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Toxicological information

Acute Toxicity: oral

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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:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
5 810 mg/kg bw
Remarks on result:
other: 95% CL not defined
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:
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.
Body weight:
There was weight loss in all treatment groups (no details given)
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.