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Formaldehyde exposure in a gross anatomy laboratory.

A gross anatomy laboratory for medical students was evaluated for formaldehyde levels throughout its eight-week term. Results indicated that exposures for students and instructors were below the 3-ppm permissible exposure limit (assuming a maximum of five hours of daily exposure) established by the Occupational Safety and Health Administration. However, about one third of the eight-hour time-weighted-average exposures were greater than 1 ppm under the same assumptions. Exposure levels for students and instructors did not differ. Exposures tended to decrease over the term unless internal cadaver cavities were being dissected. These exposures are significant in light of the recent implication of formaldehyde as an animal carcinogen and the trend to reduce permissible levels to 1 ppm or lower.

Anatomy↗

Pulmonary effects of simultaneous exposures to MDI formaldehyde and wood dust on workers in an oriented strand board plant.

A study was undertaken in a plant producing oriented strand board (OSB) from aspen and balsam wood, bonded by methylene diisocyanate (MDI) and phenol formaldehyde. A group of 127 production workers in the plant was compared to 165 oil workers from the same geographic area. Measurements of MDI ranged from 6 to 33 micrograms/m3 (0.001-0.003 ppm), of respirable dust ranged from 0.05 to 0.5 mg/m3, and of formaldehyde were 0.05 ppm or less. The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) was significantly lower among the OSB workers compared to the oil workers, and this was more pronounced for ex-smokers and current smokers. A number of respiratory symptoms suggestive of airway reactivity were significantly more common among the OSB workers. It was known that changes to reduce worker exposure had been made in the plant before the study, and it is unclear whether the health effects documented were the result of these low levels or if previous, probably higher levels were responsible.

Adult↗

Chromic-acid formaldehyde fixation of nucleic acids of bacteriophage phi6 and infectious bovine rhinotracheitis virus.

Bacteriophage phi6 nucleic acid was present as a torus after chromic acid-formaldehyde-OSO4 fixation and acetone and propylene oxide dehydration. A herpes virus, infectious bovine rhinotracheitis virus, had its DNA mostly as a torus, collapsed in the centre, or as a network, after glutaraldehyde-OSO4 fixation, but in an uncollapsed torus or network formation after chromic acid-formaldehyde-OSO4. This fixative stabilized nucleic acids, allowing acetone dehydration and plastic embedding without collapse of nucleic acid to the centre of the virion.

Chromium↗

Characterization of formaldehyde-inactivated poliovirus preparations made from live-attenuated strains.

Formaldehyde-inactivated virus samples from type 1 poliovirus live-attenuated strains were prepared in the laboratory. The effect of treatment with formaldehyde on virus infectivity and immunogenicity in mice was investigated and the results compared with those from Mahoney wild-type poliovirus strain, the common type 1 component in commercial inactivated polio vaccines (IPV). Differences in the potency and specificity between these experimental vaccines were identified in both normal mice and transgenic mice expressing the human poliovirus receptor. The possible advantages/disadvantages of using live-attenuated strains for IPV production are discussed in the context of the global polio eradication initiative. A novel transgenic mouse model to study in vivo the immune protection induced by IPV preparations is described.

Animals↗

FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin.

DNA segments that actively regulate transcription in vivo are typically characterized by eviction of nucleosomes from chromatin and are experimentally identified by their hypersensitivity to nucleases. Here we demonstrate a simple procedure for the isolation of nucleosome-depleted DNA from human chromatin, termed FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements). To perform FAIRE, chromatin is crosslinked with formaldehyde in vivo, sheared by sonication, and phenol-chloroform extracted. The DNA recovered in the aqueous phase is fluorescently labeled and hybridized to a DNA microarray. FAIRE performed in human cells strongly enriches DNA coincident with the location of DNaseI hypersensitive sites, transcriptional start sites, and active promoters. Evidence for cell-type-specific patterns of FAIRE enrichment is also presented. FAIRE has utility as a positive selection for genomic regions associated with regulatory activity, including regions traditionally detected by nuclease hypersensitivity assays.

Cells, Cultured↗

Contact allergy to 4,4'-dihydroxy-(hydroxymethyl)-diphenyl methanes: sensitizers in a phenol-formaldehyde resin.

A particular phenol-formaldehyde resin of the resol type (P-F-R-2) was shown in a previous study to be a good tracer of patients with contact allergy to phenol-formaldehyde resins. Eleven patients with sensitivity to P-F-R-2 participated in the study in which chromatographically separated fractions of P-F-R-2 were patch tested. This procedure was repeated until a positive reaction to a single substance was noted. In this study 3 new sensitizers are reported. Investigations by mass spectrometry and nuclear magnetic resonance spectrometry identified the compounds to be 4,4'-dihydroxy-3-(hydroxymethyl)-diphenyl methane (4,4'-H-3-HPM), 4,4'-dihydroxy-3,3'-di-(hydroxymethyl)-diphenyl methane (4,4'-H-3,3'-HPM), and 4,4'-dihydroxy-3,5-di-(hydroxymethyl)-diphenyl methane (4,4'-H-3,5-HPM). Six of the 11 patients reacted to at least one of these compounds. All 6 patients reacted to 4,4'-H-3,3'-HPM and 5 reacted simultaneously to 4,4'-H-3-HPM. Four patients reacted to all 3 compounds tested. By patch testing with serial dilutions (ethanol 99.5%) of the three 4,4'-H-HPM, positive reactions were noted down to 0.5 X 10(-6)%, 1.0 X 10(-6)%, and 1.3 X 10(-3)% w/v for 4,4'-H-3-HPM, 4,4'-H-3,3'-HPM, and 4,4'-H-3,5-HPM, respectively.

Allergens↗

Inductions of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by formaldehyde.

Administration of formaldehyde at doses of 11 to 110 mg/kg body weight by gastric intubation to male F344 rats induced up to 100-fold increase in ornithine decarboxylase activity with a maximum after 16 hr and up to 49-fold increase in DNA synthesis with a maximum after 16 hr in the pyloric mucosa of the stomach. These results suggest that formaldehyde has tumor-promoting activity in carcinogenesis in the glandular stomach.

Animals↗

Fixation with formaldehyde induces expression of activation dependent platelet membrane glycoproteins, P selectin (CD62) and GP53 (CD63).

Platelet activation in vivo is important in the pathogenesis of thrombosis. Accurate measurement is difficult due to artefactual in vitro preparation related activation. This can be overcome by using whole blood techniques, such as flow cytometry. However, there is little consensus on methods of platelet preparation, procedures for use of fixation, or the optimal types/amounts of fixative. The use of unfixed platelets has received little attention. We describe a series of experiments comparing platelet activation antigen expression detected by flow cytometry in fixed and unfixed samples. Formaldehyde increased the expression of both CD62 and CD63. We recommend that fixation with formaldehyde should not be used when studying platelet activation.

Antigens, CD↗

Microspectrofluorometric studies on the formaldehyde-induced reaction product of 5-hydroxytryptamine.

A new model incorporating Sephadex G-25 as an inert carrier has been developed for studying the reaction between biogenic amines and formaldehyde vapour. Both the fluorescence yield and the spectral characteristics of the 5-HT formaldehyde reaction product are influenced appreciably by the relative humidity at which paraformaldehyde is equilibrated, the duration of the reaction, the glycine concentration and pH of the suspending solution and the duration of exposure to ultraviolet light. It is concluded that care should be exercised in attempting to identify or quantify 5-HT on the basis of microspectrofluorometric analysis.

Animals↗

Carbon 13 nuclear magnetic resonance studies on formaldehyde reactions with polyfunctional amino-acids.

Addition and condensation reactions of formaldehyde with polyfunctional amino-acids and their N alpha-acetyl derivatives have been studied in neutral or mildly acid solutions using 13 C n.m.r. The first addition reaction, giving hydroxymethyls, is fast and incomplete with the amine, guanidyl, hydroxyl, indole and imidazole groups of the side chains, fast and complete with the sulfhydryl group, slow and complete with the amide group. For asparagine, threonine, histidine and tryptophan, the N alpha-hydroxymethyl condenses with the basic group of the side chain to give a cyclic compound. In the case of cysteine, it is the S-hydroxymethyl which condenses with the alpha-amino group. The value of the chemical shifts of the hydroxymethyls and of the methylene bondings will be of help in the study of the reactions of formaldehyde with proteins.

Amides↗

Problems associated with use of the benzyloxymethyl protecting group for histidines. Formaldehyde adducts formed during cleavage by hydrogen fluoride.

The use of N alpha-tert.-butyloxycarbonyl-N pi-benzyloxymethylhistidine in peptide synthesis resulted in significant levels of several different side products attributable to the generation of formaldehyde during the hydrogen fluoride cleavage reaction. Methylated impurities in a decapeptide were isolated and identified. These methylated impurities were attributed to the use of the benzyloxymethyl protecting group for the histidines, since the impurities did not form when the dinitrophenyl protecting group was used. Also, peptides containing benzyloxymethyl-protected histidines in addition to N-terminal cysteines quantitatively yielded their respective N-terminal thiazolidine derivatives upon isolation from standard hydrogen fluoride cleavage mixtures. Thiazolidine ring formation was circumvented by including in the cleavage reaction a formaldehyde scavenger such as cysteine hydrochloride or resorcinol.

Amino Acid Sequence↗

Equilibrium studies on the formaldehyde reaction with native DNA.

Equilibrium analysis of the reaction of formaldehyde with native calf thymus DNA was carried out at temperatures below the thermal transition zone by the spectrophotometric method. The apparent equilibrium constant, Kconf., for the conformational opening and closing reaction of base pairs along the double-helical chain, was measured in various concentrations of formaldehyde, and these values were extrapolated to the zero concentration. The value of KOconf. thus obtained in the absence of the chemical probe was 0.12 in 5 mM 2-(N-morpholino)ethane sulfonic acid buffer (Mes), and 0.003 in 0.15 M NaCl plus 5 mM Mes, pH 7.0, at 50 degrees C. These results make it possible to calculate roughly that 230 base pairs and 7 base pairs are open respectively, at 50 degrees C in the native DNA molecule composed of 2300 base pairs, using Mr = 1.5 x 10(6) for the sample used. This conformational reaction was also characterized by the following thermodynamic parameters: deltaGOconf. = 1.36 kcal - mol-1 (5.68 kJ - mol-1), deltaHOconf. = 36.8 kcal - mol-1 (154 kJ - mol-1), and deltaSOconf. = 110 cal - mol-1 - K-1 (460 J - mol-1 - K-1) in 5 mM Mes, pH 7.0, at 50 degrees C, and the nature of the 'breathing' of base pairs was discussed.

Animals↗

Dependence on membrane components of methanogenesis from methyl-CoM with formaldehyde or molecular hydrogen as electron donors.

Methane formation from 2-(methylthio)-ethanesulfonate (methyl-CoM) and H2 by the soluble fraction from the methanogenic bacterium strain Gö1 was stimulated up to tenfold by the addition of the membrane fraction. This stimulation was observed with membranes from various methanogenic species belonging to different phylogenetic families, but not with membranes from Escherichia coli or Acetobacterium woodii. Treatment of the membranes with strong oxidants, i.e. O2 and K3[Fe(CN)6], or with SH reagents, i.e. Ag+, p-chloromercuribenzoate or iodoacetamide, caused an irreversible decrease or loss in stimulatory activity, as did heat treatment at temperatures above 78 degrees C. Methanogenesis from methyl-CoM with formaldehyde instead of H2 as electron donor depended similarly on the membrane fraction. With membranes, 1 mol HCHO was oxidized to 1 mol CO2 and allowed the formation of 2 mol CH4 from 2 mol CH3-CoM. Without membranes, per mol of HCHO oxidized 1 mol H2 was formed and 1 mol CH4 was produced from CH3-CoM; the rate was 10-20% of that in the presence of membranes. When methyl-CoM was replaced by an artificial electron acceptor system consisting of methylviologen and metronidazole, the formaldehyde-oxidizing activity was no longer stimulated by the membrane fraction. These results demonstrate for the first time an essential function of membrane components in methanogenic electron transfer.

Cell Wall↗

Formaldehyde vapour effects in chicken embryo.

A total of 763 fertile chicken eggs were divided in two groups. The eggs of the first group were manipulated intact. The shell of each egg of the second group was drilled at the air chamber position. The eggs of both groups were divided in 6 subgroups and they were placed in an automatic incubator. Between the second and the fourth day of incubation each subgroup of eggs was moved to another incubator saturated with formaldehyde vapour, and it was exposed for a certain time. The hatched chicks were examined, measured, and processed, in order to search for any external, visceral, and skeletal malformation. Although the chicks of the first group did not show any particular abnormalities after their exposure to formaldehyde vapours, those of the second group were found to be affected in a rate of about 29:100. The observed embryotoxic effects of the hatched chicks of the second group were mainly early and late prenatal deaths, extensive and limited congenital anomalies as well as reduction deformities.

Abnormalities, Drug-Induced↗

The effect of N-duopropenide (a new disinfectant with quaternary ammonium iodides) and formaldehyde on survival of organisms of sanitary interest in pig slurry.

The counts of different groups of organisms (mesophilic total aerobic and anaerobic bacteria, enterobacteriaceae, faecal coliform bacteria and faecal streptococci type D), as well as the presence or absence of Pseudomonas spp. and Salmonella spp., were recorded in both unfiltered and filtered pig slurry samples at 1, 8 and 29 days of storage, before and after applying N-duopropenide (a new disinfectant with a quaternary ammonium structure) at 1, 2 x 1, 5 and 2 x 5% concentrations of the commercial product (equivalent to 0.11, 2 x 0.11, 0.55 and 2 x 0.55%, respectively, of active ingredient) for 1 h, or 0.5% commercial formaldehyde for 6 days. Before disinfection, anaerobic and aerobic organisms resulted in the highest counts (between 6 and 7 log units/ml), followed by enterobacteriaceae, faecal coliforms and streptococci (4-5 log units/ml). The unfiltered slurry showed higher bacterial counts than the filtered slurry. The variation in counts was similar for all the groups studied, with the highest count on day 1 of storage with a continuous decrease over the 3 days studied. N-duopropenide efficacy depended on the dose used, but a 2 x 5% concentration resulted in total inactivation (100% reduction) of all the bacteria studied, except for the total aerobic and anaerobic organisms present in unfiltered slurry. Formaldehyde efficacy was much lower. In respect of Pseudomonas spp., more isolates were obtained after using N-duopropenide at lower concentrations (1 and 2 x 1%) than before treatment, thus suggesting its suitability for selective isolation of this genus. Finally, no Salmonella spp. strains were isolated in any of the cases considered in this study.

Aldehydes↗

Chronic ethanol administration impairs degradation of formaldehyde-treated albumin by the perfused rat liver.

Nonparenchymal cells of the liver appear to be important in the pathogenesis of various liver diseases, including that caused by ethanol. It is known that chronic ethanol administration impairs the process of receptor-mediated endocytosis in hepatocytes. Liver endothelial cells are also actively endocytic cells, playing a prominent role in the clearance from the circulation of a variety of macromolecules. In this study, we assessed the effect of ethanol administration on this "scavenger" function of liver endothelial cells by measuring the degradation of formaldehyde-treated albumin in isolated, perfused livers of ethanol-fed rats. Rats were pair-fed for 1 or 4 weeks with a liquid diet containing either ethanol as 36% of total calories or an isocaloric amount of carbohydrate. Chronic ethanol administration in this manner for 1 or 4 weeks significantly impaired the degradation of this endothelial cell ligand (by 60 +/- 9% and 37 +/- 9%, respectively). Liver perfusions were also performed on rats that had been administered ethanol acutely or in which ethanol was added to the perfusate. No acute effect of ethanol on the degradation of this ligand was seen. These results demonstrate that chronic ethanol ingestion impairs receptor-mediated endocytosis of formaldehyde-treated albumin by liver endothelial cells, indicating that the adverse effects of ethanol on protein trafficking within the liver are not limited to the hepatocytes.

Animals↗

Lack of effect of ascorbic acid, hippuric acid, and methenamine (urinary formaldehyde) on the copper-reduction glucose test in geriatric patients.

Ascorbic acid and hippuric acid (from cranberry juice) are commonly used to acidify the urine for the purpose of enhancing the degradation of therapeutic methenamine mandelate to urinary formaldehyde. A study was made of 27 nondiabetic geriatric patients with indwelling Foley catheters and chronic bacteriuria who were treated with methenamine mandelate (4 gm), ascorbic acid (4 gm), and cranberry cocktail (1 liter) daily. All of 972 urine samples showed formaldehyde in mean concentrations between 14 and 25 microgram/ml. No glucose was found when the urine was tested by the copper-reduction method. In vitro false positive reactions reported in the literature do not appear to be duplicated as an in vivo problem.

Aged↗

Occupational eczema from para-tertiary-butylphenol formaldehyde resins: a review of the sensitizing resins.

The first case of allergy due to para-tertiary-butylphenol formaldehyde resins (PTBP resins) were found in 1958 in the shoe-making industry. These resins are found in certain neoprene adhesives. PTBP resin hypersensitivity may be due either to the para-tertiary-butylphenol, to the resin itself or less frequently to the formaldehyde. These resins may cause occupational allergy (in the automobile industry and chiefly in the shoe-making industry) and non-occupational allergy (footwear and clothing hypersensitivity). Patients allergic to PTBP resins have been found to show a cross-reaction to other resins such as Alresen PA 103, Schenectady SP 126 and Schenectady SP 154. The authors give a reference list of sensitizing neoprene adhesives and PTBP resins so that manufacturers can limit the use of these products as far as possible.

Dermatitis, Occupational↗