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Description of key information

Key value for chemical safety assessment

Absorption rate - oral (%):
20
Absorption rate - dermal (%):
1
Absorption rate - inhalation (%):
9.9

Additional information

Valence, speciation and other general or mechanistic aspects

Changes in valence of “strontium” do not occur under physiological conditions and are therefore not relevant.

 

Inorganic sulfides or hydrogensulfides as well as H2S will dissociate to the respective species relevant to the pH of the physiological medium, irrespective of the nature of the “sulfide”, which is why read-across between these substances and H2S is considered to be appropriate without any restrictions for the purpose of hazard and risk assessment of strontium sulfide. Speciation of sulfides and hydrogen sulfides may be considered to be of relevance when relating toxicity to bioavailability.

 

However, taking into account the reaction of sulfide and hydrogen sulfide in aqueous media (please refer to the Hägg graph given in IUCLID section 5.1.2 Hydrolysis), it can safely be assumed that under most physiologically relevant conditions (i.e., neutral pH) sulfide and hydrogen sulfide anions are present at almost equimolar concentrations, thus facilitating unrestricted read-across between both species. Under extreme conditions such as gastric juice (pH << 2), sulfides will be present predominantly in the form of the undissociated hydrogen sulfide.

 

Oral absorption

Sulfides:
There are only few publications that allow an assessment of the oral bioavailability of sulfide in rats, which are also somewhat of age. Nevertheless, the following conclusions can be drawn: after oral administration of sulfide to rats (Curtis et al., 1972) almost 70% are excreted within 48 hrs, 63% via urine and the remainder via faeces. In another study involving intraperitoneal administration, 90% of the injected dose could be recovered in urine and faeces (Dziewiatkowski, 1945).In conclusion, the assumption appears justified that upon oral uptake the systemic uptake is essentially complete for sulfides and hydrogen sulfides. Therefore, a conservative oral absorption factor of 100% will be taken forward for risk characterisation purposes.

For more details please refer to the attachment on section 7.

 

Strontium:

An independent review of all available toxicokinetic information was not performed by EBRC to avoid duplication of work, since a thorough evaluation by a renown scientific body is available (ATSDR, April 2004), the key conclusions of which are summarised briefly below:

 

“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 (strontium sulfide)

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 substances 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) fromliquidmedia.

 

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.

 

Consistent with the methodology proposed in HERAG guidance for metals (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metal cations and inorganic metal substances; EBRC Consulting GmbH / Hannover /Germany; August 2007), the following default dermal absorption factors for metal cations have therefore been proposed (reflective of full-shift exposure, i.e. 8 hours):

 

From exposure to liquid/wet media:                    1.0 %

From dry (dust) exposure:                                  0.1 %

 

Given that the primary cause between the lack of percutaneous transfer is considered to be the ionic nature, it is proposed to assume similar behaviour for sulfides anions as for metal cations, and to adopt the above stated dermal absorption factors for strontium sulfide.

 

Inhalation absorption (strontium sulfide)

The systemic availability of different strontium substances via the inhalation route can be expected as a function of regional deposition in the respiratory tract, which in turn depends foremost on the particle size distribution of the inhaled dust. However, product-specific physical particle size distributions do not necessarily reflect the particle size of aerosols that may be formed under practically relevant workplace conditions, for example during manual operations such as filling and emptying of bags, or under mechanical agitation as in mixing and weighing operations.

 

Strontium sulfide was subjected to an experimental testing programme. The physical particle size distribution of the commercial material was determined by laser diffraction (acc. OECD 110) and is represented by the median particle size diameter D50.

 

In addition, to simulate mechanical agitation, the sample was introduced into a rotating drum apparatus according to DIN 55992 Part 1. In this modified rotating drum method, a fraction of the material becomes airborne and is carried out of the drum by a constant air stream into a cascade impactor. From the mass fractions deposited on the impactor stages, the mass median aerodynamic diameter (MMAD) of the airborne material has been determined together with the geometric standard deviation (GSD) of the MMAD (EBRC Report: EBR-20150603/01).

 

In the absence of actual measurements of the distribution of dust particles in the workplace air, the above determined MMAD and GSD can therefore be used as surrogate parameters of the associated particle size distribution.

 

It takes into account potential particle agglomeration under mechanical agitation and the fact that larger/heavier particles show less tendency to become airborne (and are therefore not likely to be available via inhalation of workplace air).

 

The relative density of the sample was taken of different handbooks, which could be seen as reliable data under REACH. However, the methods used were not stated. Data on particle size, relative density and calculated MMAD and associated GSD are presented in the table below:

 

Table:Data on particle size, dustiness and relative density of strontium sulfide (EBRC Report: EBR-20150603/01)

Test item

relative density

d50*

(mm)

MMAD of airborne particles

(mm)

Geometric standard deviation of MMAD

Strontium sulfide

3.7 at 20°C

197

27.72

1.65

*d50 = median physical particle size
#MMAD = mass median aerodynamic diameter

In order to estimate the deposition in the respiratory tract (head, tracheobronchial and pulmonary region) of particles the Multiple Path Particle Deposition (MPPD) model (CIIT, 2002-2006) was used with the following input data; The human–five lobular lung model, a polydisperse particle distribution, oronasal (normal augmenter) mode, a full shift breathing volume of 10 m3- corresponding to a tidal volume of 1042 ml and a breathing frequency of 20 breaths * min-1, and an aerosol concentration of 500 µg/m3.

 

 

Table:Calculated deposited fractions of strontium sulfide (EBRC report no.: EBR-20130807/01).

Test item

Head [%]

TB [%]

PU [%]

Strontium sulfide

49.41

0.09

0.03

 

Based on the MPPD model, the following conclusions can be drawn for risk characterisation purposes for strontium sulfide:

(i)     the tested “Strontium sulfide” sample has a limited deposition ability in the human respiratory tract: Only 49.51 % of airborne material is estimated to deposit. The rest of the airborne material is not inhaled due to physical phenomena related to air streams and turbulences close to the mouth or simply exhaled (i.e. not deposited).

 

(ii)    about 0.03 % or less of inhaled material are predicted to deposit in the pulmonary region (PU), whereas the material deposited in the tracheobronchial (TB) and the extrathoracic region (Head) may be assumed to be cleared to the GI tract (i.e., by mucociliary escalation and subsequent swallowing).

 

The fate and uptake of deposited particles depends on the clearance mechanisms present in the different parts of the airways of the respiratory tract. 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.

 

In consequence, the material deposited in the head and tracheobronchial regions would be translocated to the gastrointestinal tract where it would be subject to gastrointestinal uptake at a ratio of 20% (see oral absorption). 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 factor can be derived for strontium sulfide (calculation details given in the following table):

 

Table: Absorption factors, strontium sulfide

 

absorption factors*
via inhalation [%]

Test item

Strontium sulfide

9.9

*: rounded values

 

Distribution, metabolism and elimination

Sulfide:

Following oral administration, sulfides are absorbed rapidly and extensively, and distributed widely throughout all tissues without any particular target tissue (Curtis et al., 1972; Dziewiatkowski, 1945). Upon distribution, sulfide is rapidly oxidised and excreted as sulfate, with thiosulfate having been identified as an intermediate metabolite (Bartholomew et al., 1980). The resulting sulfate is excreted almost quantitatively via urine; experiments with bile duct cannulated rats have shown that biliary excretion is minimal by comparison (Curtis et al., 1972). Methylation with subsequent elimination via exhaled air has been excluded for sulfides (Susman et al., 1978).

Strontium:
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 which 90Sr 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 compound. 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).