Sodium hydrogensulphate

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
Inhalation absorption: based on particle size dependant deposition modelling (MPPDl), an inhalation absorption factor of 36.65% was derived for sodium hydrogensulfate.
Dermal absorption: in the absence of measured data on dermal absorption, dermal absorption factors of 1% (exposure to liquid media) and 0.1% (exposure to dry solids/dust) are assumed (HERAG).
Oral absorption: according to animal toxicokinetic data (70-95% absorption), an oral absorption factor of 100% was derived.
Metabolism: inorganic substances such as hydrogensulfites/sulfates are not subject to metabolism as such.
Distribution and elimination: upon systemic uptake, hydrogensulfates/sulfates are distributed widely between tissues because of their high solubility/bioavailability, and are cleared almost exclusively by renal excretion.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Sodium hydrogensulfate readily dissociates in water with an acidic reaction, resulting in hydrogensulfate anions and sodium cations. The hydrogensulfate anion (pKa=1,99¹) partly dissociates further to sulfate anions and hydrogen cations, which are responsible for the acidic reaction. Based on these dissolution characteristics, and the essentiality of sodium and sulfate, it can be concluded that any toxicity of sodium hydrogensulfate is primarily induced by the acidic reaction, whereas the sulfate anion is not expected to contribute to any relevant extent to overall toxicity. This is reflected in the the SIAR on Sodium sulfate, which concluded an overall low hazard profile for human health and environment.

¹Lide, D. R. (Ed.) (2007): Physical constants of inorganic compounds. CRC Handbook of chemistry and physics, 88th edition

Read-across concept for sodium hydrogensulfate:

Read-across proposals were developed according to the two expected toxicological effects caused by sodium hydrogensulfate:

(i) the local effect caused by the acidic reaction after contact with water, to which the effects data on sulfuric acid have been referenced

(ii) the systemic effect of the sulfate anion after dissolution in water, for which reference is made to the effects data on sodium sulfate.

Sodium sulfate:

From Source: SODIUM SULFATE CAS N°: 7757-82-6 OECD SIDS April 2005

Absorption

Oral

In humans, absorption of small amounts of sulfate from the gut occurs rapidly and almost completely. In a study with 8 volunteers, small amounts (60-80mCi) of radioactive sulfate-35 (³⁵S) were administered orally or intravenously. Plasma equilibrium was reached within 60 to 105 and 60 to 90 minutes respectively, and in both cases 80% or more of the administered amount of radioactivity was recovered in the urine within 24 hours (Baueret al,1976). In contrast, absorption studies with very large amounts of sodium sulfate (18.1 gram as decahydrate = 8 g as Na₂SO₄) demonstrated incomplete absorption (53% urinary recovery of sulfate in 72 hours), which was associated with severe diarrhea (Cocchetto and Levy, 1981). When the same amount was given in four fractions over several hours, urinary recovery was 62% in 72 hours and no or only mild diarrhea occurred. Similar results were obtained with magnesium sulfate, although absorption seems to be less complete and more erratic, thus leading to more adverse effects (Morris and Levy, 1983). Apparently, the capacity of intestinal transport mechanism for sulfates can be exceeded. In a human volunteer study described 3.1.2 (Heizer 1999), 40-80% of a single dose of 63 mg/kg of sodium sulfate was resorbed and excreted in urine. Effects of saturation of absorption could not be detected over a dose range of 21-63 mg/kg/day in the range-finding part of this study.

In conclusion, it is considered reasonable for risk characterisation purposes to assume 100% oral absorption for sodium hydrogensulfate.

Dermal

There is no publicly available or other scientific information concerning dermal absorption of sodium hydrogensulfate.

In the absence of measured data on dermal absorption, previous guidance primarily directed at organic chemicals with a defined lipophilicity and corresponding percutaneous transfer potential, suggests the assignment of either 10% or 100% default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of inorganic ionic substances (predominantly based on the experience from previous EU risk assessments on metals and their inorganic substances) yields substantially lower figures, which can be summarised briefly as follows:

Measured dermal absorption values for metal cations and their inorganic 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 such ionic species. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn, Sb, Pb, Cu), 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 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 and their inorganic substances (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption; EBRC Consulting GmbH / Hannover /Germany; August 2007), the following default dermal absorption factors for inorganic substances 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 sulfate and hydrogensulfite anions as for metal cations.

 Inhalation

Data on inhalation absorption of sodium hydogensulfate are not available from the public domain. Thus, in view of the lack of such reliable data, the following approach was adopted for the derivation of inhalation absorption factors, in line with the HERAG approach for metals and their inorganic substances:

After completion of a testing programme on dustiness testing and particle size analysis of the airborne fraction on commercially available sodium hydrogensulfate, the collected information can be used to estimate inhalation absorption factors based on a prediction of deposition patterns in the respiratory tract (MPPD model).

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.

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 100%. 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 further information on particle size and dustiness, see IUCLID section 4.5):

Absorption factors (rounded values):

 

Test item		absorption factor via inhalation [%]
Sodiumhydrogensulfate[IB1]		36.65

Metabolism, Distribution and Elimination

Sulfate is a normal constituent of the blood and is a normal metabolite of sulfur-containing amino acids, and excess sulfate is excreted in the urine. Daily sulfate excretion is reported to be 0.20 to 0.25 mmol/kg bw/day and higher in children (Health Canada, 1994).

After absorption free sulfate ions rapidly distribute over the extracellular space, the apparent volume of distribution being ~ 20% of the body volume. The serum concentration of sulfate in humans ranges between 1.4 and 4.8 mg/100 mL, with a mean of about 3.1 mg/100 mL. Excretion is mainly in urine. The renal clearance is approximately one third of the glomerular filtration rate, indication tubular re-absorption. However, the total free sulfate excretion rate is not dependent on urine flow rate. Organically bound sulfate may follow different excretion patterns. (Cocchetto and Levi, 1981).

About 800 mg of elemental sulfur are eliminated daily through the urine of humans, compared with 140 mg in the faeces. (ICRP, 1984) Some 85% of urinary sulfur is present as inorganic sulfates and a further 10% as organic sulfates, whereas the remainder is excreted as conjugated alkyl sulfates (Diem, 1972).

Similar data are available from experimental animals: In a study on male wistar rats using³⁵S labelled Na₂SO₄, rapid and almost complete absorption occurred. When the radioactively labelled material was added to a large amount of unlabeled sodium sulfate and subsequently orally administered, the plasma peak occurred at the same time, but the amount of radioactivity decreased as the dose of unlabeled sulfate increased. This indicates that there is a saturation of the absorption mechanism (Krijgsheld, 1979). In male adult Wistar rats, approximately 73% of dietary calcium or magnesium sulfate salts was absorbed, although absorption was partly dependent on other dietary elements (Health Canada, 1994).

Since disturbances in sulfate metabolism are possibly associated with only one rare form of inherited dwarfism, this area is largely unexplored. Therefore, no attempts have been made to fully describe sulfate metabolism. Sulfate incorporation has been observed with such biologically important compounds as chondroitin, fibrinogen, l-tyrosine derivatives, bilirubin, and steroids. A number of amino acids contain sulfur and take part in the sulfate cycle. Hydrolytic (sulfatase) activity has been demonstrated in liver, kidney, pancreas, serum, and urine. Sulfates play an important role in sulfoconjugation processes, which are of great importance in a variety of detoxification/excretion processes (Percy, 1964).

In ruminants, excess amounts of sodium sulfate in feed may result in considerable toxicity due to formation of sulfides through bacterial action in the rumen.

Conclusion:relatively large amounts of sodium and sulfate are normally taken up by the gut from food and drinking water through a saturatable mechanism. Oral absorption may be considered to be complete, whereas inhalation absorption is partice size dependent. Dermal absorption is considered negligible in view of the strong ionic nature of the sodim and sulfate anions. Absorbed sodium and sulfate ions circulate freely throughout the entire body and form part of a large intra- and extracellular sodium and sulfate pool respectively. Sulfates are normally incorporated in a great variety of body compounds and as such are essential to life.

 [IB1]Analog sulfite partikelegrößenabhängig vervollständigen….

Discussion on bioaccumulation potential result:

Bioaccumulation:

Under physiologically relevant conditions, the substance readily dissociates in aqueous solution to sulfate, hydrogen and sodium ions. Bioaccumulation is not expected because of the strong anionic and hydrophilic nature of the substance.