Sodium hydrogensulphate

Endpoint summary

Description of key information

Test results are available for sodium sulfate and sulfuric acid for acute toxicity rat (oral and inhalation).
Sodium sulfate:
LC50, 4h (rat, inhalation) > 2400 mg/m3 air
LCLo,72h (rat, inhalation) > 10 mg/m3 air
LD50 (rat,oral) > 2000 mg/kg bw (Areclin) 
LD50 (rat, oral) > 10 g/kg bw (Henkel) 
Sulfuric acid:
LD50 2140 mg/kg bw
Based on the results of several acute toxicity inhalation studies for sodium sulafte it is unlikely that short-term inhalation of respirable sodium sulfate particles cause pulmonary irritation or systemic effects; 
The acute dermal toxicity (rat) is waived:   Annex XI adaptation- inorganic ionic substance low potential for absorption through the skin.  Based on the assumption described in the read-across concept, read-across from sodium sulfate and sulfuric acid to sodium hydrogensulfate is considered justified. Threfore it can be concluded that sodium hydrogensulfate has no acute-toxic propoerties.

Additional information

In view of the acidic reaction to be expected upon dissociation of sodium hydrogensulfite in aqueous media, partial read-across needs to be considered to sulfuric acid, as outlined below. However, the applicability is somewhat restricted since during the gastric passage, an acidic pH (1-2) is already established under normal physiological conditions. Concerning inhalation particle size considerations render solid, commercially available sodium hydrogensulfate as practically unavailable via the inhalation route. Finally, dermal absorption and thus dermal toxicity may be considered negligible. For all other aspects, read-across to sodium sulfate is taken into account in the absence of data specifically for sodium hydrogensulfate.

Sodium hydrogensulfate:

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 anion and the hydrogen cation, which is responsible for the acidic reaction. Based on these dissolution characteristics, it can be concluded that the toxicity of sodium hydrogensulfate is primarily induced by the acidic reaction. The sulfate anion is not expected to contribute to a relevant extent to overall toxicity

Acute oral toxicity:

Rreliable data on acute oral toxicity for sodium hydrogensulfate is not available.

Acute inhalation toxicity:

According to regulation (EC) 1907/2006 (column 2), testing is not considered necessary for sodium hydrogensulfate because any relevant exposure of humans via inhalation is not to be expected for particle size considerations, and by way of read-across in view of the absence of any inhalation toxicity of sodium sulfate.

Acute dermal toxicity:

Any relevant acute dermal toxicity is not to be expected in view of the strong ionic nature of the dissociation products of sodium hydrogensulfite and the thus resulting lack of percutaneous transfer.

Sulfuric acid:

Acute oral toxicity

The single available acute oral toxicity study (Smythet al, 1969) performed with sulfuric acid reports an LD50 value of 2140 (1540 -2990) mg/kg bw. The study is reported in summary form only but the protocol design is comparable to OECD 401. The results of this study indicate that sulfuric acid is of low acute systemic toxicity when administered by gastric intubation. However it should be noted that the route of administration used in this study eliminates the potential for local corrosive effects of the test material on the upper gastrointestinal tract (mouth, pharynx and oesophagus). Following accidental/intentional oral ingestion of sulfuric acid by humans, the local effects on the upper gastrointestinal tract are likely to dominate the clinical presentation and the potential for systemic toxicity is likely to be low. Further testing of sulfuric acid for acute oral toxicity in animals (i. e. in a guideline- and GLP-compliant study) is not proposed for acute oral toxicity and for reasons of animal welfare, due to the corrosivity of the substance.

Acute dermal toxicity

No data on acute dermal toxicity in animals are available. Although this is a potential route of exposure for workers, testing is not justified for scientific reasons and on animal welfare grounds. The effects of acute dermal exposure to sulfuric acid on animals can be readily predicted, and the data from human exposure are sufficient to characterise the effects.

Sodium sulfate:

ORAL

LD₅₀(rat, oral) > 2000 mg/kg bw (Areclin)

LD₅₀(rat, oral) > 10 g/kg bw (Henkel)

DERMAL

No data. Waived. Given the complete dissociation in solution, penetration through the intact skin is not to be expected.

INHALATION

LC₅₀, 4h (rat, inhalation) > 2.4 mg/L air (gravimetrically determined mean aerosol concentration)

LC_Lo, 72h (rat, inhalation) > 10 mg/m3 air

In an acute inhalation study performed at Harlan Labs (Pothmann D., 2010) the ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats. All animals survived the scheduled observation period.

Ruffled fur was recorded in all animals one hour after the end of exposure and on test day 2. From test day 3 onwards no clinical signs were observed. Slight effects on body weight were recorded during the observation period. There were no macroscopic findings during necropsy.

It was concluded that the LC₅₀of Sodium Sulfate obtained in this study was estimated to be greater than 2.4 mg/L air (gravimetrically determined mean aerosol concentration) which was the highest technically feasible aerosol concentration. There was no indication of relevant sex-related differences in toxicity of the test item.

In an inhalation toxicity study (according to Last and Cross, J. Lab. Clin. Med. 91: 328-339 (1978)), 6 male Sprague-Dawley rats were exposure to aerosols of sodium sulfate at levels of 10 mg/m³for 72 hours. The responses to breathing these aerosols were evaluated by measurements of glycoprotein, RNA and DNA contents of homogenates of the lungs and quantification of wet to dry weight ratios of the lung lobs. No mortality was reported. The RNA, DNA and protein levels were 99, 100 an 107, respectively (the control values were 100). The lung wet to dry ratio was 4.35 in the first experiment and 4.5 in the second experiment (control value was 4.5) (Last, 1980).

In another experiment the bronchial mucociliary clearance was measured in 5 male rabbits by brief inhalation of radiolabelled, insoluble tracer microspheres (99mTc-tagged ferric oxide). The thoracic retention was measured externally in vivo. These measurements began within 2 min. after the inhalation and were repeated after 24 hours to determine a value for residual activity. The mucociliary clearance was determined as mean residence time (MRT) of the tracer. No effect on mucociliary clearance was found (one way ANOVA, two tailed) (Schlessinger, 1984).

The intestinal effects of sulfate in drinking water (up to 1200 mg/l) on normal human subjects (10) have been investigated. The health of the subjects was determined by studying their history, physical examination, urine analysis, blood cell counts and serum chemistry. During the study stool mass, frequency and consistency in mouth to anus appearance of coloured markers were measured. No significant change in bodyweight was observed. All blood and urine test results were normal. At 1200 mg/l 8 subjects rated the taste of the water as neutral-slightly unpleasant, 1 subject as moderately unpleasant and 1 subject as very unpleasant. Significant decreases in stool consistency and appearance time were noted at 1200 mg/l, compared to the control (Heizer, 1997).

The following information is taken into account for any hazard / risk assessment:

Test results are available for sodium sulfate and sulfuric acid for acute toxicity rat (oral and inhalation).

 

Sodium sulfate:

LC₅₀, 4h (rat, inhalation) > 2400 mg/m3 air

LC_Lo, 72h (rat, inhalation) > 10 mg/m3 air

LD₅₀(rat, oral) > 2000 mg/kg bw (Areclin)

LD₅₀(rat, oral) > 10 g/kg bw (Henkel)

 

Sulfuric acid:

LD₅₀2140 mg/kg bw

Based on the results of several acute toxicity inhalation studies for sodium sulfate it is unlikely that short-term inhalation of respirable sodium sulfate particles cause pulmonary irritation or systemic effects.

The acute dermal toxicity (rat) is waived: Annex XI adaptation- inorganic ionic substance low potential for absorption through the skin. Based on the assumption described in the read-across concept, read-across from sodium sulfate and sulfuric acid to sodium hydrogensulfate is considered justified. Therefore it can be concluded that sodium hydrogensulfate has no acute-toxic properties.

Justification for classification or non-classification

Based on the test results, supporting data (rat: oral and inhalation) and on waiving (dermal), the substance sodium hydrogensulfate does not require classification for acute oral, inhalation or dermal toxicity according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) andEC Regulation No. 1272/2008 and subsequent regulations.