Registration Dossier

Administrative data

Description of key information

Data on the effects in animals following inhalation exposure towards sulfur dioxide were merely included for completeness reasons. Since adequate human data are available the animal data will not be taken forward for human health risk assessment.
Data from experiments in various animal species with acute or short-term exposure support the finding in humans, in that sulfur dioxide causes irritation to the upper respiratory tract and eyes. Furthermore, reduced respiratory defence mechanisms against bacterial infections, changes in lipid metabolism, and changes in liver and blood enzyme activities are also reported. However, animals were exposed to very high sulfur dioxide concentrations (up to 267 mg/m³ in sub-chronic studies or >1000 mg/m³ in acute studies).
The exposure levels in long-term animal studies on guinea pigs, monkeys, and dogs were lower (0.35 up to 133 mg/m³) than in short-term animal studies. However, no concentration-response relationships could be established because data were too limited to be useful for quantitative risk assessment.

Key value for chemical safety assessment

Additional information

From the most comprehensive studies with cynomolgous monkeys and dogs a LOAEC of 5 ppm results from the investigation of biological parameters and from histological examinations of several organs. Oxidative damage has been observed in the blood and many organs with a LOAEC of 10 ppm. In addition there are numerous studies available, which investigate the effects of sulfur dioxide on the respiratory tract. In animals repeated inhalation of sulfur dioxide induced changes of respiratory tract tissues within the first days of exposure. With increasing concentration and duration of exposure effects increased in incidence and severity and penetrated to deeper and more peripheral regions of the respiratory tract. In the high concentration range lesions resemble those seen in human chronic bronchitis including cough and mucous hypersecretion. In the lung histological changes included thickening of epithelium, changes in the secretory apparatus and the appearance of an inflammatory response. Furthermore airway obstruction was observed. In summary many endpoints were affected at 10 ppm in studies where this concentration was the lowest concentration tested. A few studies demonstrated specific changes at 5 or 8 ppm. Based on all these studies the overall LOAEC is 5 ppm. Entry adopted from the OECD SIAR on sulfur dioxide without modification.

Justification for classification or non-classification

According to regulation (EC) 1272/2008, a classification for specific target organ toxicity – repeated exposure shall be taken into account only when reliable evidence associating repeated exposure to the substance with a consistent and identifiable toxic effect demonstrates support for the classification. These adverse health effects include consistent and identifiable toxic effects in humans, or, in experimental animals, toxicologically significant changes which have affected the function or morphology of a tissue/organ, or have produced serious changes to the biochemistry or haematology of the organism and these changes are relevant for human health.

Nose and throat irritation, depressed lung function and increased airway resistance were identified as critical local effects of sulfur dioxide on the respiratory tract.

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – repeated exposure, inhalation are not met since the toxic effects observed following inhalation and skin/eye exposure already leads to an acute oral toxicity and skin corrosion classification. No additional effects in animals or humans are known that would justify a specific target organ toxicant (STOT) – repeated exposure: inhalation classification.