2-chloro-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: OECD Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-N,N-dimethyl-3-oxobutyramide

EC Number:

227-372-9

EC Name:

2-chloro-N,N-dimethyl-3-oxobutyramide

Cas Number:

5810-11-7

Molecular formula:

C6H10ClNO2

IUPAC Name:

2-chloro-N,N-dimethyl-3-oxobutanamide

Details on test material:

Name: Dimetbyl- 2-ch1oroacetoacetamide
Batch No.: 502001
Physical state: clear yellowish liquid
Density: 1.20 g/m3
Storage: ambient, protected from light

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species: rat
Strain: Hsd/Cpb:WU
Source: Fa. Harlan Winkelmann GmbH, Gartenstr. 27, 33178 Borchen
Date of receipt: July 12, 1995
Acclimatization period: 15 days (range finding), 20 days (main test)
Animal selection: random
Animal identification: with colored markings; cage labelled with dosage, sex, date of study initiation, project no.
Weight range at study initiation: m: 221 - 254 g, f: 181 - 192 g

Husbandry
Housing: collective housing up to a maximum of 5 animals per cage (Makrolon@ type 111)
lllumination: artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.
Temperature: 22:+/-3 °C
Relative humidity: 30 -70 %
Measurement: twice daily

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Prior to study initiation, the animals were acclimatized to laboratory conditions for 15 days (range finding) or 20 days (main test). Only healthy animals were used in the test. 24 h before treatment, the fur was removed with elec-tric clippers from an area of roughly 5 x 10 cm on the back of each animal. The skin was subsequently examined
for abrasions and animals with healthy, intact skin were then colored for individual identification.
A single dermal application of the test article was performed. The substance was held in contact with the skin with a porous gauze dressing. .

Duration of exposure:

The exposure period was 24 h

Doses:

The test article was applied undiluted in a volume of 1.67 ml/kg. A preliminary range finding test with a dose of 2000 mg/kg body weight was conducted on two female rats.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin-Screening procedure (Screening Methods in Pharmacology, R. A. Turner, 1965, p. 26). Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The
animals were examined at the following post-treatment intervals: 10 min, I h, 2 h, 6 h, 24 h, 28 h and thereafter once daily up to day 14. After patch removal, dermal irritation was evaluated once daily for 14 days according
to a scheme based on Draize Body weights were recorded immediately before treatment (day 0) and on days 7 and
14 p.a. (termination). The animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological
examinations were subsequently

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: none

Mortality:

No animal died during the course of the main study.

Clinical signs:

other: Severe abnormal clinical signs were observed between 28 h and day 3 p.a. in one female animal. The findings were reduced activity, abnormal gait, sunken flanks, squatting position, piloerection and no pain reaction. The last finding was seen in a second f

Gross pathology:

Gross pathological examinations at 14 days p. a. (terminal necropsy) revealed no test article-dependent findings concerning the inner organs.
In 4 of 5 female animals marked skin lesion was observed. It concerned the upper dermal layers in 3 female animals, but in one female the complete skin and the adjoining muscular tissue were injured. In this female, the small intestine was reddened at an area of 15 em in lenght and filled with yellowish small plates.

Other findings:

There was an obvious sex difference concerning skin reactions. In fue male animals, very slight erythema was observed in 4 of 5 animals at day 1 p.a.
and in 2 animals at day 2 p.a. Additionally, scale formation on the treated skin area was seen in all males up to day 8 p.a., in 2 animals at day 9 p.a. and in one animal up to day 13 p.a. Very slight to well-defined erythema was observed in the female animals up to day 3 p.a. This finding was still apparent in 4 females at days 4 and 5 p.a. and in one female at days 6 and 7 p.a. Additionally, blackish or black-reddish discoloration of the treated skin areas, partly accompanied by induration was observed in all females on a different scale up to day 8 p.a. Subsequently, one female had no findings; in the other females discoloration and induration were still apparent or the indurated skin areas were partly separated and replaced by regenerated cutaneous tissue.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance is noit toxic to the skin of rats under the conditions of the study.

Executive summary:

The acute dermal toxicity of Dimetbyl- 2-ch1oroacetoacetamide was investigated according to OECD Guideline 402 in 5 male and 5 female Wistar rats. On the basis of the range finding results, each animal was given a single dermal administration of Dimetbyl- 2-ch1oroacetoacetamide at a dose of 2000 mg/kg body weight. The skin was exposed to the test article for 24 h and signs of erythema and oedema were subsequently evaluated once daily for 14 days.

Clinical observations were conducted at regular intervals during the l4-day observation period. Body weights were measured at days 0, 7 and 14 p.a. Gross pathological examinations were performed on animals at termination.

Severe clinical signs were observed in one female animal between 28 h and day 3 p.a. Very slight signs of erythema (males) or very slight to well-defined erythema (females) were observed. Additionally, dark discoloration, induration and subsequently separation of treated skin areas were observed in female animals. In the male animals scale formation on the treated skin area was seen. The development of the body weight was not normal in female animals during the entire observation period and in male animals during the first week of the study. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed no test article-dependent findings apart from marked skin injury in 4 of 5 female rats. 5. According to the requirements of the limit test, the LD50 values were for male and female > 2000 mg/kg.