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Formaldehyde induced symptoms in day care centers.

A questionnaire study among 70 employees at seven mobile day care centers where urea formaldehyde glued particle board has been used for indoor paneling and among 34 employees at three control institutions selected at random where no particle board has been used as building materials, showed a significantly higher frequency of the following symptoms among the staff at the mobile institutions: mucous membrane irritation, headache, abnormal tiredness, menstrual irregularities and use of analgetics (p less than 0.01). As there was no difference in the age distribution or smoking habits of the two groups working in day care institutions from the same geographical locations, we are, therefore, of the opinion that the differences in the frequency of symptoms discovered must be attributed to the differences in the indoor climate conditions prevalent in the institutions. The median concentration of formaldehyde in the mobile institutions was 0.43 mg/m3 in contrast to a concentration in the control institutions of about 0.08 mg/m3. We assume, therefore, that the higher concentration of formaldehyde in the mobile institutions was a cause of the increased frequency of symptoms among the staff. The National Health Service should be aware of the fact that non-specific symptoms such as headache and abnormal tiredness can be the result of unfavorable indoor climate conditions due to the presence of formaldehyde in building materials.

Air Pollutants↗

Exposure of embalmers to formaldehyde and other chemicals.

Seven funeral homes were surveyed in 1980 to determine the magnitude of embalmers' exposure to formaldehyde, other chemical vapors, and total and respirable particulates. Air was monitored for formaldehyde by personal and area samples, and assayed using the chromotropic acid method. Personal sampling revealed time-weighted average formaldehyde concentrations which ranged from 0.1 to 0.4 ppm (mean 0.3 ppm) and 0.5 to 1.2 ppm (mean 0.9 ppm) during the embalming of intact and autopsied bodies, respectively. Concentrations of other airborne chemicals and of particulates were negligible. In preparing autopsied bodies, embalming technique and condition of the body itself appeared to be major determinants of formaldehyde exposure.

Air Pollutants, Occupational↗

A method for personal sampling and analysis of nanogram amounts of formaldehyde in air.

An air sampling and analytical system for formaldehyde measurements based on a solid sampler is described. The samplers were tested on a standard atmosphere in the range of 0.2 to 0.8 mg/m3 dry air. A single 340 mg sorbant section had without drying sections a capacity of 16 micrograms formaldehyde in dry air and 3 micrograms at 70% RH, 23 degrees C. The precision of fluorimetric analysis was better than 6% for samples of 300, 600 and 1200 ng formaldehyde, and the accuracy was better than 10%. The precision of a colorimetric analysis was 12% for a 300 ng sample and 2% for 600 and 1200 ng samples. The accuracy of this method was better than 7%. Both the fluorimetric and the colorimetric analyses are found to be accurate and sensitive analytical methods for the determination of low formaldehyde concentrations. However, if measurements of more than 15 minutes duration are taken and a dessicant is used, the accuracy still remains to be verified. Positive interference from acrolein (5-7% interference when equimolar amounts are present) was found, but there was no interference from other aldehydes.

Air Pollutants, Occupational↗

Generation of constant formaldehyde levels for inhalation studies.

Development of the described formaldehyde generator was undertaken to provide researchers engaged in inhalation studies with the capability to produce constant and controllable levels of formaldehyde in air. Depolymerization of purified paraformaldehyde under rigorously controlled conditions in a modified Freeland calibration manifold is employed. The desired formaldehyde concentration in the exposure chamber is achieved by adding an appropriate fraction of the generator effluent to the normal air supply to the chamber. Variation in generator formaldehyde concentration is less than +/- 11% over a three-day period and less than +/- 2% over short periods (36 seconds).

Air↗

Validation of a colorimetric method for determination of atmospheric formaldehyde.

Aqueous formaldehyde was stabilized in pH 7 phosphate buffer with excess sodium bisulfite of fixed and known concentration. The 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) procedure described previously was used to determine excess bisulfite colorimetrically. The slope of the calibration line (absorbance at 412 nm vs. formaldehyde concentration) is -0.350 A.U./ug CH2O/mL (correlation coefficient: 0.9995). The precision of the method at the 95% confidence level is indicated by the mean percentage relative error (1.81 +/- 1.67) and mean percentage standard error (0.42 +/- 0.39). Gaseous formaldehyde of known concentrations (ppm) in air was absorbed from air samples in pH 7 buffer and determined by the DTNB method. For the determination of formaldehyde in air, the precision and accuracy were demonstrated at the 95% confidence level by the mean percentage relative error (5.04 +/- 3.2), the mean percentage standard error (1.72 +/- 1.0), the mean percentage recovery (99.9 +/- 2.7), and the mean percentage absolute error (1.86 +/- 1.6). The graphic comparison of air concentration found vs. air concentration calculated shows a slope of 0.993 ppmfound/ppmcalcd (correlation coefficient: 0.9993).

Air Pollutants↗

An automated system for the handling, diluting, and dispensing of formaldehyde.

Automation can be applied to the repetitive and mechanical handling, mixing, and dispensing of formaldehyde, the most common tissue fixative in routine clinical laboratory use. A closed automated system is described that aspirates 37% formaldehyde from large, commercial sized 490 pound drums at a remote location, and delivers 10% formalin in ready-to-use form at a special faucet in the histology laboratory without human intervention. In addition to economy from a decrease in personnel handling time and from purchasing formaldehyde in bulk, it decreases the exposure of laboratory personnel to formaldehyde fumes.

Fixatives↗

Investigation of determinants of past and current exposures to formaldehyde in the reconstituted wood panel industry in Quebec.

OBJECTIVES: Past and present formaldehyde measurements made in facilities manufacturing reconstituted wood panels in Quebec have been collected in order to assess formaldehyde exposure and its determinants in this industry. METHODS: All 12 plants manufacturing Oriented-strand board (OSB), Medium density fibreboard (MDF) and Particle board (PB) in Quebec were visited by a research team which took area and personal measurements. Past measurements taken by governmental occupational health teams in these plants were also collected. Log-transformed formaldehyde concentrations were analysed with extended linear mixed-effects models. RESULTS: During 2001-2002, 275 measurements were taken by the research team, while 590 measurements dating back to 1984 were collected from governmental files. The area measurements had a global geometric mean (GM) of 0.28 p.p.m. [geometric standard deviation (GSD): 3.1]. The GM of the personal measurements was 0.17 p.p.m. (GSD: 2.3). The fixed-effects of the models for personal and area measurements explained 61 and 57% of the variance, respectively. Job (working area for area concentrations), process (PB, MDF, OSB), season of sampling, origin of the data (research, governmental) and year of sampling were significant determinants of exposure. Proximity to the press, winter conditions, PB and MDF processes and governmental data resulted in the highest exposures. Significant within-sampling campaign correlation was found for both personal and area models. The final models include different residual variances by process for personal measurements and by working area for area measurements. CONCLUSIONS: Several determinants of exposure to formaldehyde in the reconstituted wood panel industry were successfully identified. Higher levels found in governmental data as compared to research data may be explained by a 'worst-case' strategy bias. The observed intra-sampling campaign correlation supports existing results suggesting that measurements taken in a small time frame tend to be correlated. Exposures in this sector are low compared to most 8 h-TWA occupational exposure limits (e.g. 1 p.p.m.) but close to the most demanding ones (e.g. 0.3 p.p.m.).

Data Collection↗

Formation of methyl radicals during the catalase-mediated oxidation of formaldehyde hydrazone.

It has been suggested that formaldehyde hydrazone, a condensation product of hydrazine with formaldehyde, plays an important role in hydrazine-promoted DNA methylation in vivo. The present study demonstrated by spin-trapping experiments with 5,5-dimethyl-1-pyrroline-N-oxide and tert-nitrosobutane that catalase-mediated oxidation of formaldehyde hydrazone generates methyl radicals. Both the use of two spin-traps and parallel studies of oxygen consumption were important for excluding possible artefacts of spin-trapping experiments with tert-nitrosobutane. Hydrazine was also oxidized by catalase but only hydroxyl radicals were detected. Metabolic activation of formaldehyde hydrazone to methyl radicals may be of importance in regard to hydrazine-mediated toxicity and carcinogenicity.

Catalase↗

The in vitro methylation of DNA by microsomally-activated dimethylnitrosamine and its correlation with formaldehyde production.

Utilizing the microsomal fraction isolated from hamster liver we have identified and quantitated some of the alkylation lesions introduced into exogenous DNA as a consequence of the microsomally-mediated decomposition of 14C-labeled dimethylnitrosamine and have established correlations between this DNA alkylation and formaldehyde formation. The yield of radiolabeled formaldehyde was assessed by the formaldemethone-precipitation method and the yields of the major methylated purines present in a mild acid hydrolysate of modified DNA determined using cation exchange high pressure liquid chromatography techniques. We found 7-methylguanine, 3-methyladenine and O(6)-methylguanine in our DNA hydrolysates in the same relative proportions as observed in DNA isolated from similar incubation mixtures containing methylnitrosourea as the methylating compound. The rate of DNA methylation was observed to correlate well with the rate of formaldehyde formation and, even thought the absolute formaldehyde and DNA methylation yields varied in experiments done on different days, the relative yields were found to be consistent. Both processes were NADPH dependent, both were inhibited by carbon monoxide, and both were equally sensitive to chemical agents which appear to interfere with dimethylnitrosamine metabolism in vivo.

Animals↗

Formaldehyde generators: relationship between stability, lipophilicity and carcinogenic potency.

The rate of hydrolysis to formaldehyde of methylenedimorpholine (MDM), hexamethylenetetramine (HMT) and dinitrosopentamethylenetetramine (DNPT) have been compared with the enzyme-mediated formation of formaldehyde from hexamethylphosphoramide (HMPA). The bio-distribution of [14C]HMPA following nasal instillation in rats has also been studied and compared with that of [14C]methyl methanesulphonate (MMS). These data are used to relate the several carcinogenic/genotoxic properties of the chemicals named above. It is concluded from these data and related considerations that three classes of formaldehyde-generators should be recognized (a) labile agents such as MDM (and formaldehyde) which are likely to be locally active as carcinogens, (b) lipophilic and relatively stable agents such as HMPA which may be both locally active (if bio-accumulated) and systemically active as carcinogens, and (c) agents such as HMT and DNPT, of intermediate stability, which are unlikely to be systemically active and to be of low or zero activity locally.

Alcohols↗

Quantitation of formaldehyde, acetaldehyde, and acetone in sidestream cigarette smoke by high-performance liquid chromatography.

A method is described for the collection and quantitation of formaldehyde, acetaldehyde, and acetone in sidestream cigarette smoke. Using the "fishtail" chimney procedure (1), sidestream smoke is drawn by vacuum through the chimney, a Cambridge filter pad (Performance Systematics Inc.; Caledonia, MI), and into an impinger containing a solution of 2,4-dinitrophenylhydrazine (DNPH), whose solubility in acetonitrile was increased by using diglyme as a constituent of the collection derivatization solution. The chimney is rinsed with DNPH solution to remove "formaldehyde", and the rinse is added to the impinger solution. This combined wash and impinger solution is used to extract the Cambridge pad. An aliquot of the extract is analyzed by high-performance liquid chromatography using a reversed-phase column, ultraviolet detection, and a mobile phase gradient with tetrahydrofuran as a modifier. Acrolein is detected but gives poor precision and recovery because of dimer formation. For formaldehyde, acetaldehyde, and acetone, both the precision (7.30, 2.49, 2.88% relative standard deviation, respectively) and recovery (90.0, 95.2, 102.8%, respectively) are acceptable. The response for formaldehyde, acetaldehyde, and acetone is linear and a function of the number of cigarettes smoked. The minimum detectable quantity for the analytes ranges from 5 to 16 micrograms per cigarette.

Acetaldehyde↗

HPLC analysis of metabolically produced formaldehyde.

Radiolabelled (-)-deprenyl is orally administered to rats, and urinary elimination of radiolabelled formaldehyde is detected. The separation is performed using high-performance liquid chromatography on octadecyl-silica stationary phase. Both the radioactivity and the UV absorbance of the dinitrophenylhydrazine formaldehyde peak are determined. Formaldehyde generation takes place by N-demethylation. Low levels of formaldehyde may have a beneficial role in counterbalancing the oxidative stress of the everyday person's life.

Animals↗

Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees C: practical and theoretical implications.

Scrapie-infected hamster brains and their extracted amyloid fibrils were subjected to formaldehyde and steam autoclaving, alone or in combination. Treatment with formaldehyde before autoclaving stabilized infectivity, whereas treatment after autoclaving was either inactive or further reduced infectivity. In additional experiments on specimens (not treated with formaldehyde) that were subjected to dry heat, a small amount of infectivity still survived a 1-h exposure to temperatures as high as 360 degrees C. These results are consistent with the operation of a comparatively primitive molecular mechanism for the initiation of scrapie agent replication (perhaps an inorganic crystal nucleation step) and the subsequent participation of an organic macromolecule (scrapie amyloid protein) that is susceptible to intramolecular cross-stabilization by formaldehyde.

Animals↗

DNA sequence analysis of methylene chloride-induced HPRT mutations in Chinese hamster ovary cells: comparison with the mutation spectrum obtained for 1,2-dibromoethane and formaldehyde.

Glutathione-S-transferase-mediated metabolism of methylene chloride (MC) generates S-chloromethylglutathione, which has the potential to react with DNA, and formaldehyde, which is a known mutagen. MC-induced mutations in the HPRT gene of Chinese hamster ovary cells have been sequenced and compared with the mutations induced by 1, 2-dibromoethane (1,2-DEB), which is known to act through a glutathione conjugate, and formaldehyde. All three compounds induced primarily point mutations, with a small number of insertion and deletion events. The most common point mutations induced by MC were GC-->AT transitions (4/8), with two GC-->CG transversions and two AT-->TA transversions. This pattern of mutations showed greater similarity with 1,2-DBE, where the dominant point mutations were GC-->AT transitions (7/9), than formaldehyde, where all mutations were single base transversions and 5/6 occurred from AT base pairs. The mutation sequence results for MC suggest that S-chloromethylglutathione plays a major role in MC mutagenesis, with only a limited contribution from formaldehyde. The involvement of a glutathione (GSH) conjugate in MC mutagenicity would be analogous to the well-characterized pathway of activation of 1,2-DBE.

Animals↗

Formaldehyde activation of mitoxantrone yields CpG and CpA specific DNA adducts.

Recently we have found that mitoxantrone, like Adria-mycin, can be activated by formaldehyde and subsequently form adducts which stabilise double-stranded DNA in vitro. This activation by formaldehyde may be biologically relevant since formaldehyde levels are elevated in those tumours in which mitoxan-trone is most cytotoxic. In vitro transcription analysis revealed that these adducts block the progression of RNA polymerase during transcription and cause truncated RNA transcripts. There was an absolute requirement for both mitoxantrone and formaldehyde in transcriptional blockage formation and the activated complex was found to exhibit site specificity, with blockage occurring prior to CpG and CpA sites in the DNA (non-template strand). The stability of the adduct at 37 degrees C was site dependent. The half-lives ranged from 45 min to approximately 5 h and this was dependent on both the central 2 bp blockage site as well as flanking sequences. The CpG specificity of mitoxantrone adduct sites was also confirmed independently by a lambda exonuclease digestion assay.

Base Sequence↗

Non-enzymatic formation of formaldehyde in mouse oocyte freezing mixtures.

Three cryoprotectant solvents, dimethylsulphoxide, 1,2-propanediol and glycerol, were investigated for a non-enzymatic reaction product, formaldehyde. All three cryoprotectants demonstrated a direct relationship between increasing solvent molarity and increasing formaldehyde concentration which was independent of temperature and protein (bovine serum albumin). Medium composition significantly influenced the formaldehyde concentration with HTF > T6 > M16 = M2. The formaldehyde could be effectively removed by reduced glutathione, cysteine and dithiothreitol with cysteine being the most effective scavenging agent. A reaction mechanism for this scavenging is proposed. The combination of cysteine and cryoprotectant reduced the zona pellucida 'hardening' effect in mouse oocytes.

Animals↗

Resorcinol-formaldehyde resin "Russian Red" endodontic therapy.

Resorcinol-formaldehyde resin is a material used in endodontic therapy in many foreign countries. With immigration to the United States increasing, American dentists need to become familiar with resorcinol-formaldehyde therapy. It contains two potentially toxic components, formaldehyde (liquid) and resorcinol (powder). Zinc oxide or barium sulfate may be used for radiopacity. When 10% sodium hydroxide is added to the mixture, polymerization occurs, which can form a brick-hard red material that has no known solvent. Several variations in technique exist. The catalyst can be mixed in before insertion into the tooth, added after the mixture is inserted, or not used. Providers believe pulp tissue will be fixed and bacteria destroyed apical to the level of resorcinol-formaldehyde resin placement. Canals are frequently not instrumented or obturated to their full length. Few success-failure studies have been published and results are contradictory. Consequently, providers have little guidance regarding when to retreat or for predicting the difficulty of retreatment.

Drug Combinations↗

Modifications of drug-induced cardiac slow inward current block by cooling, pH variations, and formaldehyde in mammalian ventricular myocardium.

In microelectrode experiments on ventricular myocardium of guinea pigs, the dependence of verapamil-induced cardiac slow inward current (Isi) block on pH and temperature and the modulation of block after chemical channel modification by formaldehyde was studied taking Vmax of Isi-mediated action potentials as an estimate for Isi. Higher verapamil concentrations (1 X 10(-6) M) evoked in addition to phasic Vmax inhibition a second type of block, tonic Vmax blockade. With increasing stimulation frequencies, phasic Vmax block became stronger and developed faster. Alkalization (pH 9.0) failed to enhance the verapamil action, but cooling accentuated the drug effect. Thus, the apparent Km for tonic blockade declined from 1.72 X 10(-5) M at 35 degrees C to 1.22 X 10(-5) M at 30 degrees C. The decrease of the dissociation constant for the phasic block from 8.6 to 4.4 X 10(-7) M (interstimulus interval, 5 s) was more markedly pronounced. Chemical channel modification produced by short applications of formaldehyde (10 mM) sensitized the Isi system of the cardiac membrane and facilitated verapamil binding preferentially under resting state conditions. Block intensification persisted after withdrawal of the chemical for at least 30 min. Block potentiation by formaldehyde is not specifically related to the drug applied to inhibit Vmax of Isi-mediated action potentials. Thus, nifedipine-induced Vmax block rises significantly in response to an intervention with formaldehyde. The increase of apparent Km for nifedipine-induced blockade from 1.4 X 10(-6) to 2.7 X 10(-7) M suggests an increase in receptor affinity.

Action Potentials↗