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[Evaluation of the irritative action of formaldehyde and glutaraldehyde aldehyde].

The irritative effect of formaldehyde and glutaraldehyde on the rabbit skin was determined under conditions of a single, closed exposure and under conditions of multiple, open exposure. It was revealed that the irritative effect was dependent on the concentration used, application mode and exposure duration. Under conditions of a single, 4 and 24-hour, closed exposure, threshold concentration which was inducing only slight inflammatory reaction of skin was equal to 2% of aqueous solution for both formaldehyde and glutaraldehyde. Under conditions of a 10 open exposure, threshold concentration of irritative effect on the skin was determined as 5% aqueous solution for formaldehyde and 2.5% aqueous solution for glutaraldehyde. A single administration of 0.5% aqueous solution of formaldehyde and of 0.2% aqueous solution of glutaraldehyde into the rabbit's eye induced a slight and short lasting inflammatory reaction. These concentrations were recognised as threshold ones.

Animals↗

[Occupational exposure to formaldehyde and risk of cancer].

Formaldehyde is a widespread animal carcinogen with limited evidence of carcinogenesis in humans. We investigated the occupational risk of cancer (1970-84) among men and women in Denmark. Relative risks (RR) were estimated from standardized proportionate incidence ratios among patients whose longest employment had been held since 1964, at least 10 years before diagnosis, in 265 companies in which exposure to formaldehyde was identified. The only biologically plausible increased risk was for nasal cancer, for which relative risks of 2.3 (95% confidence interval = 1.3-4.0) and 2.4 (0.6-6.0) appeared for men and women, respectively. In the subgroup of blue-collar men with no probable exposure to wood-dust, the major confounder, the relative risk for this cancer was 3.0 (1.4-5.7). It is concluded that occupational exposure to formaldehyde may increase the risk of nasal cancer, but formaldehyde does probably not affect other cancers.

Adult↗

Oxidation of Tris and formaldehyde to CO2 by neutrophil oxidants.

The buffer substance Tris is oxidized to formaldehyde by two microbicidal neutrophil oxidants, the hydroxyl radical and sodium hypochlorite. By the intact neutrophil, Tris is converted to CO2 in a process which is enhanced by stimulation with zymosan indicating that CO2 formation reflects neutrophil function. CO2 formation is more extensive at pH 6.0 than at pH 7.5 suggesting higher microbicidal activity at the low pH of inflamed tissue. In addition to Tris, its oxidation product formaldehyde is also oxidized to CO2 by hydroxyl radicals, and the formation of CO2 from formaldehyde by intact neutrophils exhibits the same features as CO2 formation from Tris. It is suggested that CO2 formation from Tris or from formaldehyde may be suitable to test for the formation of microbicidal oxidants by neutrophils.

Carbon Dioxide↗

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of nitrite and formaldehyde from foods.

A high-performance liquid chromatographic (HPLC) procedure with fluorometric detector has been developed for the determination of nitrite and formaldehyde from foods by the use of hydralazine. Hydralazine reacts with nitrite and formaldehyde under acidic conditions in boiling water-bath for 15 min to form tetrazolo-(5,1-a)-phthalazine (Tetra-P) and triazolo-(3,4-a)-phthalazine (Tri-P) quantitatively. Without extraction, the determination of Tetra-P and Tri-P was simple, specific, sensitive and reliable over the range of 0.003-0.3 ppm of sodium nitrite and 0.02-0.4 ppm of formaldehyde. This procedure using hydralazine is one of the most useful methods for routine analysis of nitrite and formaldehyde in foods, biological fluids and ambient waters.

Animals↗

Health aspects of formaldehyde in the indoor environment. Czech and Slovak experience.

The effects of formaldehyde on human beings has been a subject of study in the former Czechoslovakia since the beginning of the 1980s. The first studies quite naturally arose from concern over its effects in occupational settings. Initially, the allergic effects of formaldehyde on the skin were studied. Two main approaches to the study of the biologic effects of formaldehyde on humans were employed. The cytogenetic analyses of peripheral lymphocytes and immunological analysis of selected humoral immunity parameters were used to demonstrate the formaldehyde exposure in both occupational and non-occupational indoor environment. The analysis of the results, especially from the non-occupational settings (e.g. school classrooms), was beset with problems with interpretation and lead to suggested maximum acceptable concentration (MAC) values that were unrealistically low, ranging from 0.035 mg.m-3 (whole day mean) and short term-up to 30 minute sampling 0.050 mg.m-3. These rather stringent requirements are fully acceptable for the open air. However, they are difficult to achieve in indoor air settings, and are open to criticism from the point of view of exposure assessment. Because of the problems in interpreting genotoxic and immunological parameters, a risk assessment approach was adopted for this discussion.

Air Pollution, Indoor↗

Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class.

The frequency of micronuclei (MN) in cells of the nasal mucosa, oral mucosa and in lymphocytes was evaluated for 25 students in anatomy classes exposed to formaldehyde (FA) over an 8-week period. Each student served as his or her own control. The time-weighted average concentration (TWA) of formaldehyde in anatomical laboratories and in students' dormitories was 0.508 +/- 0.299 mg/m3 and 0.012 +/- 0.0025 mg/m3, respectively. A higher frequency of micronuclei was observed in nasal and oral exfoliative cells after formaldehyde exposure (3.85 +/- 1.48 vs 1.20 +/- 0.676 and 0.857 +/- 0.558 vs 0.568 +/- 0.317, paired-t test: P < 0.001 and P < 0.01, respectively). No significant increase in the frequency of lymphocyte micronuclei was found after formaldehyde exposure (P > 0.05). The present study shows that nasal mucosa cells exposed through respiration are the chief target of FA-induced genotoxic effects.

Embalming↗

Redox chemistry of tungsten and iron-sulfur prosthetic groups in Pyrococcus furiosus formaldehyde ferredoxin oxidoreductase.

Formaldehyde oxidoreductase (FOR) is one of the tungstopterin iron-sulfur enzymes of the five-membered family of aldehyde oxidoreductases in the hyperthermophilic archaeon Pyrococcus furiosus. In dye-mediated equilibrium redox titrations, the tungsten in active P. furiosus FOR is a two-electron acceptor, W(VI/IV). The intermediate, paramagnetic W(V) state can be trapped only by reduction with substrate, with consecutive one-electron intraprotein electron transfer to the single [4Fe-4S](2+;+) cluster and partial comproportionation of the tungsten over W(IV, V, VI); this is a stable state in the absence of an external electron acceptor. Electron paramagnetic resonance (EPR) spectroscopy reveals a single "low-potential" W(V) spectrum with gxyz values 1.847, 1.898, and 1.972, and a [4Fe-4S]+ cubane in a spin mixture of S = 1/2 (10%) and S = 3/2 (90%) of intermediate rhombicity (E/D = 0.21, greal = 1.91). The development of this intermediate in vitro is slow even at elevated temperature and with a nominal 50:1 excess of substrate over enzyme presumably owing to the very unfavorable hydration equilibrium of the formaldehyde/methylene glycol couple with KD approximately 10(3). Rapid intermediate formation of enzyme at concentrations suitable for EPR spectroscopy (200 microM) is only obtained with extremely high nominal substrate concentration (1 M formaldehyde) and is followed by a slower phase of denaturation. The premise that the free formaldehyde, and not the methylene glycol, is the enzyme's substrate implies that KM for formaldehyde is 3 orders of magnitude less that the previously reported value.

Aldehyde Oxidoreductases↗

Human liver class III alcohol and glutathione dependent formaldehyde dehydrogenase are the same enzyme.

Human liver class III alcohol dehydrogenase (chi chi-ADH) and glutathione dependent formaldehyde dehydrogenase are the same enzyme. The enzyme, chi chi-ADH, exhibits a kcat of 200 min-1 and a km of 4 microM for the oxidation of formaldehyde, but only in the presence of GSH. In the absence of GSH the enzyme is essentially inactive toward formaldehyde but very active toward long chain alcohols. Thus, as in the rat (Koivusalo, M., Baumann, M., and Uotila, L. (1989) FEBS Letters 257, 105-109), the class III alcohol dehydrogenase and the GSH dependent formaldehyde dehydrogenase are identical enzymes. S-Hydroxymethyl derivatives of 8-thiooctanoate and lipoate are also very active substrates. The activity is specific for class III alcohol dehydrogenase; neither the class I and II nor the horse EE, ES, and SS isozymes oxidize hemithiolacetals. o-Phenanthroline competitively inhibits both activities and the two substrate types compete with each other.

Alcohol Dehydrogenase↗

Measurements of formaldehyde and acetaldehyde in the atmosphere of Mexico City.

Ambient levels of carbonyls were measured at the University of Mexico campus, Mexico City. Only formaldehyde and acetaldehyde were measured, since aldehydes with higher molecular weight were not detected. The most abundant aldehyde was formaldehyde, with an overall ratio CH3CHO/H2CO of 0.43. Maximum concentrations occurred for formaldehyde at 10:00 h while for acetaldehyde at 8:00 h. Comparing the concentration measured in this work with those in urban areas it was found that the formaldehyde and acetaldehyde levels in Mexico City are among the highest reported in the literature.

Journal Article↗

Influence of heat treatment of rayon-based activated carbon fibers on the adsorption of formaldehyde.

The influence of heat treatment of rayon-based activated carbon fibers on the adsorption behavior of formaldehyde was studied. Heat treatment in an inert atmosphere of nitrogen for rayon-based activated carbon fibers (ACFs) resulted in a significant increase in the adsorption capacities and prolongation of breakthrough time on removing of formaldehyde. The effect of different heat-treatment conditions on the adsorption characteristics was investigated. The porous structure parameters of the samples under study were investigated using nitrogen adsorption at the low temperature 77.4 K. The pore size distributions of the samples under study were calculated by density functional theory. With the aid of these analyses, the relationship between structure and adsorption properties of rayon-based ACFs for removing formaldehyde was revealed. Improvement of their performance in terms of adsorption selectivity and adsorption rate for formaldehyde were achieved by heat post-treatment in an inert atmosphere of nitrogen.

Journal Article↗

Mechanisms and kinetics of noncatalytic ether reaction in supercritical water. 2. Proton-transferred fragmentation of dimethyl ether to formaldehyde in competition with hydrolysis.

Noncatalytic reaction pathways and rates of dimethyl ether (DME) in supercritical water are determined in a tube reactor made of quartz according to liquid- and gas-phase 1H and 13C NMR observations. The reaction is studied at two concentrations (0.1 and 0.5 M) in supercritical water at 400 degrees C and over a water-density range of 0.1-0.6 g/cm3. The supercritical water reaction is compared with the neat one (in the absence of solvent) at 0.1 M and 400 degrees C. DME is found to decompose through (i) the proton-transferred fragmentation to methane and formaldehyde and (ii) the hydrolysis to methanol. Formaldehyde from reaction (i) is consecutively subjected to four types of redox reactions. Two of them proceed even without solvent: (iii) the unimolecular proton-transferred decarbonylation forming hydrogen and carbon monoxide and (iv) the bimolecular self-disproportionation generating methanol and carbon monoxide. When the solvent water is present, two additional paths are open: (v) the bimolecular self-disproportionation of formaldehyde with reactant water, producing methanol and formic acid, and (vi) the bimolecular cross-disproportionation between formaldehyde and formic acid, yielding methanol and carbonic acid. Methanol is produced through the three types of disproportionations (iv)-(vi) as well as the hydrolysis (ii). The presence of solvent water decelerates the proton-transferred fragmentation of DME; the rate constant is reduced by 40% at 0.5 g/cm3. This is caused by the suppression of low-frequency concerted motion corresponding to the reaction coordinate for the simultaneous C-O bond scission and proton transfer from one methyl carbon to the other. In contrast to the proton-transferred fragmentation, the hydrolysis of DME is markedly accelerated by increasing the water density. The latter becomes more important than the former in supercritical water at densities greater than 0.5 g/cm3.

Journal Article↗

Adsorbed intermediates of formaldehyde oxidation and their role in the reaction mechanism.

Formaldehyde oxidation was studied on the basal planes of platinum single crystals. Electrochemical and IR spectroscopy data give new information on the mechanism of oxidation. Formaldehyde oxidation at platinum electrodes is a surface-sensitive reaction. From the three basal planes of Pt(hkl), Pt(111) is the most active one. The less active surfaces Pt(100) and Pt(110) are blocked by adsorbed carbon monoxide at the initial stages of the reaction as the formaldehyde is admitted in the solution with the electrode polarized at 0.05 V. Besides CO(ad), other adsorbed species are formed. From these, methylene glycolate, H2COO(ad), is the intermediate of the fast oxidation pathways forming CO2 and HCOOH as soluble products. According to IR data the yields of soluble products at Pt(111) were calculated at 0.6 V, giving 63% for HCOOH and 37% for CO2. At 0.05 V the Pt(111) surface becomes slowly blocked by CO(ad), as observed when the electrode was left in contact with the formaldehyde solution over a period of several minutes. The same blockage occurs during a cyclic voltammogram, which causes a lowering of activity during the second potential scan. A general scheme of the reaction is proposed.

Journal Article↗

Multiple forms of formaldehyde dehydrogenase from human red blood cells.

Red cell hemolysates from nonrelated Finns were analyzed by electrofocusing on polyacrylamide gel, and formaldehyde dehydrogenase (EC 1.2.1.1) was located by an activity-staining method. Three forms of the enzyme were constantly found for all the individuals studied but no variants were observed in this population (n = 217). Human liver also had three formaldehyde dehydrogenase forms with locations identical to those of the red cell formaldehyde dehydrogenase. Population genetic studies of formaldehyde dehydrogenase can easily be performed with red cell hemolysates with the techniques described here, and there is no need to use liver biopsy samples.

Aldehyde Oxidoreductases↗

Cloning, sequence analysis, and expression of the gene encoding formaldehyde dismutase from Pseudomonas putida F61.

The gene (fdm) coding for formaldehyde dismutase (EC 1.2.99.4) from a genomic library of formaldehyde-tolerant Pseudomonas putida F61 was cloned and expressed in Escherichia coli. The nucleotides of the cloned DNA were sequenced; they included a single open reading frame of 1200 base pairs, coding for a putative protein with a molecular weight of 42,848. Sequencing of the first 20 N-terminal amino acid residues and of an internal part of the enzyme purified from P. putida F61 established the identity and the start codon of fdm. Comparison of the amino acid sequence predicted from fdm with that of alcohol dehydrogenase from horse liver suggested a putative pyridine-dinucleotide-binding domain in fdm, and also potential ligands for the catalytic domain and the second zinc atom-folding domain. fdm seemed to be expressed in E. coli under control of the promoter of fdm; there was an E. coli promoter-like sequence upstream from the gene. The enzyme expressed in E. coli was purified to homogeneity. The molecular weight and the sequence of the first 20 N-terminal amino acid residues were identical with those of P. putida formaldehyde dismutase. Each subunit contained 1 mol of NAD(H) and 2 mol of zinc per mol of protein. The enzyme produced in E. coli catalyzed the dismutation of formaldehyde to form methanol and formic acid at the ratio of 1:1 in the absence of the exogenous electron acceptor, NAD(H).

Alcohol Dehydrogenase↗

A case of claimed persistent neuropsychological sequelae of chronic formaldehyde exposure: clinical, psychometric, and functional findings.

Many anecdotal cases and some clinical studies have demonstrated that formaldehyde exposure can cause multiple health-related problems and cerebral dysfunction. The U.S. Consumer Product Safety Commission has documented multiple hazards related to formaldehyde exposure. Some of this research has suggested that low levels of exposure can be very hazardous to one's health and can potentially result in heightened chemical sensitivities, seizures, and cognitive decline. Some research suggests that exposure results in long-term immunological changes, cell neurofilament protein changes, and demyelination. Symptomatically, exposure has been associated with respiratory problems, excessive fatigue, headaches, mood changes, and impaired attention, concentration, and memory functioning. This article outlines the case of a biology teacher whose chronic formaldehyde exposure resulted in heightened sensitivity to formaldehyde, three tonic-clonic seizures, and dramatic amnesia as well as other cognitive dysfunction.

Journal Article↗

Sclerosing cholangitis induced by formaldehyde solution injected into the biliary tree of rats.

Sclerosing cholangitis has been reported after surgical treatment of hydatid disease of the liver and has been hypothetically attributed to the caustic effect of the parasiticide solution injected into the cyst and diffusing into the biliary tree through a cystic-biliary fistula. In this experimental study, we showed that, in rats, injection into the biliary tract of 20% hypertonic saline solution or 2% formaldehyde solution, the most commonly used scolicidal solutions, was followed by lesions of the biliary epithelium. As compared with 20% hypertonic saline solution, the 2% formaldehyde solution caused more severe lesions of the biliary epithelium and, in addition, induced the development of sclerosis. This experimental study confirms the deleterious effect of scolicidal solutions to the biliary epithelium, shows that their effect is mainly related to the causticity of the scolicidal solution, and indicates that intracystic injection of 2% formaldehyde solution should be abandoned.

Animals↗

Expression cassettes for formaldehyde and fluoroacetate resistance, two dominant markers in Saccharomyces cerevisiae.

We employed two genes in constructing yeast expression cassettes for dominant, selectable markers. The Saccharomyces cerevisiae gene SFA1, encoding formaldehyde dehydrogenase, was placed under the control of the GPD1 promoter and CYC1 terminator. The Moraxella sp. strain B gene dehH1, encoding fluoroacetate dehalogenase, was placed under the control of both the GPD1 and CYC1 promoters. With these constructs it was possible to select directly for yeast strains resistant to either formaldehyde or fluoroacetate. Both selective agents are completely metabolized and inexpensive, making them very useful in the pursuit of yeast gene functions and for industrial applications. An additional advantage of the formaldehyde dehydrogenase marker is that it is an S. cerevisiae gene, thus allowing 'all yeast' constructs.

Aldehyde Oxidoreductases↗

Selective binding of a monoclonal antibody to Aspergillus niger glucose oxidase by formaldehyde fixed human polymorphonuclear leukocytes.

BACKGROUND: Many of the procedures used in handling neutrophils may affect the expression of surface antigens, and hence their quantitation by flow cytometry. METHODS: Because the enzyme glucose oxidase of Aspergillus niger is absent in human tissues, an IgM against it (mAb GO) was used as negative control in a study involving the normal expression of neutrophil specific BH2-Ag in different age groups. RESULTS: When peripheral blood leukocytes (PBL) were freshly prepared, processed and stained with FITC-mAb GO without fixation or when the cells were stained with FITC-mAb GO prior to fixation with 2% formaldehyde, both median fluorescent intensity (MFI) and per cent of positively stained polymorphonuclear leukocytes (PMN) were similar to that obtained with a background sample without any antibody. However, when PBL were fixed after isolation with different concentrations of formaldehyde and for varying durations, MFI and per cent of positively stained PMN but not of monocytes or lymphocytes with FITC-mAb GO increased in a time and concentration dependent manner. Saturation was achieved at a finite concentration of the antibody. In a competition assay unlabelled mAb GO reduced binding of FITC-mAb GO to PMN by 79% and 95% at concentrations 100 and 200 times that of FITC labelled antibody, respectively. CONCLUSIONS: These observations strongly suggest that formaldehyde fixation causes the expression or accessibility of an epitope on PMN that is specifically recognized by the mAb GO.

Adult↗