Barium oxide, obtained by calcining witherite

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

BaO rapidly hydrolyzes to Ba(OH)2, a strongly alkaline substance, upon contact with water. Barium chloride dihydrate as well soluble barium salt was used to assess the potential of barium for accumulation after ingestion. Primary data are only partly accessible.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Subchronic Oral Toxicity of BaCl2 in Rats

Author:

Tardiff et al

Year:

1980

Bibliographic source:

Journal of Environmental Pathology and Toxicology 4:267-275

Materials and methods

Objective of study:

other: accumulation in organs

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Animals were dosed with BaCl2 (0-250 ppm) in drinking water for 13 weeks. Liver, bone (femur), muscle, and heart were analyzed at 4, 8, and 13 weeks for concentrations of barium.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Barium chloride

EC Number:

233-788-1

EC Name:

Barium chloride

Cas Number:

10361-37-2

IUPAC Name:

barium dichloride

Details on test material:

- Name of test material (as cited in study report): Barium chloride
- Analytical purity: >= 98%

Test animals

Species:

rat

Strain:

other: Charles River rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 4 weeks
- Diet (e.g. ad libitum): ad libitum (Tekland Mouse/Rat Diet, Tekland Mills, Winfield, IA)
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

Test substance solutions were checked periodically and results showed less than 2% deviation from target concentrations.

Duration and frequency of treatment / exposure:

13 weeks / 90 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10, 50, 250 ppm

No. of animals per sex per dose / concentration:

30

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: test studies conducted with adult animals resulted in an LD50 of 132 mg barium/kg bw. The maximum test concentration used in the study was approx. 1/3 the LD50.
- Rationale for selecting satellite groups: At weeks 4 and 8 during the study, subgroups of at least 5 animals per sex per dose were sacrificed for measurement of biochemical and hematological parameters, histopathological assessment and analysis of barium concentrations in selected tissues.

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues sampled: liver, bone (femur), muscle, heart
- Time and frequency of sampling: at 4, 8, and 13 weeks of treatment

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The barium levels increased in all organs investigated over the treatment period of 13 weeks. By far the strongest increase was observed in bone, in accordance with other reports showing that barium is integrated more readily into bone than calcium.

Any other information on results incl. tables

Barium concentration in tissues after 4 weeks (µg/kg± SE):

		n	Liver	Bone	Muscle	Heart
Females	0	5	0.11± 0.03	8.3± 0.7	0.18± 0.03	0.22± 0.05
	10	5	0.26± 0.05	9.6± 0.9	0.35± 0.06	0.36± 0.07
	50	10	0.42± 0.11	50.3± 4.6	0.56± 0.08	0.56± 0.09
	250	5	0.50± 0.08	230.2± 9.9	1.40± 0.85	0.44± 0.05
Males	0	5	0.11± 0.06	8.1± 0.8	0.26± 0.10	0.26± 0.12
	10	5	0.30± 0.06	9.6± 0.05	0.51± 0.10	0.45± 0.06
	50	5-9	0.33± 0.05	65.0± 5.7	0.56± 0.04	0.58± 0.12
	250	5	0.77± 0.07	198.4± 9.5	1.46± 0.37	0.93± 0.20

Barium concentration in tissues 13 weeks after initiation of treatment (µg/kg± SE):

	Dose (ppm)	n	Liver	Bone	Muscle	Heart
Females	0	5	0.15± 0.05	10.3± 1.2	0.22± 0.07	0.18± 0.05
	10	5	0.35± 0.04	16.2± 3.3	0.49± 0.08	0.29± 0.01
	50	10	0.36± 0.05	50.5± 7.4	0.70± 0.14	0.40± 0.04
	250	5	0.38± 0.07	214± 9.3	0.48± 0.09	0.44± 0.08
Males	0	5	0.12± 0.05	7.9± 0.7	0.16± 0.06	0.25± 0.09
	10	5	0.37± 0.07	12.8± 1.4	0.46± 0.07	0.36± 0.01
	50	10	0.36± 0.04	50.5± 5.7	0.45± 0.04	0.45± 0.04
	250	5	0.25± 0.05	226± 15.9	0.40± 0.06	0.31± 0.03

Applicant's summary and conclusion

Conclusions:

Barium levels strongly increase in bone, however absorption efficiencies are unclear.

Executive summary:

The authors of this publication investigated the deposition of barium in different organs after ingestion. They reported increased levels of barium in all organs investigated (liver, bone, heart, kidney), however the strongest increase was oberserved in the bone (femur). Already 4 weeks after beginning of the treatment, the barium levels in bone were increased in the 50 and 250 ppm treatment groups. The barium concentrations were the same as after 13 weeks treatment, suggesting that not the length of treatment, but the dose administered determine the accumulation in bone. These findings in return would suggest that large amounts of barium can be excreted or are not resorbed. In the absence of reliable data on barium absorption, the accumulation potential of barium cannot be assessed.