Registration Dossier

Skin Irritation:

Primary Dermal Irritation score for N,N-Diethyl-3-oxobutyramide was Grade 1.

Based on the grade, N,N-Diethyl-3-oxobutyramide was considered to be not irritating to skin.

Eye Irritation:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach,it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances.

Therefore, N,N-diethyl-3-oxobutanamide was estimated to be not irritating to eyes and it can be further classified under the category “Not Classified” as per CLP regulation.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Primary dermal irritation study was performed in rabbits to assess the irritation potential of N,N-diethyl-3-oxobutanamide

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : N,N-diethyl-3-oxobutanamide- Molecular formula: C8H15NO2- Molecular weight: 157.212 g/mol- Smiles notation: N(C(CC(C)=O)=O)(CC)CC- InChl : 1S/C8H15NO2/c1-4-9(5-2)8(11)6-7(3)10/h4-6H2,1-3H3- Substance type: Organic- Physical state: Liquid

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

open

Preparation of test site:

other: closely clipped abdominal skin

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.01 ml of undiluted sample

Duration of treatment / exposure:

24 hours

Observation period:

24 hours

Number of animals:

5

Details on study design:

TEST SITEArea of exposure: closely clipped, intact abdominal skin% coverage: No dataType of wrap if used: no wrap used REMOVAL OF TEST SUBSTANCEWashing (if done): no dataTime after start of exposure: no dataSCORING SYSTEM:Primary skin irritation on rabbits was recorded in a 10-grade ordinal series. Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

10

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Grade 1- no isgns of irritation observed

Interpretation of results:

other: not irritating

Conclusions:

Acute dermal irritation study was carried out to assess the irritation potential of N,N-Diethyl-3-oxobutyramide.Primary Dermal Irritation score for N,N-Diethyl-3-oxobutyramide was Grade 1.Based on the grade, N,N-Diethyl-3-oxobutyramide was considered to be not irritating to skin.

Executive summary:

Acute dermal irritation study was carried out to assess the irritation potential of N,N-Diethyl-3-oxobutyramide.

Primary skin irritation on rabbits was recorded in a 10-grade ordinal series and was based upon the severest reaction that develops on the clipped abdominal skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 ml of undiluted sample or of solutions in water, propylene glycol, or acetone.

Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution.Primary Dermal Irritation score forN,N-Diethyl-3-oxobutyramidewas Grade 1.

Based on the grade, N,N-Diethyl-3-oxobutyramide was considered to be not irritating to skin.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: weight of evidence based on structurally similar read across chemicals

Justification for type of information:

weight of evidence based on structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Weight of evidence approach based on similar chemicals

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: N,N-diethyl-3-oxobutanamide- Molecular formula: C8H15NO2- Molecular weight: 157.212 g/mol- Smiles notation: N(C(CC(C)=O)=O)(CC)CC- InChl : 1S/C8H15NO2/c1-4-9(5-2)8(11)6-7(3)10/h4-6H2,1-3H3- Substance type: Organic- Physical state: Liquid

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

1. 0.5 ml2. 0.1 ml

Duration of treatment / exposure:

1. 24 hours2. single

Observation period (in vivo):

1. 24 hours2. 1,4,24 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

1. 52. 6

Details on study design:

The study is based on the results from the read across chemicals

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no signs of irritation observed

Interpretation of results:

other: not irritating

Conclusions:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, N,N-diethyl-3-oxobutanamide was estimated to be not irritating to eyes and it can be further classified under the category “Not Classified” as per CLP regulation.

Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of N,N-diethyl-3 -oxobutanamide.

Acute toxicity studies were carried out to estimate the toxicity of the structurally similar chemical.

Eye injury in rabbits was recorded in a 10- grade ordinal series and was based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical. Grade 1 indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.

Primary Eye Irritation score after 24 hours for the test chemical was Grade 2. Based on the grade, the test chemical was considered to be not irritating to eyes.

This is supported by the results of a study was performed to determine the primary ocular irritation potential of the other structurally similar chemical in rabbits.

0.1 ml of the test chemical was instilled Into the Inferior Conjunctival Sac of One Eye of Each of Six New Zealand white Rabbits. The eyelids were held together for 1 second. The treated eyes were observed for conjunctival redness, chemosis and iridial inflammation, corneal injury at1,4,24 hours and 2,3,7 days post instillation. Corneal integrity was checked before dosing by the instillation of 2% Fluorescein and irrigation with water 20 seconds later. Only animals without Fluorescein staining were used.

There was no evidence of corneal injury on macroscopic inspection or following the instillation of 2% fluorescein.

At 1-hr post instillation there was just detectable excess conjunctival redness in 5 rabbits, of which 2 showed slight chemosis and 1 a moderate chemosis. Mild iritis was seen in 2 animals, persisting up to 4 hr. All eyes got completely healed by 24 hr post instillation.

The Primary irritation scores after 24 hours for conjunctival redness, chemosis, discharge and iris were 0.

Based on the scores and observations, the test chemical can be considered to be not irritating to eyes.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, N,N-diethyl-3-oxobutanamide was estimated to be not irritating to eyes and it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

In different studies,N,N-diethyl-3-oxobutanamidehas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical as well as its structurally similar read across chemicals. The results are summarized as follows:

Acute dermal irritation study was carried out to assess the irritation potential of N,N-Diethyl-3-oxobutyramide. Primary skin irritation on rabbits was recorded in a 10 -grade ordinal series and was based upon the severest reaction that develops on the clipped abdominal skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 ml of undiluted sample or of solutions in water, propylene glycol, or acetone.

Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution. Primary Dermal Irritation score for N,N-Diethyl-3-oxobutyramide was Grade 1.

Based on the grade, N,N-Diethyl-3-oxobutyramide was considered to be not irritating to skin.

This is supported by the results of another study performed to determine the dermal irritation potential of the test chemical in rabbits.500 mg of the test chemical was applied to the skin of rabbits and observed for signs of irritation till 24 hours.

Mild irritation was observed after 24 hours exposure toN,N-diethyl-3-oxobutanamide to rabbit skin.

Hence, N,N-diethyl-3-oxobutanamide can be considered to be irritating to skin.

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database forN,N-diethyl-3-oxobutanamide. Based on estimation, no severe skin irritation effects were known when N,N-diethyl-3-oxobutanamidewas exposed to rabbit skin. Hence, N,N-diethyl-3-oxobutanamide can be considered not irritating to skin.

The above results are supported by an acute dermal irritation study carried out to assess the irritation potential of the structurally similar chemical.

Primary skin irritation on rabbits was recorded in a 10-grade ordinal series and was based upon the severest reaction that develops on the clipped abdominal skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 ml of undiluted sample or of solutions in water, propylene glycol, or acetone.

Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solution. Primary Dermal Irritation score for the test chemical was Grade 2.

Based on the grade, the test chemical was considered to be not irritating to skin.

These results are further supported by the study performed to determine the primary dermal irritation potential of the structurally similar chemical in rabbits.

0.5 ml undiluted test chemical was applied to the clipped dorsal skin of 6 New Zealand White rabbits under occlusive wrapping for 4 hours. After 4 hours of exposure, the occlusive dressing was removed and the excess test chemical was gently removed. The test sites were inspected for erythema and edema at 1 hour, 1, 2, 3, 7 and 14 days post removal of the dressing. The dermal reactions were scored by the methods of Draize.

5of6rabbits had a very slight local erythema, which also developed in the sixth animal by 24 hr. Edema, slight in 5 rabbits and moderate in one, was also present. After 3 days, only half the animals had just detectable erythema, and one had mild edema. Apart from mild desquamation, no effects were seen at7days.

Since the effects were completely healed by 7 days, the test chemical can be considered to be not irritating to skin.

Even though one study for the target chemical claims that N,N-diethyl-3-oxobutanamide can cause mild irritation to rabbit skin. But results from other experimental and estimated studies for the target chemical, indicate a possibility of it being not irritating to skin. These results are also supported by the information available for the strongly structurally similar read across chemicals. Hence by applying the weight of evidence approach, N,N-diethyl-3-oxobutanamide can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation,N,N-diethyl-3-oxobutanamidecan be classified under the category “Not Classified”.