N,N-dimethylacetamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to Guideline study with acceptable restrictions (no details about the test substance or decrease in body weight; no non-lethal dose in females; no necropsy at termination).

Data source

Reference

Reference Type:

publication

Title:

Acute and subchronic toxicity of dimethylformamide and dimethylacetamide following various routes of administration

Author:

Kennedy GL & Sherman H

Year:

1986

Bibliographic source:

Drug Chem Toxicol 9: 147-170

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylacetamide

EC Number:

204-826-4

EC Name:

N,N-dimethylacetamide

Cas Number:

127-19-5

Molecular formula:

C4H9NO

IUPAC Name:

N,N-dimethylacetamide

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material: dimethylacetamide (DMAC) No details available.

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult rats
- Weight at study initiation: males 198-224 g, females 166-183 g

No further details available.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

50 % solution in water; average of 2.17-2.84 mL per male rat or 1.58-2.05 mL per female rat

Doses:

5000, 5500, 6000, 6500 mg/kg bw in males
4500, 5000, 5500, 6000 mg/kg bw in females

No. of animals per sex per dose:

10 rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14-15 days
- Observations (frequency): yes (presumably daily)
- Weighing: yes, but no details
- Necropsy of survivors performed: no
- Sacrifice: 14-15 days after application

Statistics:

Probit analysis (Finney)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

5 810 mg/kg bw

Remarks on result:

other: 95% CL not defined

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

4 930 mg/kg bw

Remarks on result:

other: 95% CL not defined

Mortality:

Details are presented in Table 1.
In males 3/10 animals died at 5500 mg/kg bw, 9/10 at 6000 mg/kg bw and 7/10 at 6500 mg/kg bw. No males died at 5000 mg/kg bw.
In females 4/10 animals died at 4500 mg/kg bw, 2/10 at 5000 mg/kg bw, 9/10 at 5500 mg/kg bw and 10/10 at 6000 mg/kg bw.

Clinical signs:

other: Belly-to-cage posture; wet and/or stained mouth, nose and perineal area; eyes half closed; diarrhea, tremors, piloerection, pallor, prostration, lethargy, chromodacryorrhea and cyanosis were noted.

Gross pathology:

No data

Any other information on results incl. tables

Table 1: Mortality in male and female ChR-CD rats after gavage within the post exposure observation period of 14 days

Dose (mg/kg bw)	Mortality in males	Mortality in females
6500	7/10	not tested
6000	9/10	10/10
5500	3/10	9/10
5000	0/10	2/10
4500	not tested	4/10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 = 5810 mg/kg bw (males); LD50 =and 4930 mg/kg bw (females).

Executive summary:

Groups of 10 ChR-CD rats per sex per dose were gavaged with 4500 - 6500 mg/kg bw (4 dose levels per sex). The post exposure observation period was 2 weeks.

Male rats died at a dose level >=5500 mg/kg bw and no mortality was found at 5000 mg/kg bw. In females even at the low dose level lethal effects were seen.

Clinical signs like belly-to-cage posture, wet and/or stained mouth, nose and perineal area, half closed eyes, diarrhea, tremors, piloerection, pallor, prostration, lethargy, chromodacryorrhea, and cyanosis were recorded.

Conclusion: In male ChR-CD rats the oral LD50 was 5810 mg/kg bw and in females 4930 mg/kg bw.