Occupational asthma in salbutamol process workers

Occupational asthma after exposure to salbutamol in the pharmaceutical industry has not been previously reported. The occurrence of occupational asthma is described in two pharmaceutical process workers who were likely to have inhaled doses appreciably in excess of the therapeutic dose range. The findings do not lead to an unequivocal conclusion on the mechanism of the asthma but it was probably a pharmacological consequence ofhigh exposure. ing samplers showed values ranging from 0 05 mg m-3 in the background of the finishing suite to an indeterminate value that exceeded 0-2 mg m-3 inside the milling cubicle. Two further airborne background environmental samples in 1982 taken in the finishing suite at a time of day when no work was in progress showed values of 0-015 mgMi3 of airborne "active" salbutamol dust. In 1981, 18 swab test samples were taken over areas of about 40 cm2 in the finishing suite and showed values ranging from nil to in excess of 6 (median 0. 1) mg salbutamol. (Occup Environ Med 1994;51:397-399) Occupational asthma has been described after the inhalation of a number of drugs or their precursors including glycyl compound, an intermediate in the production of salbutamol,' but not to salbutamol itself. We report two pharmaceutical production workers with occupational asthma caused by inhaled salbutamol and describe the circumstances of their exposure. Salbutamol has been used extensively worldwide in the treatment of bronchial asthma because of its effective bronchodilator properties. Salbutamol base is used in metered dose aerosols whereas salbutamol sulphate is used in other preparations.' Department of Public Health Sciences, The University of Edinburgh Medical School, Edinburgh, EH8 9AG, UK R M Agius Department of Cardiothoracic Medicine, Southend Hospital, Southend, Essex, SSO ORY, UK A G Davison Department of Occupational and Environmental Medicine, The Royal Brompton National Heart and Lung Hospital, London SW3 6NP, UK E R Hawkins A J Newman Taylor Correspondence to: Dr R M Agius Accepted for publication 23 February 1994 Description ofprocess and exposure The process commenced with pure salbutamol base delivered to the site as a raw material and therefore did not include the primary synthesis previously described.' Part of the salbutamol base was repackaged for distribution by scooping from large drums into smaller bags in a corner of an area measuring about 150 m2 where other agents were also handled. The rest of the salbutamol base was sent to a separate finishing suite on the same site for conversion to the sulphate. Here, salbutamol base in batches of 35 kg was tipped into a reaction vessel and dissolved in dilute sulphuric acid. Crystalline salbutamol sulphate was precipitated by the addition of industrial methylated spirit. The salbutamol sulphate was filtered, the material hand scooped on to trays, and oven dried and tipped into a mechanical hopper for milling down to a size of 2 to 5 ,um. The standard personal protection worn while handling the material was an airhood extending down to the waist and supplied by breathing air. Limited exposure data were available. In 1979, one personal sampler on an operator in the finishing suite was reported as showing an airborne concentration of 0-5 mg M-3, whereas three other environmental monitorCase descriptions