Malonic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Study predates introduction of GLP and OECD guidelines, but follows acceptable scientific methods.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

Study carried out before introduction of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Malonic acid

EC Number:

205-503-0

EC Name:

Malonic acid

Cas Number:

141-82-2

Molecular formula:

C3H4O4

IUPAC Name:

propanedioic acid

Test material form:

solid: crystalline

Details on test material:

Batch No: 20160723Purity: 99.5 %

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Fasted albino rats weighing 200-300 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The product under test was placed in a glass syringe and introduced through the esophagus into the stomach with a stainless steel catheter.

Doses:

6 dose groups (males & females) + control group (males & females) with dosages of:- 1 000 mg/kg - 2 000 mg/kg- 2 500 mg/kg- 3 200 mg/kg- 4 000 mg/kg- 8 000 mg/kg

No. of animals per sex per dose:

5 per sex per dose5 per sex per control group

Control animals:

yes

Details on study design:

A group of approximately 70 albino male and female rats, fasted for twenty-four hours were employed to establish an LD50 range for each product under test.Young adult rats which had not been used for previous test purposes were assigned to various dose levels at random. Both sexes were equally distributed.The product under test was placed in a glass syringe and introduced through the esophagus into the stomach with a stainless steel catheter.Animals on the same dosage level were then placed in a common cage with free access to food and water. The animals were observed daily for atwo week period. No postmortem, or histopathology examinations were performed in this particular study

Statistics:

No data available

Results and discussion

Preliminary study:

No preliminary study performed.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

3 250 mg/kg bw

Based on:

test mat.

95% CL:

> 2 630 - < 4 000

Effect levels 2

Sex:

male

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male

Dose descriptor:

LD100

Effect level:

8 000 mg/kg bw

Based on:

test mat.

Effect levels 4

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 750 mg/kg bw

Based on:

test mat.

95% CL:

> 2 280 - < 3 390

Effect levels 5

Sex:

female

Dose descriptor:

LD0

Effect level:

1 000 mg/kg bw

Based on:

test mat.

Effect levels 6

Sex:

female

Dose descriptor:

LD100

Effect level:

4 000 mg/kg bw

Mortality:

No mortality was observed at dose concentrations of 4000 mg/kg in males. Animals were found dead at 8000 mg/kg on day 4 and above (>8000 -32000 mg/kg) in male rats.No mortality was observed at dose concentrations of 4000 - 10000 mg/kg in females. Animals were found dead at 12500 mg/kg and above (>12500 -32000 mg/kg) in female rats.Details are given in the table below.

Clinical signs:

other: Male rats: unkempt coats were noted for 36-48 hours at 4000 mg/kg. At levels of 8000 mg/kg, 10000 mg/kg and 12500 mg/kg, lethargy was accompanied with spasmodic movements, nasal hemorrhage and unkempt coats. Survivors appeared normal by the ninth day.The

Gross pathology:

No Postmortem, or histopathology examinations were performed in this particular study.

Other findings:

No other findings

Any other information on results incl. tables

Mortality:

Dose Level (mg/kg)	No. of deaths (males)	Number of deaths (females)
1000	0	0
2000	0	1 (at day 2)
2500	1 (at day 1)	2 (at day 1)
3200	2 (at day 1)	3 (at day 1)
4000	4 (3 at day 1; 1 at day 2)	5 (at day 1)
8000	5 (at day 1)	5 (at day 1)

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 for malonic acid in male albino rats is 3250 mg/kg bw and for female albino rats 2750 mg/kg bw in the acute toxicity study.

Executive summary:

In an oral acute toxicity study, the LD50 for malonic acid in male albino rats was 3250 mg/kg bw and for female albino rats 2750 mg/kg bw.