Propanoic acid, 2-hydroxy-, compd. with 7-[[4,6-bis[[3-(diethylamino)propyl]amino]-1,3,5-triazin-2-yl]amino]-3-[2-(2,3-dihydro-2-oxo-1H-benzimidazol-6-yl)diazenyl]-4-hydroxy-2-naphthalenesulfonic acid (1:1)

Endpoint summary

Description of key information

The substance registered exhibits no skin- or eye irritation potential.

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:

2004

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

Principles of method if other than guideline:

The animals were not sacrificed. On completion of the observation period they were reallocated to the eye irritation study (RCC Study 857564).

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 16 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 68/04) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

Up to 72h after treatment

Number of animals:

3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

Other effects:

- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- The test item caused red staining of the treated skin one hour after treatment in all animals which persisted up to the 24-hour reading in two animals. - The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

not relevant for classification and labelling

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:

2005

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

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 16 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 68/04) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

Single exposure into the conjuntival sac of the left eye.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
The test substance was not removed after instillation.

SCORING SYSTEM:
The ocular reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, at approximately 1, 24, 48 and 72 hours, as well as 7 days after instillation. When present, corrosion and/or staining of conjunctivae, sclerae and cornea by the test item were recorded and reported.

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1h

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 24h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 48h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 7d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 48h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 7d

Score:

0

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24h

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 48h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 72h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 7d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 48h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 48h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 7d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

not relevant for classification and labelling;

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two valid in-vivo studies on skin and eye irritation have been conducted with the test registration substance. In order to assess the skin irritating potential of the test substance, 500 mg of the test item were topically applied onto 6 cm² intact dorsal skin of each of three young adult New Zealand rabbits. The test item caused red staining of the treated skin one hour after treatment in all animals which persisted up to the 24-hour reading in two animals. Under the conditions of this experiment, the substance was found to cause a primary irritation score of 0.00 when applied to healthy intact rabbit skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

In order to assess the primary eye irritating potential of the test substance, 0.1 g of the registration substance was instilled undiluted into one eye of each of three young adult New Zealand rabbits. The treated eyes were not rinsed after application. Individual mean scores for opacity and iris were 0.00 in all three animals, and for the conjunctivae scores were 1.00, 0.33 and 0.00 for reddening and 0.33, 0.00 and 0.00 for chemosis, respectively. Slight red staining of the eyes produced by the test substance was noted after one and 24 hours reading in all animals and persisted up to 72 hours in two of three animals. No corrosion was observed at any of the measuring intervals.

Justification for selection of skin irritation / corrosion endpoint:
The selected study was performed under GLP and in accordance with OECD TG 404. No other studies are available.

Justification for selection of eye irritation endpoint:
The selected study was performed under GLP and in accordance with OECD TG 405. No other studies are available.

Justification for classification or non-classification

Skin irritation: No adverse effect observed (not irritating). The substance is classified as "not irritating" to rabbit skin.

Eye irritation: No adverse effect observed (not irritating). The substance is classified as "not irritating" to the eye.