Sulphur dioxide; health-based recommended occupational exposure limit

Scope

At the request of the Minister of Social Affairs and Employment, the Health Council of the Netherlands sets Health-Based Recommended Occupational Exposure Limits (HBR-OEL) for chemical substances in air in the workplace. These recommendations are made by the Council’s Dutch Expert Committee on Occupational Standards (DECOS). They constitute the first step in a three-step procedure, which leads to legally binding occupational exposure limits.
In this report, the committee discusses the consequences of occupational exposure to sulphur dioxide and recommends a health-based occupational exposure limit. The committee’s conclusions are made on the documents produced by the Scientific Committee on Occupational Exposure Limits of the European Commission (SCOEL; SCO93, SCO98) and on additional scientific papers published prior to May 2002.

Physical and chemical properties

Sulphur dioxide (SO2; CAS no. 7446-09-5) is a colourless gas, with an irritating odour. Its odour threshold ranges between 0.8 and 8 mg/m³. The molar mass of sulphur dioxide is 64.06 g/mol, its melting point -72.7 °C and its boiling point -10.0 °C. Sulphur dioxide is highly hydrophilic and dissolves easily in water.
Sulphur dioxide is used in the inorganic and petrochemical industries, such as in the production of cellulose pulp and chemicals. The substance has a lot of functions: as an antioxidant in the bromine production; as a bleaching gas in casting magnesium parts and bleaching kaolin; as a rapid catalyst in furfural resins for manufacturing casting moulds; as a fruit and vegetable preservative in the food; and, as a disinfectant in the wine and brewery industry.

Monitoring

Various sampling and analysis techniques are available for determining ambient concentrations of sulphur dioxide in an occupational setting. Both passive and active samplers may be used. Samples obtained from passive sampling are analysed by spectrophotometry or ion exchange chromatography. The National Institute for Occupational Safety and Health (NIOSH) recommends the latter (Method 6004; detection range: 0.5-20.0 mg/m³ per 100 L air sample).
Concerning personal exposure, direct reading pocket dosimeters may be used, as is described in a protocol, called ‘Voornorm NVN 2950’, from the Dutch Normalisation Institute.

Limit values

In 1985, the DECOS recommended an HBR-OEL for sulphur dioxide of 1.3 mg/m³, as an 8-hour time weighted average (8-hour TWA). However, due to socio-economic constraints, the Netherlands has set a legal occupational exposure limit (OEL) of 5 mg/m³ (8-hour TWA). In addition, the SCOEL has set a limit of 1.3 mg/m³ (8-hour TWA) and of 2.7 mg/m³ (15-minute TWA). Both in Germany and Denmark, OELs have been set at 1.3 mg/m³, averaged over an 8-hour period of time; and, in the United Kingdom and Sweden of around 5 mg/m³ (8-hour TWA) and 13 mg/m³ (15-minute TWA, for Sweden a Ceiling). Finally, the American Conference of Governmental Industrial Hygienists has proposed a TLV of 5 mg/m³ and a STEL of 13 mg/m³.

Kinetics

Inhaled sulphur dioxide is mainly absorbed in the body through the epithelium of the upper respiratory tract (nose and throat). However, the substance may reach the lower respiratory tract (bronchi and alveoli in lungs) when it is deeply inhaled, as happens with doing heavy work or physical exercise.
Sulphur dioxide is a highly hydrophilic gas. Therefore, it reacts easily with water, which is present at the surface of the respiratory tract. When sulphur dioxide reacts with water sulphurous acid is formed. This sulphurous acid dissociates easily into sulphite and bisulphite ions. Sulphite ions are then rapidly converted into sulphate, whereas bisulphite ions bind to proteins to form S-sulphonates. In the blood most of the sulphur dioxide is present as S-sulphonate and only a minor part as free sulphite/sulphate or bisulphite ions. Sulphates are quickly absorbed in the large endogenous sulphate pool of the body and then slowly released via the blood into the urine. Circulating S-sulphonates slowly decompose into sulphates or sulphur dioxides. The latter substance is exhaled.

Effects

In humans, sulphur dioxide is irritating to the eyes and the upper respiratory tract. Inhaling high concentrations may cause: rhinorrhae; coughing; shortness of breath; chest tightness; and, a choking sensation.
Epidemiological studies have associated chronic sulphur dioxide exposure with chronic coughing; bronchitis; increased susceptibility to airway infections; and, increased susceptibility to allergy by airborne allergens. However, because these studies included several confounding factors, they are considered insufficient for quantitative risk assessment.
A number of laboratory studies have been carried out with healthy, non-smoking volunteers, who were exclusively exposed to sulphur dioxide. These volunteers were exposed to concentrations of as low as 0.53 mg/m³ to more than 60 mg/m³ . The exposures lasted from minutes up to several hours and were carried out with or without physical exercise. The main adverse effects observed were irritation of the upper respiratory tract and the eyes, and decreased lung function, such as increased pulmonary airway resistance. These adverse effects were clearly present at exposure levels of 2.7 mg/m³ or higher. None of these effects were observed at exposure levels below 2.0 mg/m³ , with the exception of three studies (two of the same research group): these three studies were, however, not considered for risk assessment, because of limitations in study design or the lack of toxicological relevance of the findings. In addition, at 2.0 mg/m³ , two independent studies were performed with volunteers, who were exposed for 40 minutes and 4 hours, respectively, with moderate physical exercise. In all these volunteers lung function remained normal. Based on these outcomes, the committee considers 2.0 mg/m³ as the No Observed Adverse Effect Level (NOAEL) after short-term exposure.
Epidemiological data obtained from the general population indicate that people with asthma or with other diseases concerning the respiratory tract, are more vulnerable to sulphur dioxide exposure than healthy people. Concerning asthma, this finding is supported by laboratory data. However, numerous studies with asthmatics show that the level of susceptibility is strongly influenced by non-specific factors, such as physical activity and atmospheric conditions (dry, cold air). These factors alone may aggravate asthma. Therefore, the committee cannot conclude whether or not asthmatics are more vulnerable to sulphur dioxide exposure in the absence of these non-specific stimuli. However, it is concerned that asthmatics are at higher risk when exposed to sulphur dioxide in combination with these non-specific asthma-aggravating factors.
Data from experiments in animals with acute or short-term exposure support the findings in humans, that sulphur dioxide irritates the (upper) respiratory tract and eyes and reduces respiratory defence mechanisms against bacterial infections. In addition, changes in enzyme activities in liver and blood were observed. However, the committee noted that the quality of the reporting of most of these studies was insufficient. Apart from that, most animals were exposed to very high levels (up to 267 mg/m³ (subchronic) or >1,000 mg/m³ (acute)).
The exposure levels in long-term animal studies were lower than in short-term animal studies (0.35 up to 133 mg/m³ ). However, no concentration-response relationships could be established, because data were too limited to be useful for quantitative risk assessment.
Few animal studies have been directed towards the carcinogenicity of sulphur dioxide. Although tumour formation was observed, the studies showed considerable limitations, including: the use of animals with very high spontaneous tumour incidence; exposure to high levels of the substance; and, incomplete reporting on the tumour promoting activity of sulphur dioxide in combination with benzo[a]pyrene.
In regard to genotoxicity, mutagenicity tests in bacteria scored positive in conditions not relevant for humans. Also, sulphur dioxide induced chromosomal aberrations in vitro, and micronuclei in vitro and in vivo.
In a limited number of experiments, the adverse effects of sulphur dioxide have been studied on reproduction. Litter of rabbits and mice were exposed to 187 and 67 mg/m³ , respectively. This resulted in minor skeletal variations and mild maternal toxicity. In another study, offspring of exposed mice (13.4 to 80 mg/m³ ) showed no defects in reproductive performance, and in somatic and neurobehavioral development.

Evaluation

From the current data, the committee concludes that the acute effects of sulphur dioxide on the respiratory tract, such as nose and throat irritation, depressed lung function and increased airway resistance, should be prevented. In order to do this, the committee recommends deriving a health-based occupational exposure limit for short-term exposure (Short-Term Exposure Limit (STEL); 15-min TWA).
From the human database a NOAEL of 2.0 mg/m³ was derived (see previous paragraph). In addition, to the committee’s opinion the NOAEL needs to be adjusted for inter-individual differences. This is needed, because the number of studies at the NOAEL and the number of participants in those studies were limited. Also, the committee is aware of the reporting of variable responses among healthy people at levels near the NOAEL. To compensate for these uncertainties, a factor of 3 was chosen. Consequently, the committee recommends a STEL for sulphur dioxide of 0.7 mg/m³ (approximatly 0.25 ppm).
Both epidemiological and animal data suggest that chronic exposure to sulphur dioxide may lead to chronic irritation (bronchitis) and increased susceptibility to airway infections. However, these data were not reliable or insufficient to assess concentration-response relationships. For this reason, the committee does not recommend an HBR-OEL (8-h TWA).
Concerning workers with a possible extra risk, the committee likes to express its concern that asthmatics are at a higher risk when not only exposed to sulphur dioxide, but also to other (non-specific) factors which incite asthma.
Carcinogenicity and genotoxicity data are too limited to make a definite conclusion about the carcinogenic potential of sulphur dioxide in humans. Therefore, the committee recommends not classifying sulphur dioxide as a suspected carcinogen. In addition, the database is too restricted to allow any conclusion to be drawn on the adverse effects on fertility and development.

Health-based recommended occupational exposure limit

The Dutch Expert Committee on Occupational Standards recommends a health-based occupational exposure limit for sulphur dioxide of 0.7 mg/m³ (approximatly 0.25 ppm), as a 15-minute time weighted average concentration (STEL).

Committee