Critique of available studies on the toxicology of kretek smoke and its constituents by routes of entry involving the respiratory tract

Abstract

Kreteks are tobacco cigarettes containing clove, imported into North America from Indonesia. Health effects, including severe pulmonary toxicity, are suspected to be associated with kretek use among adolescents and young adults. The most likely candidate for a specific toxic effect among the chemical constituents of kreteks is eugenol. Eugenol is a natural compound found in high concentrations in clove buds and is the active ingredient that distinguishes kreteks from conventional cigarettes. It is a potent and valuable topical anesthetic, as well as a pungent spice constituent. Until kretek use became a fad in North America in the early 1980s, the toxicity of eugenol by routes of exposure involving the respiratory tract had not been considered because human exposure had been predominantly oral and topical. Concern over the possible pulmonary toxicity of kretek smoke has stimulated studies on the smoke, eugenol itself, and other chemical constituents of kreteks. Two sets of studies are now available for review, one series conducted by La Voie et al. of the American Health Foundation and another conducted by Clark et al. of the Huntingdon Research Centre in the United Kingdom. Their methods and findings are very different. Common problems include low statistical power, methods of exposure that do not duplicate human exposure, and failure of the models to replicate the circumstances of the extant clinical reports, which suggest that aspiration, idiosyncratic or allergic reactions, or impaired host defense mechanisms may be involved. The available toxicologic studies must be considered preliminary. Contrary to the implied claims of an industry association, the inconsistency in findings and the generally negative results of most inhalation studies does not refute clinical evidence for human toxicity. Animal studies are an important resource in the evaluation of this and other products but are part of a much larger picture.