Formaldehyde (0)

Formaldehyde
Formaldehyde is a colorless, flammable gas at room temperature. It has a pungent, distinct odor and may cause a burning sensation to the eyes , nose , and lungs at high concentrations . Formaldehyde is also known as methanal, methylene oxide, oxymethylene, methylaldehyde, and oxomethane. Formaldehyde can react with many other chemicals , and it will break down into methanol ( wood alcohol ) and carbon monoxide at very high temperatures .
Formaldehyde is naturally produced in very small amounts in our bodies as a part of our normal, everyday metabolism and causes us no harm. It can also be found in the air that we breathe at home and at work , in the food we eat, and in some products that we put on our skin . A major source of formaldehyde that we breathe every day is found in smog in the lower atmosphere. Automobile exhaust from cars without catalytic converters or those using oxygenated gasoline also contain formaldehyde. At home, formaldehyde is produced by cigarettes and other tobacco products, gas cookers, and open fireplaces. It is also used as a preservative in some foods , such as some types of Italian cheeses, dried foods, and fish . Formaldehyde is found in many products used every day around the house, such as antiseptics, medicines, cosmetics, dish-washing liquids, fabric softeners, shoe-care agents , carpet cleaners, glues and adhesives, lacquers, paper , plastics, and some types of wood products. Some people are exposed to higher levels of formaldehyde if they live in a new mobile home, as formaldehyde is given off as a gas from the manufactured wood products used in these homes.
Formaldehyde is used in many industries. It is used in the production of fertilizer, paper, plywood, and urea-formaldehyde resins. It is present in the air in iron foundries. It is also used in the production of cosmetics and sugar , in well-drilling fluids, in agriculture as a preservative for grains and seed dressings, in the rubber industry in the production of latex, in leather tanning, in wood preservation, and in photographic film production. Formaldehyde is combined with methanol and buffers to make embalming fluid. Formaldehyde is also used in many hospitals and laboratories to preserve tissue specimens.
Physical -chemical date :
CAS number: 50-00-0
IUPAC name: Methanal
Structure formula: HCHO
Physical characteristics :
Colorless gas (normal.),
Odor: Pungent, suffocating odor; highly irritating ,
Density: 0.815 g/mL (8153 g/cm³ (–20°C) )
Molar mass 30.03 g mol−1 s,
Solubility: Freshwater at 20°C Very soluble; up to 55%
Partition coefficients: Log Pow=0.35 (25°C), Log Koc= 1.567
Melting and boiling point: Tm=-92°C,Tb=-19°C
Autoignition temperature: 300 °C
Henry 's law constant at 25°C H: 0,034 Pa*m3/mol
TOXICOKINETICS
The toxicokinetics of formaldehyde after inhalation, oral , or dermal exposure has been reported in several species by many investigators. The toxicokinetics in all of the animals studied is similar across species lines. Formaldehyde is an essential metabolic intermediate in all cells. It is produced during the normal metabolism of serine, glycine, methionine, and choline and also by the demethylation of N-, S-, and O- methyl compounds. After oxidation of formaldehyde to formate, the carbon atom is further oxidized to carbon dioxide (CO2) or incorporated into purines, thymidine, and amino acids via tetrahydrofolatedependent one-carbon biosynthetic pathways. Exogenous formaldehyde appears to be readily absorbed from the respiratory and gastrointestinal tracts, but poorly absorbed following dermal application . Formaldehyde is metabolized to formate by the enzyme formaldehyde dehydrogenase; this appears to take place at the initial site of contact. Being normal components of intermediary metabolism, neither formaldehyde nor formate are stored to any significant extent in any tissue of the body . Formate is excreted in the urine (primarily as formic acid), incorporated into other cellular molecules, or oxidized to carbon dioxide and exhaled.
Formaldehyde vapors are readily absorbed from the respiratory tract . Due to rapid metabolism to formate, little, if any, intact formaldehyde can be found in the blood of humans or animals exposed to formaldehyde. Formaldehyde is also readily absorbed from the gastrointestinal tract and meets with the same metabolic fate as formaldehyde after inhalation exposure. The studies available in the open literature suggest that very little formaldehyde is absorbed via the dermal route. In all cases , absorption appears to be limited to cell layers immediately adjacent to the point of contact. Entry of formaldehyde into the blood (i.e., systemic absorption) occurs to a very limited extent, if at all.
ENVIRONMENTAL FATE
In reviewing the fate of formaldehyde in the environment, it should be noted that the environmental factors that influence the bioavailability to humans of formaldehyde from contaminated air, water, or plant material have not been studied.
Air
Formaldehyde is removed from the atmosphere by direct photolysis and oxidation by photochemically produced hydroxyl radicals. Formaldehyde absorbs ultraviolet (UV) radiation at wavelengths of 360 nm and longer; therefore, it is capable of photolyzing in sunlight. A half -life of 6 hours has been measured for photolysis in simulated sunlight. There are two photolytic pathways, one producing H2 and CO, and the other producing H and HCO radicals. When the rates of these reactions are combined with estimates of actinic irradiance, the predicted half-life of formaldehyde due to photolysis in the lower atmosphere is 1.6 hours at a solar zenith angle of 40 degrees. Based on its rate of reaction with photochemically produced hydroxyl radicals, formaldehyde has a predicted half-life of approximately 19 hours in clean air and about half that time in polluted air.
Water
When released to water, formaldehyde will biodegrade to low levels in a few days . In nutrient-enriched seawater, there is a long lag period (40 hours) prior to measurable loss of formaldehyde by presumably biological processes . Formaldehyde in aqueous effluent is degraded by activated sludge and sewage in 48–72 hours. In a die- away test, using water from a stagnant lake, degradation was complete in 30 hours under aerobic conditions and 48 hours under anaerobic conditions. Bhattacharya and Parkin used anaerobic chemostats to study fate and kinetic effects of sludge and continuous additions of formaldehyde to acetate and propionate enrichment systems. The high reduction of formaldehyde with continuous addition is indicative of biodegradation, since the combination of volatilization, adsorption, and chemical transformation should account for less than 25% of the removal. Up to 80% of the formaldehyde was removed, with biodegradation accounting for 55–60%.
Sediment and Soil
The fate of formaldehyde in soil has not been determined
HEALTH EFFECTS
Acute toxicity
The major acute effects are a result of the irritating properties of formaldehyde. After acute inhalation, irritation of the eyes, nose, throat , and lungs, as well as cellular changes , such as ciliar lesions and cellular swelling in the upper respiratory tract have been observed . A 4- hour LC50 value of 480 ppm has been determined for rats. The oral LD50 was 600-800 mg/kg b.w. in rats. In humans, no reports of deaths following acute inhalation exposure to formaldehyde were located .
In humans, serious ulceration and damage of the gastrointestinal tract have been found after ingestion of formaldehyde (45 ml of a 37 % v/v solution ) or a gulp of a 40 % v/v solution. No reports on deaths following acute inhalation exposure were located.
Irritation
Skin irritation
Studies in Animals
Formaldehyde was irritating to the eyes of rabbits. 0.005 ml of a 5% and a 15% aqueous solution was applied to the eyes of rabbits. The scores were read 18 - 20 hours post application. The irritation score was 8 (on a scale of 0 -10).
Studies in Humans
Formaldehyde causes skin irritation in humans. Transient and reversible sensory irritation of the eyes and respiratory tract has been observed in clinical studies and epidemiological surveys. Airborne concentrations associated with sensory irritation are above 0.3 to 0.5 ppm, eye irritation being the most sensitive endpoint. Moderate eye, nose and throat irritation occurs at 2 to 3 ppm. However some individuals may experience adverse effects such as watery eyes; burning sensations in the eyes, nose, and throat; coughing; wheezing; nausea; and skin irritation at lower concentrations.
Sensitization
Studies in Animals
Formaldehyde was tested and found to be a skin sensitizer in numerous tests . The induction with a 5% aqueous solution and challenge with 2 and 4% aqueous solutions, for instance , gave a positive result in a guinea pig maximization test.
Studies in Human
Skin
The thresholds for elicitation of allergic contact dermatitis in sensitized subjects range from 30 ppm(w/w), aqueous solution, for patch testing to 60 ppm (w/w) for products containing formaldehyde. A threshold for induction has not been clearly established , but it is estimated to be less than 5 % aqueous solution
Respiratory Tract
Formaldehyde induced asthma has been studied and findings from detailed clinical evaluations of suspected subjects suggest that it is rare, if it exists at all.
Repeated Dose Toxicity
Studies in Animals
The most extensive database is available for inhalation exposure in rats.
Studies with repeated inhalative exposure of rats
duration
NOAEL(ppm)
LOAEL(ppm)
4-6 weeks
2
6,2
3 months
1 to 2
4
>12 month
1 to 2
2 to 6
*LOAEL=lowest-observed-adverse- effect level
*NOAEL=no observed adverse effect level
*The ranges of the values are caused by the different concentrations selected in the various studies.
High concentrations of formaldehyde (10 - 20 ppm) cause marked hyperplasia and squamous metaplasia of the nasal respiratory epithelium. The lesions are primarily located in the anterior part of the nose and spread with increasing exposure time and concentrations to more distal locations in the nasal cavity.
Dermal
Repeated exposure studies in mice were performed using dermal application, mostly in the context of skin initiation promotion. None of these studies showed evidence of substance- specific systemic toxicity.
Studies in Humans
Because a variety of substances and conditions can cause histological changes in the nasal mucosa, the weight of scientific evidence does not support an association between formaldehyde exposure alone and histopathological changes in human nasal mucosa. Although several studies have found changes, these cannot be associated with formaldehyde exposure alone and are confounded by other air contaminants. Boysenet al.(1990) found no significant histopathology differences in nasal mucosa of 37 workers and 37 controls exposed to 0.5 ppm to over 2 ppm of formaldehyde.
Mutagenicity
In vitro , formaldehyde is able to induce gene mutations and chromosomal aberrations in mammalian cells without (and also in presence of) external metabolic activation. DNA- protein crosslinks are a sensitive measure of DNA interaction by formaldehyde.
In vivo , the overall evidence of available studies supports the conclusion that the genotoxic effects after exposure via relevant routes are limited to those cells which are in direct contact with formaldehyde and no effects are observed in distant-site tissues. This is consistent with formaldehyde's high reactivity with many cellular nucleophiles and its rapid metabolic degradation.
Results of human cytogenetic population monitoring studies are somewhat equivocal, as noted in WHO IARC (1995). An increased incidence of micronucleated buccal or nasal mucosal cells was observed in occupationally exposed subjects Chromosomal aberrations and sister chromatid exchanges (SCE) in peripheral lymphocytes of exposed persons were seen in some studies but not in others . Interpretation of these results is difficult because of the small number of subjects, co- exposure to wood dust, and lack of details in the reports. At best a weak positive response is indicated, at the site of initial contact.
Carcinogenicity
Studies in animals
Formaldehyde has been tested in chronic animal studies and a number of other experimental models to assess its carcinogenic potential in different species. Inhalation of concentrations of 10 ppm (12 mg/m 3 ) or above leads to clear increases in nasal tumor incidence in rats. Marked non- neoplastic pathological lesions of the nasal cavity were present at tumorigenic concentrations. In contrast , no significant numbers of tumors were seen in mice and Syrian hamsters following chronic exposure to concentrations up to 14.3 or 30 ppm (17 - 36 mg/m 3 ), respectively.
These clear species differences appear to be related , in part, to the local dosimetry and disposition of formaldehyde in nasal tissues. For example, mice possess the capacity to minimize inhalation of irritating substances more efficiently than rats through a reflex depression of respiratory rate.
Studies in humans
The finding of nasal tumors in rodents exposed to high levels of airborne formaldehyde in the early 1980s led to a concern for cancer effects in occupationally exposed workers. There are now more than 40 epidemiology studies examining the potential for occupational formaldehyde exposure to cause cancer in humans. The studies include cohort mortality studies of formaldehyde-exposed industrial workers, cohort mortality studies of formaldehyde-exposed professionals or medical specialists , and case -control studies that looked for associations between occupational exposure to formaldehyde and cancers of the nose, pharynx, or lung . Although many different ways to calculate relatively risk of human cancer were used all this studies showed similar results.
Conclusions of those studies are:
National Toxicology Program (1998): formaldehyde is reasonably anticipated to be a human carcinogen
International Agency of Research for Cancer (1995): “Taken together, the epidemiological studies suggest a causal relationship between exposure to formaldehyde and nasopharyngeal cancer, although the conclusion is tempered by the small numbers of observed and expected cases in the cohort studies”. IARC’s overall evaluation is that formaldehyde is probably carcinogenic to humans (Group 2A). Later IARC classified formaldehyde as human carcinogen.
Evaluating Pesticides for Carcinogenic Agency classified formaldehyde in Group B1 - probable human carcinogen, under conditions of unusually high or prolonged exposure.
The National Toxicology Program, an interagency program of the Department of Health and Human Services, named formaldehyde as a known human carcinogen in its 12th Report on Carcinogens (2011).
Toxicity for Reproduction
Studies in Humans
No increased risk of spontaneous abortion was seen after maternal or paternal exposure to formaldehyde based upon survey questionnaire. In one study of cosmetologists who used formaldehyde based disinfectant products as well as other chemicals a slight excess of spontaneous abortions is reported, but that finding could not be linked to any chemical exposure. Formaldehyde exposure levels were not reported in these studies. Low birth weight was not statistically significant associated with formaldehyde exposure in a population-based epidemiological study. No effects on sperm morphology were seen in exposed individuals exposed to formalin from a hospital autopsy service .
In WHO IARC it is concluded that “whether administered by inhalation, ingestion or the skin to various species, formaldehyde did not exert adverse effects on reproductive parameters or fetal development ” (WHO IARC, 1995).
Studies in Animals
Effects on Fertility
No studies devoted solely to reproductive effects using formaldehyde were performed. Doses that induced stomach lesions in the chronic drinking water study with rats approx. 82 and 109 mg/kg b.w./day for male and female rats, respectively, did not reveal adverse effects on reproductive organs .
Developmental Toxicity
An inhalation prenatal toxicity study using up to date methodology showed the absence of teratogenicity after inhalation of 2, 5, or 10 ppm (2.4, 6, 12 mg/m 3 ) of formaldehyde during gestation days 6 - 15 in the rat.
Conclusion
In humans, transient and reversible sensory irritation of the eyes and respiratory tract has been observed in clinical studies and epidemiological surveys. Odor threshold for most people ranges between 0.5 and 1 ppm. In general, eye irritation, the most sensitive endpoint, is associated with airborne concentrations beginning in the range of 0.3 to 0.5 ppm. Eye irritation does not become significant until about 1 ppm, and rapidly subsides. Moderate to severe eye, nose and throat irritation occurs at 2 to 3 ppm. Sensory irritation has also been reported at lower levels, but is then difficult to distinguish from background. Most studies show no effect on lung function in either asthmatics or non-asthmatics. Formaldehyde causes skin irritation and has corrosive properties when ingested. In some sensitized individuals, contact dermatitis may occur at challenge concentrations as low as 30 ppm.
Formaldehyde as a gas is highly reactive and is absorbed quickly at the point of contact. It is rapidly metabolised and is also produced by endogenous metabolism. Exposure to high concentrations (up to 15 ppm in rats) does not result in increased blood concentrations. Repeated formaldehyde exposure caused toxic effects only in the tissues of direct contact after inhalation, oral or dermal exposure characterised by local cytotoxic destruction and subsequent repair of the damage. The typical locations of lesions in experimental animals were the nose after inhalation, the stomach after oral administration and the skin after dermal application.
Formaldehyde is weakly genotoxic and was able to induce gene mutations and chromosomal aberrations in mammalian cells. However, the genotoxic effects were limited to those cells, which are in direct contact with formaldehyde, and no effects could be observed in distant-site tissues. DNA-protein crosslinks are a sensitive measure of DNA modification by formaldehyde. In conclusion, formaldehyde is a directly acting locally effective mutagen.
In epidemiological studies in occupationally exposed human populations, there is limited evidence of a causal association between formaldehyde exposure and nasal tumors. Taking into account the extensive information on its mode of action , formaldehyde is not likely to be a potent carcinogen to humans under low exposure conditions.
However many epidemiological and case-control studies as well as meta -analysis studies were conducted for workers with formaldehyde and it’s resins and scientists who work with formaldehyde.
There are no indications of a specific toxicity of formaldehyde to fetal development and no effects on reproductive organs were observed after chronic oral administration of formaldehyde to male and female rats. Amounts of formaldehyde, which produce marked toxic effects at the portal of entry, do not lead to an appreciable systemic dose and thus do not produce systemic toxicity. This is consistent with formaldehyde’s high reactivity with many cellular nucleophiles and its rapid metabolic degradation.
Ecotoxicity
Releases into the environment are likely to occur during production and processing as intermediate as well as from use of products containing the substance.
Aquatic Effects
Distribution modelling estimates water to be the main target compartment for formaldehyde. The most sensitive organism in an valid acute aquatic toxicity test was Daphnia pulex with an EC50 (48 h) of 5.8 mg/l. For the derivation of the PNECaqua an assessment factor of 1000 is applied on this value resulting in a PNECaqua of 5.8 μg/l.n. (EC50 - half maximal effective concentration ; PNEC - Predicted No Effect Concentration)
Terrestrial Effects
Nematodes in peat were killed by application of formalin (37 % formaldehyde solution) at 179 ml/m³ (Lockhart 1972). Pollen grains of Lilium longiflorum which had been sown in a straight line on a culture medium were exposed separately to various concentrations of injurious gases. A 5 h exposure to formaldehyde at 0.44 mg/m³ (0.37 ppm) resulted in a significant reduction in pollen- tube length , whereas a 1 or 2 h exposure was innocuous. When the formaldehyde concentration was increased to 2.88 mg/m³ (2.4 ppm), a 1 h exposure caused a decrease in tube length.
Conclusion
The substance is a candidate for further work. No information is available about releases into surface water from production and processing sites . Due to the low PNECaqua of 5.8 μg/l a risk to the aquatic environment cannot be excluded.
HUMAN EXPOSURE
Outdoor
Air concentrations of formaldehyde near the ground in coastal , mountain or oceanic areas in different parts of the world were in good agreement and ranged from 0.05 to 14.7 μg/m³ (0.00004075-0.12ppm) (WHO IPCS , 1989). Measurements conducted in Germany and considered to be representative for the air in the rural areas of Central Europe ranged from 0.1 to 4.5 μg/m³, with a mean value of about 1.5 μg/m³. Measurements in a highly industrialised area with also heavy traffic conducted in Germany (1979 –1984) gave annual mean values of 7 – 12 μg/m³ (WHO IPCS, 1989). Additional measurements conducted in recent years in different locations indicate mean outdoor concentrations ranging from 2.5 μg/m³ to 15.7 μg/m³ (Jurvelin, 2001).
Indoor (non-workplace)
Indoor air levels, measured in various countries, ranged between risk is high
Occupational exposure: as measurements showed exposure range is below limits , however there is always the risk to be exposed to formaldehyde vapor or gas because of its volatility > risk is moderate
Risk for the environment
As descried in environmental fate section formaldehyde is removed from the atmosphere quite fast .
The fate of formaldehyde in soil has not been determined.
The main target in the environment for formaldehyde is water. Taking into account that PNECaqua has low limit the risk is moderate for aquatic ecosystem.
List of literature:
http://www.atsdr.cdc.gov/ToxProfiles/tp111.pdf
http://www.inchem.org/documents/sids/sids/FORMALDEHYDE.pdf
http://www.cancer.gov/cancertopics/factsheet/Risk/formaldehyde
http://monographs.iarc.fr/ENG/Monographs/vol88/index.php