N-(2-ethoxyphenyl)-N'-(2-ethylphenyl)oxamide

Endpoint summary

Description of key information

In-vitro Skin irritation, Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.41: non-irritant
In-vitro Eye irritation, Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.42: non-irritant
Respiratory irritation: not tested

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:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well conducted study according to that prescribed by Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.41. The principle of the test method is similar to the principle of the OECD Guideline 404 and no deviations have been reported.

Qualifier:

according to guideline

Guideline:

other: Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.41

Deviations:

no

Principles of method if other than guideline:

Primary irritation to the skin is measured by a patch test technique on the abraded and intact skin of the albino rabbits, clipped free of hair. A minimum of six subjects are used in abraded and intact skin tests. Introduce under a square patch such as surgical gauze measuring 1 inch x 1 inch, two single layer thick, 0.5 ml (in case of liquids) or 0.5 gram (in the case of solids and semisolids) of the test substances. Dissolve solids in an appropriate solvent and apply the solution as for liquids. the animals are immobilized with pathes secured in place by adhesive tape. After 24 h exposure, the patches are removed and the resulting reactions are evaluated on the basis of designed values.

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) to slight eschar formation (injuries in depth): 4

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


Reading are again made at the end of a total of 72h (48h after the first reading). An equal number of exposures are made on areas of skin that have been prevoiusly abraded. the abrasion are minor incision through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.The values for oedema and eschar at 24 and 72h for intact skin are addedd to the values for abraded. The total of the eight values is divided by four to give the primary irritation score.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

six albino rabbits are used in abraded and intact skin tests.

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g of test item powder was mixed with 0.5 ml of distilled water before application to the skin

Duration of treatment / exposure:

72 h

Observation period:

72 h

Number of animals:

12 rabbits

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Classification system recommended by ETAD subcommitee for toxicology:

0.0 - 0.5 - non-irritant
0.6 - 3.0 - slightly irritant
3.1 - 5.0 - moderately irritant
5.1 - 8.0 - severely irritant

None of the animals showed any observable response to treatment throughout the 72 hours observation period.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test item is considered to be "non-irritant" to rabbit skin according to the system of classification recommended by the ETAD subcommitee for toxicology.

Executive summary:

A study conducted according to Consumer Product Safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.41. Primary irritation to the skin is measured by a patch test technique on the abraded and intact skin of the albino rabbits, clipped free of hair. A minimum of six subjects are used in abraded and intact skin tests. Introduce under a square patch such as surgical gauze measuring 1 inch x 1 inch, two single layer thick, 0.5 ml (in case of liquids) or 0.5 gram (in the case of solids and semisolids) of the test substances. Dissolve solids in an appropriate solvent and apply the solution as for liquids. the animals are immobilized with pathes secured in place by adhesive tape. After 24 h exposure, the patches are removed and the resulting reactions are evaluated on the basis of designed values.

Reading are again made at the end of a total of 72h (48h after the first reading). An equal number of exposures are made on areas of skin that have been prevoiusly abraded. the abrasion are minor incision through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.The values for oedema and eschar at 24 and 72h for intact skin are addedd to the values for abraded. The total of the eight values is divided by four to give the primary irritation score.

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:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well conducted study according to that prescribed by Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.42. The principle of the test method is similar to the principle of the OECD Guideline 405 and no deviations have been reported.

Qualifier:

according to guideline

Guideline:

other: Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.42

Deviations:

no

Principles of method if other than guideline:

The ocular reactions were scored by the method described by J.H. Draize in "Appaisal of the Safety of Chemicals in Food, Drugs and Cosmetics".
The test material is placed in one of the eye while the other one serves as control. The eyes are examined and the grade of ocular reaction is recorded at 24, 48 and 72 hours.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Six albino rabbits are used for each test substance.
Animal facilities were mantained so that to exclude sawdust, wood chips or other extraneous materials that might produce eye irritation.

Vehicle:

unchanged (no vehicle)

Controls:

other: not required since the control was the eye not treated with the test item.

Amount / concentration applied:

75 mg pf the test item powder was instilled into one eye of each animal.

Duration of treatment / exposure:

7 days

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

Single application. Instillation of 75 mg of the test material into one eye of the animal by gently gently putting the lower lid away from the eyeball to form a cup into which the test item is dropped. The lids are then getly held together for one second and the animal is released.The other eye remained untreated to serve as a control for the treated eye. Each eye was graded according to the criteria reported in "illustration".

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 days

Score:

0.8

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 2 days

Score:

0.8

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 3 days

Score:

0.8

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 7 days

Score:

0.7

Max. score:

110

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applixcable

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

not fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48 h

Score:

1

Max. score:

3

Reversibility:

not fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

not fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 7d

Irritant / corrosive response data:

Mild conjunctival inplammation only was observed in three animals.
The three remaining animals did not show any observable response to treatment throughout the 7 day observation period.

Other effects:

not reported.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test item is considered to be "non-irritant" to the rabbit eye when classified as recommended by the ETAD Sub-commitee for Toxicology.

Executive summary:

The potential for eye irritation following exposure to the test item was assessed in 6 albino rabbits (75 mg of unchanged test item). Observations were carried out at regular intervals over 7 days following exposure. Mild conjunctival inplammation only was observed in three animals. The three remaining animals did not show any observable response to treatment throughout the 7 day observation period.

This eye irritation information for euthe test item is based on the standard Draize scale which has an overall score based on a 110 point rating scale. This rating scale is not directly compatible with Regulation (EC) No 1272/2008, Annex I section 3.3 classification criteria. However, based on guidance from various agencies, N-(2-ethoxyphenyl)-N'-(2-ethylphenyl)oxamide appears to be "non-irritant" to the rabbit eye when classified as recommended by the ETAD Sub-commitee for Toxicology.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The potential of the test item to cause skin and eye irritation was evaluated in 2 key studies in rabbits. The skin irritation study was compared to OECD Guideline No. 404 and the eye irritation study was compared to OECD Guideline No. 405. 

 

The key skin irritation study was conducted according to Consumer Product Safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.41. Primary irritation to the skin is measured by a patch test technique on the abraded and intact skin of the albino rabbits, clipped free of hair. A minimum of six subjects are used in abraded and intact skin tests. Introduce under a square patch such as surgical gauze measuring 1 inch x 1 inch, two single layer thick, 0.5 ml (in case of liquids) or 0.5 gram (in the case of solids and semisolids) of the test substances. Dissolve solids in an appropriate solvent and apply the solution as for liquids. the animals are immobilized with pathes secured in place by adhesive tape. After 24 h exposure, the patches are removed and the resulting reactions are evaluated on the basis of designed values.

Reading are again made at the end of a total of 72h (48h after the first reading). An equal number of exposures are made on areas of skin that have been prevoiusly abraded. the abrasion are minor incision through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.The values for oedema and eschar at 24 and 72h for intact skin are addedd to the values for abraded. The total of the eight values is divided by four to give the primary irritation score.

The potential for eye irritation following exposure to the test item was assessed in 6 albino rabbits (75 mg of unchanged test item). Observations were carried out at regular intervals over 7 days following exposure. Mild conjunctival inplammation only was observed in three animals. The three remaining animals did not show any observable response to treatment throughout the 7 day observation period.

This eye irritation information for euthe test item is based on the standard Draize scale which has an overall score based on a 110 point rating scale. This rating scale is not directly compatible with Regulation (EC) No 1272/2008, Annex I section 3.3 classification criteria. However, based on guidance from various agencies, N-(2-ethoxyphenyl)-N'-(2-ethylphenyl)oxamide appears to be "non-irritant" to the rabbit eye when classified as recommended by the ETAD Sub-commitee for Toxicology.

A supporting study of Klimish 4 reliability is available which anyway confirms that the substance does not show irritating effects on the rabbit eye.

Justification for selection of skin irritation / corrosion endpoint:
Well conducted study according to that prescribed by Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.41. The principle of the test method is similar to the principle of the OECD Guideline 404 and no deviations have been reported.

Justification for selection of eye irritation endpoint:
Well conducted study according to that prescribed by Consumer Product safety Commission of the USA in The Code of Federal regulations, Title 16, section 1500.42. The principle of the test method is similar to the principle of the OECD Guideline 405 and no deviations have been reported.

Justification for classification or non-classification

The available studies for eye and skin irritation indicate that the notifiable substance is not irritating to the eyes or skin. Thus, the data are conclusive but not sufficient for classification for eye and skin irritation.

 

No information is available for respiratory irritation, thus the notifiable is not classified as a respiratory irritant as data are lacking.