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Reactions of hydrated formaldehyde in nasal mucus.

Formaldehyde is a well known toxic air impurity affecting the upper respiratory tract. It rapidly forms methylene glycol in water. Reactions of the hydrated formaldehyde with nasal mucus were studied by C-13 NMR spectroscopy. In the NMR spectra methylene glycol dominated and only minor signals from possible reactions were observed. This finding suggests that nasal mucus effectively protects nasal epithelium against formaldehyde.

Carbon Isotopes↗

Solubility and diffusion coefficients of gaseous formaldehyde in polymers.

The solubility and diffusion (desorption) coefficients of gaseous formaldehyde in 14 materials have been measured at different temperatures. Cellulose, paper, polyamide (Nylon 6), polyester and natural rubber (latex) show very high values of formaldehyde solubility and very low diffusion coefficients, with a weak or inversed influence of the temperature, leading to the conclusion that a chemical reaction occurs with the formaldehyde. The behaviour of the other polymers follows the classical laws of solubility and diffusion of gases except for silicone rubber which shows two-phase desorption curves.

Biocompatible Materials↗

The aluminum-formaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indoleamines. I. A detailed account of the methodology for central nervous tissue using paraffin, cryostat or Vibratome sections.

This present paper presents a new aluminum-formaldehyde (ALFA) histofluorescence method for highly sensitive visualization of central monoamine-containing neurons, based on perfusion with or immersion in buffers containing high concentrations of aluminum ions. Our previous studies have shown that perfusion or immersion of tissues with solutions containing high concentrations of magnesium results in an improvement in the visualization of intraneuronal catecholamines in the reaction with formaldehyde and glyoxylic acid. This study demonstrates that aluminum is considerably more efficient as a fluorescence-promoting agent, thus causing a further increase in the sensitivity of the formaldehyde method. Detailed protocols are given for the ALFA-method applied to paraffin sections of freeze-dried tissue, and to cryostat and Vibratome sections. The present ALFA technique applied to paraffin sections of freeze-dried tissue visualizes all known catecholamine neuron systems with a sensitivity comparable to, and for certain noradrenergic systems higher than, that of the previously published glyoxylic acid-Vibratome method. Furthermore, the use of freeze-dried, paraffin embedded tissue makes possible convenient storage and parallel processing of many specimens. This mode of processing also allows en bloc reaction, which is the only way by which consistent and reproducible fluorescence yields can be obtained throughout large series of sections and parallelly processed specimens. In animals pretreated with L-tryptophan and MAO-inhibitor the technique is also useful for studies on central indoleamine-containing systems in freeze-dried tissue. The ALFA procedure applied to cryostat and Vibratome sections gives a more sensitive and reproducible visualization of central catecholamine neurons than previous methods.

Aluminum↗

Sperm count, morphology and fluorescent body frequency in autopsy service workers exposed to formaldehyde.

A battery of monitoring tests that could indicate genetic damage was used to investigate occupational formaldehyde exposure in a population of a hospital autopsy service workers. 11 exposed individuals and 11 matched controls were evaluated for sperm count, abnormal sperm morphology and 2F-body frequency. Subjects were matched for sex, age and customary use of alcohol, tobacco and marijuana. Additional information was collected on health, medications and other exposures to toxins. 10 subjects were employed for 4.3 months (range 1-11 months) prior to the first sample and 1 was employed for several years. Formaldehyde exposures were episodic but with a time weighed average between 0.61 and 1.32 ppm (weekly exposure range 3-40 ppm X h). Exposed and control subjects were sampled 3 times at 2-3 month intervals. Sperm morphology was also evaluated in B6C3F1 mice after 5 daily oral doses of 100 mg/kg formalin. No increase in abnormal morphology was detected in the treated animals. In humans, no statistically significant differences were observed between the exposed and control groups for the observed variables. Reduced sperm count correlated with increased abnormal morphology and 2F-body frequency in the exposed group but not in the control group. Evaluation of the impact of incidental exposures suggests a reduced count with marijuana use and increased abnormal morphology with medications used by controls. No effects on sperm were seen from formaldehyde or its metabolites in this population after occupational exposure, nor in mice following a high acute exposure. It is possible that minor effects might have occurred. The lack of an effect in this study may be due to a lack of statistical power to detect effects at this exposure level.

Air Pollutants, Occupational↗

Mutagenic characteristics of formaldehyde on bacterial systems.

The mutagenic characteristics of formaldehyde on bacteria were examined. All the tester strains of Escherichia coli deficient in DNA-repair enzymes tested in the present study were significantly more sensitive to the killing effect of formaldehyde than the corresponding wild-type strain. Among the E. coli B strains, H/r30R (wild-type) and Hs30R (uvrA) were mutable, whereas NG30 (recA) and O16 (polA) were not. There is no appreciable difference in mutation frequency of E. coli B between the wild-type and the uvrA strains in a dose range below 4 mM. However, the mutation frequency of the wild-type strain started to decrease in a higher concentration range, whereas that of the uvrA strain continued to increase linearly. This was confirmed with the E. coli B/r tester strains. The decrease in mutation frequency may be produced by prolongation of the lag period before entering the S-phase so as to give the cells a greater chance for DNA repair through the excision mechanism. In fact, it was evidenced that formaldehyde retarded to a remarkable extent the initiation of DNA synthesis of the cells at the higher dose range used for mutation assay. Some discrepancies found between the results obtained in this study and those previously reported by Nishioka (1973) were pointed out.

Bacterial Proteins↗

Formaldehyde-induced and spontaneous alterations in human hprt DNA sequence and mRNA expression.

Human lymphoblast mutants at the X-linked hprt locus have been examined by Southern blot, Northern blot and DNA sequence analysis. A previous study had shown that approximately a third of the spontaneously-arising mutants and half those induced by formaldehyde showed no alteration in restriction fragment pattern and thus were classified as point mutations. In this report, Northern blot analysis was used to show that these point mutants fall into 4 categories: normal size and amount of RNA, normal size but reduced amounts, reduced size of RNA or no RNA. Sequence analyses of cDNAs prepared from hprt mRNAs were performed on 1 spontaneous and 7 formaldehyde-induced mutants with normal Northern blots. The spontaneous mutant was caused by an AT----GC transition. 6 of the formaldehyde-induced mutants were base substitutions, all of which occurred at AT base-pairs. There was an apparent hot spot, in that 4/6 independent mutants were AT----CG transversions at one specific site. The remaining mutant had lost exon 8.

Base Sequence↗

Mucosal and systemic immunogenicity of a recombinant, non-ADP-ribosylating pertussis toxin: effects of formaldehyde treatment.

The effect of formaldehyde treatment on the mucosal and systemic immunogenicity of the genetically detoxified pertussis toxin (PT-9K/129G) was investigated. Groups of BALB/c were immunized intranasally (i.n.) or subcutaneously (s.c.) with untreated, lightly formaldehyde treated (LFT) or heavily formaldehyde treated (HFT) recombinant pertussis toxin (PT) mutant, PT-9K/129G. Intranasal immunization with native PT-9K/ 129G induced significant levels of anti-toxin antibodies in serum and IgA anti-toxin responses in nasal and lung lavages of these mice. Similar local and systemic responses were observed following intransal immunization with LFT toxin. However, i.n. immunization with HFT toxin failed to induce a local IgA response and elicited a much diminished anti-toxin response in the serum. In contrast, the total antibody response following s.c. immunization was not significantly affected. In addition, i.n. immunization with native PT-9K/129G induced low but detectable levels of toxin neutralizing antibodies in the serum. These results show that native PT-9K/129G protein acts as a mucosal immunogen in mice and that this activity is greatly diminished by HFT of the protein.

Administration, Intranasal↗

Acute low-level formaldehyde behavioural and neurochemical toxicity in the rat.

The purpose of the present study was to determine the effects of low-level formaldehyde exposure upon behavior and neurochemistry in the male rat. Rats were exposed to either air or formaldehyde vapor (5, 10 or 20 parts per million) for 3 hours on 2 consecutive days during which behavioral observations were made. Following the second exposure session the rats were sacrificed and their brains analyzed for norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites. Formaldehyde exposure resulted in decreased motor activity and neurochemical changes in dopamine and 5-hydroxytryptamine neurons.

Animals↗

The effects of formaldehyde gas in a flow-through rat tracheal implant system.

A flow-through rat tracheal implant system is described which permits the quantitative and repetitive exposure of respiratory epithelia to test gaseous substances. To investigate the acute toxicity of formaldehyde gas with this new system, open-ended rat tracheal implants were exposed to the gas for 1 h twice a week for up to 8 weeks. The formaldehyde gas was gene-rated from paraformaldehyde, mixed with humidified air and introduced into the lumens of the tracheal implants through microbore tubing. Concentrations of 4.1 +/- 0.9, 8.1 +/- 1.2 or 12.7 +/- 1.5 ppm, were introduced into the trachea by passing an airstream moving at 50, 225 or 475 ml/min, respectively, over the paraformaldehyde heated to 42 degrees C. These formaldehyde concentrations induced mucociliary hypertrophy and increasing amounts of atrophic, transitional and metaplastic epithelia in the tracheal mucosa.

Animals↗

Cytotoxic and adaptive effects in rat nasal epithelium after 3-day and 13-week exposure to low concentrations of formaldehyde vapour.

To study in detail possible effects of low concentrations of formaldehyde on the nasal epithelium, Wistar rats were exposed to 0, 0.3, 1 and 3 ppm formaldehyde vapour for 6 h/day, 5 days/week during 3 days or 13 weeks, using in vivo [3H]thymidine labeling for cell proliferation studies, and light and electron microscopy for detecting morphological effects. Compound related histopathological nasal changes varying from epithelial disarrangement to epithelial hyperplasia and squamous metaplasia were found in the 3 ppm group, and were restricted to a small area of the anterior part of the nose which is normally covered with respiratory epithelium. These changes were confirmed by electron microscopy and were not observed in the other groups. Increased cell turnover in the same anterior location confirmed high mitotic activity in the 3 ppm group after 3 days and 13 weeks of exposure. At a slightly more posterior level in the nose a transient response in cell turnover was observed. After 3 days of exposure a nearly log-linear relationship was found between cell turnover and exposure concentration reaching a 10-fold increase in the 3 ppm group, and suggesting challenge of the mucociliary and/or regenerative defence systems not only at 3 ppm but also at 0.3 and 1 ppm. After 13 weeks of exposure mean turnover rates in all exposed groups were markedly lower than after 3 days, and the mean rates of the formaldehyde-exposed groups tended to be below that of the controls. The variation in turnover rate after 13 weeks had increased in a concentration related way, suggesting individual variation in adaptation. The most likely adaptive mechanism at this more posterior level of the nose seemed to be the mucociliary defence apparatus.

Adaptation, Physiological↗

Possible role of the control of arginase and methionine adenosyl transferase in the transport processes of endogenous formaldehyde and in hypermethylation.

The authors believe the normal formaldehyde equilibrium in the organism to be governed by a biological control mechanism, which is thought to be closely connected to L - arginine and - indirectly - to the arginase enzyme. Arginine reacts with formaldehyde in a spontaneous equilibrium reaction yielding methylol - derivatives thus mobilizing formaldehyde. The methylol - derivatives of L - arginine were found in serum and urine. The authors assume the methylol - derivatives of L - arginine to have an inhibiting effect on cell - proliferation.

Animals↗

Fluorescence of catechol amines and related compounds condensed with formaldehyde.

The reaction under mild conditions between formaldehyde and phenylalanine and phenylethylamine derivatives has been studied. When the amines included in a dried protein film were exposed to formaldehyde vapour a very intense green to yellow fluorescence was given only by those that as well as being primary amines also have hydroxyl groups at the 3 and 4 positions (3,4-dihydroxyphenylalanine, dopamine, noradrenaline). The 3-OH group seems to be essential for the reaction. The catechol amines, which are secondary amines (adrenaline, epinine), gave a much weaker fluorescence that developed more slowly. The results obtained on further examination of the reaction favour the view that the amines primarily condense with formaldehyde to 1,2,3,4-tetrahydroisoquinolines which are involved in a secondary reaction to become highly fluorescent and at the same time insoluble. This secondary reaction may be a binding to protein, an oxidation with the formation of double bonds in the heterocyclic ring, or both.

Catecholamines↗

Cloning and analysis of a Candida maltosa gene which confers resistance to formaldehyde in Saccharomyces cerevisiae.

A gene (FDH1) of Candida maltosa which confers resistance to formaldehyde in Saccharomyces cerevisiae was cloned and its nucleotide sequence determined. The gene has a single intron which possesses the highly conserved splicing signals found in S. cerevisiae introns. We demonstrated that processing of the pre-mRNA of the cloned gene occurred identically in both S. cerevisiae and C. maltosa. The predicted amino acid sequence from the cloned gene showed 65.5% identity to human alcohol dehydrogenase (ADH) class III and 23.9% identity to S. cerevisiae ADH1. The most probable mechanism of resistance to formaldehyde is thought to be the glutathione-dependent oxidation of formaldehyde which is characteristic for ADH class III. The cloned FDH1 gene was successfully employed as a dominant selectable marker in the transformation of S. cerevisiae.

Alcohol Dehydrogenase↗

Characterization of the immunogenicity of formaldehyde detoxified Pasteurella multocida toxin.

The immunogenicity of the Pasteurella multocida toxin (PMT) was studied in murine model systems. Mice were vaccinated with either formaldehyde treated pure PMT (pure toxoid) or formaldehyde treated crude extract of toxigenic P. multocida (crude toxoid). The corresponding mean anti-PMT titres, sero-conversion rates and survival rates after challenge with affinity purified PMT were compared. When assessed both by anti-PMT titres and seroconversion and challenge, pure toxoid was a more potent immunogen than crude toxoid. This greater immunogenic potency was unaffected by the addition of killed cell preparations of Bordetella bronchiseptica, non-toxigenic P. multocida and B. pertussis. Increasing anti-PMT titres and seroconversion rates were induced by increasing doses of formaldehyde treated PMT (fPMT) in the pure toxoid vaccines, but not in the vaccines containing crude toxoid. However, improved survival rates were observed for both types of vaccine, when the fPMT content was raised. Immunization of pregnant mice with vaccines containing fPMT induced protection of the offspring against challenge with PMT; the protection of the offspring corresponded to that of the mother.

Animals↗

Reactions of formaldehyde with guanosine.

Formaldehyde reacted with guanosine and the products were assayed using fluorescence spectroscopy at different pHs. The reaction products were fluorescent in alkali only as was found with commercial N-2 methylguanosine. Thus, formaldehyde appeared to react with N-2 of guanosine. The reaction was completed with 30s both at 0 degrees C or at 21 degrees C. The stability of the reaction products was further investigated by the addition of glycine. When formaldehyde was allowed to react with guanosine for 30s, 90% of the fluorescence disappeared when glycine was added suggesting a labile adduct such as a methylol derivative. By contrast, after a 20 h incubation only 20% of fluorescence was abolished with glycine suggesting a stable adduct such as a methylene derivative.

Chemical Phenomena↗

Urinary sulfur containing metabolites after administration of ethanol, acetaldehyde and formaldehyde to rats.

Acetaldehyde and formaldehyde react in vitro with cysteine to form a product, probably a thiazolidine derivative, which eluted as a single peak in cation exchange chromatography. The reactivity of formaldehyde was much higher than that of acetaldehyde. Rats were injected with single dose of 7.6, 6.2 and 2.5 mmol, respectively of ethanol, acetaldehyde and formaldehyde, and urine was analysed for alkali-hydrolysable thiol groups. Acetaldehyde caused a significant increase in urinary alkali-hydrolysable thiols. Ethanol and acetaldehyde treatment stimulated the ability of the urine to catalyse the iodine-azide reaction suggesting the presence of an excess of compounds containing C-S-atoms.

Acetaldehyde↗

Degradation of plastic polyoxymethylene brackets and the subsequent release of toxic formaldehyde.

PURPOSE: Heat, acids, alkalis, oxygen, abrasion, enzymes, and radiation are all viable mechanisms for the chemical breakdown of polyoxymethylene (POM), a plastic material used in some esthetic orthodontic brackets. The aim of this study was to establish the thermal characteristics of POM brackets and the chemical by-products in the as-received bracket, during thermal analyses of the bracket, and after abrasion of the slot and base of the bracket. MATERIAL: Plastic brackets and control rods made of POM were evaluated ex vivo by thermal and chemical analyses. RESULTS: POM brackets produce toxic formaldehyde gas whether heated or mechanically abraded. Patients who wear these brackets are being exposed to, at the very least, a potential irritant. Thermal analyses showed that the melting temperature of a POM bracket was approximately 178 degrees C, comparable to that for a commercial rod of POM. Both POM products started to degrade at approximately 250 degrees C, and, by 420 degrees C, both products had completely decomposed into their fundamental molecular structure, formaldehyde. A colorimetric assay with a fuchsin-aldehyde reagent (Schiff's reagent) showed that aldehydes were present in the effluent from thermal heating, from mechanical abrasion of the bracket's slot or base, and even from the as-received bracket. The only difference between the 6 to 8-week assays and the 12 to 14-week assays was the intensification of the color, which occurred because of an increase in aldehyde formation and the concomitant increase in double-bond formation. These observations are consistent with a report in the tribologic (ie, friction and wear) literature, which documented the degradation of POM when it rubs against steel. CONCLUSIONS: Because formaldehyde's inherent uses as a disinfectant base and embalming fluid preclude its beneficial presence in the human body, further use of POM for orthodontic brackets, crowns for children, and other prosthetic appliances is contraindicated because even radiography will promote its degradation.

Biodegradation, Environmental↗

Photocatalytic degradation of formaldehyde containing wastewater from veterinarian laboratories.

The photocatalytic destruction of methanol, formaline (mixture of formaldehyde, methanol and water) and formaline wastes from the preservation of vertinarian physiologic samples has been attempted by two different processes, at high concentrations of reagents and by dossification of reagents, varying pH in both. Experiment evolution has been monitored by measuring the organic matter such as TOC and formaldehyde concentrations [H2CO]. Also, methanol and methanol-formaldehyde interactions with the TiO2 surface have been analysed by FTIR spectroscopy. Results indicate that at high concentrations the catalyst surfacial alterations given by methoxy, formates or carbonates, according to the pH of the sample can profoundly affect catalyst behaviour. It has been established that reagent dossification is advantageous for enhancing photonic efficiency as it minimizes the adsorbate presence that hampers the photocatalytic process.

Carbon↗