Dimethyl 2-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azo]terephthalate

Endpoint summary

Description of key information

The test material is not irritating to skin under test conditions. Since the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin) the test results are considered adequate to fulfill the endpoint requirements.

The test item did not reveal any remarkable irritation potential on the eyes of rabbits, tested in this study according to OECD test guideline no. 405 and GLP conditions.

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:

key study

Study period:

From 31 AUG 1976 to 16 SEP 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: FDA guideline (minor deviations from OECD guideline)

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: FDA guideline (Federal register 38, No. 187, 27.9.1973, p.27019)

Deviations:

no

GLP compliance:

no

Remarks:

study was performed previous to GLP implementation

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- weight at study initiation: 1.5 -2.0 kg
- Housing: single
- Diet: ERKA 8300, Robert Koch oHG/ Hamm, ad libitum
- Water: tap water, ad libitum

Type of coverage:

occlusive

Preparation of test site:

other: clipped intact and clipped scarified

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

24 h

Observation period:

48 h after removal of patch with observation time points immediately after removal and 24 h later.

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: erythema and edema scores ranging from 0-4.

Skin was evaluated immediately, 24 h and 48 h after after removal of the patch. Mean values of the readings 24 and 48 h after removal are reported in the results table.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Remarks on result:

other: clipped intact and clipped scarified

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Remarks on result:

other: clipped intact and clipped scarified

Irritant / corrosive response data:

Immediately after removal of patch no erythema score could be determined due to coloration of the skin. Erythema scores at later time points were 0. No edema was detectable at any time point.
Results with scarified skin were the same.

Interpretation of results:

GHS criteria not met

Remarks:

Regulation (EC) no. 1272/2008

Conclusions:

The test material is not irritating to skin under these test conditions.
This conclusion is legitimate even though the applied testing regime differs from today's standard methods. Since the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin) the test results are considered adequate to fulfill the endpoint requirements.

Executive summary:

The test material was tested for skin irritancy according to FDA guidelines. Both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance for 24 h under occlusive conditions and the skin responses were watched for 48 hours after end of exposure. No erythema or edema were seen at any time point (score 0). Immediately after removal of the patch no erythema score could be determined due to pigmet overlay. The test item is not irritating under these test conditions.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

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:

key study

Study period:

From 17 FEB 2004 to 27 FEB 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to Guideline (OECD 405) and GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute 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: Charles River Deutschland GmbH, Kißlegg, Germany
- Weight at study initiation: 2.3 - 2.8 kg
- Housing: single in air conditioned room, cages arranged in battery
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: tap water in plastic bottles, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 20
- 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:

24 h after application washing was performed

Observation period (in vivo):

72 h with observation time points at 1, 24, 48 and 72 h.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with isotonic saline at approx. 37 °C.
- Time after start of exposure: 24 h

SCORING SYSTEM: according to the score of Draize

TOOL USED TO ASSESS SCORE: not indicated, at the 24 and 72 h reading fluorescein was used additionally

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not relevant since no effect

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #2 and #3 each

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not relevant since no effect

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effect

Irritant / corrosive response data:

Individual animal data for 1/24/48/72 h after application, animal #1, animal #2 animal #3:

cornea: 0/0/0/0, 0/0/0/0, 0/0/0/0
iris: 1/0/0/0, 0/0/0/0, 0/0/0/0
conjunctivae redness: 2/2/0/0, 2/0/0/0, 2/0/0/0
chemosis: 2/0/0/0, 1/0/0/0, 1/0/0/0
discharge: 2/0/0/0, 2/0/0/0, 2/0/0/0

Interpretation of results:

GHS criteria not met

Remarks:

Regulation (EC) 1272/2008

Conclusions:

The test item did not reveal any remarkable irritation potential on the eyes of rabbits, tested in this study according to OECD test guideline no. 405 and GLP conditions.

Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD test guideline no 405.The test item was applied by instillation of 0.1 g into the left eye of each of three young New Zealand White rabbits. The scoring of irritating effects was performed 1, 24, 48 and 72 hours after test item instillation.

The test item did not induce corneal effects under the conditions of this test. Effects on iris, conjunctivae redness and chemosis were sligtht to moderate (maximum score observed: iris =1; chemosis = 2 (1 -hour reading); conjunctival redness = 2 (1- and 24 - hour reading)) and fully reversible within 48 hours after start of the exposure.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

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: No adverse effects observed