Hardwood and softwood dust. Evaluation of the carcinogenicity and genotoxicity

Hardwood dust is a human carcinogen; upon inhalation it can cause sinonasal adenocarcinoma. Whether it is able to induce other tumours, especially nasopharyngeal carcinoma, a cancer deeper down the airways, is unresolved, but the outcome of a meta-analysis suggests that it is. Softwood, on the other hand, is suspected of carcinogenic properties. The epidemiological data available suggest that it can cause sinonasal squamous-cell carcinoma. The data do not prove or disprove a causal relationship between hardwood dust and nasopharyngeal carcinoma, nor between softwood dust and sinonasal squamous-cell carcinoma. This may mainly be due to uncertainty as to the nature of the exposure (hardwood, softwood or mixed) and to lack of statistical power of the studies concerned.

The animal experiments do not provide any clues as to the questions of the types of tumour caused by the two species of wood dust. From only one long-term inhalation experiment, with hardwood dust, the results have been published. It did not provide any indication of carcinogenicity. The cause of the discrepancy between the human and animal findings as regards carcinogenicity is unknown.

The genotoxicity of the wood dusts cannot be and has not been tested directly. Preparations like extracts and condensates have been used as substitutes. The picture emerging from the results of the genotoxicity tests is that hardwood and softwood both possess genotoxic properties and that their genotoxicity is similar, with regard to nature and strength (weak). It is unknown, however, to what extent the properties of the dust surrogates represent those of the original material. According to the Committee, the relevance of the genotoxicity observed for the (possible) carcinogenicity of the dusts is questionable. Other lines of evidence that could lend plausibility to the assumption that the genotoxicity is crucial to the carcinogenic process, such as specific mutations in adenocarcinomas from individuals with a history of wood dust exposure, are inconclusive.

Doubt as to their significance for carcinogenicity also holds true for the findings pointing to inflammatory and cytotoxic potential in vivo, viz. higher incidences of functional and histological changes in the sinonasal cavities of wood dust-exposed individuals. Due to the mixed nature of the exposure it has not been possible to determine whether both dusts can cause these effects. Together the findings are taken as indications of local tissue damage. The effects observed are weak, however. Correspondingly, animal experiments, with hardwood dust, aimed at detection of local cytotoxicity and regenerative cell proliferation (hyperplasia), were negative or virtually negative. A much stronger in vivo response than that observed is expected from an agent like wood dust, that is relatively resistant to degradation by the immune system. Why the inflammation and cytotoxicity are weak, only reflected in diminished nasal function and mild histological abnormalities, is enigmatic. The observations on local tissue damage, in humans and animals, have all been made upon semi-chronic and chronic exposure. It is not known whether they occur earlier upon exposure. This hampers interpretation, because only early presentation of such phenomena would convince the Committee that the wood dust does not cause tumours through genotoxicity, but promotes tumour formation predominantly by cytotoxicity and ensuing regenerative hyperplasia, and that tumours can largely be prevented by preventing tissue damage.

Another unresolved matter is that of the constituents to be held responsible for the effects observed: the wood dust itself, or components added to the wood deliberately or contaminating it, such as preservatives or moulds, respectively. Perhaps the physical characteristics, particle size for example, also play a role.

According to the Committee toxicology-based recommended exposure limits for hardwood and softwood dust should be derived identically, bearing in mind that hardwood dust is a proven, softwood dust a suspected carcinogen. The decisive factor here was the similarity of their genotoxicity.

In view of the dubious significance of both the genotoxicity findings and the functional and histological findings the Committee cannot answer the question whether the wood dusts are

• direct genotoxic carcinogens with a major role for their genotoxicity
• indirect genotoxic carcinogens with a major, if not an essential role for inflammatory or regenerative hyperplastic changes
• non-genotoxic carcinogens with an essential role for regenerative hyperplasia following recurrent tissue damage.

Consequently, the decision how toxicology-based occupational exposure limits should be derived, with a threshold or linear model, cannot be made. In the past the suggestion to apply linear extrapolation to carcinogens with unresolved mechanism has been honoured. Therefore, calculations along this line have been added.

Committee

GBBS (OSH)

This publication may be cited as follows

Health Council of the Netherlands: Hardwood and softwood dust. Evaluation of the carcinogenicity and genotoxicity. The Hague: Health Council of the Netherlands, 2000; publication no.2000/08OSH. ISBN  90-5549-327-9