by 4 (scoring). The classification is: 0.0 - 0.5: non irritant, 0.6 - 3.0: slightly irritant, 3.1 - 5.0 (moderately irritant), 5.1 - 8.0: severely irritant

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

based on erythema and oedema score

Basis:

mean

Time point:

other: 24 and 72 h

Score:

0

Max. score:

8

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation observed.

Other effects:

- Other adverse local effects: none
- Other adverse systemic effects: none

Endpoint		24 h	48 h	72 h
Scarified skin sum of 6 animals	Erythema	0	0	0
	Oedema	0	0	0
Intact skin sum of 6 animals	Erythema	0	0	0
	Oedema	0	0	0
Sum		0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

No skin irritation (erythema and oedema scoring) was observed at 24h, 48h and 72h after a 24h patch exposure with the pure substance on rabbits. Therefore, the substance is not considered to be irritating to skin according to CLP criteria.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1979-10-29 to 1979-11-01

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FDA Patch Test

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

- Test animal weight: 1.5 - 2.0 kg
- One cage per animal
- Feeding: standard food ERKA 8300, ad libitum
- Water: tap drinking water, ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL pure substance (liquid)

Duration of treatment / exposure:

1 treatment at 0 h

Observation period:

72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm²
- Type of wrap if used: gaze and PVC sheet (coverage)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

OBSERVATION TIME POINTS: 24 h, 48 h, 72 h

SCORING SYSTEM:
- Method of calculation: erythema (scoring 0-4) and oedema (scoring 0-4)
- The erythema and oedema scores were calculated for each individual animal after 25 and 72 h. The sum of the scores for all rabbits was divided by 6 (number of test animals) and then by 4 (scoring). The classification is: 0.0 - 0.5: non irritant, 0.6 - 3.0: slightly irritant, 3.1 - 5.0 (moderately irritant), 5.1 - 8.0: severely irritant

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.56

Max. score:

4

Reversibility:

not fully reversible within: 72 h (last time-point observed)

Remarks on result:

no indication of irritation

Remarks:

1 out of 6 rabbits still showed minimal reddening at 72 h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.056

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight initial irritation observed.

Other effects:

- Other adverse local effects: none
- Other adverse systemic effects: none

Endpoint		24 h	48 h	72 h
Scarified skin sum of 6 animals	Erythema	6	3	1
	Oedema	0	0	0
Intact skin sum of 6 animals	Erythema	6	3	1
	Oedema	1	0	0
Sum		13	6	2

Interpretation of results:

GHS criteria not met

Conclusions:

Very slight irritation (erythema and oedema scoring) was observed at 24h, 48h and 72h after a 24h patch exposure with the pure substance on rabbits. Therefore, the substance is not considered to be irritating to skin according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1979-10-29 to 1979-11-01

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FDA Mucuous Membrane Test

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

- Test animal weight: 1.5 - 2.0 kg
- One cage per animal
- Feeding: standard food ERKA 8300, ad libitum
- Water: tap drinking water, ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of pure substance (liquid)

Duration of treatment / exposure:

1 treatment at 0 h

Observation period (in vivo):

72 h

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h after treatment

SCORING SYSTEM:
- cornea: opacity (0 - 4) and effected area (0 - 4)
- iris: viability (0 - 4)
- conjunctiva: erythema (0 - 4), swell (0 - 4), secretion (0 - 4)

0 is no effect, 4 is a severe effect. The sum of all values from cornea, iris and conjunctiva is multiplied by 2. The mean value for all animals is divided by the number of animals (6). The score is determined at all points of observation (1, 7, 24, 48, 72 h after treatment). The highest score at any point of time is used for the assessment (worst case).

Overall scoring: 0 - 10: non irritant, 11 - 25: slightly irritant, 26 - 56: moderately irritant, 57 - 110: severely irritant

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 24 and 72 h

Score:

1

Max. score:

110

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Minimal reddening was observed in some animals up to 48 hours. One rabbit showed minimal chemosis at 1 and 7 hours after test substance application. No signs of irritation were observed.

Other effects:

None.

Endpoint		1 h	7 h	24 h	48 h	72 h
Cornea	Opacity	0	0	0	0	0
	Area involved	0	0	0	0	0
	Mean Score A (max. 80)	0	0	0	0	0
Iris	Damage	0	0	0	0	0
	Mean Score B (max. 10)	0	0	0	0	0
Conjunctivae sum of 6 rabbits	Redness	5	3	2	2	0
	Chemosis	1	1	0	0	0
	Discharge	0	0	0	0	0
	Mean Score C (max. 20)	2	1.3	0.7	0.7	0
Overall Mean	Score	2	1	1	1	0

Interpretation of results:

GHS criteria not met

Conclusions:

No irritation (overall scoring) was observed after a 24h exposure with the pure substance on rabbits. Therefore, the substance is not considered to be irritating to eyes according to CLP criteria.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977-05-09 to 1977-05-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FDA Mucuous Membrane Test

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

- Test animal weight: 1.5 - 2.0 kg
- One cage per animal
- Feeding: standard food ERKA 8300, ad libitum
- Water: tap drinking water, ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of pure substance (powder)

Duration of treatment / exposure:

1 treatment at 0 h

Observation period (in vivo):

72 h

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h after treatment

SCORING SYSTEM:
- cornea: opacity (0 - 4) and effected area (0 - 4)
- iris: viability (0 - 4)
- conjunctiva: erythema (0 - 4), swell (0 - 4), secretion (0 - 4)

0 is no effect, 4 is a severe effect. The sum of all values from cornea, iris and conjunctiva is multiplied by 2. The mean value for all animals is divided by the number of animals (6). The score is determined at all points of observation (1, 7, 24, 48, 72 h after treatment). The highest score at any point of time is used for the assessment (worst case).

Overall scoring: 0 - 10: non irritant, 11 - 25: slightly irritant, 26 - 56: moderately irritant, 57 - 110: severely irritant

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.61

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks:

1 out of 5 rabbits with erythema still showed minimal reddening at 72 h

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.167

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 and 72 h

Score:

10

Max. score:

110

Reversibility:

not fully reversible within: 72 h

Remarks:

1 out of 5 rabbits with erythema still showed minimal reddening at 72 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight irritation observed for conjunctivae.

Other effects:

None.

Endpoint		1 h	7 h	24 h	48 h	72 h
Cornea	Opacity	6	5	0	0	0
	Area involved	15	12	0	0	0
	Mean Score A (max. 80)	12.5	10	0	0	0
Iris	Damage	0	0	0	0	0
	Mean Score B (max. 10)	0	0	0	0	0
Conjunctivae	Redness	6	6	5	5	1
	Chemosis	11	9	3	0	0
	Discharge	11	9	3	0	0
	Mean Score C (max. 20)	9.3	8	3.7	2	0
Overall Mean	Score	22	18	4	2	0

Interpretation of results:

GHS criteria not met

Conclusions:

No irritation (overall scoring) was observed at 24/72 h mean after a 24h exposure with the pure substance on rabbits. The substance is not considered to be irritating to eyes according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available