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PubMed1999

An alleged poisoning with methanol and formaldehyde.

It was alleged that a defendant added an unspecified amount of undyed formalin solution, containing formaldehyde and methanol, to the victim's bottle of ice and drinking water. The medical report indicated that except for a slight elevation of total creatine kinase, all other chemistry profiles were within normal ranges. The elevation of creatine kinase suggested muscle injury and inflammation; however, the significance of this elevation was not clear. Toxicological evaluations were made by conducting risk assessments. Based upon the medical report and risk assessments, the following conclusions were made: The calculated exposure doses of methanol and formaldehyde were too low to cause appreciable adverse effects; however, formaldehyde may have irritated the gastrointestinal tract causing smooth muscle and mucosal inflammation. The doses of methanol and formaldehyde were too low to cause death. The exposure scenario (a single oral exposure to formaldehyde) would not likely increase the cancer risk in the victim. The risk assessments provided resulted in a reduction in charge from attempted murder to felony.

Adult↗

PubMed1998

Formaldehyde generators and capturers as influencing factors of mitotic and apoptotic processes.

There is a growing amount of evidence pointing to the fact that several endogenous and exogenous methylated compounds are potential formaldehyde generators in their biological reactions. N(G)-methylated lysines, N(G)-methylated as well as hydroxymethylated arginines, and 1'-methyl-ascorbigen have been examined in this respect. The apoptosis-inducing effect of formaldehyde molecules formed from methyl groups was earlier first published by our group. Dimedone, an artificial capturer molecule for formaldehyde, has been found to prevent the apoptosis-inducing effect of 1'-methyl-ascorbigen as well as N(G)-hydroxymethylated arginines. More recently resveratrol, present in grapes and wines, has been shown to have cardioprotective and cancer chemopreventive effect. Our group has been successful in demonstrating that this natural formaldehyde capturer molecule can also influence cell proliferation and apoptosis. The apoptosis-inducing or -preventing effect of formaldehyde generators and capturers seems to be dose-dependent and may be utilized in various disturbances of cell proliferation and active cell death.

Apoptosis↗

PubMed1998

The effect of heat shock on the formaldehyde cycle in germinating acorns of European Turkey oak.

The effect of heat shock (40 degrees C) on the formaldehyde cycle has been studied in European Turkey oak (Quercus cerris L.) acorns germinated to a 10% increase in mass. Hydroxy-methyl groups bonded to sulfur, oxygen and nitrogen atoms were made to react with dimedone and the derivative obtained (formaldemethone), which represented the endogenous formaldehyde level, was determined by high performance liquid chromatography. Qualitative alterations of methyl donors and acceptors in the response of acorns to the heat shock have been mapped by MALDI (matrix assisted laser desorption ionization) mass analysis. In the first experiment the acorns were prevented from withering by wrapping them in aluminium foil and in the second they were not. The relatively high temperature of the acorns wrapped in aluminium foil was the dominant stress effect and the role of withering was subsidiary. Alteration of the endogenous formaldehyde level in the seed-leaves reflected the phases of the stress syndrome. If the withering were not hindered, two local minima in the alteration of endogenous formaldehyde level were found. First, the increase in temperature decreased the endogenous formaldehyde level and after a local maximum a repeated local minimum was observed as a delayed response. It is presumed that the second minimum was induced by the decreasing water amount becoming more and more significant in the seed-leaves.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

[Diagnosis of formaldehyde allergy].

Exposure to small-dose environmental agents is a risk factor of immunopathological reactions. The levels of formaldehyde-specific IgE were comparatively analyzed in 50 children of whom 25 live in the area exposed to formaldehyde. Children with varying respiratory allergic reactions comprised a study group. To identify allergen-specific IgE, the authors used a method that determined formaldehyde antibodies by using the tested allergen (formaldehyde on the paper). There were significant group-specific differences in the levels of formaldehyde antibodies (3.8 times higher in the study group than in the controls). Combined therapy substantially reduced specific IgE whose levels returned to the levels observed in the controls. The findings may recommend the use of this test for the diagnosis of immune-depended abnormalities and the evaluation of their effective treatment.

Age Factors↗

PubMed1999

[Formaldehyde in dental materials].

The use of formaldehyde in dentistry has been discussed for years. This because of the possible systemic effects of its use. This paper addresses the possible systemic effects of the use of formaldehyde and the question in which dental products formaldehyde is a component. The indications for the use of formaldehyde as its alternatives are listed. The conclusion is that for nearly all dental indications for the use of formaldehyde good alternatives are available.

Dental Cements↗

PubMed2001

[Extraction of residual formaldehyde in polymer complex and high performance liquid chromatographic analysis].

This paper presents a simple and accurate method for analyzing formaldehyde in polymer complex by headspace extraction derivatization and HPLC analysis. The sample preparatio of formaldehyde in polymer complex was based on a simple thermodynamic equilibrium in a closed and thermostat jar, and the gaseous formaldehyde in equilibrium could be absorbed and extracted by the liquid in the bottom of the jar. The formaldehyde was derivatized with 2,4-dinitrophenyl hydrazine before chromatography. The influences of temperature, equilibrium time, sample quantity and geometric form on the extraction efficiency were studied. The extraction and HPLC conditions were optimized. The limit of detection (LOD) was 0.1 mg/kg, and the relative standard deviation (RSD) was below 5%, and the recoveries were between 96%-103%. As a result, this method would meet the demands for analyzing microamounts of residual formaldehyde in polymer complex.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Level of endogenous formaldehyde in maple syrup as determined by spectrofluorimetry.

The level of endogenous formaldehyde in maple syrup was established from a large number (n = 300) of authentic maple syrup samples collected during 2000 and 2001 in the province of Quebec, Canada. The average level of formaldehyde from these authentic samples was measured at 0.18 mg/kg in 2000 and 0.28 mg/kg in 2001, which is lower than previously published. These average values can be attributed to the improved spectrofluorimetric method used for the determination. However, the formaldehyde values obtained demonstrate a relatively large distribution with maximums observed at 1.04 and 1.54 mg/kg. These values are still under the maximum tolerance level of 2.0 mg/kg paraformaldehyde pesticide residue. Extensive heat treatment of maple syrup samples greatly enhanced the formaldehyde concentration of the samples, suggesting that extensive heat degradation of the sap constituents during evaporation could be responsible for the highest formaldehyde values in maple syrup.

Acer↗

PubMedDate not supplied

[The effect of milk consumption on the activity of the formaldehyde detoxification system in sensitization to this compound].

The activity of formaldehyde dehydrogenase (FDG) and total nonspecific formaldehyde oxidative activity of nasal mucosa and liver and the amount of reduced glutathione in the liver were measured in guinea pig subjected to epicutaneous or inhalative action of formaldehyde and additionally fed with cow milk. Glutathione-deficient animals demonstrated an increase in FDG activity following formaldehyde sensitization both in the liver and in nasal mucosa, whereas FDG activity in glutathione-supplied animals did not change significantly. The concentration of formaldehyde in the internal environment is supposed to be controlled by the levels of coenzyme (reduced glutathione) and FDG activity.

Aldehyde Oxidoreductases↗

PubMed1992

[Does formaldehyde-induced asthma exist?].

Formaldehyde is a ubiquitous airborne pollutant in our modern environment. There are many potential sources of formaldehyde in the industrial setting. Ambient formaldehyde affects primarily the upper airways and eyes. Lower airway and pulmonary effects occur at exposure levels between 6-38 mg/m3. It is so soluble and rapidly metabolized that it seldom reaches the lower respiratory tract to inflict damage. There is no consistent evidence indicating that formaldehyde can be a respiratory sensitizer. It may, on rare occasions, induce bronchial asthma at relatively high exposure doses. There are no conclusive studies that would prove the development of de novo-IgE-mediated respiratory tract symptoms as resulting from inhalation of formaldehyde.

Air Pollutants, Occupational↗

PubMed1977

Production of formaldehyde from N5-methyltetrahydrofolate by normal and leukemic leukocytes.

Extracts of human normal and leukemic leukocytes contain an enzyme that catalyzes a transfer of labeled methyl carbon from N5-[14C]methyltetrahydrofolate to tryptamine. Evidence is presented that this reaction is not attributable to a methyltransferase but to the following reaction sequence: (a) an oxidation of N5-[14C]methyltetrahydrofolate to N5, N10-[14C]methylenetetrahydrofolate that is catalyzed by N5, N10-methylenetetrahydrofolate reductase (EC 1.1.1.68); (b) spontaneous release of [14C]formaldehyde from N5, N10-[14C]methylenetetrahydrofolate; and (c) nonenzymatic condensation of [14C]formaldehyde with tryptamine to form a radioactive carboline derivative. The occurrence of this sequence in leukocytes is suggested by data that show that the enzyme reaction is strongly stimulated by addition of flavin adenine dinucleotide and that the final product is chromatographically identical to the adduct formed in the reaction of [14C]formaldehyde with tryptamine. In the absence of tryptamine, a product accumulates that can react with other HCHO acceptors, i.e., beta-phenylethylamine and dimedone; another reaction product is tetrahydrofolate. Production of formaldehyde is relatively more active in normal lymphocytes than in normal granulocytes, but it is even higher in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Formaldehyde production in leukocytes is only slightly stimulated by addition of various cobalamins, and activity is normal in leukocytes from a vitamin B12-deficient patient. We conclude that the system is cobalamin independent. Thus, there exists an active pathway from N5-methyltetrahydrofolate to tetrahydrofolate other than the one catalyzed by cobalamin-dependent N5-methyltetrahydrofolate-homocysteine methyltransferase.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2004

Very fast (and safe) inactivation of foot-and-mouth disease virus and enteroviruses by a combination of binary ethyleneimine and formaldehyde.

For FMD vaccine production, inactivation of the FMD virus is the most critical step. Formerly, from 1940 onwards, the virus was inactivated with formaldehyde. This inactivation was relatively slow, about 0.2 - 0.3 log 10 per hour. Because formaldehyde not only reacts with the virus produced but with many other components in the medium, such as proteins and amino acids, its concentration can become rate-limiting and inactivation plots may show tailing-off, resulting in residual infectivity. Many of the bad stories of post-vaccination outbreaks date back to the use of formaldehyde-inactivated vaccines (e.g. the outbreaks in France in 1981 and in Eastern Germany causing the Danish outbreak in 1982). Much faster and safer inactivation was obtained with aziridines and in the 1980s binary ethyleneimine (BEI) was introduced in practically all vaccine production laboratories. If inactivation plots are made of every production batch, as is now required by the European Pharmacopoeia, and these plots show proper inactivation rates, vaccines can considered to be completely safe. Under optimal conditions, inactivation rates are in the range of 0.5 - 1.0 log 10 per hour. In general, the inactivation takes 40-48 hours,which will guarantee complete inactivation of all virus particles in a batch. Since formaldehyde (FA), the 'classical' inactivating agent, inactivates at a rate of 0.3 logs per hour only, a significant contribution of FA to the inactivation of BEI can hardly be expected. However, here it is shown that FA added during the BEI-inactivation process strongly augments inactivation rates with a hundred to thousand-times (to 2.5-3.5 logs per hour). This will enable inactivation during a working day or just overnight with even higher safety levels of the vaccines. Also, it is known that formaldehyde cross-links viral proteins which will stabilise the antigen. The short inactivation times will limit proteolytic destruction of 146 S antigen and increase antigen yields. It is expected that by the cross-linking activity of FA the stability of the antigen (and of vaccines) and the endurance of the immune response will be favourably influenced.

Animals↗

PubMedDate not supplied

[Modern methods for formaldehyde, methanol and ethanol analysis].

It is necessary to create very specific and sensitive methods for assaying formaldehyde and methanol which are produced on the large scale and are very toxic and have mutagenic and carcinogenic action on living organisms. The methods for determination of formaldehyde, methanol and ethanol in the environment and fermentation products published and developed by the authors are reviewed in this paper. Most of the known methods are not sufficiently selective and sensitive and some of them are very expensive. Classical chemical, enzymatic, chemosensor and biosensor approaches used for methanol and formaldehyde assay are described. Enzymatic methods exploiting alcohol oxidase isolated from the mutant over-producing strain of methylotrophic yeast Hansenula polymorpha permit efficient determination of formaldehyde in industrial wastewaters. Enzymatic-chemical method based on the use of alcohol oxidase and 4-amino-5-hydrazine-3-mercapto-1,2,4-triazole (AHMT) allows simultaneous determination of methanol and formaldehyde. The technology of biosensor construction and their bioanalytical characteristics are described. Experimental data concerning amperometric and potentiometric biosensors based on the use of genetically modified cells of methylotrophic yeast Hansenula polymorpha are reviewed. The possibility to use alcohol oxidase-based biosensor for the assay of methanol in wastewater is demonstrated.

Biosensing Techniques↗

PubMedDate not supplied

A new enzymo-chemical method for simultaneous assay of methanol and formaldehyde.

A new enzymo-chemical method for the simultaneous assay of methanol and formaldehyde in mixtures is described which exploits alcohol oxidase (AO) and aldehyde-selective reagent, 3-methyl-2-benzothiazolinone hydrazone (MBTH). The enzyme is used for methanol oxidation to formaldehyde and MBTH plays a double role: 1) at the first step of reaction, it forms a colorless azine adduct with pre-existing and enzymatically formed formaldehyde and masks it from oxidation by AO; 2) at the second step of reaction, non-enzymatic oxidation of azine product to cyanine dye occurs in the presence of ferric ions in acid medium. Pre-existing formaldehyde content is assayed by colorimetric reaction with MBTH without treating samples by AO, and methanol content is determined by a gain in a colored product due to methanol-oxidising reaction. Possibility of differential assay of methanol and formaldehyde by the proposed method has been proved for model solutions as well as for real samples of industrial waste and technical formaline. A threshold sensitivity of the assay method for both analytes is near 1 microM that responds to 30-32 ng analyte in 1 ml of reaction mixture and is 3.2-fold higher when compared to the chemical method with the use of permanganate and chromotropic acid. Linearity of the calibration curve is reliable (p < 0.0001) and standard deviation for parallel measurements for real samples does not exceed 7%. The proposed method, in contrast to the standard chemical approach, does not need the use of aggressive chemicals (concentrated sulfuric, phosphoric, chromotropic acids, permanganate), it is more simple in fulfillment and can be used for industrial wastes control and certification of formaline-contained stuffs.

Alcohol Oxidoreductases↗

PubMedDate not supplied

[Evaluation of total exposure to benzene and formaldehyde in the European countries].

Benzene and formaldehyde are among the principal components in the air of various indoor occupational and non-occupational environments. Both compounds are toxicologically relevant for humans as recognized carcinogens. In order to evaluate the total exposure and to assess the possible health risk caused by benzene and formaldehyde for different population groups at European level, the JRC Institute for Health and Consumer Protection in Ispra launched the AIRMEX (IndoorAir Monitoring and ExposureAssessment Study) project in October 2003. It aims at identifying and quantifying the main indoor pollutants particularly in kindergartens, schools and public buildings. It also intends to evaluate the overall exposure of people working and occupying these areas. Measuring campaigns were carried out in pre-selected indoor environments in various European cities (Catania, Athens, Arnhem, Nijmegen, Brussels, Thessaloniki). Preliminary results clearly indicate that indoor air concentrations for volatile compounds (VOC) including benzene are higher than/or similar to those found outdoors, ranging from a few micrograms (about 8 microg/m3) to 281 microg/m3. Outdoor concentrations vary from 7 to 153 microg/m3. Personal exposure concentrations are generally higher than the indoor/outdoor concentrations. In most cases they are twice as high as indoor concentrations (or even higher) and significantly higher than outdoor concentrations. Air concentrations of aldehydes inside buildings/kindergartens were up to 7-8 times higher than outside. This mostly concerns formaldehyde, and it seems that strong indoor sources exist which clearly determine the indoor air concentrations. Formaldehyde concentrations in public buildings and offices vary from 3 to 30 microg/m3, and those in kindergartens vary from 6 to 11 microg/m3 (Arnhem/Nijmegen). The highest values for formaldehyde, up to 29,9 microg/m3, were found in Catania, Athens and Thessaloniki.

Air Pollution↗

PubMed1991

The prevalence of atopy and hypersensitivity to formaldehyde in pathologists.

Sixty-three pathologists in active practice in the province of Alberta, Canada, provided a history regarding atopy and sensitivity to formaldehyde. Serum samples were assayed for total IgE level and the presence of IgE with specificity toward timothy grass, cat, house dust, and formaldehyde. Twenty-nine of the subjects (46.0%) gave a history of atopy that was confirmed in 12 by either IgE level or a positive radioallergosorbent test. Twenty-nine (46.0%) complained of formaldehyde sensitivity. In this study, no pathologist had allergen-specific IgE directed against formaldehyde, and there was no evidence of a tendency for atopic subjects to be more prone to sensitivity to formaldehyde. However, this may be related to a deliberate reduction in exposure by individuals experiencing adverse effects.

Drug Hypersensitivity↗

PubMed1991

Formaldehyde: an analysis of its respiratory, cutaneous, and immunologic effects.

Formaldehyde is truly ubiquitous in our ecology and continuing important commercial applications. Most of us have daily contact with this chemical. The most significant outdoor source of this chemical is gasoline and diesel fuel combustion. The primary indoor source is combustion of tobacco products. Formaldehyde is associated with a disagreeable odor that can produce "annoyance" symptoms and at higher concentrations can be a transient and completely reversible irritant to the eyes and mucous membranes of the respiratory tract. It is so soluble and rapidly metabolized that it rarely reaches the lower respiratory tract to inflict damage. The exception is in cigarette smokers who actively inhale. Formaldehyde may on rare occasions induce bronchial asthma at relatively high exposure doses. There are no conclusive studies that prove the development of de novo IgE-mediated respiratory tract symptoms secondary to inhalation of formaldehyde vapors. The approach to formaldehyde-induced symptoms should be one of careful documentation of objective physiologic changes.

Air Pollutants↗

PubMed1985

Induction of formaldehyde contact sensitivity: dose response relationship in the guinea pig maximization test.

The sensitizing potential of aqueous formaldehyde was evaluated with the guinea pig maximization test (GPMT) in two laboratories (Copenhagen and Stockholm) using different guinea pig strains. Six intradermal (0.01%-3%), and 6 topical (0.5%-20%) concentrations were used for induction, and formaldehyde 1% and 0.1% was used for challenge. The incidence of contact sensitivity depended on the intradermal, but not on the topical induction dose. Statistical analyses showed a non-monotonous (non-linear) dose response relationship. The estimated maximal sensitization rate in Copenhagen was 80% after intradermal induction with 0.65% formaldehyde; in Stockholm it was 84% after induction with 0.34%. The data from the two laboratories could be described by parallel displaced dose response curves suggesting that the guinea pig strain used in Stockholm was significantly more susceptible to formaldehyde than the strain used in Copenhagen. The EC50 (formaldehyde concentration at which 50% of the guinea pigs were sensitized) at the 72 h scoring and a 1% challenge concentration, was 0.061% in Copenhagen and 0.024% in Stockholm.

Administration, Topical↗

PubMed1986

Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.

Ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide were tested for tumor-promoting activity in a two-stage stomach carcinogenesis experiment. Male outbred Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/liter) and a diet supplemented with 10% sodium chloride for 8 weeks. Thereafter, they were maintained on drinking water containing either 10% ethanol, 1% potassium metabisulfite, 0.5% formalin (formaldehyde) or 1% hydrogen peroxide for 32 weeks and then sacrificed for necropsy and histological examination. In the pylorus of the glandular stomach, potassium metabisulfite and formaldehyde significantly increased the incidence of adenocarcinoma after initiation with MNNG and sodium chloride. Hydrogen peroxide did not enhance the tumor yield, and ethanol showed a tendency to decrease neoplastic development. In the forestomach the incidence of squamous cell papilloma was significantly increased in the groups given hydrogen peroxide or formaldehyde, irrespective of prior initiation. Duodenal adenocarcinoma was induced by the initiation alone (10%) and the incidence was not affected by the subsequent treatments. The results indicate that potassium metabisulfite and formaldehyde both exert tumor-promoting activity in the rat glandular stomach.

Adenocarcinoma↗