Barium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

March/April 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 for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(see rational for reliability)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

barium(2+) dichloride dihydrate

EC Number:

600-412-6

Cas Number:

10326-27-9

Molecular formula:

BaCl2.2(H2O)

IUPAC Name:

barium(2+) dichloride dihydrate

Test material form:

solid: crystalline

Details on test material:

Test substance: Barium chloride dihydrate
Molecular weight: 208.23 g/mol
Supplier: American Chemical Society
Purity: reagent-grade

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. A. Ivanovas, 7964 Kisslegg/Allgäu
- Age at study initiation: Not reported
- Weight at study initiation: Males: 105-135 g; Females: 105-120 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%

MAXIMUM DOSE VOLUME APPLIED: 5.0 ml/kg
The control animals received the vehicle alone.

Doses:

464 mg/kg, 562 mg/kg, 681 mg/kg, 825 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:

R Core Team (2012). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org/
Please refer to the attachment

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

619 mg/kg bw

Based on:

test mat.

95% CL:

506 - 756

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

676 mg/kg bw

Based on:

test mat.

95% CL:

590 - 774

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

645 mg/kg bw

Based on:

test mat.

95% CL:

612 - 681

Mortality:

Number of dead males per dose:
Control: 0/5
464 mg/kg: 0/5
562 mg/kg: 0/5
681 mg/kg: 4/5 (within 6 hours after dosing)
825 mg/kg: 4/5 (within 6 hours after dosing)

Number of dead females per dose:
Control: 0/5
464 mg/kg: 0/5
562 mg/kg: 3/5 (within 6 hours after dosing)
681 mg/kg: 2/5 (within 6 hours after dosing)
825 mg/kg: 5/5 (within 6 hours after dosing)

Clinical signs:

other: Signs of reaction to treatment included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), increased or decreased respiratory rate, irregular respiration, gasping respiration, increased or decreased motility, diarrhoea, sedat

Gross pathology:

Autopsy mainly revealed congestion of liver and spleen. Haemorrhaging and swelling of the glandular gastric mucosa was also observed.

Any other information on results incl. tables

Based on the resuls of this study, an LD50 of 645 mg/kg bw has been calculated for males and females for BaCl2.

According to the test result the substance has to be classified as harmful im swallowed (Xn; R22) due to the fact that mortality was observed at dose levels of > 200 mg/kg bw (according to 67/548/EEC) and toxic category IV (LD50 >300 and<2000 mg/kg bw.) according to GHS.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of this study, an LD50 of 645 mg/kg bw has been calculated for males and females for BaCl2.

Executive summary:

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 401, the test item BaCl2 was administered to groups of 5 male and 5 female Sprague Dawley rats at dose levels of 464, 562, 681 and 825 mg/kg body weight.

Mortalities occurred within 6 hours after dosing. Signs of reaction to treatment included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), increased or decreased respiratory rate, irregular respiration, gasping respiration, increased or decreased motility, diarrhoea, sedation, loss of righting reflex, loss of coordination, paralysis of the hind legs, tremors and coarse body tremors. Complete recovery was evident in surviving animals by day 3 as judged by external appearance and behaviour.

Autopsy mainly revealed congestion of liver and spleen. Haemorrhaging and swelling of the glandular gastric mucosa was also observed.

The animals showed normal weight gain throughout the study.

In conclusion, the LD50 of BaCl2 is calculated to be 645 mg/kg body weight by oral route in the rat.