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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:
not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Minor deviations: - Information on source of animals and environmental conditions were missing

Data source

Reference
Reference Type:
publication
Title:
The acute toxicity of barium sulfate administered intragastrically
Author:
Boyd, E.M &Abel, Miriam
Year:
1966
Bibliographic source:
Canad. Med. Ass. J. 94: 849-853
Report date:
1966

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted: 24 Feb. 1987
Deviations:
yes
Remarks:
See principles of method other than guideline
Principles of method if other than guideline:
Minor deviations:
- Information on source of animals and environmental conditions were missing
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Barium sulfate
EC Number:
231-784-4
EC Name:
Barium sulfate
Cas Number:
7727-43-7
Molecular formula:
BaO4S
IUPAC Name:
barium sulfate
Details on test material:
- Name of test material (as cited in study report): Barium sulfate
- Analytical purity: Fisher Certified Reagent grade
No further significant information on test material was stated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 130-160 g
- Fasting period before study: 16 hours (overnight)
- Housing: rats were housed individually in a metabolism cage

No further significant information on test animals were stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
DOSAGE PREPARATION: Barium suspensions in distilled water were stabilised by the addition of 0.2 % (w/v) gum tragacanth.
The study consisted of divided administration of 150 % (w/v) suspension. The suspension was divided as follow: 40 % of the total dose in the first administration, 35 % after three hours and the remaining 25 % after a further four hours. This was done according to an outcome of a pilot study in which a suspension containing 150 g in a final volume of 100 ml produced stomach rupture when given in a single administration much larger than 100 ml/kg.

MAXIMUM DOSE VOLUME APPLIED: 375000 mg/kg bw

No further significant information on oral expsoure was stated


Doses:
Treatment group: 188000,225000, 263000, 300000, 338000,and 375000 mg/kg of Barium sulfate
Control group: Received distilled water in similarly divided administration and at a total volme of 185 ml./kg
No. of animals per sex per dose:
Treatment group: 16 to 26 animals
Control group: 50 animals
Control animals:
yes
Details on study design:
- Duration of observation period following administration: for three to 14 days, or until death occurred or recovery appeared obvious

- Necropsy of survivors performed: yes. Gross pathology was recorded on all animals which died. Organ weights and water levels were measured in animals which could be autopsied within one hour of death. Wet weight was measured on the following organs: adrenal glands, brain, cardiac stomach, pyloric stomach, small bowl, cecum, colon, heart, kidneys, liver, lungs, muscle (left half of the anterior abdominal wall muscle layer) skin, spleen, testes, thymus gland and residual carcass. Microscopic examinations were made on blocks of tissue fixed in Lillie's buffered formalin and sections stained with hematoxylinphloxine-saffron.

- Other examinations performed: Daily measurements included body weight, food consumption, water consumption, and colonic temperature

Statistics:
Statistical methods were those of Croxton.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
307 other: g/kg
Based on:
test mat.
Remarks on result:
other: S.E. +/- 29 g/kg; death due to stomach rupture
Sex:
male
Dose descriptor:
LD50
Effect level:
364 other: g/kg
Based on:
test mat.
Remarks on result:
other: S.E. +/- 41 g/kg; death due to bowel obstruction
Sex:
male
Dose descriptor:
LD0
Effect level:
163 other: g/kg
Based on:
test mat.
Remarks on result:
other: no death due to bowel obstruction
Sex:
male
Dose descriptor:
LD100
Effect level:
564 other: g/kg
Based on:
test mat.
Remarks on result:
other: death due to bowel obstruction
Mortality:
Fifty animals died from stomach rupture. The interval to death decreased with increasing dose of barium sulfate. Death in animals which survived stomach rupture was due to bowel obstruction. The interval to death was not dose-dependent and averagd (+/- S.D.) 40 +/- 12 hrs.
Clinical signs:
other: FINDINGS- STOMACH RUPTURE Following drug administration, the animals exhibited sedationand piloerection but otherwise appeared and acted normally. All rats which died of stomach rupture ate little or no food, drank little or no water, produced no urine, b
Gross pathology:
FINDINGS- STOMACH RUPTURE
Stomach autopsy revealed that the ruptures varied from 0.4 to 1.0 cm. in length, depending on dose, and were most commonly found on the lesser curvature never on the greater curvature. In 90 % of animals there were hemorrhagic areas in the gastric mucosa, mainly on the anterior and posterior surfaces rather than on the lateral borders. The adrenal glands were enlarged, the liver was small and the stretched abdominal muscle had a watery consistency.
Microscopically, the gastric hemorrhagic areas seen to be due to local penetration from barium sulfate through the mucosal layer to about the muscularis mucosae or occasionally into the submucosa.
FINDINGS- BOWEL OBSTRUCTION
At autopsy, impactation was always found in the small bowel and usually in the colon as well. Other gross pathology was limited to gastric haemorrhages and enteritis.
Microscopically, it could be seen that masses of barium sulfate had penetrated areas of the stratified squamous epithelium of the cardiac stomach and the glandular lining of the pyloric stomach, producing the hemorrhages visible macroscopically.
Other findings:
FINDINGS -STOMACH RUPTURE
Histology: Histopathology in other parts of the body appeared to be due mainly to arteriovenous thrombosis which apparently had occurred in the interval between stomach rupture and death.
FINDINGS - BOWEL OBSTRUCTION
- Organ weights and water levels: Most organs lost weight and water. Exceptions were adrenal glands and cardiac stomach, which gained weight, brain with an unaltered weight and water level, and stomach, liver and abdominal wall muscle which gained water, the latter possibly as a result of stretching.
- Histopathology: Arteriovenous thrombosis, seen in animals which died of stomach rupture, was even more marked in those which died of bowel obstruction and could be found in all organs.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 >5000 mg/kg bw. Hence, Barium sulfate must not be classified according to GHS.
Executive summary:

Barium sulfate administered intragastrically to albino rats did not produce death until doses administered reached 25 % to 40 % of body weight. These doses produced stomach rupture with death from four to 28 hours or bowel obstruction with death in 28 to 52 hours. In both instances there was gastrointestinal bleeding and extensive arteriovenous thrombosis of body organs. The latter was apparently responsible for other toxic reactions in many organs. The immediate cause of death was hypothermic respiratory failure. The LD 50 +/- S.E. producing death by bowel obstruction was 364 +/- 41 g/kg. The results suggest that barium sulfate used as a diagnostic radiopaque agent could probably not be taken in a single dose sufficiently great enough to produce signs of acute toxicity.

LD50 (male): 307 g/kg +/- 29 g/kg (death due to stomach rupture)

LD50 (male): 364 g/kg +/- 41 g/kg (death due to bowel obstruction)

LD0 (male): 163 g/kg (no death due to bowel obstruction)

LD100: 564 g/kg (death due to bowel obstruction)