N,N-dimethyl-3-oxobutyramide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted in accordance with international guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyl-3-oxobutyramide

EC Number:

218-059-8

EC Name:

N,N-dimethyl-3-oxobutyramide

Cas Number:

2044-64-6

Molecular formula:

C6H11NO2

IUPAC Name:

N,N-dimethyl-3-oxobutyramide

Test material form:

other: Colourless to yellow

Details on test material:

Name of test material (as cited in study report): LZ705

Test animals

Species:

rat

Strain:

other: Crl: (WI) BR rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
Species / Strain: Crl:(WI)BR rats
Hygienic level: SPF at arrival and kept in a good conventional environment during the study
Number of animals (preliminary study): 2 animals/dose
Number of animals (main study): 5 animals/dose
Age of animals: Young adult rats, females were nulliparous and non-pregnant
Sex: female and male
Body weight range in preliminary study at starting: 218 - 246 g
Body weight range in main study at starting (male): 243 - 290 g
Body weight range in main study at starting (female): 212 - 228 g
Acclimatization time: 5 days in preliminary study, 20 days in main study

HOUSING CONDITIONS:
Animal health: Only healthy animals were used for the study. The health status was certified by the breeder.
Number of animal room: IV (E building)
Housing: during acclimatization: 3 animals/sex/cage
During the study: animals were housed individually.
Cage type: Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.

ENVIRONMENTAL CONDITIONS:
Illumination: Artificial light, from 6 a.m. to 6 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 8-12 air exchanges/hour by central air-condition system.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

aqua purificata

Details on dermal exposure:

The back of animals was shaven (approximately 10 % area of the total body surface) 24 hours prior to the treatment. The test item was applied in a single 2000 mg/kg bw dose uniformly over the shaved skin throughout a 24- hour exposure period. Sterile gauze pads were placed on the skin of rats. These gauzes were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped with semi occlusive plastic wrap for 24 hours.
At the end of the exposure period, residual test item was removed, using body temperature water.

Duration of exposure:

24 hours

Doses:

Preliminary study: 5 mg/kg bw, 50 mg/kg bw, 300 mg/kg bw and 2000 mg/kg bw
Main study: 2000 mg/kg bodyweight.

No. of animals per sex per dose:

Preliminary study: 2 Females per dose
Main study: 5 Males and 5 Females.

Control animals:

not required

Details on study design:

The test item was applied in original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.
The test item was not expected to be lethal at 2000 mg/kg bw on the basis of result of preliminary study.
A limit test was performed.
The test substance was moistened sufficiently with water to ensure good contact with the skin.
Mortality: Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day.
Clinical observations: Careful clinical observation was made at the following intervals: 1h, 5h after the treatment and once each day for 14 days thereafter.
Body weight: The body weight was recorded on day 0 (shortly before the treatment) in preliminary study and on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g in main study.
Pathology: At the end of the observation period all rats of main study were sacrificed under isofluran anaesthesia.

Results and discussion

Preliminary study:

There were no deaths in preliminary study at 5, 50, 300 and 2000 mg/kg bw dose levels.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred after the 24-hour dermal exposure to LZ705 in male and female rats during the study.

Clinical signs:

other: No behavioural changes or systemic toxic signs were noted during the study.

Gross pathology:

All animals survived until the scheduled necropsy on Day 15.
Slight hydrometra was found in two animals (No.: 5461, 5471). The hydrometra is physiological finding and connected to the cycle of the animal. No macroscopic alterations due to the systemic toxic effects of the test item were found.

Other findings:

No other findings.

Any other information on results incl. tables

Dermal irritation symptom as erythema and other sign as wound were observed on the treatment site. The very slight redness (score +1) appeared in all males and was detectable between Day 1 and Day 2. This very slight symptom (score +1) was observed in four females (No.: 5461, 5462, 5463, 5472) and was detectable between Day 1 and Day 2. Wound was recorded in three males (No.: 5396, 5397, 5398) between Day 2 and Day 7.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions, the acute dermal LD50 value of the test item LZ705 was determined to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Executive summary:

The acute dermal toxicity study was performed in year 2012 in accordance with international guidelines and GLP. No death occurred after the single 2000 mg/kg bw dermal dose of LZ705. There were no systemic toxic clinical signs at both sexes and no any related effect of the test item found in body weights and body weight gains of animals during the study. Autopsy revealed no treatment related pathological changes. Under the experimental conditions, the acute dermal LD50 value of the test item LZ705 was determined to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.