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Description of key information

No toxicokinetic data (animal or human studies) are available on this substance.  The data presented here are based on physico-chemical parameters which allow a qualitative assessment of the toxicokinetic behaviour of the divalent cation (Ba +2) rather than a quantitative assessment. The toxicokinetic behaviour of the counter ion is not evaluated. The toxicokinetic behaviour of other barium salts is described to support this assessment.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
7
Absorption rate - dermal (%):
1
Absorption rate - inhalation (%):
21

Additional information

Barium nitrate is a solid inorganic salt of barium, a metallic alkaline earth metal. Barium does not exist in nature in the elemental form but occurs as the divalent cation in combination with other elements. There are no other oxidation states than the +2 state.

Barium nitrate is a high water-soluble compound (94 g/L at 20°C) with a molecular weight of 261.35 and a very low vapor pressure (based on its high melting point). No log P value has been defined for barium nitrate as it is an inorganic compound.

Barium nitrate is not considered to be a skin irritator (in vitro nor in vivo) and it is not a skin sensitizer (LLNA test; OECD 429).

Absorption

Oral/Gastro-intestinal absorption

Barium nitrate is a very soluble compound in water with a molecular weight of 261.35. Based on this information, it is expected that barium nitrate will readily dissolve into the gastrointestinal fluid and be present in its ionic form.

Absorption from the gastro-intestinal lumen can occur by passive diffusion but also by specialized transport system. With respect to absorption by passive diffusion, the lipid solubility and the ionization are important. However, inorganic salts of metals are usually not lipid soluble and are thus poorly absorbed by passive diffusion (Beckett et al., 2007). No log P value or pKa value have been defined for barium nitrate; the metal ion (Ba+2) is an ionic substance and thus it is not expected to readily diffuse across biological membranes.

It has been reported that absorption mechanisms for some essential metal ions (specialized transport systems) sometimes serve to transfer nonessential metals into body as well. Large differences in gastrointestinal absorption have been reported for ionized cadmium, indium, tin and uranium (less than 10%) but almost complete absorption for water-soluble inorganics salts of arsenic, germanium and thallium (William S, 2007). There is no specific information on barium salts available.

The water solubility of barium compounds increases with decreasing pH (IPCS 1991). Therefore it could be expected that substance becomes more and more insoluble from the stomach through the intestinal lumen.

Based on the qualitative assessment of the physic-chemical properties of barium nitrate, reduced absorption is expected.

Studies evaluating the absorption of barium nitrate following oral exposure in animals are not available. However information on other barium salts, including the water soluble barium chloride, is available.

It has been reported, from animal studies, that the absorption of barium from the gastrointestinal tract is compound dependent. Barium sulfate is extremely insoluble and very little, if any, ingested barium sulfate is absorbed. Soluble barium compounds, such as barium chloride, are absorbed through the gastrointestinal tract, although the amount of barium absorbed is highly variable. Experiments in rats have shown that younger animals (22 days old or less) absorb about 10 times more barium chloride from the gastrointestinal tract (63–84%) than do older animals (about 7%). Absorption was higher in fasted adult rats (20%) as compared to fed rats (7%) (Taylor et al. 1962; ASTDR 2007). It is likely to expect a similar behavior for barium nitrate than for barium chloride.

In an acute oral toxicity study (van Huygevoort A.H.B.M, 2013), barium nitrate was administered to young rats (10-week old) at 50, 300 and 2000 mg/kg in a step-by-step manner. LD50 value was derived to be 300 mg/kg body weight. Mortality was observed at all the doses except 50 mg/kg. Clinical sigs were could not be recorded at 2000 mg/kg dose. Clinical signs at 300 and 50 mg/kg included flat posture, lethargy, piloerection, uncoordinated movements, labored respiration, slow breathing. Macroscopic observations at necropsy were only reddish foci in the jejunum in all the animals at 2000 mg/kg. Only one animal at 300 mg/kg showed red foci in the gastric mucosa and in the thymus. No macroscopic abnormalities were observed in the remaining animals and in animals at 50 mg/kg. Body weight of the surviving animals were similar to the control animals.

As macroscopic changes were mainly observed at gastrointestinal level, it could be concluded that, clinical signs are a response to disconformity after compound administration due to local effects of the compound rather than a systemic effect. Nevertheless, oral absorption can not totally excluded. Therefore result of this study do not provide reasons to deviate to the assumption that a similar behavior for barium nitrate than for barium chloride is expected.

Studies evaluating the absorption of barium nitrate following oral exposure in humans are not available. However 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 (ICRP 1993).” ICRP estimations are taken forward for risk characterization purposes.

Based on the available data an oral absorption factor of 7% is derived for barium nitrate. This value is proposed for human health risk assessment purposes.

Respiratory absorption

Given the anticipated low vapor pressure and relatively high melting / decomposition point, barium nitrate is not considered to be a volatile substance and the availability for inhalation as a vapor is expected to be limited.

The particle size of a substance can be used as surrogate to assess the presence of inhalable/respirable particles. In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. As the substance contains particles in the range of 370 – 880 μm no significant deposition of particles in the respiratory tract is to be expected.

Following the above considerations, any significant exposure via the inhalation route is not be expected.

No studies were located regarding absorption of barium nitrate in humans or animals following inhalation exposure. Several animal studies have investigated the absorption of barium chloride or barium sulfate following inhalation, intratracheal injection, or nasal deposition. The results of these 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 (ASTDR, 2007).

Approximately 50–75% of inhaled barium chloride or barium sulfate is absorbed from the respiratory tract (Cuddihy and Griffith 1972; Morrow et al. 1968); approximately 65% of the barium chloride deposited in the nose is absorbed (Cuddihy and Ozog 1973b). Most of the barium absorption occurs within the first 24 hours (Cuddihy and Griffith 1972; Cuddihy et al. 1974). Barium chloride appears to be more rapidly absorbed than barium sulfate (Cuddihy et al. 1974), although the differences in particle size may have influenced the absorption rate (ASTDR, 2007).

Differences in water solubility appear to account for observed differences in respiratory tract clearance rates for barium compounds (ASTDR, 2007).

There is no dustiness study with cascade impactor available for barium nitrate, so there is no data on the deposited dust fractions. Therefore, the available data on barium chloride are used. For barium chloride, the fraction deposited in the head is 43.18%, in the tracheobronchial region 0.05% and in the pulmonary region 0.01%. The majority of the particles is deposited in the upper airways; only a minor fraction is deposited in the pulmonary region. Barium chloridedeposited in the head and tracheobronchial regions would be translocated to the gastrointestinal tract, where it would be subject to gastrointestinal absorption at a ratio of 20%. The absorption factor for barium chloride is predicted to be 8.7%.

 

Based on the abovementioned information, a respiratory absorption factor of 21% is proposed. This proposed absorption factor would be three-fold higher than the oral absorption factor (7%) and lies within the range of the absorption via the gastrointestinal tract (as mentioned above). Compared to the predicted respiratory absorption factor for barium chloride (8.7%), an uncertainty factor of nearly 2.5 is taken into account.

 

Dermal absorption

Studies evaluating absorption following dermal exposure in humans are not available. One animal study showed that barium applied to the skin of piglets was found in the various layers of the skin (Shvydko et al. 1971).

Barium is not expected to cross the intact skin because of the high polarity of the forms in which it is most commonly encountered (ASTDR, 2007). This conclusion is also supported when toxicokinetic behavior based on physic-chemical properties is assessed. Barium nitrate is a solid substance and dry particulates will have to dissolve into the surface moisture of the skin before uptake can begin. Furthermore, as barium nitrate is a well water soluble compound with a molecular weight of 261.35, it is expected that barium nitrate will not be able to cross the stratum corneum.

Partition from the stratum corneum into the epidermis after penetration would be enhanced due to high water solubility of the substance.

Barium nitrate is neither a skin irritant nor a skin sensitizer in rabbits or mice, respectively. The results of these studies do not provide reasons to deviate from the assumption that absorption of barium through the skin is very low.

In the absence of measured data on dermal absorption, ECHA guidance on IR&CSA, R.7c suggests the assignment of either 10% or 100% default dermal absorption rates.

Furthermore, the currently available scientific evidence on dermal absorption of metals (predominantly based on the experience from previous EU risk assessments) yields substantially lower figures than the lowest proposed default value of 10% (HERAG, 2007). In the Health Risk Assessment Guidance for Metals (HERAG) document, an overview of most recent developments of several aspects of risk assessment methodology specific to metals and inorganic metal compounds is proposed, with the aim to reduce uncertainty of future risk assessment. In accordance to HERAG, measured dermal absorption values for metals or metal compounds in studies corresponding to the most recent OECD test guidelines are typically 1 % or even less. Therefore, the use of a 10 % default absorption factor is not scientifically supported for metals. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn), which have derived dermal absorption rates of 2 % or far less (but with considerable methodical deviations from existing OECD methods) from liquid media. However, considering that under industrial circumstances many applications involve handling of dry powders, substances and materials, and since dissolution is a key prerequisite for any percutaneous absorption, a factor 10 lower default absorption factor may be assigned to such “dry” scenarios where handling of the product does not entail use of aqueous or other liquid media. This approach was taken in the in the EU RA on zinc. A reasoning for this is described in detail elsewhere (Cherrie and Robertson, 1995), based on the argument that dermal uptake is dependent on the concentration of the material on the skin surface rather than it’s mass.

Based on the above considerations, very low dermal absorption is expected. The following default dermal absorption factors for metal cations are therefore proposed (reflective of full-shift exposure, i.e. 8 hours):

·        From exposure to liquid/wet media: 1.0

·        From dry (dust) exposure: 0.1 %

The dermal absorption factor of 1.0% is selected for risk assessment purposes, as worst-case scenario.

Distribution/Accumulation

One day after rats were exposed to barium chloride aerosols, 78% of the total barium body burden was found in the skeleton; by 11 days post-exposure, more than 95% of the total body burden was found in the skeleton (Cuddihy et al., 1974). The uptake of barium into the bone appears to be rapid (EPA, 2005).

The remainder of the barium in the body is found in soft tissues (i.e., aorta, brain, heart, kidney, spleen, pancreas and lung). Additionally, the levels in the heart, eye, skeletal muscle, and kidneys were higher than the whole-blood concentration, suggesting the ability of soft tissue to concentrate barium (EPA, 2005).

In humans, barium is predominantly found in bone; approximately 90% of the barium in the body was detected in the bone (Schroeder et al. 1972). 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, summarized here below:

Significant increases in the levels of barium in bone were found in rats administered barium chloride in the diet or barium as a component of Brazil nuts for 29 days (Stoewsand et al. 1988); this study did not examine other tissues. A study (McCauley and Washington, 1983) in which rats were exposed to barium chloride and barium carbonate in drinking water found the following non-skeletal distribution (skeletal tissue was not examined in the study) 24 hours after ingestion: heart > eye > skeletal muscle > kidney > blood > liver (ASTDR, 2007).

Metabolism

As an element, barium is neither created nor destroyed within the body (ASTDR, 2007).

Excretion

Barium is expected to be excreted in the urine and feces following oral, dermal, inhalation, and parenteral exposure.

The feces are the primary route of excretion following oral intake, with just 2%-5% excreted in the urine (EPA, 2005).

Excretion from the system (hence, after the substance has been absorbed into the body), is expected mainly via urine as the substance is a small well water-soluble ion.

References

Cuddihy RG, Griffith WC (1972). A biological model describing tissue distribution and whole-body retention of barium and lanthanum in beagle dogs after inhalation and gavage. Health Phys 23:621-633.

Cuddihy RG, Ozog JA. (1973). Nasal absorption of CsCl, SrCl2, BaCl2 and CeCl3 in Syrian hamsters. Health Phys 25:219-224.

Cuddihy RG, Hall RP, Griffith WC (1974). Inhalation exposures to barium aerosols: Physical, chemical, and mathematical analysis. Health Phys 26:405-416.

Health risk assessment guidance for metals (HERAG) fact sheet: assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal compounds. EBRC Consulting GmbH (2007).

ICRP (1993). Age-dependent doses to members of the public from intake of radionuclides: Part 2. Ingestion dose coefficients. IRCP publication 67.23(3/4). New York, NY: Pergamon Press.

McCauley PT, Washington IS (1983). Barium bioavailability as the chloride, sulfate or carbonate salt in the rat. Drug Chem Toxicol 6:209-217.

Morrow PE, Gibb FR, Davies H, et al. (1968). Dust removal from the lung parenchyma: An investigation of clearance stimulants. Toxicol Appl Pharmacol 12:372-396.

Schroeder HA, Tipton IH, Nason AP (1972). Trace metals in man: Strontium and barium.J Chronic Dis 25:491-517.

Shvydko NS, Il'in LA, Norets TA, et al.(1971). Comparative behavior of Sr89and Ba140in skin following cutaneous application. Gig Sanit 36:386-390.

Stoewsand GS, Anderson JL, Rutzke M, et al. (1988). Deposition of barium in the skeleton of rats fed Brazil nuts. Nutr Rep Int 38:259-262. 

Taylor DM, Bligh PH, Duggan MH (1962). The absorption of calcium, strontium, barium and radium from the gastrointestinal tract of the rat. Biochem J 83:25-29. 

U.S. Environmental protection agency (2005). Toxicological review of barium and compounds in support of summary information on the integrated risk information system (IRIS). 

U.S. Department of health and human services (2007). Public Health Service. Agency for toxic substances and disease registry (ATSDR). Toxicological profile for barium and barium compounds.

William S. Beckett et al. Routes of exposure, dose and metabolism of metals. Chapter 3 of Handbook on the toxicology of metals. (3rd Edition, 2007).