Calcium dibenzoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-01-09 to 1979-02-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Limited study summary, no GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

This study used Swiss albino mice. In the range finding study, mice (10 males and 10 females) were administered 500, 1000, 2500, 5000 and 7500 mg/kg of test substance by oral gavage. In the main study, 30 male and 30 female mice, received 1500, 2000, 2500, 3000, 3500 and 4000 mg/kg of test substance. All the animals were closely observed until day 14 post-dosing for signs of acute intoxication and mortality.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzoic acid

EC Number:

200-618-2

EC Name:

Benzoic acid

Cas Number:

65-85-0

Molecular formula:

C7H6O2

IUPAC Name:

Benzoic acid

Test material form:

not specified

Details on test material:

not specified

Test animals

Species:

mouse

Strain:

other: Swiss albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bio Breeding Laboratories of Canada Ltd., Ottawa, Canada
- Age at study initiation: Approximately 30 days old
- Weight at study initiation: 18-22 grams
- Fasting period before study: 14-16 hours
- Housing: shoebox bins
- Diet (e.g. ad libitum): a pelleted diet (Purina Mouse Chow)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature: 70-75 °F
- Humidity: 40-50 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Tween-80

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1.5%
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: Due to its relative innocuous nature and ability to provide a stable homogeneous suspension.

Doses:

Range finding study: 500, 1000, 2500, 5000, 7500 mg/kg
Main study: 1500, 2000, 2500, 3000, 3500, 4000 mg/kg

No. of animals per sex per dose:

Range finding study: 2 males and 2 females per dose
Main study: 5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and histopathology

Statistics:

From the accumulated mortality data the LD50 value and its 95% confidence limits were calculated according to the method of Litchfield and Wilcoxon, Journal of Pharmacology and Experimental Therapeutics, Vol. 96, 99-113, 1949.

Results and discussion

Preliminary study:

Within 24 hours and 14 days after administration, there was 100% mortality in the 2500 and 7500 mg/kg dose groups, and 50% mortality within the 5000 mg/kg dose group. No mortality was observed in the 500 mg/kg and 1000 mg/kg dose groups within 24 hours and 14 days. Animals surviving the 14-day observation period showed increased body weights. In no animal gross lesions were observed at necropsy.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 250 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 875 - <= 2 700

Mortality:

24-hour mortality was 0, 30%, 70%, 50%, 80% and 100% for the respective dose groups. 14-day mortality was 0, 50%, 70%, 60%, 90% and 100% for the respective dose groups.

Clinical signs:

other: Signs of acute intoxication were absent in animals receiving 1500 mg/kg; however, in animals receiving 2000 mg/kg or greater, signs of acute intoxication consisted of decreased muscle tone, decreased activity and alertness as well as tonic convulsions and

Gross pathology:

All animals in both the range finding and definitive study were subjected to gross necropsy at the termination of the respenctive observation times. There was no lesions observed at necropsy in animals that had received 1500 mg/kg of the test substance; however, in animals that had received 2000 mg/kg or greater, there was evidence of gastric hemorrhage as demonstrated by the presence of coagulated blood in the stomach.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance produced signs of acute intoxication at doses greater than 2000 mg/kg.
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.

Executive summary:

This study used Swiss albino in the range finding study, mice ( 2/sex/dose) were administered 500, 1000, 2500, 5000 and 7500 mg/kg of test substance by oral gavage. In the main study mice (5/sex/dose) were exposed to 1500, 2000, 2500, 3000, 3500 and 4000 mg/kg of test substance. All the animals were closely observed until day 14 post-dosing for signs of acute intoxication and mortality.

The test substance produced signs of acute intoxication at doses greater than 2000 mg/kg. The LD50 was set at 2250 mg/kg bw