Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No studies are available.
Additional information

No relevant studies investigating the reproductive effects of sulphur trioxide or sulphuric acid exposure in animals are available. The testing of sulphur trioxide for effects on fertility in a conventional two-generation study in the rat is not proposed.

The likely corrosive nature of the substance means that testing cannot be justified for reasons of animal welfare. The usual route of exposure in the two-generation reproductive toxicity study is not relevant to human exposure as effects will be dominated by local irritation of the gastrointestinal tract. Similarly, testing of sulphur trioxide using dermal exposure cannot be justified.

In terms of worker exposure, the inhalation route is most relevant. However numerous inhalation toxicity studies performed with sulphuric acid in a number of different species and of various durations have not demonstrated any systemic effects of exposure at levels up to those causing mortality. The effects of inhalation of sulphuric acid are limited to the respiratory tract (structure and function); effects on other organs and tissues have not been identified. Specifically, no gross effects on the reproductive organs were observed in two species (rat and guinea pig) following chronic exposure. Following a comprehensive literature review, the OECD SIDS for sulphuric acid (2001) concluded that sulphuric acid '...is not expected to be absorbed or distributed throughout the body. Therefore it is not likely that it will reach male and female reproductive organs following exposures by any route'. The ATSDR (1998) comes to a similar conclusion, stating that 'Because sulfuric acid is a direct-acting toxicant and not likely to reach reproductive organs or the fetus, reproductive and developmental effects are unlikely to occur in humans exposed to sulfuric acid'.

Sulphur trioxide will rapidly react with atmospheric moisture or moisture present at the initial site of contact (skin, respiratory tract) to produce sulphuric acid. The toxicity of sulphur trioxide is therefore essentially the toxicity of sulphuric acid. As previously discussed, sulphuric acid will immediately dissociate on contact with the body to form sulphate and hydrogen (carbonium) ions. The hydrogen ion is likely to be entirely responsible for the site of contact effects of sulphuric acid. Any hydrogen ion absorbed into the systemic circulation will be subject to the normal homeostatic mechanisms governing physiological pH, and will be excreted in the urine when in excess. Sulphate ions are also a normal product of metabolism and are present in significant amounts in the body. Studies have demonstrated the absorption of sulphate following inhalation exposure to sulphuric acid, however levels of sulphate are under homeostatic control and any 'excess' sulphate will be excreted in the urine.

It is therefore considered that the testing of sulphur trioxide (or sulphuric acid) for effects on fertility cannot be justified, both on scientific grounds (due to the lack of systemic exposure) and for reasons of animal welfare (due to the corrosive nature of these substances). A waiver is therefore proposed for this endpoint.


Short description of key information:
No studies of the effects of sulphur trioxide or sulphuric acid exposure on fertility have been identified.

Effects on developmental toxicity

Description of key information
No studies of developmental toxicity have been performed with sulphur trioxide.  A study of developmental toxicity in the rabbit and mouse (using inhalation exposure) has been performed with sulphuric acid, to a protocol broadly comparable to OECD 414.  No evidence of teratogenicity was seen in either species, at exposure levels sufficient to cause mild maternal toxicity.
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
19.3 mg/m³
Additional information

No studies of the developmental toxicity of sulphur trioxide have been performed. Sulphur trioxide will rapidly react with atmospheric moisture or moisture present at the initial site of contact (skin, respiratory tract) to produce sulphuric acid. The toxicity of sulphur trioxide is therefore essentially the toxicity of sulphuric acid.

No evidence of teratogenicity or developmental toxicity was seen in the mouse and rabbit in an inhalation study comparable to OECD 414, and at exposure levels (19.3 mg/m3) sufficient to cause mild maternal toxicity. Given the results of this study and the dataset as a whole, which indicates the absence of systemic exposure, further testing (e.g. in the rat) is not proposed. Testing cannot be justified on scientific grounds (given the absence of systemic exposure, detailed above) or (due to the corrosive nature of the substance) for reasons of animal welfare. Both the OECD SIDS (2001) and the US ATSDR (1998) concluded that the exiting information do not show any evidence of developmental toxicity and that further testing is not required based on a lack of systemic exposure.

Toxicity to reproduction: other studies

Additional information

No studies have ben performed and none are proposed in the absence of any effects in the existing dataset and given the absence of systemic exposure. Further studies cannot be justified on scientific grounds and (given the corrosive nature of the substance) also cannot be justified for reasons of animal welfare.

Justification for classification or non-classification

No classification is proposed for reproductive or developmental toxicity. The existing data and the absence of systemic exposure do not indicate that classification is required.

Additional information

Categories Display