International Agency for Research on Cancer (IARC) - Summaries & Evaluations

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 54 (1992) (p. 131)

Sulfur dioxide
: 7446-09-5

Sodium sulfite
: 7757-83-7

Sodium bisulfite
: 7631-90-5

Sodium metabisulfite
: 7681-57-4

Potassium metabisulfite
: 16731-55-8

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Sulfur dioxide is produced commercially by burning sulfur or various sulfides or by recovering it from flue gases or non-ferrous metal smelting gases. Large quantities are used as intermediates in the manufacture of sulfuric acid and sulfite pulp. It is also used in agriculture and in the food and beverage industries as, among other things, a biocide and a preservative. Sulfite pulp workers have been exposed to fluctuating levels of sulfur dioxide, often exceeding 10 ppm (26 mg/m3), but levels have decreased with modernization of facilities and processes. In metal industries, the roasting of ores and the combustion of various sulfur-containing fuels have resulted in mean exposures to sulfur dioxide in the range of 1-10 ppm (2.6-26 mg/m3) in copper smelters, but at about 1 ppm (2.6 mg/m3) or less in other facilities. Mean levels exceeding 1 ppm (2.6 mg/m3) have also been reported in the manufacture of sulfuric acid and of superphosphate fertilizers, as well as at certain fire sites during fire fighting. Levels of sulfur dioxide in ambient air do not usually exceed 0.05 ppm (0.1 mg/m3), except in some urban areas.

Sodium sulfite is used mainly in the pulp industry. Both sodium and potassium metabisulfure are used in food processing, chemical industries, water treatment, photoprocessing and the textile industry. Levels of occupational exposure have not been reported.

5.2 Human carcinogenicity data

In four US and one Swedish cohort studies of copper smelters, increased lung cancer risks were observed in relation to exposure to arsenic, but no independent effect of sulfur dioxide was seen.

One proportionate mortality study from the USA and Canada, as well as two US and one Finnish cohort studies, analysed cancer risks among sulfite pulp mill workers. Three of them suggested an increase in risk for stomach cancer; however, potential confounding factors were not adequately controlled. Lung cancer risks were not elevated in any of these studies.

In case-control studies performed at a chemical facility in Texas with a complex exposure environment, increased risks for lung cancer and brain tumours were indicated in workers with high exposure to sulfur dioxide; however, the findings using two different control groups were not consistent.

A population-based case-control study from Canada suggested an increased risk for stomach cancer in men exposed to sulfur dioxide, but no excess was indicated for lung cancer.

No epidemiological studiy was available on cancer risks associated with exposure to sulfites, bisulfites or metabisulfites.

5.3 Carcinogenicity in experimental animals

Sulfur dioxide was tested for carcinogenicity in one study in mice by inhalation exposure. A significant increase in the incidence of lung tumours was observed in females.

Sulfur dioxide was tested for enhancement of carcinogenicity when administered with benzo[a]pyrene in two studies in rats and in one study in hamsters. One incompletely reported study found an increase in the incidence of lung tumours in rats exposed to sulfur dioxide in conjunction with benzo[a]pyrene. The other study in rats suffered from limitations owing to the high incidence of lung tumours in controls given benzo[a]pyrene. The study in hamsters was inadequately reported.

Potassium metabisulfite was tested for carcinogenicity in one study in mice by oral administration in the drinking-water and sodium metabisulfite in one study in rats by oral administration in the diet. No increase in tumour incidence was observed in mice, and there was no indication of a dose-related increase in tumour incidence in rats, but both studies had some inadequacies in reporting of data.

Potassium metabisulfite was tested for enhancement of carcinogenicity in one study in rats. It significantly increased the incidence of gastric adenocarcinoma after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.

No data were available on the carcinogenicity in experimental animals of sulfites or bisulfites.

5.4 Other relevant data

At high concentrations, sulfur dioxide irritates the upper airways and can induce acute and chronic bronchitis. At lower levels (less than 0.25 ppm [0.65 mg/m**3]), no effect of sulfur dioxide is seen on the airways of sensitive individuals in the general population who take exercise, presumably since this relatively hygroscopic gas is removed by the nose and mouth.

Conflicting results for the induction of chromosomal aberrations in lymphocytes were obtained in two studies of workers exposed to sulfur dioxide, among other agents. In a single study, no increase was reported in the frequency of sister chromatid exchange in lymphocytes of exposed workers.

Sulfur dioxide and its aqueous forms did not induce sister chromatid exchange, chromosomal aberrations or micronucleus formation in bone marrow of mice or Chinese hamsters. In a single study, sister chromatid exchange and chromosomal aberrations were induced in human lymphocytes. In cultured mammalian cells, bisulfite induced transformation and sister chromatid exchange but not gene mutation, chromosomal aberrations or DNA repair synthesis. In plants, chromosomal aberrations, micronuclei and gene mutation were induced. Sulfur dioxide and bisulfite induced gene mutation but not gene conversion in yeast. Mutations were induced in bacteria and phage.

Bisulfite solutions at high concentrations caused deamination of cytosine in DNA in vitro.

5.5 Evaluation

There is inadequate evidence for the carcinogenicity in humans of sulfur dioxide, sulfites, bisulfites and metabisulfites.

There is limited evidence for the carcinogenicity in experimental animals of sulfur dioxide.

There is inadequate evidence for the carcinogenicity in experimental animals of sulfites, bisulfites and metabisulfites.

Overall evaluation

Sulfur dioxide, sulfites, bisulfites and metabisulfites are not classifiable as to their carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.

Synonyms for Sulfur dioxide

Synonyms for Sodium sulfite

Synonyms for Sodium bisulfite

Synonyms for Sodium metabisulfite

Synonyms for Potassium metabisulfite

Last updated: 21 November 1997

    See Also:
       Toxicological Abbreviations