Trisodium 5-[[4-chloro-6-[(o-tolyl)amino]-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Endpoint summary

Description of key information

Skin irritation

The Primary Irritation Index (PII) of the substance was 0 and was categorized as non-irritant (OECD TG404).

 

Eye irritation

The substance was categorized as mildly irritating to eyes (OECD TG405). Based on the testing results, the test substance is not classified under CLP regulation.

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:

From February 16, 2016 to November 08, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: WEI XIN HANG
- Weight at study initiation: 2.6952 to 3.0700 kg
- Housing: individually in a stainless steel cage
- Water: ad libitum
- Acclimation period: 7 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Photoperiod: 12hrs dark / 12hrs light

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

yes, concurrent vehicle

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.5 mL normal saline

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

three

Details on study design:

- Area of exposure: upper left and lower right dorsal area
- Washing (if done): with distilled water

Irritation parameter:

primary dermal irritation index (PDII)

Score:

0

Remarks on result:

no indication of irritation

Table 1. Body weight of the rabbits

Animal ID	Sex	Body weight (kg)
		Day 1	Day 4
16	Female	3.0700	3.1088
17	Female	2.6952	2.7374
23	Female	2.9372	2.9776

Table 2. Individual skin reactions

Animal I.D.	Observation time (hours)	Grading (erythema / edema)
		Test area		Control area
16	1	0/0	0/0	0/0	0/0
	24± 1	0/0	0/0	0/0	0/0
	48 ± 1	0/0	0/0	0/0	0/0
	72 ± 1	0/0	0/0	0/0	0/0
17	1	0/0	0/0	0/0	0/0
	24 ± 1	0/0	0/0	0/0	0/0
	48 ± 1	0/0	0/0	0/0	0/0
	72 ± 1	0/0	0/0	0/0	0/0
23	1	0/0	0/0	0/0	0/0
	24 ± 1	0/0	0/0	0/0	0/0
	48 ± 1	0/0	0/0	0/0	0/0
	72 ± 1	0/0	0/0	0/0	0/0

Table 3. Individual animal primary irritation scores

Animal I.D.	Scores^a		Primary Irritation Scores (PIS)^b
	Test area	Control area
16	0	0	0
17	0	0	0
23	0	0	0
Primary Irritation Index (PII)^c= 0

^a Sum of scores at all time intervals on backside skin in each rabbit and divided the sum by the total number of observation.

^b PIS = (scores of test area) – (scores of control area).

^c PII = Sum of PIS÷number of animals.

Interpretation of results:

GHS criteria not met

Conclusions:

According to OECD 404 test method and Evaluation table for single dermal irritation, the PII for the substance was 0 and was categorized as non-irritant. Therefore, the substance has not met a category based on GHS criteria.

Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100093001EN which is based on the SOP for the OECD 404 (SOPP-305) and OECD 404 (OECD, 2015). The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal. No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. All animals was no formation of erythema, eschar or edema on the test area within 72 hours after patch removal. The Primary Irritation Index for the substance was calculated to be 0. On the basis of the test results given above and according to Evaluation table for single dermal irritation, the response of the substance was categorized as non-irritant.

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:

From February 16, 2016 to November 08, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: WEI XIN HANG
- Weight at study initiation: 2.6412-3.4180 kg
- Housing: individually in a stainless steel cage
- Water: ad libitum
- Acclimation period: 7 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Photoperiod: 12-hrs dark / 12-hrs light

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

Three

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 1 day

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 1 day

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

probability of weak irritation

Table 1. Body weight of the rabbits

Animal ID	Sex	Body weight (kg)
		Day 1	Day 4
21	Female	3.4180	3.4394
22	Female	2.8186	2.8698
24	Female	2.6412	2.6926

Table 2. Individual response of the test rabbits

Animal I.D.	Time^a (hour)	Observation site	Grades of the irritation reaction
			Cornea		Conjunctivae			Iris
			Opacity	Area	Redness	Chemosis	Discharge
21	1	Test^b	0	0	1	2	0	1
		Control^c	0	0	0	0	0	0
	24 ± 1	Test	0	0	1	0	0	1
		Control	0	0	0	0	0	0
	48 ± 1	Test	0	0	0	0	0	0
		Control	0	0	0	0	0	0
	72 ± 1	Test	0	0	0	0	0	0
		Control	0	0	0	0	0	0
22	1	Test	0	0	1	1	0	1
		Control	0	0	0	0	0	0
	24 ± 1	Test	0	0	1	0	0	1
		Control	0	0	0	0	0	0
	48 ± 1	Test	0	0	0	0	0	0
		Control	0	0	0	0	0	0
	72 ± 1	Test	0	0	0	0	0	0
		Control	0	0	0	0	0	0
24	1	Test	0	0	1	2	0	1
		Control	0	0	0	0	0	0
	24 ± 1	Test	0	0	1	0	0	1
		Control	0	0	0	0	0	0
	48 ± 1	Test	0	0	0	0	0	0
		Control	0	0	0	0	0	0
	72 ± 1	Test	0	0	0	0	0	0
		Control	0	0	0	0	0	0

^a Observation time was started after application of the test article

^b Left eye of the test rabbits

^c Right eye of the test rabbits

Interpretation of results:

GHS criteria not met

Conclusions:

According to OECD 405 test method, the substance cause mildly irritating to the eye. Based on the testing results, the substance is not classified under the CLP criteria.

Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100094001EN which is based on the SOP for the OECD 405 (SOPP-306) and OECD 405 (OECD, 2012). The substance was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. There were no test article effects on body weight. Redness and chemosis of conjunctivae and iris with score of 1 -2 were observed within 24 hours after test article application and fully recovered within 48 hours. On the basis of the test results given above, the response of the test article cause mildly irritating to the eye. Based on the testing results, the substance is not classified under the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal. No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. All animals was no formation of erythema, eschar or edema on the test area within 72 hours after patch removal. The Primary Irritation Index for the substance was calculated to be 0. On the basis of the test results given above and according to Evaluation table for single dermal irritation, the response of the substance was categorized as non-irritant.

 

Eye irritation

The substance was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. There were no test article effects on body weight. Redness and chemosis of conjunctivae and iris with score of 1-2 were observed within 24 hours after test article application and fully recovered within 48 hours. On the basis of the test results given above, the response of the test article cause mildly irritating to the eye.

Based on the testing results, the test substance is not classified under CLP regulation.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the material does not require classification with respect to skin or eye irritation.