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PubMed1998

Research on chronic, low-level exposure to formaldehyde: implications for neuropsychological assessment.

Findings from empirical research serve as the foundation for neuropsychological assessment of individuals suspected of exposure to formaldehyde. Insofar as conclusions regarding causal relationships between exposure and neuropsychological deficits are based on research methodologies that are reliable, findings can be informative. Unfortunately, existing research is not rooted in sound methodology and findings may mislead rather than enlighten clinicians. Two prominent shortcomings in formaldehyde research are discussed: selection bias in recruitment of research participants and unreliability of participant recall for obtaining data on important background variables and exposure levels. Selected examples illustrate the influence of these shortcomings on research showing a causal relationship between long-term, low-level exposure to formaldehyde and chronic neurobehavioral deficiencies. The implications of these weaknesses for assessment of individual patients are discussed.

Chronic Disease↗
PubMedDate not supplied

Quantitative TLC determination of formaldehyde in hard tissues of teeth.

Levels of formaldehyde, which is formed within cells as an indispensable part of biological processes, have been determined by means of TLC in hard tissues of human teeth, with and without pathological changes. A wide variety of formaldehyde levels was determined according to the physiological state of a tooth. The results show that caries can be of immense importance in the process of formaldehyde formation and its release in hard tissues of human teeth.

Chromatography, Thin Layer↗
PubMed2001

Modification and inhibition of vancomycin group antibiotics by formaldehyde and acetaldehyde.

It is shown that several vancomycin group antibiotics (vancomycin, eremomycin, and avoparcin) undergo spontaneous chemical modifications when kept at room temperature at neutral pH in aqueous solutions containing traces of formaldehyde or acetaldehyde. This chemical modification predominantly results in a mass increase of 12 Da in the reaction with formaldehyde and 26 Da in the case of acetaldehyde. By using tandem mass spectrometry the modification can unambiguously be identified as originating from the formation of a ring-closed 4-imidazolidinone moiety at the N-terminus of the glycopeptide antibiotics, that is, near the receptor binding pocket of the glycopeptide antibiotics. Bioaffinity mass spectrometry shows that this ring-closure results in a dramatically decreased affinity for the peptidoglycan-mimicking D-alanyl-D-alanine receptor. Additionally, in vitro inhibition measurements on two different strains of bacteria have revealed that the modified antibiotics display reduced antibacterial activity. The ring-closure is also shown to have a dissociative effect on the dimerization of the vancomycin-analogue eremomycin. The spontaneous reaction of vancomycin with formaldehyde or acetaldehyde may have implications not only for the clinical use of this class of antibiotics, but also for the effectiveness of these antibiotics when they are used in chiral separation chromatography or capillary electrophoresis.

Acetaldehyde↗
PubMed1989

Prospective study of respiratory effects of formaldehyde among healthy and asthmatic medical students.

We conducted a prospective evaluation of pulmonary function and respiratory symptoms among 103 medical students exposed to formaldehyde over a 7-month period to determine the incidence of bronchoconstriction and respiratory symptoms in response to exposure. Time-weighted average formaldehyde exposures were generally less than 1 part per million (ppm) and peak exposures were less than 5 ppm. Acute symptoms of eye and upper respiratory irritation were significantly associated with exposure. There was no pattern of bronchoconstriction in response to exposure after either 2 weeks or 7 months. Twelve subjects had a history of asthma; they were no more likely to have symptoms of respiratory irritation or changes in pulmonary function than those without such a history. These findings are consistent with previous case reports that indicate exposure to formaldehyde vapor at levels that are commonly encountered in occupational and residential settings do not commonly cause significant bronchoconstriction, even among subjects with preexisting asthma.

Adult↗
PubMed1994

Formaldehyde exposure, acute pulmonary response, and exposure control options in a gross anatomy laboratory.

Formaldehyde exposure, acute pulmonary response, and exposure control options were evaluated in a group of 34 workers in a gross anatomy laboratory. Time-weighted average (TWA) exposure to formaldehyde ranged from 0.07-2.94 parts per million (ppm) during dissecting operations. More than 94% were exposed to formaldehyde in excess of the ceiling value of 0.3 ppm recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). The eight-hour TWA exposure of 31.7% of the subjects exceeded the action level of 0.5 ppm set by the Occupational Safety and Health Administration (OSHA). Reported symptoms included irritation of eye (88%), nose (74%), throat (29%), and airways (21%). Forced vital capacity (FVC) and forced expiratory volume in 3 seconds (FEV3) decreased, and FEV1/FVC increased during the exposure. The changes of FEV3 were statistically different from those of the controls. The results strongly support the necessity for designing and testing special local exhaust-ventilated worktables with necessary flexibility for dissecting operations.

Adult↗
PubMed1984

Phenoxyethanol as a nontoxic substitute for formaldehyde in long-term preservation of human anatomical specimens for dissection and demonstration purposes.

Formaldehyde has recently been declared a potential carcinogen. Occupational health authorities throughout the world are therefore likely to put stricter regulations to its use also within anatomical disciplines. We have been able to reduce the atmospheric concentration of formaldehyde in our dissection rooms to below the detection limit of a conventional Dräger tube multigas analyzer (i.e., below 0.5 ppm or 0.6 mg formaldehyde/m3 air), by extracting previously formaldehyde-fixed material for more than 3 months in 1% phenoxyethanol in tap water. In this fluid our material has remained soft and flexible with a consistency and color retention suitable for dissection and demonstration purposes for up to 10 years. Fungal attacks are rare and we have been unable to raise bacteria from such specimens. Even the microscopical structure of most tissues remains satisfactory after 5 years in 1% phenoxyethanol. The unpleasant and irritating smell traditionally felt in dissection rooms is almost absent in our facilities, but some of our students still mention slight odor, headache, drowsiness, and mild eye, nose, and throat irritation during their dissection practice periods.

Aged↗
PubMed1976

Bacterial yields on methanol, methylamine, formaldehyde, and formate.

Several bacteria utilizing C1-compounds as sole carbon sources were grown on these substrates in continuous culture. The molar yield values (g of cell dry wt/mol of substrate utilized) of bacteria which utilize C1-compounds via the ribulose monophosphate pathway were between 15.7 to 17.3 when grown on methanol; while the molar yield values of bacteria which use the serine pathway for the assimilation of C1-compounds varied between 9.8 and 13.1. The molar yield values of different bacteria which use the serine pathway decreased as the oxidation levels of the C1-growth substrates increased. On formaldehyde the values were between 7.2 to 9.6, whereas on formate the values varied from 3.3 to 6.9. It appears that bacteria utilize C1-compounds more efficiently via the ribulose monophosphate pathway than via the serine pathway. The oxidation step from methanol to formaldehyde (and from methylamine to formaldehyde) in the bacteria studied may be energy yielding. A comparison has been made between the experimental yield values obtained and theoretical values.

Formaldehyde↗
PubMed1983

The cytoskeleton of murine leukemia virus (MuLV)-infected mouse fibroblasts as observed under varying conditions of formaldehyde fixation.

Mouse fibroblasts chronically infected with Moloney murine leukemia virus (MuLV) were fixed using variable amounts of formaldehyde, then examined by indirect immunofluorescence light microscopy. Several antisera were employed to detect both external and internal antigens associated with the cells, eg, MuLV gp70, tubulin, vimentin, and actin. Our results indicate that the cell membranes could be partially permeabilized to IgG molecules directed against the three cytoskeletal antigens only after 3.7%, but not 1%, formaldehyde treatment. Complete permeabilization was achieved by subsequent acetone treatment of cells after 3.7% formaldehyde fixation. In such cells, normal-appearing cytoskeletal networks of microtubules and intermediate filaments were observed. Stress fibers were also seen; however, they appeared less numerous and thinner than those of uninfected mouse fibroblasts. Further, a significant amounts of F-actin fluorescence was localized in granules in the cytoplasm of infected cells. Similar observations were made using JLS-V9 mouse cells chronically infected with 334C virus, another MuLV. These results taken together suggest that subtle differences exist in the organization of actin within MuLV-infected and uninfected mouse fibroblasts.

Actins↗
PubMed1986

Formaldehyde and cancers of the pharynx, sinus and nasal cavity: II. Residential exposures.

To investigate the possible association between residential formaldehyde exposures and risk of cancer of the oro- and hypopharynx (OHPC, N = 205), nasopharynx (NPC, N = 27) and sinus and nasal cavity (SNC, N = 53), a population-based case-control investigation was carried out in 13 counties of western Washington. Controls (N = 552) were selected by random digit dialing. Subjects' residential histories, including type of dwelling, were determined from a structured telephone interview which also collected smoking, alcohol and demographic information. Multiple logistic regression was used to estimate exposure odds ratios (OR) while adjusting for known risk factors. A strong association was found between a history of having lived in a mobile home and NPC, but not OHPC or SNC. The NPC risk increased with the number of years lived in a mobile home: for those with 1 to 9 years the OR = 2.1 (95% confidence interval = 0.7-6.6), and for those with 10 or more years, the OR = 5.5 (95% CI = 1.6-19.4). No associations were found between any of the cancers and a history of exposure to new constructions containing particle board and plywood, or to urea-formaldehyde foam insulation. The association found with living in a mobile home must be interpreted with caution since it is based on a small number of cases, and may be due to factors other than formaldehyde. This report emphasizes the need for additional studies focusing on potential associations between indoor air pollutants and respiratory cancers.

Adult↗
PubMed1985

Effects of formaldehyde and acetaldehyde inhalation on rat pulmonary mechanics.

Two groups of 12 male Wistar rats received either 243 ppm of acetaldehyde or 5.7 ppm of formaldehyde for 8 h a day, 5 days a week during 5 weeks. These levels represent three times the threshold limit values (TLV) for these substances in Brazilian legislation. The animals were evaluated by pulmonary function tests before and after exposure to the pollutants. The data obtained from these rats were compared with those of 12 controls, housed in identical conditions for the same length of time but breathing normal air. The results showed an increase of the functional residual capacity, residual volume, total lung capacity and respiratory frequency in the rats exposed to acetaldehyde atmosphere. The animals exposed to formaldehyde did not present pulmonary function alterations when compared with the controls. The damage caused by acetaldehyde to the peripheral regions of the lung parenchyma, affecting small airways or altering pulmonary elastic properties, is discussed. It is suggested that the Brazilian TLV for acetaldehyde (78 ppm) is not as safe as that for formaldehyde (1.6 ppm).

Acetaldehyde↗
PubMed1987

Subacute (4-week) inhalation toxicity study of formaldehyde in male rats: 8-hour intermittent versus 8-hour continuous exposures.

Male Wistar rats were exposed for 4 weeks, 5 days a week, to 0 (controls), 5 or 10 ppm formaldehyde continuously (8 hours a day), or to 10 or 20 ppm formaldehyde interruptedly (eight 30 min exposure periods separated by 30 min non-exposure periods). Histopathology and cell proliferation studies indicated that under the conditions of exposure used, concentration rather than the total dose of formaldehyde determined the severity of the cytotoxic effects on the nasal epithelium.

Animals↗
PubMed2004

Alcohol dehydrogenases that catalyse methyl formate synthesis participate in formaldehyde detoxification in the methylotrophic yeast Candida boidinii.

Methyl formate synthesis during growth on methanol by methylotrophic yeasts has been considered to play a role in formaldehyde detoxification. An enzyme that catalyses methyl formate synthesis was purified from methylotrophic yeasts, and was suggested to belong to a family of alcohol dehydrogenases (ADHs). In this study we report the gene cloning and gene disruption analysis of three ADH-encoding genes in the methylotrophic yeast Candida boidinii (CbADH1, CbADH2 and CbADH3) in order to clarify the physiological role of methyl formate synthesis. From the primary structures of these three genes, CbAdh1 was shown to be cytosolic and CbAdh2 and CbAdh3 were mitochondrial enzymes. Gene products of CbADH1, CbADH2 and CbADH3 expressed in Escherichia coli showed both ADH- and methyl formate-synthesizing activities. The results of gene-disruption analyses suggested that methyl formate synthesis was mainly catalysed by a cytosolic ADH (CbAdh1), and this enzyme contributed to formaldehyde detoxification through glutathione-independent formaldehyde oxidation during growth on methanol by methylotrophic yeasts.

Alcohol Dehydrogenase↗
PubMed1996

Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein.

Formaldehyde, acetaldehyde, and acrolein are well-known upper respiratory tract irritants and occur simultaneously as pollutants in many indoor and outdoor environments. The upper respiratory tract, and especially the nose, is the prime target for inhaled aldehydes. To study possible additive or interactive effects on the nasal epithelium we carried out 1- and 3-day inhalation studies (6 hr/day) with formaldehyde (1.0, 3.2, and 6.4 ppm), acetaldehyde (750 and 1500 ppm), acrolein (0.25, 0.67, and 1.40 ppm), or mixtures of these aldehydes, using male Wistar rats and exposure concentrations varying from clearly nontoxic to toxic. The (mixtures of) aldehydes were studied for histopathological and biochemical changes in the respiratory and olfactory epithelium of the nose. In addition, cell proliferation was determined by incorporation of bromodeoxyuridine and proliferating cell nuclear antigen expression. Effects were primarily observed after 3 days of exposure. Histopathological changes and cell proliferation of the nasal epithelium induced by mixtures of the three aldehydes appeared to be more severe and more extensive in both the respiratory and the olfactory part of the nose than those observed after exposure to the individual aldehydes at comparable exposure levels. As far as nasal histopathological changes and cell proliferation are concerned neither dose addition nor potentiating interactions occurred at no-toxic-effect levels, except for a possible potentiating effect of acetaldehyde at noneffect levels. The results did not indicate a major role for aldehyde dehydrogenases in the biotransformation of the aldehydes studied. Activities of glutathione S-transferase and glutathione reductase after 3 days of exposure to acrolein, alone or in combination with formaldehyde and acetaldehyde, were depressed whereas the glutathione peroxidase activity was elevated. No decrease of nonprotein sulphydryl levels were observed. These findings suggest that, for no-toxic-effect levels, combined exposure to these aldehydes with the same target organ (nose) and exerting the same type of adverse effect (nasal cytotoxicity), but partly with different target sites (different regions of the nasal mucosa), is not associated with a greater hazard than that associated with exposure to the individual chemicals.

Acetaldehyde↗
PubMed1999

Formaldehyde cross-linking for studying nucleosomal dynamics.

Methods are described for the utilization of formaldehyde as a reversible cross-linking agent for the characterization of protein-protein and protein-DNA interactions. The methods include a description of procedures to: (1) isolate and characterize transcriptionally active chromatin from cells cross-linked with formaldehyde; (2) study histone mobility during replication and transcription by the characterization of the formaldehyde-cross-linked histone octamer that is isolated from cells labeled with density-labeled amino acids; and (3) cross-link the in vitro reconstituted histone-DNA complex in order to maintain its structural state during subsequent characterization. Included in these methods are procedures for a second dimensional analysis of protein-protein cross-links in which the monomer components are electrophoretically resolved in the second dimension. The methods also include procedures to selectively reverse protein-DNA cross-links while maintaining the protein-protein cross-links. Potential artifacts are also discussed; i.e., data are presented which indicate that the helical pitch of DNA can be altered if the ionic strength is not properly controlled. The stability of the cross-linked nucleosome in the presence of altered pH or salt/urea concentrations is described in order to indicate that there are limitations to procedures that can be used for the subsequent characterization of the cross-linked complex.

Cross-Linking Reagents↗
PubMed1995

Formaldehyde inactivation of measles virus abolishes CD46-dependent presentation of nucleoprotein to murine class I-restricted CTLs but not to class II-restricted helper T cells.

To induce an MHC-restricted specific CTL or Th response, an antigen must be delivered into the appropriate cellular compartment. We explored the role of CD46 in the presentation of measles virus (MV) nucleoprotein (NP) to murine NP-specific and MHC Class I-restricted polyclonal CTLs and the effect of inactivating MV by uv or formaldehyde. CD46(-)- and CD46(+)-transfected murine cells were used as target cells. After MV infection, only the targets which expressed CD46 were lysed by NP-specific class I-restricted CTLs. When MV was uv-inactivated, NP presentation by MHC class I molecules was retained but could be blocked by fusion inhibitors which block virus cell entry. When MV was inactivated with formaldehyde, NP was no longer presented by MHC class I molecules, although it was still presented by MHC class II molecules to a NP-specific class II-restricted T cell hybridoma. These data show that MV binding to the CD46 molecule is a prerequisite for virus-to-cell fusion and that cytosolic delivery of NP is necessary for presentation by class I molecules. Moreover, formaldehyde inactivation of virus induces the loss of class I-restricted presentation of NP due to selective abrogation of fusion and cytosolic delivery of NP.

Amino Acid Sequence↗
PubMed1990

Mechanism of formaldehyde biodegradation by Pseudomonas putida.

Formaldehyde biodegradation by a strain of Pseudomonas putida has been studied. The results indicate that this biodegradation is initiated by a dismutation reaction, yielding as products formic acid and methanol. The degradation of methanol and formic acid begins after exhaustion of formaldehyde in the medium, and presents a diauxic pattern: first formic acid is consumed followed by methanol. Moreover, cell viability, which is affected by the amount of added formaldehyde, has been determined.

Alcohol Oxidoreductases↗
PubMed1976

Denudation of the urinary bladder mucosa in the cat by formaldehyde.

Chemical Stripping of the urinary bladder mucosa was studied in 38 cats using 5 to 25% formaldehyde solutions. The contact time varied from 1 to 20 min. With a 20% solution and contact time of 1 min, total denudation was possible without necrosis of subepithelial layers. In such cases, complete reepithelialisation and normal bladder dynamics were seen within 3-4 weeks after formaldehyde instillation. Signs of formaldehyde intoxication due to vesical resorption were not observed.

Animals↗
PubMed1987

Computer-operated microspectrofluorimetry to identify formaldehyde-induced fluorophores of biogenic monoamines and precursor substances in models and tissue sections.

By means of a histochemical reaction using formaldehyde vapour (Falck and Owman 1965), biogenic monoamines and precursor substances, i.e., L-DOPA, dopamine, noradrenaline, adrenaline, 5-hydroxytryptophan and 5-hydroxytryptamine, may be converted into fluorophores with specific spectral characteristics, i.e., the emission spectrum, excitation spectrum and fading curve. The registration and correction of the spectral properties and changes induced by acidification with hydrochloric acid vapour or treatment with ammonia vapour, of these formaldehyde-induced fluorophores, are performed by an automated microspectrofluorimeter, developed by modification of a Leitz MPV 2 system. This work deals with the instrumental configuration and certain methodological features in order to identify the fluorogenic biogenic monoamines and precursor substances in models and tissue sections. Registrations of excitation peak values, for the first time extended to a wavelength range from 240-460 nm, are discussed, which enable the calculation of peak ratio values 410/260, 380/320, 320/260 or 385/315, suitable as identification parameters for formaldehyde-induced fluorophores of biogenic monoamines and precursor amino acids.

5-Hydroxytryptophan↗