In June of last year, the IARC (International Agency for Research into Cancer) upgraded its classification of formaldehyde from a ‘probable’ to a ‘confirmed’ human carcinogen. This decision was based on evidence of increased incidence of naso-pharyngeal cancer among certain individuals exposed in the past to high levels of formaldehyde. There were also some implications among such individuals of a link with leukemia.
The impact of this announcement has not yet been felt but it is certainly on the agenda of several regulatory authorities and could potentially have quite widespread and major repercussions in practically all aspects of the wood based panel industry.
Basically, there are four groups of individuals for whom this issue may have an impact:Consumers of panel products

·  Consumers of panel products

·   Furniture manufacturers, compounded by issues with wood dust

·   Workers in panel, resin and formaldehyde manufacturing plants

·   Neighbours living around and downwind of such factories

The background
Most of us working in this industry are familiar with the symptoms of formaldehyde exposure, such as lachrymation (tears) and a stinging sensation in the nose and the back of the throat. This could be conceived as a useful warning that our body is under threat and has often been considered as a cause for concern.
Thus in the early 1980’s, the CIIT in the US studied rats and mice which were forcibly exposed to two, six and fifteen parts per million (ppm) for six hours a day; six days a week over 24 months.
These studies indicated that, under such extreme conditions, the rats developed nasal tumours at 15ppm, and to a lesser degree at six ppm, while mice only developed them at 15ppm. There was no response at two ppm. Consequently, formaldehyde was classified as a confirmed carcinogen in rats and mice and a possible carcinogen in humans.
The immediate outcome was major concern throughout the formaldehyde-consuming industries.
As a response, exposure levels in the workplace were typically regulated to two ppm – the zero-response level in rat studies – and, with concern for end-users of products, emission levels were reduced progressively from E3, through E2 to E1 and today, even below those levels.
But where is all this formaldehyde coming from? Presumably, from the formaldehyde- based resins employed? However, as we shall see, this is only part of the story.
Thus, in the manufacture of a UF resin, formaldehyde’s (F) propensity to react with amine groups (-NH2), in this case on urea (U), is utilised: U + F ↔ U-F + H2O
This reaction, like many reactions of formaldehyde, always exhibits some degree of reversibility: U-F ↔ U + F (free). Thus, such resins and their products with wood can potentially give rise to some degree of free formaldehyde.
However, Professor Roffael demonstrated that practically all constituents of the wood substrate itself can potentially liberate formaldehyde and certainly do, particularly under the effective steam distillation conditions of drying and the high temperature and pressure of the hot press.
Furthermore, formaldehyde is released from many combustion processes, particularly hydrocarbons, which exacerbates further the problems of emissions from driers. 
What is formaldehyde?
The chemical formula of formaldehyde is CH2O.When discovered by the Russian chemist, Butlerov, in 1869, he also discovered that under mild conditions it could be transformed into sugars by the so-called formose reaction.
In fact, there is ample evidence that it is involved in the mechanisms by which  carbohydrates are formed in plants. Considering that (CH2O)n is the generic formula for carbohydrates, it might not be surprising that formaldehyde acts in such a role. It acts, effectively, as a 1-C building block – a term which we shall see again further on.
Considering its role in the formation of such constituents as cellulose, hemicellulose, starch, etc and its reversibility in many reactions, it is, furthermore, perhaps not  urprising that wood contributes so much to formaldehyde emissions.
However, it has been proposed by various theorists that formaldehyde may well be the progenitor of life itself!
A closer look at CH2O reveals that it consists of a carbon (C) atom – the basic backbone of organic life and H2O – the acknowledged basis of terrestrial life. Many investigators consider that the formose reaction may well have been an integral part in the formation of life on this planet.
Further proposals on its role in early life envisage formation of ribose from the formose reaction and then on to RNA and DNA. Furthermore, reaction with hydrogen cyanide produces amino acids such as serine:
2HCHO + HCN + H2O ↔HOCH2CH(NH2)COOH  Amino acids form the backbone of proteins and are thus the major elements of animal tissues. 
Natural sources
Where might the formaldehyde have originally come from? In the 1950’s, Miller subjected mixtures of gases such as methane, ammonia, water and hydrogen, believed to form earth’s early atmosphere, to spark discharges in order to simulate lightning and obtained formaldehyde and, interestingly, urea.
Even in the absence of such a mechanism, formaldehyde is believed to be one of the most widespread molecules in interstellar space and comet tails are said to contain around 25% organic matter, of which 4% may be formaldehyde and 7% HCN.
It is believed that with earth’s early atmosphere (absence of oxygen), organisms such as anaerobic bacteria developed which were able to utilise formaldehyde, HCN, etc as energy sources. However, and importantly, there are still remnants of this ability to handle formaldehyde even in higher beings such as ourselves.
In today’s atmosphere, formaldehyde is produced from various natural sources. One precursor of it is methane from the escape of gases from the earth, certain bacteria, rice paddies and ruminant animals, etc. Additional natural and major precursors are the many terpenes given off from trees – particularly those emitted from pine forests.
In man, formaldehyde has an important role in the synthesis of folic acid enzymes and is either used or liberated in inter-conversion reactions between amino acids. In such reactions, formaldehyde, once again, acts as a 1-C source or building block. Its role in the formation of both plant and animal tissues means that it acts like a form of natural currency for exchange and is available from a whole gamut of our food sources.
Thus formaldehyde has been detected in many fruits and vegetables, with typical values ranging from 3-60mg/kg. Pears have been measured with levels of 6mg/kg. Meat and fish (shellfish up to 100mg/kg) are additional sources.
Formaldehyde is metabolised in the body to formic acid and, thereafter, excreted in the urine and faeces. Two principle enzymes are involved; glutathione and alcohol  dehydrogenase III or formaldehyde dehydrogenase – the ancestral dehydrogenase, present throughout the greater part of evolution.
Considering its presence in the air and the very food which we eat, it is perhaps not surprising that formaldehyde has been detected in body fluids such as blood, urine as well as in human breath. Blood levels have been measured in the region of two to three mg/litre. 
Concerns about formaldehyde
If formaldehyde is in the air we breathe and the food we eat and we have a whole system to handle it, why the concern? The answer is in its predilection for amino groups (as used in resin synthesis). Thus, it’s attack on the amino groups of proteins; for example on the glycoproteins of the mucous membranes, is responsible for the symptoms of exposure.
At very elevated exposure levels it can potentially attack the amino groups on RNA and DNA, causing DNA-protein cross links or DPX’s.
However, formaldehyde only binds to RNA and single-stranded DNA, not double stranded DNA (so attack on DNA only occurs during cell division or during mitosis). Furthermore, such damage has been found to be reversible and, therefore, subject to repair.
In the CIIT rat studies, at 15ppm, the replication rate of the respiratory mucosae increased 70 times above that of normal. The progression through hyperplasia to metaplasia, coupled with potential DPX formation, was believed to increase the risk of errors leading to so-called dysplasia and tumours.
Epidemiological studies following on from the rat studies in the 1980’s and, importantly, in E3 days, displayed some interesting findings.
Of particular interest was that such studies often indicated a statistically significant lower incidence of cancer among exposed individuals. Buccal cavity, pharynx and respiratory tract cancers were not elevated.
A study of British pathologists indicated excesses of lymphatic and haemopoietic neoplasms.
One chemical worker study showed some excesses of prostate and lymphopoietic  cancers, but limited to workers of shortest duration.
Thus, in the light of insufficient and, often, totally conflicting evidence in humans, formaldehyde was rated as a ‘possible’ carcinogen. Thus, over the last 20 years, formaldehyde has been used with an ever-increased degree of responsibility. 
Use of formaldehyde in medicine
Interestingly, formaldehyde has something of a history in medicine. Thus formaldehyde itself has been used in a wide range of treatments, such as for a considerable number of skin infections, root canals in dentistry, to reduce excessive perspiration as well as in the preparation of numerous vaccines.
Products which release formaldehyde are commonly used in anti-perspirants where it is used to both kill odour-causing bacteria and reduce perspiration. Of particular note is the use of formaldehyde’s product with ammonium salts, hexamethylene tetramine or HMTA, as formed in the board producing process with, for example, ammonium sulphate.
In the form of urotropine or methenamine, HMTA was one of the first pharmaceuticals and has been used for literally decades to treat urinary disorders. Taken orally, this only liberates formaldehyde under acid conditions, ie in urine. This is an example of formaldehyde being utilised therapeutically and produced in the body at the right place and time.
However, without doubt, one of the most interesting uses of formaldehyde is in the very treatment of cancer itself. This is particularly interesting in the light of those  epidemiological studies which demonstrated a lower incidence of cancer among certain exposed individuals. A whole host of investigators are utilising sophisticated formaldehyde-generating agents to liberate formaldehyde at the strategic right place, time and dose in the combat of various forms of cancer. 
Epidemiological studies 2000+
In 2001 WHO reported reviews on over 25 cohort studies whereby:
Some studies indicated excesses of nasopharyngeal cancer but incidences appear to be, once again, polarized between so-called professional and industrial workers. Thus, a study of 6,000 pathologists in the US showed 4.7 times higher risk

  •  Some professionals had been exposed to very high levels. As an example, levels
    were found in dissection rooms of 6ppm in middle of the hall, 20ppm over bodies and 100ppm in storage vaults. Several studies have indicated that anatomists and embalmers are at increased risk of leukemia and brain cancer
  • Fabric workers again confronted very high levels with fabric sample levels of up to
    351mg/100g
  • Mortality from brain cancer and leukemia among industrial workers was not found to be excessive compared to professional workers
  • Suggestions that excesses among professional workers were due to conditions other than formaldehyde

So, what might be happening?
Firstly, pathologists are exposed to numerous chemicals in their work. Independent studies reveal that:

  • Glutathione-detoxification in rats becomes saturated above 4ppm exposure
  • 88 out of 99 in a group of patients with prostate cancer possessed a genetic defect for production of glutathione-S-transferases
  • Genotypes for glutathione transferases vary considerably among races
  • Furthermore, many oriental individuals lack ALDH2 activity, characterised by a flush reaction after ingestion of alcohol
  • Thus, it may well be that certain individuals are less able to detoxify certain chemicals – that is, their metabolic defences are more limited and
  • In the case of many professional workers they have to metabolise a greater number and degree of toxic chemicals.

Where does this leave us?
Whatever the arguments, the IARC, having considered all the historical evidence over the full range of exposed individuals, has ruled that formaldehyde is a confirmed human carcinogen. However, on the other hand, we have to weigh this ruling against the fact that formaldehyde is a natural substance present in the air we breath and the food we eat.
We even make it, we need it and we have systems to handle it.
Where’s the balance? The answer is the dose – the level of exposure.
Thus, in order to avoid the whole chain of events which provoke hyperplasia, metaplasia and dysplasia etc in the respiratory tissues, the level of exposure needs to be sub-irritant. In this respect, studies have indicated detection levels for smell at about 0.3ppm, eye irritation at 0.5 to 1ppm and moderate irritation to nose and throat above 2ppm.
The Agency for Toxic Substances and Disease Registry derived an inhalation minimum risk level (MRL) of 0.4ppm. Note that this is in line with many, but by no means all, current European levels for the workplace.
The World Health Organisation in 2001 recommended a level of 0.1mg/m3 for the general public. This was more than an order of magnitude lower than the considered threshold for cytotoxic damage to nasal mucosae, thus representing negligible risk of upper respiratory tract cancer.
Note again that this is the level of E1 by the chamber method, albeit under relatively favourable conditions of temperature, relative humidity and air changes. Furthermore, this chamber level is at a 1:1 loading factor. New levels need to be derived for worst case scenarios.

So, what can we expect ?

  • With an ‘ever-smaller world’ and rapid communication – global normalization
  •  Legislated emission from products by representative test methods to guarantee zero-risk levels
  • Similar emission levels in the workplace, normalised and enforceable.

The latter presents, perhaps, the greatest challenge, since most of the board process is completely open to the working environment, a factor which needs to be addressed by the equipment manufacturers.
Emissions from the press depend not only on wood species but, importantly, furnish geometry and moisture content. In particleboard, particle thickness is a major determinant of emissions and needs tighter control.
Obviously, the most important factor is the resin, which needs to be very efficient to run at economical and fast press factors at extremely low emission. It also needs to be very consistent to allow confident press optimisation at fast press factors.
Note that variations can put the product or the working environment out of the specified emission range. The majority of traditional, operator-controlled, batch processes cannot deliver these requirements.
However, the ART (Advanced Resin Technology) resin process, developed by the author, uses a completely different chemical route to produce more efficient resins at low emission.
It is a fully-automated process with computer control and results in a batch-to batch reproducibility on a par with a pharmaceutical product.
Summary
We can see that formaldehyde plays an integral role in our lives and is part of both our natural, internal, as well as external, environments. Our bodies need reactive substances.
However, like many reactive substances such as oxygen, a certain level of exposure is appropriate and above this level it can present a hazard.We should keep this dose concept in mind since the whole livelihood of our industry depends on maintaining this issue firmly in perspective.