The role of combination effects on the etiology of malignant nasal tumours in the wood-working industry.

Adenocarcinomas of the nose are regarded as an occupational disease in Germany and other European countries, and workers exposed to oak or beech wood-dust in the course of their work receive compensation if they incur adenocarcinoma of the nose. This has prompted a joint research project to record the functional and morphological changes of the nasal mucosa and/or paranasal sinus of 149 exposed subjects and 33 controls in accordance with a defined occupational exposure. To ensure the quantitative and qualitative reliability of the exposure data, 1,349 measurements at the company workplace were taken and analyses of 614 wood samples performed; parallel to this, the genotoxic effects of the most important substances used in the wood-working industry were tested. Apart from this, latency periods and morbidity rates in Germany were investigated. Partial findings of this research projects have been evaluated by the International Agency for Research on Cancer (IARC). According to these evaluations and the findings presented here, the following points can be made: i) Morphological changes in the nasal mucosa after exposure to wood-dust resulted in an increase in cylindrocellular hyperplasias and, in functional terms, a tendency towards improved nasal clearance was observed. Chromium and formaldehyde, on the other hand, tended to give rise to an increase in the number of squamous metaplasias. This might explain the preference for the histological types of adenocarcinoma among subjects exposed to wood-dust. ii) In tissue samples more dysplasias were found among those exposed to oak and beech wood-dust. Subjects exposed to wood preserving agents had dysplasias only if they were simultaneously exposed to oak and beech wood-dust. The latter effect did not quite reach the level of significance (p = 0.07) on account of the low numbers of cases. iii) The investigation of genotoxic effects showed that oak and beech contain genotoxic substances that can be dissolved by means of ethanol and cyclohexane; they also showed that 3 out of 8 wood preservatives, 5 out of 16 stains, and 2 out of 11 paints from the wood-working industry are genotoxic too. Apart from this, lindane and PCP have proved to be genotoxic in the nasal cells of rats and human beings. Analysis of 614 wood samples from wood-preserving agents showed that almost 73% contained agents of this type, even in woods described by the companies as being guaranteed free of wood preservatives. iv) According to an analysis of 147 cases accepted since 1985 as a pensionable occupational illness by the Holz-Berufsgenossenschaft (an industrial compensation society for employees in the wood-working industry), the disease was much more apparent in small companies where there is multi-factorial exposure, than in large companies where the exposure factor tends to have a single component. This points to the combined effects of hardwood dusts and chemicals as being the cause. v) According to published findings, the incidence of the disease in England seems to be on the decline. In Germany, increasing latency periods also point to a decline in the number of cases, although both countries have only very recently introduced effective prevention measures against exposure to wood-dust. This also leads to the assumption that wood-dusts cannot be the only cause of this type of cancer. vi) These findings tally with the evaluation by the IARC confirming the special part that hardwood dusts play in the development of nasal cancer. The findings presented here also indicate combined effects as being the cause of this type of cancer. This hypothesis cannot be confirmed until the conclusion of long-term animal experiments, currently being conducted, to test how the effects of chemicals such as lindane, PCP, and chromate compare with use of oak wood-dust.