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Sulphuric acid was not found to be mutagenic in an Ames test (Ames test (03); Cipollaro et al, 1986). There are a limited number of reports of the genotoxic (mutagenic and clastogenic) activity of sulphuric acid in mammalian cells in vitro (largely in non-standard studies), which report positive results attributable to pH changes (i.e. false positive response due to extreme culture conditions). Studies with various chemicals in vitro have clearly demonstrated an association between low culture medium pH and positive responses. Changes in pH are among the criteria to be considered when determining the highest concentration of the test material according to OECD Guideline 476 (1997) for the in vitro mammalian cell gene mutation test and according to OECD Guideline 473 (1997) for the in vitro mammalian chromosome aberration test. There are also a number of literature reviews which clearly demonstrate an association between low pH and false positive responses in these assays, and this property of acidic test materials is widely accepted as a limitation of testing in vitro.

Two guideline-equivalent and GLP-compliant Ames tests have been performed with the chemicals sodium sulphate and sodium hydrogen sulphate. These studies (Herbold, 1988) gave clearly negative responses, emphasising the absence of genotoxic activity of the sulphate and hydrogen sulphate anions.

Sulphuric acid will immediately dissociate under aqueous conditions in vivo, reacting with water to form the hydrogen sulphate anion and a (hydrated) hydrogen ion, and subsequently the sulphate anion and an additional hydrated hydrogen ion. The hydrogen ion is responsible for the toxicity of sulphuric acid (local corrosivity and irritation at the site of contact).

Genotoxicity of the sulphate ion

Studies in laboratory animals using inhalation exposure to 35S-radiolabelled sulphuric acid have demonstrated that sulphate is rapidly absorbed from the lungs into the systemic circulation. Sulphuric acid per se will therefore not be absorbed into the body; there will be no systemic exposure to sulphuric acid and the toxicity of sulphuric acid is limited to the local effects of low pH. Absorbed sulphate enters the body's anion pool and the level is regulated by homeostatic mechanisms. The normal physiological plasma concentration of sulphate is 0.3 -0.36 mmol/l, and is much higher intracellularly. It is therefore concluded that the sulphate anion will not have any genotoxic effect.

Genotoxicity of the hydrogen ion

Physiological pH is tightly regulated by homeostatic mechanisms including extracellular and intracellular buffering and the renal excretion of hydrogen ions. The extent of the absorption of hydrogen ions following occupational (dermal and/or inhalation) exposure is likely to be sufficiently low such that the homeostatic mechanisms will act to maintain physiological pH within the normal range and there will, therefore, be no additional exposure to the hydrogen ion.

Further testing for the genotoxicity of sulphuric acid in vitro is not required as the results can be predicted to be false positives due to the low pH of the substance. (see review by Scott et al) Testing for the genotoxicity of sulphuric acid in vivo is not proposed; testing is not justified on scientific grounds due to the absence of systemic exposure and the lack of genotoxicity of the hydrogen and sulphate ions. Testing in vivo also cannot be justified for reasons of animal welfare, due to the corrosive nature of the substance. It is noted that similar conclusions regarding the inherent lack of genotoxicity and the lack of a requirement for further testing are expressed in the OECD SIDS (2001).

Justification for selection of genetic toxicity endpoint
The endpoint has been addressed using a weight of evidence approach.

Short description of key information:
Only limited information is available on sulphuric acid: studies are limited to a negative Ames test and a positive clastogenicity assay in CHO cells. Negative Ames tests are also available for sodium sulphate and sodium hydrogensulphate.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is proposed for genotoxicity. An absence of mutagenicity has been demonstrated in Ames tests; positive results in studies with mammalian cells are attributable to the artefactual effects of low pH. No in vivo studies are available, however the absence of systemic exposure to the substance and the lack of genotoxicity of the hydrogen and sulphate ions means that no genotoxicity is predicted and testing is not required.