Trisodium trihydrogen 5,5',5''-(1,3,5-triazine-2,4,6-triyltriimino)tris[5-sulphonatosalicylate]

Endpoint summary

Description of key information

In a OECD guideline compliant primary skin irritation test in rabbits neither erythema nor edema were observed 1, 24, 48 and 72 hours after application of the test substance. Therefore, the test item has to be regarded as not irritating to skin.

The primary eye irritation potential of the test item was investigated according to a OECD test guideline No. 405. 

The mean score was calculated separately for each animal across three scoring times (24, 48 and 72 hours after instillation) for corneal opacity, iritis, redness and chemosis of the conjunctivae. The individual mean scores for corneal opacity and iritis was 0.0 for all animals. Mean scores for the conjunctivae were 0.33 for reddening and 0.22 for chemosis.

All observed effects were reversible within 48 hours. No corrosion was observed at any of the measuring intervals. No clinical signs of toxicity were observed.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

well performed guideline study according to OECD 404

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Kleintierfarm Madoerin AG, 4414 Fuellingsdorf, Switzerland
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.3 kg to 3.0 kg
- Housing: Individually in stainless steel cages equipped with an automatic drinking water supply and cleaning system
- Diet (e.g. ad libitum): standard rabbit maintenance feed Kliba 23/341/1, Klingentalmuehle AG ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° ± 2°C (air-condition)
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: Polyethyleneglycol 400/saline (70:30)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 50 %

VEHICLE
- Amount(s) applied (volume or weight with unit):1.0 ml to moisten the test item
- Lot/batch no. (if required): Ch-B 2322 , Riedel de Haen AG
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

4 hours

Observation period:

3 days

Number of animals:

3 (2 females, 1 male)

Details on study design:

Before Treatment the entire back and the flank of the rabbits were closely clipped with electric clippers. Application was made to the intact skin site on the clipped dorsum of each rabbit.

TEST SITE
- Area of exposure: approximately 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch, covered with aluminium foil; trunk of the animals was wrapped with an occlusive bandage of elastic adhesive dressing.

- Time after start of exposure: 4 hours

SCORING SYSTEM:
the condition of the intact skin site was observed at 1, 24, 48, and 72 h following removal of bandage and gauze patch, unless the skin is normal at 7 or 14 days; assesment according to Draize J.H.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects occured

Irritation parameter:

edema score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects occured

Irritant / corrosive response data:

no destructions or irreversible alterations of the treated skin were observed. Thus it was concluded that no corrosion effect had occured on the skin.

Other effects:

In the area of application no coloration of the skin was observed.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a OECD guideline compliant primary skin irritation test in rabbits neither erythema nor edema were observed 1, 24, 48 and 72 hours after application of the test substance. Therefore, the test item has to be regarded as not irritating to skin.

Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. No effects were observed after occlusive application of a 50 % solution in PEG/saline (70:30) of 0.5 g to the intact skin of each of three young adult New Zealand White rabbits. The duration of treatment was four hours.

The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. No destructions, irreversible/reversible alterations or coloration of the treated skin were observed at any animal at any measuring interval.

Thus, the test item did not induce significant or irreversible damage to the skin.

Therefore, the test item has not to be classified as "skin irritation" according to Regulation (EC) 1272/2008.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

well performed guideline study according to OECD 405

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Kleintierfarm Madoerin AG, 4414 Fuellingsdorf, Switzerland
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.3 kg to 3.0 kg
- Housing: Individually in stainless steel cages equipped with an automatic drinking water supply and cleaning system
- Diet (e.g. ad libitum): standard rabbit maintenance feed Kliba 23/341/1, Klingentalmuehle AG ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° ± 2°C (air-condition)
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

One administration

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eye remained untreated and served as control respectively

REMOVAL OF TEST SUBSTANCE
- Washing: in 3 out of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with physiological saline for about one minute.

The eyes were examined and the grade of ocular reactions recorded at 1, 24, 48 and 72 hours after treatment and at 7, 14 and 21 days after treatment, unless the eye is normal at 72 hours, 7 or 14 days.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of six animals

Time point:

other: after 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects occured

Irritation parameter:

iris score

Basis:

mean

Remarks:

of six animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects occured

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals (eyes not rinsed)

Time point:

other: after 24, 48 and 72 hours

Score:

0.22

Max. score:

4

Reversibility:

other: grade 1 chemosis was observed in all animals at 1 hour and was fully reversible after 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of tree animals (eyes rinsed)

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: grade 1 chemosis was observed in 2 anmials at 1 hour and was fully reversible after 24 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals (eyes not rinsed)

Time point:

other: after 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

other: grade 1 redness was observed in 2 animals at 1 hour and was fully reversible after 48 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals (eyes rinsed)

Time point:

other: after 24, 48 and 72 hours

Score:

0.1

Max. score:

4

Reversibility:

other: grade 1 redness was observed in 2 animals at 1 hour and was fully reversibel after 48 hours.

Irritant / corrosive response data:

No corrosion effect was observed at each of the measuring intervals.

Other effects:

no coloration of the cornea and conjunctivae was observed in the rabbits during the entire test period which could be related to compound effects.
No acute toxicological signs were observed in the animals during the test period.

individual results:

animal sex	treatment of eye	time	cornea opacity	iris	conjunctiva redness	conjunctiva chemosis
55 male	not rinsed	1 h	0	0	2	1
56 male	not rinsed		0	0	1	1
57 male	not rinsed		0	0	2	1
58 female	rinsed		0	0	0	0
59 female	rinsed		0	0	1	1
60 female	rinsed		0	0	1	1
55 male	not rinsed	24 h	0	0	1	1
56 male	not rinsed		0	0	1	0
57 male	not rinsed		0	0	1	1
58 female	rinsed		0	0	0	0
59 female	rinsed		0	0	1	0
60 female	rinsed		0	0	0	0
55 male	not rinsed	48 h	0	0	0	0
56 male	not rinsed		0	0	0	0
57 male	not rinsed		0	0	0	0
58 female	rinsed		0	0	0	0
59 female	rinsed		0	0	0	0
60 female	rinsed		0	0	0	0
55 male	not rinsed	72 h	0	0	0	0
56 male	not rinsed		0	0	0	0
57 male	not rinsed		0	0	0	0
58 female	rinsed		0	0	0	0
59 female	rinsed		0	0	0	0
60 female	rinsed		0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the findings in this study, the test item does not meet the criteria for classification according to Regulation (EC) No. 1272/2008.

Executive summary:

The primary eye irritation potential of the test item was investigated according to a OECD test guideline No. 405. 100 mg test item was inserted into the conjunctival sac of the left eye of 3 male and 3 female young adult New Zealand White rabbits respectively. In the female animals approximately 30 seconds after treatement the treated eyes were flushed with physiological saline for about one minute. The eyes of the male animals were not rinsed. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. 

The mean score was calculated separately for each animal across three scoring times (24, 48 and 72 hours after instillation) for corneal opacity, iritis, redness and chemosis of the conjunctivae. The individual mean scores for corneal opacity and iritis was 0.0 for all animals. Mean scores for the conjunctivae were 0.33 for reddening and 0.22 for chemosis (males). The mean score for the females was 0.1 for conjunctiva reddening.

All observed effects were reversible within 48 hours. No corrosion was observed at any of the measuring intervals. No clinical signs of toxicity were observed.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

According to the findings in this study, the test item does not meet the criteria for classification according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No classification

The test material did not cause any irritant effecte on skin or eyes in vivo