Dimethyl oxalate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2.6.1997 - 10.7.1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Adopted 24.2.1987

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

Commission Directive 92/69/EEC

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

Dimethyl oxalate

EC Number:

209-053-6

EC Name:

Dimethyl oxalate

Cas Number:

553-90-2

Molecular formula:

C4H6O4

IUPAC Name:

dimethyl oxalate

Specific details on test material used for the study:

Name: Dimethyl oxalate
Description: white solid block
Storage conditions: ambient temperature (< 25 °C), stored under artifician light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Source: Charles River (UK) Ltd, Margate, Kent
- Age range: 8-12 weeks
- Weight range: females 200-229 g, males 216-233 g
- Housing: groups of up to five by sex
- Water: Ad libitum exept fasting procedure
- Diet: Ad libitum exept fasting procedure
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 48-65
- Air changes (per hr): 15
- Room lighting: Daily light/dark cycle of 12/12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

By gavage, using a metal cannula attached to a graduated syringe.

Doses:

Female:
2000 mg/kg, 200 mg/mL
1414 mg/kg, 141.4 mg/mL
1000 mg/kg, 100 mg/mL
Male:
2000 mg/kg, 200 mg/ml

No. of animals per sex per dose:

Female:
2000 mg/kg: 5 animals
1414 mg/kg: 5 animals
1000 mg/kg: 5 animals
Male:
2000 mg/kg: 5 animals.

Control animals:

no

Details on study design:

The animals were fasted overnight before dosing up to 4 hours after dosing. The animals were observed approximately 0.5; 1, 2 and 4 hours after administration of the test item and daily thereafter. The observation period was 14 days. The animals were weighed individually on day 0 and on days 7 and 14 or at death.

Statistics:

95 % confidence limits for females only

Results and discussion

Preliminary study:

Range-finding study resulted no deaths. Clinical signs were hunched posture, lethargy, pilo-erection, ptosis, decreased respiratory rate and laboured respiration. Based on range-finding stydy, dose leves were selected for the main study.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 569 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 366 - <= 1 803

Mortality:

Deaths were noted one to four days after dosing. All female animals dosed at 2000 mg/kg died on Day 1-2. 2/5 male animals died dosed at 2000 mg/kg. 1/5 female animals died at dose 1414 mg/kg.

Clinical signs:

other: Doses 1414 or 2000 mg/kg: ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration. Piloerection was noted in females. Dose 2000 mg/kg: An isolated incident of ptosis was noted in one female. Males: abdominal discomfort, ema

Gross pathology:

Animals that died during the study: common abnormalities haemorrhagic lungs, dark liver and pale kidneys.
Dose 2000 mg/kg females: Sloughing of the non -glandular epithelium of the stomach was also noted.
Dose 2000 mg/kg males: the kidneys of three males were found to be enlarged.
Dose 1414 mg/kg: Pale kidneys were noted at necropsy of animals killed at the end of the study.

Other findings:

Male animals were considered not to be markedly more sensitive to the test material than female animals.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Oral LD50 1569 (1366 - 1803) mg/kg bw
2008/1272/EC would indicate the following:
Classification: Category 4
Signal word: Warning
Hazard statement: H302 Harmful if swallowed.

Executive summary:

The acute oral toxicity of the test item dimethyl oxalate was evaluated in female and male Sprague Dawley rats according to OECD 401 and EU Method B.1 guidelines and in compliance with GLP. The test substance induced mortality in the rat following oral administration of a single dose at levels of 2000 (5/5 female, 2/5 male) and 1414 (1/5 female) mg/kg. Main clinical sings after 2000 and 1414 mg/kg were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration. Gross pathology examination showed haemorrhagic lungs, dark liver and pale kidneys for animals died during the study. Kidneys showed to be enlarged with three males and sloughing of the non -glandular epithelium of the stomach was noted with females at dose 2000 mg/kg. At dose 1414 mg/kg pale kidneys were noted at necropsy of animals killed at the end of the study. No mortality or other relevant signs of toxicity were observed following dosing at 1000 mg/kg. The results suggest the LD50 to be 1569 (1366 – 1803) mg/kg bw and indicate the classification of Acute Oral Toxicity Category 4.