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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:
key study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-compliant guideline study with the following deviations: - According to the guideline, healthy young adults should be used. The age of the rats was missing in this report. - The analytical purity of the test substance is not indicated in the report.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(Adopted: 12 May 1981)
Deviations:
yes
Remarks:
(see rational for reliability)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
No further details available

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. A. Ivanovas, 7964 Kisslegg/Allgäu
- Age at study initiation: Not reported
- Weight at study initiation: Males: 100-125 g; Females: 100-115 g
- Housing: Group housing of five animals per sex per cage in labelled Makrolon cages (type III) containing sawdust bedding material (Fa. Brandenburg, 2849 Goldenstedt-Arkeburg).
- Diet (ad libitum except overnight prior to and approx. 4 hours after dosing): Pelleted rodent diet (Ssniff R10 pellets, Ssniff Versuchstierdiäten, 4770 Soest/Westf.
- Water (ad libitum): Tap water
- Acclimation period: 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
Animals were housed in a controlled environment.
- Temperature: ca. 20°C
- Relative humidity: 40 - 60 %
- Air changes: Approx. 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1%
- pH value of suspensions: 10

MAXIMUM DOSE VOLUME APPLIED: 5.0 ml/kg
The control animals received the vehicle alone.
Doses:
1470 mg/kg, 1780 mg/kg, 2150 mg/kg
No. of animals per sex per dose:
5 male / 5 female
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of dosing animals were observed for signs of reaction to treatment at frequent intervals. On subsequent days animals were observed at leaste once daily. Individual bodyweights were recorded on the day of dosing and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The acute oral median lethal dose (LD50) based on the mortality rate (x/n) during 14 days after dosing was calculated using the method of Finney (1971), Probit Analysis (3rd Edition) Cambridge University Press.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 690 mg/kg bw
95% CL:
1 060 - 2 010
Mortality:
Mortalities occured within 72 hours after dosing.

Number of dead males per dose:
Control: 0/5
1470 mg/kg: 2/5
1780 mg/kg: 4/5
2150 mg/kg: 4/5

Number of dead females per dose:
Control: 0/5
1470 mg/kg: 1/5
1780 mg/kg: 2/5
2150 mg/kg: 4/5
Clinical signs:
Slight pilo-erection was observed in the control animals on the day of dosing. Clinical signs observed on the day of dosing in rats treated with bariumcarbonate included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), increased or respiratory rate, laboured respiration, diarrhoea, chromodakryorrhoea, decreased motility and loss of righting reflex. Diurese was observed in one female at 1780 mg/kg and one male at 2150 mg/kg. Loss of coordination and tremor was seen in one female at 2150 mg/kg. Complete recovery was evident in surviving animals by day 3, as judged by external appearance and behaviour.
Body weight:
Poor bodyweight gain was observed in the surviving male rat of the highest dose group (2150 mg/kg) and one female rat of the mid-dose group (1780 mg/kg).
Gross pathology:
Autopsy mainly revealed congestion of liver and and inflammation of the glandular region of the stomach in rats that died during the study.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, an LD50 of 1690 mg/kg bw has been calculated for males and females for BaCO3.
According to the criteria specified by Directive 67/548/EC, Regulation (EC) No 1272/2008 and subsequent regulations the test item would be harmful and requires classification (Xn; R22 according to 67/548/EEC and toxic category IV according to GHS).
Executive summary:

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 401, the test item BaCO3 was administered to groups of 5 male and 5 female Sprague Dawley rats at dose levels of 1470, 1780 and 2150 mg/kg body weight.

Mortalities occurred within 72 hours after dosing. Signs of reaction to treatment included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), increased or decreased respiratory rate, laboured respiration, diarrhoea, chromodakryorrhoea, decreased motility and loss of righting reflex. Complete recovery was evident in surviving animals by day 3 as judged by external appearance and behaviour.

Autopsy mainly revealed congestion of liver and inflammation of the glandular region of the stomach in rats that died during the study.

Body weight gain was poor in the surviving male rat of the highest dose group (2150 mg/kg) and one female rat of the mid-dose group (1780 mg/kg).

In conclusion, the LD50 of BaCO3 is calculated to be 1690 mg/kg body weight by oral route in the rat.