To remind readers of the background to the September conference, the International Agency for Research on Cancer (IARC) in June 2004 classified formaldehyde as a Group 1 carcinogen to humans (see WBPI issue 4, 2004, p3). Specifically, it warned of an increased risk of naso-pharyngeal cancer (NPC) – a rare form of the disease. The research on which this classification was based was carried out by Hauptmann et al on behalf of the National Cancer Institute of the US and has been heavily disputed ever since. It was based mainly on a study of historic workers’ exposure to formaldehyde dating back as far as 1937, when exposure levels to formaldehyde were routinely far higher than they are today. There were also anomalies in the results which appear to have been overlooked.
The purpose of the Barcelona conference was to pull together some of the reliable scientific research carried out more recently and to present it to a knowledgeable audience for discussion. That audience included representatives from the European Commission as well as from some of the most distinguished scientific institutes in Germany, Sweden, the UK, the Netherlands, Israel, the US and Brazil. The IARC recommendation is just that: it is not a regulation – in its own preamble it said: "no recommendation is given with regard to regulation or legislation….".
The risk is that the EU or the US authorities decide to legislate based on that recommendation. If the conclusions of this conference are heeded, no such legislation should follow.
"By the end of this conference, we do not expect a final and definitive state of knowledge, but new scientific facts and insights into the nature of formaldehyde to correct the misconceptions of the past and prevent them in the future," said FormaCare chairman Rob Koster.
Session 1 of the one-and-a-half day conference was dedicated to the epidemiology of formaldehyde. Significantly, it was chaired by professor Elke Anklam, director of the Institute for Health and Consumer Protection of the European Union, whose function was recently taken over by the European Chemicals Agency.
David Coggon, professor of occupational and environmental medicine at the University of Southampton, UK, and a veteran of many international advisory committees on the application of science to the assessment and management of risk, said: "In comparison with most other chemicals, there is a substantial body of epidemiological evidence on formaldehyde. If there is any risk of cancer from exposures at the levels which now occur in western countries, it must be very small".
Professor Hans-Olov Adami of the Karolinska Institute in Sweden and Harvard School of Public Health in Boston, US, showed that, although NPC is rare in most populations, it is a leading form of cancer in a few well-defined populations in southern China, South East Asia, the Arctic and the Middle East/North Africa.
Dr Peter Morfeld of the Institute of Occupational and Social Medicine, Cologne University re-examined various work on formaldehyde and certainly agreed: "According to [my] re-evaluation, Hauptmann et al (2004) missed an important interaction between the plant [factory] group 1 to 10 and the exposure variable, which prohibits a generalisation of the plant number 1 findings to the other plants investigated".
This refers to the fact that this original research found ‘significant’ clusters of NPC in only one out of the 10 plants investigated.
"Clearly the results of this re-analysis of the NCI study did not support the suggestion of a causal association with formaldehyde exposure and NPC," continued Dr Morfeld.
The next speaker, professor Gary Marsh of the University of Pittsburgh, US, threw even more doubt on the NCI findings when he reported on his work to investigate a link to external factors at Hauptmann’s factory number 1 (a plastics factory in Wallingford, Connecticut, US) as possible causal factors for NPC.
He discovered that there was a substantial ferrous and non-ferrous metal working industry in the area of Wallingford, notably in silver smithing.
"For most of the 23 pharyngeal cancer cases, the very brief periods of Wallingford employment afforded little opportunity for exposures relevant to the causation of disease," said Dr Marsh.
Day two of the conference was on toxicology and looked at cytotoxicity (toxicity to cells), genotoxicity (toxicity to DNA) and mutagenicity (the ability to cause cell mutation). This was an area which FormaCare felt relied on old data and accordingly initiated several new studies on the toxicology of formaldehyde.
The complexity of this subject for the non-expert means that we have summarised the findings rather than reporting the papers here.
At the end of the conference, FormaCare suggested that the evidence for NPC formation was highly ambiguous, citing Dr Marsh’s work in particular.
It also said that formaldehyde being related to leukaemia – another area of considerable research – was highly improbable since the only possible connections to cancer formation have been hints at possible local tumour development and not at sites far removed from areas of initial contact.
Further, no mutagenic effects have been observed in animal experiments and according to a new study, no mutagenic effect was found in cells of the mouth of human volunteers exposed to formaldehyde for short periods under workplace exposure conditions.
Finally, said FormaCare: "The threshold for sensory irritation of the eyes and nose is clearly lower than that leading to cell death [which could possibly lead to tumours]; concentrations of 0.5 or 0.3, with peaks of 0.6 parts per million will not lead to objective signs of sensory irritation".
An update of the original NCI research is due in late 2007/early 2008. But of course the human subjects of the study have aged and this could well affect recorded cancer mortality rates. However, any further re-classification of formaldehyde as a carcinogen by the EU or the US will await the outcome of that study.
At present, the EU classification of formaldehyde is category 3 – the weakest class of carcinogenic hazard. Based on a French proposal, this is currently being reviewed by the European Commission’s Technical Committee on Classification and Labelling. The industry hopes for a well-informed decision. Not only would formaldehyde be very difficult and expensive to replace (possibly an extra e10bn a year), where indeed it can be replaced, but there are four million jobs at stake in the industry.
The FormaCare conference certainly seemed to give formaldehyde the ‘all clear’ in modern processing and application.
