Sodium hydrogensulphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Sodium hydrogensulfate readily dissociates pH-dependently in aqueous media to yield an equilibrium between hydrogensulfate and sulfate anions, which is why read-across from data on sodium sulfate is considered justified without any restrictions.

Effects on fertility

The study R. Ceccatelli 2010, is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item Sodium Sulfate to rats. Sodium Sulfate was administered in highly purified water as vehicle at dosages of 100, 300, and 1000 mg/kg body weight/day, and controls received the vehicle only. Sodium Sulfate was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. In absence of any effect the general NOEL (No Observed Effect Level) was established at 1000 mg/kg/day. As no effects were observed, the NOEL (No Observed Effect Level) for reproduction/ developmental toxicity was considered to be 1000 mg/kg/day.

Short description of key information:
No data for sodium hydrogensulfate on effects on fertility are available, thus read-across to sodium sulfate was performed. Based on a OECD 421 study in which no critical effects were observed, the NOEL (No Observed Effect Level) for reproduction toxicity was considered to be 1000 mg/kg/day.

Effects on developmental toxicity

Description of key information

No data for sodium hydrogensulfate on effects on developmental toxicity are available, thus read-across to sodium sulfate was performed. Based on the absence of effects on maternal toxicity, teratogenicity or embryotoxicity in studies conduced according to or similar to OECD 414 up to the highest dose tested, the NOEL (No Observed Effect Level) for developmental toxicity was considered to be 1000 mg/kg/day.

Additional information

Sodium hydrogensulfate:

Sodium hydrogensulfate readily dissociates in water with an acidic reaction, resulting in hydrogensulfate anions and sodium cations. The hydrogensulphate anion (pKa=1,99¹) partly dissociates further to sulphate 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. This is reflected in the fact that the SIAR on Sodium sulfate 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 we referenced the effects data on sulfuric acid

(ii) the systemic effect of the sulphate anion after dissolution in water, to which we referenced the effects data on sodium sulfate

No data for sodium hydrogensulfate on development toxicity/teratogenicity are available, thus read-across to sodium sulfate has been performed.

Sodium sulfate:

The study R. Ceccatelli 2010 is

a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item Sodium Sulphate to rats. Sodium Sulphate was administered in highly purified water as vehicle at dosages of 100, 300, and 1000 mg/kg body weight/day, and controls received the vehicle only. Sodium Sulphate was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. In absence of any effect the general NOEL (No Observed Effect Level) was established at 1000 mg/kg/day. As no effects were observed, the NOEL (No Observed Effect Level) for reproduction/ developmental toxicity was considered to be 1000 mg/kg/day.

Seidenberget al.,1986 examined the developmental effects of sodium sulfate in the mouse as part of a validation effort of a developmental screening test. The test substance was administered (2800 mg/kg/day) by gavage on gestation days 8 through 12. No mortality, an unchanged average weight gain, and normal number of litters and neonates/litter were found. A 100 % perinatal survival was found, with an increased postnatal weight at day 1, normal weight at day 3 in the absence of externally visible abnormalities. In second paper of Seidenberget al, 1987 the results are summarised of this validation test, the outcome of the screening test was consideredpositive for sodium sulfate, based solely on the increased postnatal weight on day 1 post-partum. However, the significance of such an effect, in the absence of any other effect, is unclear and the reasons for taking this as a positive result are not given.

A developmental / teratogenicity study from P&G (1976)

was designed to evaluate the embryotoxic and teratogenic potential of sodium sulphate and a mixture with sodium sulphate. The two test substances when administered to albino rats by oral intubation from Day 6 through Day 12 (13 day sacrifice) or through Day 15 (19 day sacrifice) of gestation at levels of 160 mg/kg bw per day of of the test substance of concern (test substance 1, sodium sulphate) and at levels of 50, 100, and 200 mg/kg bw per day of the other tested substance (test substance 2, mixture).

Criteria evaluated for compound effect included maternal body weights, weight gain, food consumption, appearance and behavior, survival rates, pregnancy rates, and reproduction data; and embryo and fetal viability and development.

No effects attributable to the administration of either test substance were noted in comparisons of maternal body weight and food consumption values, appearance and behavior, survival rates, pregnacy rates, or implantation efficiencies. In addition, no compound-related differences were noted in evaluations of embryo or fetal viability, or fetal size, sex, and development. Therefore, test substance 1 (Sodium sulphate), when administered to rats at a level of 160 mg/kg, and test substance 2 (mixture with sodium sulphate), when administered to rats at a levels up to 200 mg/kg, were considered to be non-teratogenic and non-embryotoxic.

In the study of Arcuri and Gautieri 1973 reported teratogenic effects of morhine sulfate, atropine sulfate and physostigmine sulfate, sodium sulfate served as anion control, with sodium chloride as negative control. The study was well documented, with various endpoints (clinical observations, maternal weight ratio, uterine lef/righ horn fetal ratio and resorption ration, fetal weight, sex ratio, skeletal abnormalities, ,soft tissue abnormalities, more specifically exencephaly, cryptorchid test and axial skeletal fusions, but covered only the 8-9 day period of gestation for exposure and the dose of 60 mg/kg was relatively small. There was a statistically significant increase in skeletal abnormalities, described as delayed ossification in the phalanges, sternebrae and skull. Such variations are quite common in tests with rodents and, in the absence of skeletal malformations, generally not regarded as indicative of developmental toxicity. No abnormalities for any of the other end-points were reported.

Justification for classification or non-classification

Based on read-across from sodium sulfate and the absence of effects in a reproduction/developmental screening test and two developmental toxicity/teratogenicity studies in rats and mice with that substance, sodium hydrogensulfate likewise does not require classification for toxicity to reproduction according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.