Formaldehyde

Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its IUPAC name methanal.

Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers. In 2005, annual world production of formaldehyde was estimated to be 23 million tonnes (50 billion pounds). Commercial solutions of formaldehyde in water, commonly called formalin, were formerly used as disinfectants and for preservation of biological specimens.

In view of its widespread use, toxicity and volatility, exposure to formaldehyde is a significant consideration for human health. On 10 June 2011, the US National Toxicology Program has described formaldehyde as "known to be a human carcinogen".

Forms of formaldehyde
Formaldehyde is more complicated than many simple carbon compounds because it adopts different forms. Formaldehyde is a gas at room temperature, but the gas readily converts to a variety of derivatives, which are often used in industry in place of the gas.

One important derivative is the cyclic trimer metaformaldehyde or trioxane (CH2O)3. There is also an infinite polymer called paraformaldehyde.

When dissolved in water, formaldehyde combines with water to form methanediol or methylene glycol H2C(OH)2. The diol also exists in equilibrium with a series of oligomers (short polymers), depending on the concentration and temperature.

A saturated water solution, that contains about 40% formaldehyde by volume or 37% by mass, is called "100% formalin". A small amount of stabilizer, such as methanol, is usually added to limit oxidation and polymerization. A typical commercial grade formalin may contain 10–12% methanol in addition to various metallic impurities.

Occurrence
Formaldehyde is a naturally occurring substance in the environment made of carbon, hydrogen and oxygen. Natural processes in the upper atmosphere may contribute up to 90 percent of the total formaldehyde in the environment. Formaldehyde is an intermediate in the oxidation (or combustion) of methane as well as other carbon compounds, e.g. forest fires, in automobile exhaust, and in tobacco smoke. When produced in the atmosphere by the action of sunlight and oxygen on atmospheric methane and other hydrocarbons, it becomes part of smog. Formaldehyde has also been detected in outer space (see below).

Formaldehyde, as well as its oligomers and hydrates are rarely encountered in living organisms. Methanogenesis proceeds via the equivalent of formaldehyde, but this one-carbon species is masked as a methylene group in methanopterin. Formaldehyde is the primary cause of methanol's toxicity, since methanol is metabolised into toxic formaldehyde by alcohol dehydrogenase. Formaldehyde does not accumulate in the environment, because it is broken down within a few hours by sunlight or by bacteria present in soil or water. Humans metabolize formaldehyde quickly, so it does not accumulate, and is converted to formic acid in the body.

Small amounts of formaldehyde are produced in case of incomplete combustion of methane gas.

Interstellar formaldehyde
Formaldehyde was the first polyatomic organic molecule detected in the interstellar medium and since its initial detection has been observed in many regions of the galaxy. Because of the widespread interest in interstellar formaldehyde it has recently been extensively studied, yielding new extragalactic sources. A proposed mechanism for the formation is the hydrogenation of CO ice, shown below.


 * H + CO → HCO
 * HCO + H → H2CO (rate constant = 9.2 s−1)

Formaldehyde appears to be a useful probe for astrochemists due to its low reactivity in the gas phase and to the fact that the 110←111 and 211←212 K-doublet transitions are rather clear.

Synthesis and industrial production
Formaldehyde was first reported in 1859 by the Russian chemist Aleksandr Butlerov (1828–86) and was conclusively identified in 1869 by August Wilhelm von Hofmann. In 1867, A. W. Hofmann first announced to the Royal Prussian Academy of Sciences the production of formaldehyde by passing methanol vapor in air over hot platinum wire. See: A. W. Hofmann (14 October 1867) "Zur Kenntnis des Methylaldehyds" ([Contributions] to our knowledge of methylaldehyde), Monatsbericht der Königlich Preussischen Akademie der Wissenschaften zu Berlin (Monthly Report of the Royal Prussian Academy of Sciences in Berlin), vol. 8, pages 665 - 669. Reprinted in: However, it was not until 1869 that Hofmann determined the correct empirical formula of formaldehyde. See: A.W. Hofmann (5 April 1869) "Beiträge zur Kenntnis des Methylaldehyds", Monatsbericht der Königlich Preussischen Akademie der Wissenschaften zu Berlin, vol. ?, pages 362-372. Reprinted in:
 * A.W. Hofmann, (1868) "Zur Kenntnis des Methylaldehyds", Annalen der Chemie und Pharmacie (Annals of Chemistry and Pharmacy), vol. 145, no. 3, pages 357-361.
 * A.W. Hofmann (1868) "Zur Kenntnis des Methylaldehyds", Journal für praktische Chemie (Journal for Practical Chemistry), vol. 103, no. 1, pages 246-250.
 * A.W. Hofmann (1869) "Beiträge zur Kenntnis des Methylaldehyds", Journal für praktische Chemie, vol. 107, no. 1, pages 414-424.
 * A.W. Hofmann (1869) "Beiträge zur Kenntnis des Methylaldehyds," Berichte der Deutschen Chemischen Gesellschaft (Reports of the German Chemical Society), vol. 2, pages 152-159.

Formaldehyde is produced industrially by the catalytic oxidation of methanol. The most common catalysts are silver metal or a mixture of an iron and molybdenum or vanadium oxides. In the commonly used formox process, methanol and oxygen react at ca. 250–400 °C in presence of iron oxide in combination with molybdenum and/or vanadium to produce formaldehyde according to the chemical equation:
 * 2 CH3OH +  O2   →   2 CH2O  +  2 H2O

The silver-based catalyst usually operates at a higher temperature, about 650 °C. Two chemical reactions on it simultaneously produce formaldehyde: that shown above and the dehydrogenation reaction:
 * CH3OH → H2CO + H2

In principle formaldehyde could be generated by oxidation of methane, but this route is not industrially viable because the formaldehyde is more easily oxidized than methane.

Organic chemistry
Formaldehyde is a building block in the synthesis of many other compounds of specialised and industrial significance. It exhibits most of the chemical properties of other aldehydes but is more reactive. For example it is more readily oxidized by atmospheric oxygen to formic acid (formic acid is found in ppm levels in commercial formaldehyde). Formaldehyde is a good electrophile, participating in electrophilic aromatic substitution reactions with aromatic compounds, and can undergo electrophilic addition reactions with alkenes and aromatics. Formaldehyde undergoes a Cannizzaro reaction in the presence of basic catalysts to produce formic acid and methanol.

Examples of organic synthetic applications
Condensation with acetaldehyde affords pentaerythritol, a chemical necessary in synthesizing PETN, a high explosive. Condensation with phenols gives phenol-formaldehyde resins. With 4-substituted phenols one obtains calixarenes.

When combined with hydrogen sulfide it forms trithiane.
 * 3CH2O + 3H2S → (CH2S)3 + 3H2O

Industrial applications
Formaldehyde is a common building block for the synthesis of more complex compounds and materials. In approximate order of decreasing consumption, products generated from formaldehyde include urea formaldehyde resin, melamine resin, phenol formaldehyde resin, polyoxymethylene plastics, 1,4-butanediol, and methylene diphenyl diisocyanate. The textile industry uses formaldehyde-based resins as finishers to make fabrics crease-resistant. Formaldehyde-based materials are key to the manufacture of automobiles, and used to make components for the transmission, electrical system, engine block, door panels, axles and brake shoes. The value of sales of formaldehyde and derivative products was over $145 billion in 2003, about 1.2% of the Gross Domestic Product (GDP) of the United States and Canada. Including indirect employment, over 4 million work in the formaldehyde industry across approximately 11,900 plants in the U.S. and Canada.

When reacted with phenol, urea, or melamine, formaldehyde produces, respectively, hard thermoset phenol formaldehyde resin, urea formaldehyde resin, and melamine resin, which are commonly used in permanent adhesives such as those used in plywood or carpeting. It is used as the wet-strength resin added to sanitary paper products such as (listed in increasing concentrations injected into the paper machine headstock chest) facial tissue, table napkins, and roll towels. They are also foamed to make insulation, or cast into moulded products. Production of formaldehyde resins accounts for more than half of formaldehyde consumption.

Formaldehyde is also a precursor to polyfunctional alcohols such as pentaerythritol, which is used to make paints and explosives. Other formaldehyde derivatives include methylene diphenyl diisocyanate, an important component in polyurethane paints and foams, and hexamine, which is used in phenol-formaldehyde resins as well as the explosive RDX. Formaldehyde has been found as a contaminant in several bath products, at levels from 54–610 ppm: it is thought to arise from the breakdown of preservatives in the products.

Disinfectant and biocide
An aqueous solution of formaldehyde can be useful as a disinfectant as it kills most bacteria and fungi (including their spores). Formaldehyde solutions are applied topically in medicine to dry the skin, such as in the treatment of warts. Many aquarists use formaldehyde as a treatment for the parasites Ichthyophthirius multifiliis and Cryptocaryon irritans.

Formaldehyde is used to inactivate bacterial products for toxoid vaccines (vaccines that use an inactive bacterial toxin to produce immunity). It is also used to kill unwanted viruses and bacteria that might contaminate the vaccine during production. Urinary tract infections are also often treated using a derivative of formaldehyde (methenamine), a method often chosen because it prevents overuse of antibiotics and the resultant development of bacterial resistance to them. In an acid environment methenamine is converted in the kidneys to formaldehyde, which then has an antibacterial effect in the urinary tract. This is not safe for long term use due to the carcinogenic effect of formaldehyde. Some topical creams, cosmetics and personal hygiene products also contain derivatives of formaldehyde as the active ingredients that prevent the growth of potentially harmful bacteria.

Tissue fixative and embalming agent
Formaldehyde preserves or fixes tissue or cells by reversibly cross-linking primary amino groups in proteins with other nearby nitrogen atoms in protein or DNA through a -CH2- linkage. This is exploited in ChIP-on-chip transcriptomics experiments, where nucleotide-binding proteins are cross-linked to their cognate binding sites on the chromosome and analyzed to determine what genes are regulated by the proteins. Formaldehyde is also used as a denaturing agent in RNA gel electrophoresis, preventing RNA from forming secondary structures.

Formaldehyde solutions are used as a fixative for microscopy and histology, although the percentage formaldehyde used may vary based on the method of analysis. Additionally, the methanol used to stabilize formaldehyde may interfere with the ability to properly fix tissue or cells, and therefore commercial formaldehyde preparations are available that are packaged in glass ampules under an inert gas to prevent the use of contaminating methanol for stabilization. Formaldehyde-based solutions are also used in embalming to disinfect and temporarily preserve human and animal remains. It is the ability of formaldehyde to fix the tissue that produces the tell-tale firmness of flesh in an embalmed body. In post mortem examinations a procedure known as the "sink test" involves placing the lungs of an animal in an aqueous solution of formaldehyde; if the lungs float it suggests the animal was probably breathing or able to breathe at the time of death.

Formaldehyde solutions are commonly used as a biological preserving medium, usually for smaller specimens.

Several European countries restrict the use of formaldehyde, including the import of formaldehyde-treated products and embalming. Starting September 2007, the European Union banned the use of formaldehyde due to its carcinogenic properties as a biocide (including embalming) under the Biocidal Products Directive (98/8/EC). Countries with a strong tradition of embalming corpses, such as Ireland and other colder-weather countries, have raised concerns. Despite reports to the contrary, no decision on the inclusion of formaldehyde on Annex I of the Biocidal Products Directive for product-type 22 (embalming and taxidermist fluids) had been made.

Miscellaneous applications
Formaldehyde is a common component of many uses.

In photography, formaldehyde is still used in low concentrations for process C-41 (color negative film) stabilizer in the final wash step, as well as in the process E-6 pre-bleach step, to obviate the need for it in the final wash.

Formaldehyde is used extensively in the woodworking and cabinet-making industries. Formaldehyde is used in the glues that bond particle-board together. The particle board is used underneath wood veneer and plastic laminate. Cabinets, bank counters, and veneered and laminated woodwork all use particle board containing formaldehyde under the plastic laminate and wood veneer.

Safety
Formaldehyde is highly toxic to humans, regardless of method of intake. Ingestion of as little as 30 mL (1 oz.) of a solution containing 37% formaldehyde has been reported to cause death in an adult. Water solution of formaldehyde is very corrosive and its ingestion can cause severe injury to upper gastrointestinal tract.

Occupational exposure to formaldehyde by inhalation is mainly from three types of sources: thermal or chemical decomposition of formaldehyde-based resins, formaldehyde emission from aqueous solutions (for example, embalming fluids), and the production of formaldehyde resulting from the combustion of a variety of organic compounds (for example, exhaust gases). Formaldehyde can be toxic, allergenic, and carcinogenic. Because formaldehyde resins are used in many construction materials it is one of the more common indoor air pollutants. At concentrations above 0.1 ppm in air formaldehyde can irritate the eyes and mucous membranes, resulting in watery eyes. Formaldehyde inhaled at this concentration may cause headaches, a burning sensation in the throat, and difficulty breathing, as well as triggering or aggravating asthma symptoms.

A 1988 Canadian study of houses with urea-formaldehyde foam insulation found that formaldehyde levels as low as 0.046 ppm were positively correlated with eye and nasal irritation. Although many studies have failed to show a relationship between formaldehyde and asthma, a recent review of studies has shown a strong association between exposure to formaldehyde and the development of childhood asthma. Chronic exposure at higher levels, starting at around 1.9 ppm, has been shown to result in significant damage to pulmonary function, resulting in reduced maximum mid-expiratory flow and forced vital capacity. There is also research that supports the theory that formaldehyde exposure contributes to reproductive problems in women. A study on Finnish women working in laboratories at least 3 days a week found a significant correlation between spontaneous abortion and formaldehyde exposure, and a study of Chinese women found abnormal menstrual cycles in 70% of the women occupationally exposed to formaldehyde compared to only 17% in the control group. There have been no studies done on the effect of formaldehyde exposure on reproduction in men.

The primary exposure concern is for the workers in the industries producing or using formaldehyde. As far back as 1987, the U.S. EPA classified it as a probable human carcinogen and after more studies the WHO International Agency for Research on Cancer (IARC), in 1995, also classified it as a probable human carcinogen. Further information and evaluation of all known data led the IARC to reclassify formaldehyde as a known human carcinogen associated with nasal sinus cancer and nasopharyngeal cancer. Recent studies have also shown a positive correlation between exposure to formaldehyde and the development of leukemia, particularly myeloid leukemia. In the residential environment, formaldehyde exposure comes from a number of different routes; formaldehyde can off-gas from wood products, such as plywood or particle board, but it is produced by paints, varnishes, floor finishes, and cigarette smoking as well.

The United States Environmental Protection Agency (EPA) allows no more than 16 ppb formaldehyde in the air in new buildings constructed for that agency. A U.S. Environmental Protection Agency study found a new home measured 0.076 ppm when brand new and 0.045 ppm after 30 days. The Federal Emergency Management Agency (FEMA) has also announced limits on the formaldehyde levels in trailers purchased by that agency. The EPA recommends the use of “exterior-grade” pressed-wood products with phenol instead of urea resin to limit formaldehyde exposure, since pressed-wood products containing formaldehyde resins are often a significant source of formaldehyde in homes.

For most people, irritation from formaldehyde is temporary and reversible, though formaldehyde can cause allergies and is part of the standard patch test series. People with formaldehyde allergy are advised to avoid formaldehyde releasers as well (e.g., Quaternium-15, imidazolidinyl urea, and diazolidinyl urea). People who suffer allergic reactions to formaldehyde tend to display lesions on the skin in the areas that have had direct contact with the substance, such as the neck or thighs (often due to formaldehyde released from permanent press finished clothing) or dermatitis on the face (typically from cosmetics). Formaldehyde has been banned in cosmetics in both Sweden and Japan. The eyes are most sensitive to formaldehyde exposure: The lowest level at which many people can begin to smell formaldehyde is about 0.05 ppm and the highest level is 1 ppm. The maximum concentration value at the workplace is 0.3 ppm. In controlled chamber studies, individuals begin to sense eye irritation at about 0.5 ppm; 5 to 20 percent report eye irritation at 0.5 to 1 ppm; and greater certainty for sensory irritation occurred at 1 ppm and above. While some agencies have used a level as low as 0.1 ppm as a threshold for irritation, the expert panel found that a level of 0.3 ppm would protect against nearly all irritation. In fact, the expert panel found that a level of 1.0 ppm would avoid eye irritation—the most sensitive endpoint—in 75-95% of all people exposed.

Formaldehyde levels in building environments are affected by a number of factors. These include the potency of formaldehyde-emitting products present, the ratio of the surface area of emitting materials to volume of space, environmental factors, product age, interactions with other materials, and ventilation condition. Formaldehyde emits from a variety of construction materials, furnishings, and consumer products. The three products that emit the highest concentrations are medium density fiberboard, hardwood plywood, and particle board. Environmental factors such as temperature and relative humidity can elevate levels because formaldehyde has a high vapor pressure. Formaldehyde levels from building materials are the highest when a building first opens because materials would have less time to off-gas. Formaldehyde levels decrease over time as the sources suppress.

Formaldehyde levels in air can be sampled and tested using a few different means, including impinger, treated sorbent, and passive monitors. The National Institute for Occupational Safety and Health (NIOSH) has measurement methods numbered 2016, 2541, 3500, and 3800.

Studies on the interactions between formaldehyde and proteins at the molecular level have been reported on the effects of the body’s carrier protein, bovine serum albumin. The binding of formaldehyde loosens the skeletal structure of BSA and exposure of aromatic ring amino acids in the internal hydrophobic region. Symptoms may affect personal awareness, making one feel tired or fatigue.

Formaldehyde inhalation has also shown to cause oxidative stress and inflammation in animals. Mice studied over an exposure to a high dose of formaldehyde (3ppm), showed increased levels of NO$− 3$ levels in plasma. This result suggests that FA inhalation either decreased NO production or increased NO scavenging, which may be an anti-stress mechanism in the body. Formaldehyde inhalation changes the sensitivity of immune system, which influences oxidative stress.

In June 2011, the twelfth edition of the National Toxicology Program (NTP) Report on Carcinogens (RoC) changed the listing status of formaldehyde from “reasonably anticipated to be a human carcinogen” to “known to be a human carcinogen”. Concurrently, a National Academy of Sciences (NAS) committee was convened and issued an independent review of the draft United States Environmental Protection Agency IRIS assessment of formaldehyde, providing a comprehensive health effects assessment and quantitative estimates of human risks of adverse effects.

International bans
There are several web articles claiming that formaldehyde has been banned from manufacture or import into the European Union (EU) under REACH (Registration, Evaluation, Authorization, and restriction of Chemical substances) legislation. This appears to be misinformation, as official EU chemical databases contradict these claims as of February 19, 2010. This misconception has gained some ground. Formaldehyde is not listed in the Annex I of Regulation (EC) No 689/2008 (export and import of dangerous chemicals regulation), nor on a priority list for risk assessment. However, formaldehyde is banned from use in certain applications (preservatives for liquid-cooling and processing systems, slimicides, metalworking-fluid preservatives, and antifouling products) under the Biocidal Products Directive. In the EU, the maximum allowed concentration of formaldehyde in finished products is 0.2%, and any product that exceeds .05% has to include a warning that the  product contains formaldehyde.

In the United States, a bill was passed in congress on July 7, 2010 regarding the use of formaldehyde in hardwood plywood, particle board, and medium density fiberboard. The bill limited the allowable amount of formaldehyde emissions from these wood products to .09 ppm, a standard which companies will have to meet by January, 2013. Formaldehyde was declared a toxic substance by the 1999 Canadian Environmental Protection Act.

Hurricane Katrina & Rita
In the U.S. the Federal Emergency Management Agency (FEMA) provided travel trailers and mobile homes starting in 2006 for habitation by residents of the U.S. gulf coast displaced by Hurricane Katrina and Hurricane Rita. Some of the people who moved into the trailers complained of breathing difficulties, nosebleeds, and persistent headaches. Formaldehyde-catalyzed resins were used in the production of these homes.

The United States Centers For Disease Control and Prevention (CDC) performed indoor air quality testing for formaldehyde in some of the units. On February 14, 2008 the CDC announced that potentially hazardous levels of formaldehyde were found in many of the travel trailers and mobile homes provided by the agency. The CDC's preliminary evaluation of a scientifically established random sample of 519 travel trailers and mobile homes tested between Dec. 21, 2007 and Jan. 23, 2008 (2+ years after manufacture) showed average levels of formaldehyde in all units of about 77 parts per billion (ppb). Long-term exposure to levels in this range can be linked to an increased risk of cancer and, at levels above this range, there can also be a risk of respiratory illness. These levels are higher than expected in indoor air, where levels are commonly in the range of 10-20 ppb, and are higher than the Agency for Toxic Substance Disease Registry (ATSDR, division of the CDC) Minimal Risk Level (MRL) of 8 ppb. Levels measured ranged from 3 ppb to 590 ppb.

FEMA, which requested the testing by the CDC, said it would work aggressively to relocate all residents of the temporary housing as soon as possible. Lawsuits are being filed against FEMA as a result of the exposures.

Iowa Floods of 2008
Also in the U.S., problems arose in trailers again provided by FEMA to residents displaced by the Iowa floods of 2008. Several months after moving to the trailers, occupants reported violent coughing, headaches, as well as asthma, bronchitis, and other problems. Tests showed that in some trailers, levels of formaldehyde exceeded the limits recommended by the U.S. Environmental Protection Agency and American Lung Association. The associated publicity has resulted in additional testing to begin in November.

Sichuan Earthquake of 2008
After an earthquake hit Sichuan, China, a large number of survivors were housed in trailers made with medium-density fiberboard that emitted up to 5 times China's maximum allowable formaldehyde levels. In April, 2009, there were 100 miscarriages recorded in this community, which may have been linked to exposure to high levels of formaldehyde found in the trailers used for housing after the disaster.

Contaminant in food
Scandals have broken in both the 2005 Indonesia food scare and 2007 Vietnam food scare regarding the addition of formaldehyde to foods to extend shelf life. After a four-year absence, in 2011 Indonesian authorities have again some foods with formaldehyde being sold in markets in a number of regions across the country. Besides using formaldehyde, they also use borax, but not combined together. In August 2011, at least at 2 Carrefour supermarkets, the Central Jakarta Livestock and Fishery Sub-Department found a sweet glutinous rice drink (cendol) contained 10 parts per million of formaldehyde. Foods known to be contaminated include noodles, salted fish, tofu, and rumors of chicken and beer. In some places, such as China, formaldehyde is still used illegally as a preservative in foods, which exposes people to formaldehyde ingestion. In humans, the ingestion of formaldehyde has been shown to cause vomiting, abdominal pain, dizziness, and in extreme cases can cause death; in addition, there is limited evidence of a carcinogenic effect. Testing for formaldehyde is by blood and/or urine by gas chromatography-mass spectrometry. Other methods include infrared detection, gas detector tubes, etc., of which HPLC is the most sensitive In the early 1900s, it was frequently added by US milk plants to milk bottles as a method of pasteurization due to the lack of knowledge regarding formaldehyde's toxicity.

In Thailand, formaldehyde has been exposed in truckloads of rotten chickens in a food scare, some 11 slaughterhouses were implicated in Nakhon Ratchasima in 2011 in "a large network" run by a gang.