Barium sulfate

Endpoint summary

Description of key information

Acute toxicity, oral: LD50 >5000 mg/kg bw 
Acute toxicity, dermal: waiving (LD50 >2000 mg/kg bw (only secondary information))
Acute toxicity, inhalation: waiving

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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.

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.

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.

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)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Reason for read across from BaCl2 to BaSO4 for acute dermal toxicity:

The toxicity of barium sulfate and barium chloride is based on the Ba²⁺cation and therefore on the solubility of the test substance. Barium chloride is well water soluble (ca. 375 g/L) at pH ca. 6.5 (pH of artificial sweat solution), whereas barium sulfate is low soluble (3.1 mg/L at pH 9). Due to the fact that Barium chloride seems to be no toxic via the dermal route it can be concluded that barium sulfate will result in a dermal LD50 of >>2000 mg/kg bw and should therefore not classified as acute toxic to the dermal route.

Reason for read across from BaCO3 to BaSO4 for acute inhalation toxicity:

Barium sulfate (melting point: 1600°C) and barium carbonate (melting point: 1380°C) are very similar in view of the particle size, melting point and density (rel. density: BaSO4: 4.5) and both could be regarded as insoluble in solutions at a pH of 9 (barium sulfate ca. 3.1 mg/L and barium carbonate ca. 14 mg/L). Beside this barium sulfate (the standard powder on the marked) has a larger MMAD/GSD as barium carbonate standard.

Justification for classification or non-classification

Acute oral toxicity

The study performed by Boyd (1966) (see robust study summary chapter 7.2.1) is considered as the key study for acute oral toxicity and will be used for classification. Male Wistar rats were dosed up to 375 g/kg bw orally via gavages. During the conduct of the study mortalities occurred only due to stomach rupture or bowel obstruction, no biologically important body weight loss occurred after dosing, and no gross lesions were present in the rats at necropsy.

LD0 oral, rat 163 g/kg bw.

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2000 mg/kg body-weight, hence no classification required.

 

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw. No classification required.

 

Acute dermal toxicity

According to the SIAR 27 prepared for barium chloride, an acute dermal toxicity study on barium chloride was conducted according to OECD TG 402, in compliance with GLP. In this study, the dermal LD₅₀was greater than 2000 mg BaCl₂/kg bw in rats. The primary data could not be made available by the registrant but if using the secondary information no classification according to regulation (EC) 1272/2008 will be necessary for barium sulfate by read across from barium chloride.

 

 

Acute inhalation toxicity

A pre test on inhalation was performed with barium carbonate (rel. density: 4.3). Despite extensive effort it was not possible to generate a stable testing atmosphere with an acceptable test concentration (ideally 5.1 mg/L).

 

Barium sulfate (melting point: 1600°C) and barium carbonate (melting point: 1380°C) are very similar in view of the particle size, melting point and density (rel. density: BaSO₄: 4.5) and both could be regarded as insoluble in solutions at a pH of 9 (barium sulfate ca. 3.1 mg/L and barium carbonate ca. 14 mg/L). Beside this barium sulfate (the standard powder on the marked) has a larger MMAD/GSD as barium carbonate standard.

					deposition fractions
Sample	rel. density	D50 [µm]	MMAD [µm]	GSD	Head [%]	TB [%]	PU [%]
BaSO4HD80 (standard)	4.5 at 20°C	1.16	53.84	2.12	24.28	0.04	0.02
BaCO3(standard)	4.3 at 20°C	2.32	24.22	4.87	45.22	0.95	1.16

 

Based on the technical properties of barium sulfate which are equal or similar to barium carbonate, the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically justified. Due to the low mobility and the negligible volatility of barium sulfate (melting point: 1600°C), the test material can safely be assumed to have a very low potential for human inhalation hazard during handling or application. Hence, no classification is required.

 

Specific target organ toxicant (STOT) – single exposure: inhalation

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation dust/mist/fume are not met since no relevant exposure via inhalation is possible. Based on the technical properties of barium sulfate, the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically relevant for this type of compound, see discussion “acute inhalation toxicity”. Hence, no classification is required.