N,N-dimethyl-3-oxobutyramide

Endpoint summary

Description of key information

A skin irritation study was performed in year 1974, following the DOT (Transport Classification) Guidelines, before GLP- and OECD-testing guidelineswere available and in force and amended in year 1991 (Addendum to Lonza Report No. 0003). The intact and abraded skin of albino rabbits was employed for this study. A series of 6 rabbits was used for testing.
No erythema and no oedema was observed in all 6 animals after 4, 24 and 48 hours observation period.
Therefore, the test item is not irritating to rabbit skin. 
A further irritation study was performed on rabbit eye in October 2012 according to OECD Guideline 405 and GLP. The test item LZ705 applied to the rabbits' eye mucosa, caused slight to moderate conjunctival irritant effects, fully reversible within 72 hours. According to the EC criteria for classification and labelling requirements for dangerous substances and preparations, the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study report meets basic scientific principles. Study was conducted prior to GLP and OECD guideline implementation.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: DOT (Transport-Classification) Guideliens

Deviations:

not specified

Principles of method if other than guideline:

The study was performed before GLP- and OECD-testing guidelines were available and in force.

GLP compliance:

no

Remarks:

GLP-guidelines not yet in force at date of the study

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No information available.

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Test Substance: 50% aqeous solution.

Duration of treatment / exposure:

4 hours

Observation period:

4, 24 and 48 hours on intact and abraded skin.

Number of animals:

6 rabbits were used for testing.

Details on study design:

The hair was clipped from the backs with the aid of angora clippers. Four areas of the back, placed approximately ten centimeters apart, were
designated for the positions of the patches. Areas 2 and 3 were abraded by making four epidermal incisions (two perpendicular to two others in the
area of the patch). The patches consisted of 1.5 inch x 1.5 inch 12 ply gauze squares. The patches ware secured to the area by thin bands of adhesivetape. The material to be tested (50% aqueous solution) was introduced beneath the patch. The entire trunks of the animals were then
wrapped in clear plastic trunk bands.
The trunk bands help to hold the patches in Position and retard evaporation of volatile substances during the four hour exposure period. Upon
removal of the patches the resulting reactions were evaluated on the basis of weighted scores.

Following this initial reading, all test sites were washed with appropriate solvent to prevent further exposure. Readings were again made at 24 and 48 hours after the initial application. The test substance was evaluated on a total of site (6 abraded and 6 intact).

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 4, 24 and 48 hour

Score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 4, 24 and 48 hours

Score:

0

Irritant / corrosive response data:

No data available.

Other effects:

No data available.

The results were summarized below:

Observation	Mean values over 4, 24 & 48 hours						Mean value
	No.1	No.2	No.3	No.4	No.5	No.6
Erythema	0	0	0	0	0	0	0
Oedema	0	0	0	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Substance Acetoacet Dimethylamide was classified as non-irritant to skin.

Executive summary:

The study was performed 1974, following the DOT (Transport Classification) Guidelines, before GLP- and OECD-testing guidelines were available and in force and amended in year 1991 (Addendum to Lonza Report No. 0003). The intact and abraded skin of albino rabbits was employed for this study. A series of 6 rabbits was used for testing.

No erythema and no oedema was observed in all 6 animals after 4, 24 and 48 hours observation period.

Therefore, the test item is considered not irritating to rabbit skin.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with international guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species and strain: New Zealand white rabbit
Hygienic level during the study: good conventional
Justification of strain: The New Zealand white rabbit is one of the standard animals in acute eye irritation study.
Number of animal: 3 males
Age of animals: adult rabbits
Body weight range at the beginning of the study: 2960 - 3020 g
Body weight range at the end of the study: 3044 - 3109 g
Date of receipt: October 04, 2012
Acclimatisation time: 5 days
Housing: Animal was housed individually in metal cage.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20 ± 3 °C
Relative humidity: 30-70 %
The animals received Rabbit fattening mixed diet produced by YAQ-TÁP Kft., Nyíregyháza (Tokaji út 22), Hungary, ad libitum.
Animals received tap water from watering bottles ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 ml of the test item LZ705 was used for the study in pure state, in a single dose. The absorption of the test item was not determined.

Duration of treatment / exposure:

The eyes of the test animals were not washed out after the application of test item.

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours after the application.

Number of animals or in vitro replicates:

3

Details on study design:

Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals that had a normal eye condition, any with ocular lesions were rejected.
In the first step an initial test was performed using one animal. The test item was poured into the conjunctival sac of the left eye. The eyelids were held closed gently for several seconds to prevent the loss of the test item. The contralateral eye served as control. Immediately after the administration of
the test item, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first animal, two additional animals were treated. Before the administration the treated
eyes of animals were not anaesthetised, because the score of initial pain reaction was 3 in the first animal.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 72h

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:

conjunctivae score

Basis:

mean

Time point:

other: 72h

Score:

0.33

Max. score:

0.66

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 72h

Score:

0.33

Max. score:

0.33

Reversibility:

fully reversible

Irritant / corrosive response data:

One hour and 24 hours after the treatment some hyperemic blood vessels (score 1) were occurred in all animals. The swelling was different from normal (score 1) in all animals. Discharge with moistening of the lids and hairs just adjacent to lids (score 2) was observed in animal No.: 1746 and the
amount of discharge was different from normal (score 1) in two animals (No.: 1750, 1745).
48 hours after the treatment some hyperemic blood vessels (score 1) were found in animal No.: 1745. Two animals (No.: 1750, 1746) became free of
symptoms.
72 hours after the treatment all animals were free of eye irritation symptoms.

Other effects:

General state and the behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period.

Mean values of eye irritation scores for EU classification (24, 48 and 72 hours reading)

Species: NZW Rabbit

Dose: 0.1 ml

Sex: Male

Start of Exposition: October 09, 2012

Test Item: LZ705

Animal Number	Sex	Cornea Opacity	Iris	Conjunctivae
				Redness	Chemosis	Discharge
1750	male	0.00	0.00	0.33	0.33	0.33
1746	Male	0.00	0.00	0.33	0.33	0.33
1745	Male	0.00	0.00	0.66	0.33	0.33

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, test item LZ705 applied to the rabbits' eye mucosa, caused slight to moderate conjunctival irritant effects, fully reversible within
72 hours. According to the EC criteria for classification and labelling requirements for dangerous substances and preparations, the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.
According to Regulation (EC) No. 1272/2008, the test item has not been classified into any category.

Executive summary:

The eye irritation study to the rabbit was performed in October 2012 according to OECD Guideline 405 and GLP. The test item LZ705 applied to the rabbits' eye mucosa, caused slight to moderate conjunctival irritant effects, fully reversible within 72 hours. According to the EC criteria for classification and labelling requirements for dangerous substances and preparations, the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Acceptable for reliability but not in detail documented. Study report meets basic scientific principles.
Study was conducted prior to GLP and OECD guideline implementation.

Justification for selection of eye irritation endpoint:
GLP study conducted in accordance with international guidelines (OECD 405), reliable without restrictions.

Justification for classification or non-classification

Based on the irritation/corrosion data available, the substance is not classified as irritating and does not require labelling according to Regulation 1272/2008/EEC (CLP) and according to Directive 67/548/EEC (DSD).