5-amino-6-methyl-1,3-dihydrobenzoimidazol-2-one

Endpoint summary

Description of key information

In a dermal irritation study, no signs of irritation were evident at any time during the study and the test substance was not considered a dermal irritant. Slightly irritating effects were seen in an eye irritation study but all effects were fully reversible within 72 hours.

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:

1998-03-24 - 1998-03-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: approx. 1342 g
- Housing: individually
- Diet: Standard laboratory rabbit diet, ad libitum (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands)
- Water: tap water, ad libitum
- Acclimatisation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: Untreated skin served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 150 cm2
- Type of wrap if used: coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 4 hours after application

SCORING SYSTEM: The skin reactions were graded according to the following numerical scoring system:

ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness)* 4
*In cases where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema {= 4) is given.

OEDEMA FORMATION
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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:

1998-04-01 - 1998-04-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: 11 weeks
- Weight at study initiation: approx. 2157 g
- Housing: individually
- Diet: Standard laboratory rabbit diet, ad libitum (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent eye served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 28.7 mg

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Draize et al. (1963)

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24-72 hours

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24-72 hours

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24-72 hours

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24-72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24-72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A dermal irritation study was conducted according to OECD guideline 404 and EU method B.4. Three rabbits were exposed to 0.5 g of the test substance, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure. Exposure to the test substance resulted in very slight erythema in the treated skin-area of one rabbit and had resolved within 24 hours.

No skin irritation was observed in the remaining two animals. Yellow/brown staining of the treated skin by the test substance was observed in all animals 1 hour after exposure. The substance was not considered irritating to the skin. (NOTOX B.V., 1998)

Eye irritation

An eye irritation study was conducted according to OECD guideline 405 and EU method B.5 using a total of three rabbits. Single samples of approximately 29 mg of the test substance (a volume of approximately 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 48 hours in two animals and within 72 hours in the third animal. Remnants of the test substance were present in the eyes of all animals on day 1. The substance was not considered irritating to the eyes. (NOTOX B.V., 1998)

Justification for selection of skin irritation / corrosion endpoint:
GLP and guideline compliant study.

Justification for selection of eye irritation endpoint:
GLP and guideline compliant study.

Justification for classification or non-classification

Based on available eye and skin irritation data of the test substance, no classification and labelling is required according to Regulation (EC) No 1272/2008 (CLP) or Directive 67/548/EEC (DSD).