Strontium hydroxide

Endpoint summary

Key value for chemical safety assessment

Absorption rate - oral (%):

20

Absorption rate - dermal (%):

1

Absorption rate - inhalation (%):

8.9

Additional information

Oral absorption; ATSDR, August 2004; key conclusions

“The fractional absorption of ingested strontium has been estimated in healthy human subjects or hospital patients who received an oral dose of strontium chloride (SrCl₂) or ingested strontium in the diet (ATSDR, 2004 Table 3-7). Absorption was quantified in these studies from measurements of plasma strontium concentration-time profiles for ingested and intravenously injected strontium (bioavailability), or from measurements of the difference between the amount ingested and excreted in feces (balance). Collectively, the results of these studies indicate that approximately 20%
(range, 11–28%) of ingested strontium is absorbed from the gastrointestinal tract. Balance measurements can be expected to yield underestimates of absorption as a result of excretion of absorbed strontium in the feces; nevertheless, the two methods have yielded similar estimates of absorption.”

Regarding oral absorption, discussed in ATSDR (April 2004) and taking all available human data together approximately 20% of ingested strontium is absorbed from the gastrointestinal tract. In adult male rats, absorption of strontium as SrCl₂is in a similar range (19%). Absorption in rats was found to be age dependent with higher absorption rates in very young animals and lower absorption rates in aged rats. However, it appears appropriate to use a default absorption factor for rats of 20% for risk assessment purposes.

Dermal absorption

In the absence of measured data on dermal absorption, current guidance suggests the assignment of either 10% or 100% default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of metals (predominantly based on the experience from previous EU risk assessments) yields substantially lower figures, which can be summarised briefly as follows:

 

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.

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 %

This approach is consistent with the methodology proposed in HERAG guidance for metals

(HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal compounds; EBRC Consulting GmbH / Hannover /Germany; August 2007)

Inhalation absorption (for calculation please refer to the attached document)

The fate and uptake of deposited particles depends on the clearance mechanisms present in the different parts of the airway. In the head region, most material will be cleared rapidly, either by expulsion or by translocation to the gastrointestinal tract. A small fraction will be subjected to more prolonged retention, which can result in direct local absorption. More or less the same is true for the tracheobronchial region, where the largest part of the deposited material will be cleared to the pharynx (mainly by mucociliary clearance) followed by clearance to the gastrointestinal tract, and only a small fraction will be retained (ICRP, 1994). Once translocated to the gastrointestinal tract, the uptake will be in accordance with oral uptake kinetics.

According to ATSDR (2004) a ratio of 20% can be assumed for thegastrointestinal uptake and the material that is deposited in the pulmonary region may be assumed by default to be absorbed to 100%. This absorption value is chosen in the absence of relevant scientific data regarding alveolar absorption although knowing that this is a conservative choice. Thus, the following predicted inhalation absorption factors can be derived for strontium hydroxide:

	absorption factor* via inhalation [%]
Sample
Strontium hydroxide octahydrate	8.9

*: rounded values

Distribution

 

Following ingestion, the distribution of absorbed strontium in the human body is similar to that of calcium, with approximately 99% of the total body burden in the skeleton (ICRP 1993). The skeletal burden of stable strontium has been estimated from analyses of bone samples from human autopsies. Skeletal burden was estimated in Japanese adult males to be approximately 440 mg compared to 850 g of calcium.

 

One study was published in 1984 in which⁹⁰Sr and calcium concentrations in human bone tissues and diets of people in the United Kingdom during the period from 1955 to 1970 were analyzed. The authors concluded that approximately 4.75% of the dietary intake of⁹⁰Sr was taken up by the adult skeleton. Approximately 7.5% of the cortical bone⁹⁰Sr burden was eliminated from bone each year (equivalent to elimination halftimes of approximately 9.2 years). The rate of elimination from trabecular bone was approximately 4 times this value. The same analysis yielded estimates of skeletal uptakes of strontium that varied with age, being highest, approximately 10%, in infants and during adolescence, ages in which bone growth rates are high relative to other ages.

 

The partitioning of strontium in blood has not been extensively explored. The concentrations of strontium in the erythrocyte and plasma fractions of human blood obtained from blood banks were 7.2 μg/L in the erythrocyte fraction and 44 μg/L in the plasma fraction, suggesting that most of the strontium in blood resides in the plasma (ATSDR, 2004).

 

Elimination

 

Strontium that has been absorbed from the gastrointestinal tract is excreted primarily in urine and feces. In two dial painters, rates of urinary and fecal excretion of radium approximately 10 years after the exposure were approximately 0.03 and 0.01% of the body burden per 24 hours, respectively. The urine: fecal excretion ratio of 3 that was observed in the radium dial workers is consistent with ratios of 2–6 observed several days to weeks after subjects received an intravenous injection of a soluble strontium comound. Thus, urine appears to be the major route of excretion of absorbed strontium. The observation of fecal excretion of radioactive strontium weeks to decades after an oral exposure or over shorter time periods after an intravenous exposure suggests the existence of a mechanism for transfer of absorbed strontium into gastrointestinal tract, either from the bile or directly from the plasma (ATSDR, 2004). 

Metabolism

 

The metabolism of strontium consists of binding interactions with proteins and, based on its similarity to calcium, probably complex formation with various inorganic anions such as carbonate and phosphate, and carboxylic acids such as citrate and lactate. These types of interactions would be expected for all routes of exposure (ATSDR, 2004).