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PubMed2001

Formaldehyde promotes and inhibits the proliferation of cultured tumour and endothelial cells.

Formaldehyde was applied in various doses (0.1-10.0 mM) to HT-29 human colon carcinoma and HUV-EC-C human endothelial cell cultures. Cell number, apoptotic and mitotic index as well as proportion of cells in S-phase was investigated by morphological methods and flow cytometry. Ten mM of formaldehyde caused high degree of cell damage and practically eradicated the cell cultures. One mM of formaldehyde enhanced apoptosis and reduced mitosis in both types of cell cultures, in a moderate manner. The low dose (0.1 mM) enhanced cell proliferation and decreased apoptotic activity of the cultured cells, the tumour cells appeared to be more sensitive. The possible role of this dose-dependent effect of formaldehyde in various pathological conditions, such as carcinogenesis and atherogenesis is discussed with emphasis on the eventual interaction between formaldehyde and hydrogen peroxide.

Apoptosis↗
PubMed2002

Laser microdissection and gene expression analysis on formaldehyde-fixed archival tissue.

BACKGROUND: Analysis of renal biopsies is currently based on histological recognition of typical structural patterns and immunohistological detection of protein expression alterations. Both can be performed using formaldehyde as the tissue fixative. As a consequence of recent advances in molecular medicine, mRNA expression analysis may offer an attractive option to obtain functionally relevant information. However, quantification of mRNA expression in human renal biopsies thus far has not been possible in formaldehyde-fixed tissue. METHODS: The present study evaluated a recently reported mRNA extraction protocol. Using this approach gene expression analysis could be performed on formaldehyde-fixed archival renal tissues by laser microbeam microdissection, laser pressure catapulting and real time reverse transcription-polymerase chain reaction. RESULTS: For an initial feasibility study, the expression of two chemokines (IP-10 and RANTES) in renal transplant rejection was examined. Induction of protein expression in allografts undergoing rejection was demonstrated for both chemokines by immunohistochemistry. The mRNA expression alterations in the defined renal compartments of glomeruli, vessels and tubulointerstitium were quantified using laser microdissection from formaldehyde-fixed, paraffin-embedded or frozen tissue sections. A pronounced increase of mRNA expression compared to controls was demonstrated for IP-10 as well as RANTES with both tissue-processing protocols. CONCLUSIONS: Using formaldehyde as the tissue fixative, information on the disease process can now be obtained by histological, immunohistochemical and gene expression techniques. In the future this may allow the study of activated molecular programs in routine renal biopsies as well as archival tissue samples.

Adolescent↗
PubMed2004

Formaldehyde as a basis for residential ventilation rates.

Traditionally, houses in the US have been ventilated by passive infiltration in combination with active window opening. However in recent years, the construction quality of residential building envelopes has been improved to reduce infiltration, and the use of windows for ventilation also may have decreased due to a number of factors. Thus, there has been increased interest in engineered ventilation systems for residences. The amount of ventilation provided by an engineered system should be set to protect occupants from unhealthy or objectionable exposures to indoor pollutants, while minimizing energy costs for conditioning incoming air. Determining the correct ventilation rate is a complex task, as there are numerous pollutants of potential concern, each having poorly characterized emission rates, and poorly defined acceptable levels of exposure. One ubiquitous pollutant in residences is formaldehyde. The sources of formaldehyde in new houses are reasonably understood, and there is a large body of literature on human health effects. This report examines the use of formaldehyde as a means of determining ventilation rates and uses existing data on emission rates of formaldehyde in new houses to derive recommended levels. Based on current, widely accepted concentration guidelines for formaldehyde, the minimum and guideline ventilation rates for most new houses are 0.28 and 0.5 air changes per hour, respectively.

Air Movements↗
PubMedDate not supplied

In situ and in vitro ruminal starch degradation of untreated and formaldehyde-treated wheat and maize.

Ruminal starch degradation of untreated and formaldehyde-treated wheat and maize was measured in situ (trial 1) and in vitro (trial 2). The in situ starch degradability was higher for wheat than for maize (82.1 vs 52.3%), for untreated cereals than for cereals treated with 1% formaldehyde (77.3 vs 67.0%) and for cereals treated with 1% formaldehyde than those treated with 5% formaldehyde (67.0 vs 57.2%). The in vitro results were similar. The treatment of cereals by formaldehyde decreased starch degradability more for wheat than for maize, suggesting that the treatment was more efficient when cereal starch and/or nitrogen was highly degradable. Formadehyde treatment of wheat was more effective at decreasing the rate of wheat protein degradability than starch degradability. The difference of response to treatment between the two cereals may be due to differences in properties of the protein matrix of these two cereals.

Animal Feed↗
PubMed2001

A glutathione-dependent formaldehyde-activating enzyme (Gfa) from Paracoccus denitrificans detected and purified via two-dimensional proton exchange NMR spectroscopy.

The formation of S-hydroxymethylglutathione from formaldehyde and glutathione is a central reaction in the consumption of the cytotoxin formaldehyde in some methylotrophic bacteria as well as in many other organisms. We describe here the discovery of an enzyme from Paracoccus denitrificans that accelerates this spontaneous condensation reaction. The rates of S-hydroxymethylglutathione formation and cleavage were determined under equilibrium conditions via two-dimensional proton exchange NMR spectroscopy. The pseudo first order rate constants k(1)* were estimated from the temperature dependence of the reaction and the signal to noise ratio of the uncatalyzed reaction. At 303 K and pH 6.0 k(1)* was found to be 0.02 s(-1) for the spontaneous reaction. A 10-fold increase of the rate constant was observed upon addition of cell extract from P. denitrificans grown in the presence of methanol corresponding to a specific activity of 35 units mg(-1). Extracts of cells grown in the presence of succinate revealed a lower specific activity of 11 units mg(-1). The enzyme catalyzing the conversion of formaldehyde and glutathione was purified and named glutathione-dependent formaldehyde-activating enzyme (Gfa). The gene gfa is located directly upstream of the gene for glutathione-dependent formaldehyde dehydrogenase, which catalyzes the subsequent oxidation of S-hydroxymethylglutathione. Putative proteins with sequence identity to Gfa from P. denitrificans are present also in Rhodobacter sphaeroides, Sinorhizobium meliloti, and Mesorhizobium loti.

Carbon-Sulfur Ligases↗
PubMed2006

Molecular basis of formaldehyde detoxification. Characterization of two S-formylglutathione hydrolases from Escherichia coli, FrmB and YeiG.

The Escherichia coli genes frmB (yaiM) and yeiG encode two uncharacterized proteins that share 54% sequence identity and contain a serine esterase motif. We demonstrated that purified FrmB and YeiG have high carboxylesterase activity against the model substrates, p-nitrophenyl esters of fatty acids (C2-C6) and alpha-naphthyl acetate. However, both proteins had the highest hydrolytic activity toward S-formylglutathione, an intermediate of the glutathione-dependent pathway of formaldehyde detoxification. With this substrate, both proteins had similar affinity (Km = 0.41-0.43 mM), but FrmB was almost 5 times more active. Alanine replacement mutagenesis of YeiG demonstrated that Ser145, Asp233, and His256 are absolutely required for activity, indicating that these residues represent a serine hydrolase catalytic triad in this protein and in other S-formylglutathione hydrolases. This was confirmed by inspecting the crystal structure of the Saccharomyces cerevisiae S-formylglutathione hydrolase YJG8 (Protein Data Bank code 1pv1), which has 45% sequence identity to YeiG. The structure revealed a canonical alpha/beta-hydrolase fold and a classical serine hydrolase catalytic triad (Ser161, His276, Asp241). In E. coli cells, the expression of frmB was stimulated 45-75 times by the addition of formaldehyde to the growth medium, whereas YeiG was found to be a constitutive enzyme. The simultaneous deletion of both frmB and yeiG genes was required to increase the sensitivity of the growth of E. coli cells to formaldehyde, suggesting that both FrmB and YeiG contribute to the detoxification of formaldehyde. Thus, FrmB and YeiG are S-formylglutathione hydrolases with a Ser-His-Asp catalytic triad involved in the detoxification of formaldehyde in E. coli.

Amino Acid Sequence↗
PubMed2004

Effects of a single inhalative exposure to formaldehyde on the open field behavior of mice.

The effects of formaldehyde on the explorative behavior and locomotor activity of mice after a single inhalative exposure were examined in an open field. Adult male mice were exposed to approximately 1.1 ppm, 2.3 ppm, or 5.2 ppm formaldehyde vapour for 2 hours and the open field test was carried out two hours after the end of exposure (trial 1) and repeated 24 hours thereafter (trial 2). The following behavioral parameters were quantitatively examined: numbers of crossed floor squares (inner, peripheral, total), sniffing, grooming, rearing, climbing, and incidence of fecal boli. The results of the first trial revealed that the motion activity was significantly reduced in all exposed groups. In the 1.1 ppm group, the frequency of rearing was reduced and that of floor sniffing increased. The exposure to the two higher formaldehyde concentrations caused a significant decrease in total numbers of floor squares crossed by the subjects, air sniffing, and rearing. The open field test on the next day (trial 2) showed that the frequencies of floor sniffing, grooming, and rearing in all formaldehyde groups were significantly altered. In the 2.5 ppm group, an increased incidence of fecal boli was observed. From the results obtained, we conclude that the exposure of male mice to formaldehyde vapour affects their locomotor and explorative activity in the open field, and that some open field parameters are still altered in the exposed animals even after 24 hours.

Animals↗
PubMed1975

Effects of formaldehyde and ozone on the trigeminal nasal sensory system.

The effects of formaldehyde and ozone on the electrical activity of the nasopalatine nerve were studied in anesthetized rats. The response (increase in action potential frequency) of nasopalatine and ethmoidal nerves to brief presentations of formaldehyde, ozone, or amyl alcohol was a power function of stimulus concentration. When formaldehyde was presented continuously for one hour, it produced a decrease in nasopalatine nerve response to amyl alcohol that varied directly with the formaldehyde concentrations employed. Perfusion of the nasal cavities with air for one hour following the formaldehyde exposure resulted in a partial recovery of the neural response to amyl alcohol. Ozone exposures of 5 ppm lasting one hour produced an increase in nasopalatine nerve response to amyl alcohol. Air perfusion following the ozone exposure reduced the neural response to amyl alcohol, but not to preexposure levels.

Analysis of Variance↗
PubMedDate not supplied

Respiratory health of plywood workers occupationally exposed to formaldehyde.

This study was undertaken to enlarge our understanding of the adverse health effects of formaldehyde exposure in the workplace and community environment. The respiratory health status of 186 male plywood workers was evaluated by spirometric tests, respiratory questionnaires, and chest x-rays. Area concentrations of formaldehyde were measured in the work environment and found to range from 0.28 to 3.48 ppm. The average personal exposure was to 1.13 ppm of formaldehyde. Exposure to formaldehyde was associated with decrements in the baseline spirometric values, i.e., forced expiratory volume in 1 sec (FEV1.0), forced expiratory volume/forced vital capacity (FEV/FVC), and FEF25%-75%, and with several respiratory symptoms and diseases, including cough, phlegm, asthma, chronic bronchitis, and chest colds. The results of the study support the hypothesis that chronic exposure to formaldehyde induces symptoms and signs of chronic obstructive lung disease.

Adult↗
PubMedDate not supplied

Neurobehavioral impairment and seizures from formaldehyde.

Three patients were evaluated for effects of formaldehyde on central nervous system function. Three patients had used formalin, formaldehyde with or without phenol, to fix whole animals for 14-30 y, and a fourth patient was covered several times by formaldehyde and phenol rainout from manufacturing spills. All were disabled, and two had developed seizures. They had elevated mood state scores (82 to 162) and elevated symptom frequency scores (111 to 138), compared with referent subjects. There was excessive fatigue, somnolence, headache, difficulty remembering, irritability, and instability of mood. Compared with referents, choice reaction time was prolonged in four of four (4/4) subjects, blink latency was delayed in 2/2, balance was abnormal in 3/4, and visual fields were constricted in 2/3. Cognitive functions, measured by Culture Fair, block design, and digit symbol tests, were impaired in all. Delayed verbal recall and visual reproduction were impaired in 3/4. Perceptual motor speed on slotted pegboard and trail making A and B tests was reduced in 4/4. Errors on fingertip number writing were abnormal in all. Long-term memory was decreased in only one. Extensive use of formaldehyde at work or repeated airborne exposure to formaldehyde and phenol appears to have impaired central nervous system function.

Central Nervous System↗
PubMed2006

Migration of formaldehyde and melamine monomers from kitchen- and tableware made of melamine plastic.

Migration of one or both formaldehyde and/or melamine monomers was found in seven of ten tested melamine samples bought on the Danish market. The samples were a bowl, a jug, a mug, a ladle, and different cups and plates. No violation of the European Union-specific migration limits for melamine (30 mg kg-1) and formaldehyde (15 mg kg-1) was found after three successive exposures to the food stimulant 3% acetic acid after 2 h at 70 degrees Celsius. To investigate the effects of long-term use, migration tests were performed with two types of cups from a day nursery. Furthermore, medium-term use was studied by ten successive exposures of a plate to 3% acetic acid for 30 min at 95 degrees Celsius. The results indicate that continuous migration of formaldehyde and melamine takes place during the lifetime of these articles. The molar ratio of released formaldehyde to melamine was seen to decrease from 12 to about 5. This indicates that, first, the migration of residual monomers is most important, but in the long-term, breakdown of the polymer dominates. Two CEN methods were used to determine the concentration of monomers: a spectrophotometric method for formaldehyde and a UV-HPLC method for melamine.

Cooking and Eating Utensils↗
PubMed1989

Monitoring of parts-per-billion levels of formaldehyde using a diffusive sampler.

A diffusive sampler for formaldehyde originally designed for use in personal monitoring of worker exposure has been evaluated for static measurement of low formaldehyde levels in indoor air. The sampler consists of a 37-mm glass fiber filter impregnated with 2,4-dinitrophenylhydrazine and phosphoric acid and mounted in a polystyrene filter cassette. Formaldehyde is sampled by controlled diffusion and subsequent hydrazone formation on the filter. The hydrazone is eluted from the filter with acetonitrile and analyzed by liquid chromatography and a UV detector. The diffusive sampler was evaluated for static (area) sampling in several industries, offices, and homes with formaldehyde levels of 6-200 ppb. Results from diffusive samplers were compared with results from pumped samplers. Even at low wind velocities (less than 0.01 m.s-1) there was good agreement between pumped and diffusive samples. The sensitivity will be 1 ppb in a 24-h sample, making the sampler especially useful for indoor air monitoring of low formaldehyde levels.

Air Pollutants, Occupational↗
PubMed2001

Characterizing formaldehyde emission rates in a gross anatomy laboratory.

The evaporation of formaldehyde from cadavers in gross anatomy laboratories can produce high exposures among students and instructors. To understand the system that produces exposures and to plan for implementing control options, the generation of formaldehyde vapors must be characterized. A gross anatomy laboratory with 47 dissecting tables was studied during 15 lab sessions over a period of 16 weeks. Area concentrations were measured using National Institute of Occupational Safety and Health (NIOSH) method 3500. Average daily area concentrations in the laboratory ranged from 0.635 to 1.82 mg/m3. The ventilation was characterized on three separate days. The laboratory had a general ventilation rate of 9.8 air changes per hour. There was no local exhaust ventilation. The concentration measurements were used in a mass balance model along with ventilation rates to determine formaldehyde emission rates. The daily average formaldehyde emission rate from all sources in the laboratory ranged from 95.2-274 mg/min, with an average of 148 mg/min over the course of the study. This total emission rate was used along with the number of dissecting tables to develop an emission factor of 3.15 mg/min per table. The emission factor is a generalizable tool that can be used in laboratories of various sizes to predict emission rates and develop control strategies. This emission factor is applicable where the cadavers are prepared with similar embalming fluid consisting of approximately 10 percent formaldehyde.

Air Pollutants, Occupational↗
PubMed2001

Measurements of sulfur dioxide and formaldehyde in Taipei using a differential optical absorption spectrometer.

Taipei, the capital city of Taiwan, lies in a basin, and its topography prevents the dispersion of pollutants in the city. As a continuation of our air quality study, from February 1999 through June 1999, we measured the concentrations of SO2 at six different locations and of formaldehyde at five locations using a differential optical absorption spectrometer (DOAS). The average concentration of SO2 varied from 3.5 to 6.6 ppb. The average concentration was highest at Toucheng because of its proximity to point sources. The level in Hsientien was close to that in Toucheng, with Hsinyu showing the lowest concentrations. The DOAS and the Taiwan Air Quality Monitoring Network (TAQMN) measurements for SO2 were highly correlated (r2 > 0.9) for Toucheng, Panchiao, and Hsientien. However, DOAS SO2 concentrations were 2 times higher for Hsientien and slightly lower for Panchiao than the TAQMN concentrations were. The average concentration of formaldehyde varied from 7 to 10 ppb. Diurnal variation of formaldehyde closely followed the variation of ozone, especially when the 1-hr peak ozone concentration was > 60 ppb. Photochemical formation accounted for the ambient levels of formaldehyde in Taipei. Concentration of formaldehyde became significant on days when O3 concentration was high. Our results indicate that DOAS can replace conventional measurement techniques.

Air Pollutants↗
PubMedDate not supplied

Inhaled formaldehyde: exposure estimation, hazard characterization, and exposure-response analysis.

Formaldehyde has been assessed as a Priority Substance under the Canadian Environmental Protection Act. Probabilistic estimates of exposure of the general population in Canada to formaldehyde in ambient and indoor air are presented. Critical health effects include sensory irritation and the potential to induce tumors in the upper respiratory tract (the nasal region in rodents and potentially the lungs of humans). The majority of the general population is exposed to airborne concentrations of formaldehyde less than those typically associated with sensory irritation (i.e., 0.1 mg/m3). Based primarily upon data derived from laboratory studies, the inhalation of formaldehyde under conditions that induce cytotoxicity and sustained regenerative proliferation within the respiratory tract is considered to present a carcinogenic hazard to humans. At airborne levels for which the prevalence of sensory irritation is minimal (i.e., 0.1 mg/m3), risks of respiratory-tract cancers for the general population estimated on the basis of a biologically motivated case-specific model are exceedingly low. This biologically motivated case-specific model incorporates two-stage clonal expansion and is supported by dosimetry calculations from computational fluid dynamics analyses of formaldehyde flux in various regions of the nose and single-path modeling for the lower respiratory tract. The degree of confidence in the underlying database and uncertainties in estimates of exposure and in characterization of hazard and dose response are delineated.

Air Pollutants↗
PubMed1989

Acute pulmonary response in healthy, nonsmoking adults to inhalation of formaldehyde and carbon.

Formaldehyde (HCHO) is a common chemical found in occupational and residential environments and has been suggested as a cause of asthmalike symptoms in some individuals. Clinical and animal studies suggest that HCHO adsorbed on respirable particles may elicit a greater pulmonary physiologic and inflammatory effect than gaseous HCHO alone. The purpose of this study was to determine if respirable carbon particles have a synergistic effect on the acute symptomatic and pulmonary physiologic response to HCHO inhalation. We randomly exposed 24 normal, nonsmoking, methacholine-nonreactive subjects to 2 h each of clean air, 3 ppm formaldehyde, 0.5 mg/m3 respirable activated carbon aerosol, and the combination of 3 ppm formaldehyde plus activated carbon aerosol. The subjects engaged in intermittent heavy bicycle exercise (VE = 57 l/min) for 15 min each half hour. Measures of response included symptom questionnaires, spirometry, body plethysmography, and postexposure serial peak flows. Formaldehyde exposure was associated with significant increases in reported eye irritation, nasal irritation, throat irritation, headache, chest discomfort, and odor. We observed synergistic increases in cough, but not in other irritant respiratory tract symptoms, with inhalation of formaldehyde and carbon. Small (less than 5%) synergistic decreases in FVC and FEV3 were also seen. We observed no HCHO effect on FEV1; however, we did observe small (less than 10%) significant decreases in FEF25-75% and SGaw which may be indicative of increased airway tone. Overall, our results demonstrated synergism, but the effect is small and its clinical significance is uncertain.

Administration, Inhalation↗
PubMed1983

Automated determination of formaldehyde in air without the use of tetrachloromercurate(II).

An existing modified (no mercury reagent) pararosaniline method for the determination of formaldehyde in air has been adapted for continuous monitoring using a CEA Instruments, Inc. Model 555 automated wet chemical analyzer. The adapted instrument was checked for linearity of response, formaldehyde collection efficiency, and drift. The instrument response was highly linear (r = 0.9996) in the 1-10 ppm formaldehyde concentration range tested. Formaldehyde collection efficiency of the analyzer increased from 64 to 88% as sample flow rate was increased from 0.25 to 1.0 Lpm. When the analyzer was connected to a constant 4.1 ppm formaldehyde permeation tube source, with careful control of ambient temperature and sample cell liquid levels, 3% instrument drift occurred over a 7 hour period.

Air↗
PubMed1984

Monitoring of formic acid in urine of humans exposed to low levels of formaldehyde.

This study documented the formaldehyde exposures of a group of veterinary medicine students. It also investigated the feasibility of biologically monitoring the exposures. The biological monitoring was based on the fact that the formaldehyde is metabolized in the body to formic acid, and may then be excreted in the urine. Therefore, exposures to formaldehyde could theoretically create a shift in the formic acid levels in the urine. Normal baseline levels of urinary formic acid were first established for each subject. The baselines of most students were quite variable. Very few exhibited a "tight variability" in their baseline. Next, three sets of pre- and post-exposure urine samples were taken. A series of paired t-tests were run on these "pre" and "post" sets. The results indicated that no significant formic acid shift was seen. A subset of the samples was "corrected" for specific gravity. However, this adjustment did not have an effect upon the relative formic acid levels. In addition, no significant formic acid shift was seen in the adjusted group. Exposure levels of the students were less than 0.5 ppm of formaldehyde. Therefore, the main conclusion of the study was that biological monitoring of formaldehyde exposures (via formic acid shifts) at these low levels was not a feasible technique.

Environmental Exposure↗