Barium diboron tetraoxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: literature review

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Toxicokinetic data taken from published authoritative reviews (secondary sources) of published and proprietary studies

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Toxicological profile for Barium

Author:

ASTDR

Year:

2007

Bibliographic source:

US Department of Health and Human Services Public Health Service Agency for Toxic Substances and Disease Registry

Reference 2

Reference Type:

review article or handbook

Title:

Toxicological profile for Boron

Author:

ASTDR

Year:

2010

Bibliographic source:

US Department of Health and Human Services Public Health Service Agency for Toxic Substances and Disease Registry

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Review of published and proprietary data

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Barium and barium compounds

IUPAC Name:

Barium and barium compounds

Constituent 2

Reference substance name:

Boron, boric acid and borates

IUPAC Name:

Boron, boric acid and borates

Test material form:

other:

Details on test material:

Data relate to various soluble inorganic barium and barium compounds; boron, boric acid and borates.

Radiolabelling:

not specified

Test animals

Species:

other: various

Administration / exposure

Route of administration:

other: various

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The absorption of barium from the gastrointestinal tract is compound dependent. Acid-soluble barium compounds are absorbed through the gastrointestinal tract, although the amount of barium absorbed is highly variable. Variability depends on several factors including age and fasting. The International Commission for Radiation Protection (ICRP) estimates that the gastrointestinal absorption of barium is 20% in adults, 30% for children aged 1–15 years, and 60% in infants.
The results of studies suggest that the rate and extent of absorption of barium from the respiratory tract depend on the exposure level, how much barium reaches the alveolar spaces, the clearance rate from the upper respiratory tract, and the solubility of the particular form of barium that was administered. Barium is not expected to cross the intact skin because of the high polarity of the forms in which it is most commonly encountered.

Boron is absorbed across pulmonary tissues into the blood, as seen in workers exposed to borate dusts, who were found to have higher blood and urine boron concentrations at the end of a work shift compared to the beginning of the shift. Boron is almost completely absorbed in the gastrointestinal tract, with up to 92 and 95% of ingested dose being recovered in the urine. No data are available to indicate whether boron is actively transported or passively diffused across pulmonary or gastrointestinal tissues. Diet may influence the rate of boron absorption in the gut, as higher initial boron levels were found in the urine of humans given boron in an ointment vehicle, compared to administration via a water vehicle. Boron was found to be minimally absorbed across intact human or animal skin.

Details on distribution in tissues:

In humans, barium is predominantly found in bone; approximately 90% of the barium in the body was detected in the bone. Approximately 1–2% of the total body burden was found in muscle, adipose, skin, and connective tissue. This information is supported by a number of studies.

Boron is distributed readily to all body tissues. Tissue levels from daily doses were observed to achieve steady-state with plasma in all tissues examined, including neurological and reproductive tissues, with the exception of bone and adipose tissues. Bone serves as a storage depot for boron, while adipose tissue has a lower affinity for boron than other soft tissues. The mechanism(s) of transport across tissue membranes and into bone are not known. No data were available identifying binding of boron to a carrier protein in the blood or plasma membranes.

Details on excretion:

Fecal excretion of barium is 2–3 times higher than urinary excretion over a 30-day period. Feces is the primary route of excretion following exposure.

Excretion of systemically absorbed boron is accomplished primarily through renal elimination, with minor fractions excreted in the saliva, sweat, and feces. No data are available regarding the contribution of tubular absorption of boron in the kidney. Glomerular filtration rate is likely the dominant factor in renal elimination of boron. As such, the systemic elimination of boron may be compromised in populations with reduced glomerular filtration rates, such as preeclamptic women.

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

Barium is not metabolized in the body, but it may be transported or incorporated into complexes or tissues.

Boron is a trace element and is not metabolized in the body. Borates exist in the body as boric acid, the only form of boron recovered in the urine.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Both barium compounds and borate salts are rapidly and extensively absorbed following oral exposure; data indicate inhalation absorption but very low dermal absorption is predicted. While barium is predominantly found in bone, boron is distributed readily to all body tissues. Neither barium nor boron are metabolized in the body, but barium may be transported or incorporated into complexes or tissues and borates exist in the body as boric acid. Feces is the primary route of excretion for barium while renal elimination is the primary route of excretion for borates.

Executive summary:

The International Commission for Radiation Protection (ICRP) estimates that the gastrointestinal absorption of barium is 20% in adults, 30% for children aged 1–15 years, and 60% in infants. In humans, barium is predominantly found in bone; approximately 90%. Approximately 1–2% of the total body burden was found in muscle, adipose, skin, and connective tissue. Barium is not metabolized in the body, but it may be transported or incorporated into complexes or tissues. Feces is the primary route of excretion following exposure.

Boron is absorbed across pulmonary tissues into the blood. Boron is almost completely absorbed in the gastrointestinal tract (92 -95%). Boron was found to be minimally absorbed across intact human or animal skin. Boron is distributed readily to all body tissues. Boron is a trace element and is not metabolized in the body. Borates exist in the body as boric acid, the only form of boron recovered in the urine. Excretion of systemically absorbed boron is accomplished primarily through renal elimination, with minor fractions excreted in the saliva, sweat, and feces.