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Distribution of 14C-formaldehyde after pulpotomy with formocresol.

Pulpotomies were performed on rhesus monkeys with use of formocresol to determine if there was uptake of 14C-formaldehyde into the systemic circulation after formocresol pulpotomies. Five-minute exposure of pulpal tissue to the 14C-formocresol resulted in the systemic absorption of approximately 1% of the dose. Two hours of exposure of pulp tissue to the 14C-formocresol did not increase the systemic absorption. Multiple sequential pulpotomies resulted in proportionately higher systemic absorption of 14C-formaldehyde. Application of 131I to pulpotomy sites indicated that formocresol compromises the microcirculation of the dental pulp. Autoradiography disclosed extensive concentrations of 14C-formaldehyde in the pulp, dentin, periodontal ligament, and bone.

Absorption↗

Enzymological aspects of caffeine demethylation and formaldehyde oxidation by Pseudomonas putida C1.

1) The enzymatic demethylation of caffeine (1,3,7-trimethylxanthine) by Pseudomonas putida C1 was investigated; an inducible enzyme system has been observed. This enzyme shows an optimum pH of about 6.0, and the optimum temperature is in the range of 22-24 degrees C. The enzyme is absolutely dependent on NADH or NADPH as a cosubstrate and is activated by CO2+. 2) The formaldehyde generated by the demethylation of caffeine is oxidized by an NAD-dependent formaldehyde dehydrogenase, which is independent of Mg2+ and glutathione. The enzyme was purified from cell-free extracts of Pseudomonas putida C1 by DEAE-cellulose, Sephadex G-150 and Sephadex A-50 chromatography. The purified enzyme was homogeneous as judged by polyacrylamide gel electrophoresis and was most active at a pH between 8.5 and 9.0. The molecular weight was estimated to be about 250,000 by the gel filtration method. Kinetic analysis gave KM values of about 0.2 mM for formaldehyde and 0.5 mM for NAD+.

Aldehyde Oxidoreductases↗

Genetic engineering of baker's and wine yeasts using formaldehyde hyperresistance-mediating plasmids.

Yeast multi-copy vectors carrying the formaldehyde-resistance marker gene SFA have proved to be a valuable tool for research on industrially used strains of Saccharomyces cerevisiae. The genetics of these strains is often poorly understood, and for various reasons it is not possible to simply subject these strains to protocols of genetic engineering that have been established for laboratory strains of S. cerevisiae. We tested our vectors and protocols using 10 randomly picked baker's and wine yeasts all of which could be transformed by a simple protocol with vectors conferring hyperresistance to formaldehyde. The application of formaldehyde as a selecting agent also offers the advantage of its biodegradation to CO2 during fermentation, i.e., the selecting agent will be consumed and therefore its removal during down-stream processing is not necessary. Thus, this vector provides an expression system which is simple to apply and inexpensive to use.

Drug Resistance, Microbial↗

Immunogenicity of formaldehyde and binary ethylenimine inactivated infectious bursal disease virus in broiler chicks.

Infectious bursal disease virus (IBDV) was inactivated by two different chemicals--formaldehyde and binary ethylenimine (BEI). Formaldehyde was used at 0.1% and 0.2%, while BEI was used at concentrations of 0.001 and 0.002 mol/L. These four vaccines were tested for their efficiency in generating humoral immune response in different groups of broiler chicks. Both BEI-inactivated vaccines gave relatively higher antibody titers and were almost twice as efficient as formaldehyde-inactivated ones.

Animals↗

Cytokine production during in vitro hemodialysis with new and formaldehyde- or renalin-reprocessed cellulose dialyzers.

Critics of reuse have suggested that patients treated with reprocessed dialyzers are exposed to pyrogen trapped from the water or solutions used during the reprocessing cycle, thereby triggering the synthesis and release of proinflammatory cytokines, resulting in cachexia. To test this hypothesis, the production of interleukin (IL)-1 alpha by peripheral blood mononuclear cells (PBMC) during in vitro dialysis with new or reprocessed cellulose dialyzers was compared. An in vitro closed-loop dialysis circuit was created with standard hemodialysis blood lines and either new cellulose dialyzers or dialyzers reprocessed 10 times with either formaldehyde/bleach (formaldehyde) or peracetic acid/hydrogen peroxide mixture (Renalin). The circuit was rinsed with 2 L or more of pyrogen-free normal saline before the start of in vitro dialysis until the blood compartment tested negative for residual formaldehyde/Renalin. Heparinized whole blood from healthy volunteers was circulated for 3 h in the blood compartment at 100 mL/min at 37 degrees C. The dialysate compartment was sealed. Peripheral blood mononuclear cells (PBMC) were harvested from the blood compartment before and at the end of 3 h of in vitro dialysis. Total IL-1 alpha synthesis (cell associated plus secreted) by unstimulated and endotoxin-stimulated PBMC was measured by a specific, non-cross-reactive radioimmunoassay. After 3 h of in vitro dialysis, IL-1 alpha production (in picograms per 2.5 million PBMC) by unstimulated PBMC increased from 354 +/- 63 at baseline to 454 +/- 57 with new dialyzers (P = 0.25), from 453 +/- 101 to 450 +/- 67 with formaldehyde-reprocessed dialyzers (P = 0.98), and from 360 +/- 61 to 538 +/- 144 with Renalin-reprocessed dialyzers (P = 0.23). IL-1 alpha production by endotoxin-stimulated PBMC increased from 5,214 +/- 996 to 9,237 +/- 929 with new dialyzers (P < = 0.001), from 6,395 +/- 955 to 9,636 +/- 1,058 with formaldehyde-reprocessed dialyzers (P = 0.006), and from 7,561 +/- 1,000 to 10,092 +/- 2,470 with Renalin-reprocessed dialyzers (P = 0.32). However, there were no significant differences among groups with respect to IL-1 alpha production by unstimulated or endotoxin-stimulated PBMC either before or after 3 h of in vitro dialysis. These data argue against the suggestion that exposure to reprocessed dialyzers results in enhanced synthesis of proinflammatory cytokines. In fact, reprocessed dialyzers probably induce less cytokine production than do new cellulose dialyzers.

Cellulose↗

Formaldehyde fasciaform tympanoplasty: a reliable technique for closing large tympanic membrane perforations.

Formaldehyde fasciaform grafting tympanoplasty is a reliable method, in experienced hands, to close large tympanic membrane perforations. The technique involves using autogenous temporalis fascia shaped by formaldehyde cross-linking on a special fasciaform mold (Hear America, Palo Alto, CA). This study was undertaken with the objective of assessing if an otologist with less experience in using this technique could obtain comparable results. The results of the initial 23 patients treated in this manner by one surgeon between August 1996 and January 1998 are reviewed. Success was measured by the rate of closure of the tympanic membrane perforation and by functional closure of the air-bone gap. Favourable results were obtained, with complete closure of 86% of the perforations and closure of the air-bone gap to 20 dB or less in 90% of subjects when the ossicular chain was intact. The formaldehyde fasciaform tympanoplasty technique produces consistent, reliable, and reproducible results for large tympanic membrane perforations.

Fascia↗

The effects of progressive formaldehyde fixation on the preservation of tissue antigens.

A wide variety of fresh post-mortem tissues was fixed in 4% formaldehyde for 6 hours, 1, 3, 7, 14 and 30 days to simulate possible fixation schedules in the diagnostic laboratory, before processing through alcohol and chloroform. The immunoreactivity of paraffin-embedded sections to 25 monoclonal and polyclonal antibodies commonly used in tissue diagnosis was tested employing an avidin-biotin-peroxidase technique. There was a distinct fall-off in the staining of many antigens including the lymphocyte antigens LN1, LN2, LN3 and UCHL1 after 3 days of fixation and the intermediate filament proteins vimentin, desmin and neurofilaments failed to be labelled by monoclonal antibodies after 1 day and only variable staining for the cytokeratins was retained. S100 protein, prostate specific antigen, thyroglobulin and carcinoembryonic antigen were more resilient and showed weak staining after 14 days exposure to formaldehyde. Trypsinization improved the staining for cytokeratins, neurofilaments, desmin and Factor VIII-related protein, but for other antigens, the immunoreaction was weaker and background staining was increased. For the effective application of immunohistochemical staining as a diagnostic tool, the duration of formaldehyde fixation should be kept to a minimum and enzyme digestion should only be judiciously employed for selected antigens.

Adult↗

Subacute immunotoxicity study of formaldehyde in male rats.

Immune functions were examined in male rats following 28 day oral administration of formaldehyde by gastric tube at dose levels of 0, 20, 40, and 80 mg/kg. Routine parameters examined included hematology, clinical chemistry, and body, thymus, kidney, and liver weights. In addition, cellularity of spleen and lymph nodes, histology of spleen, thymus, lymph nodes, liver kidney, small and large intestines, and histochemistry of spleen and lymph nodes were evaluated. Immune parameters evaluated included serum hemagglutinin antibody response; antibody plaque forming cell response to sheep erythrocytes (lymphocyte-dependent antigen); microbicidal activity of Candida albicans; and phagocytic activity by adhesion of microspheric hydrophilic synthetic particles to leukocyte cell membrane. Body weights were slightly decreased at high dose level (80 mg/kg). The difference was significant when compared to the controls. The lymph node weights were significantly increased in rats receiving formaldehyde. The cellularity of lymphoid organs was not influenced after 28 day exposure to formaldehyde.

Administration, Oral↗

Oral toxicity of formaldehyde and its derivatives.

Formaldehyde (FA) has been commercially produced since the early 1900s. Its widespread use in a variety of applications is known to result in appreciable exposure of workers and of a section of the general population. Formaldehyde is a normal metabolite in mammalian systems. It occurs in air as a product of the natural photooxidation of automobile exhaust, combustion processes, incinerators; formaldehyde has been found in municipal and industrial effluents and is present in food either naturally (fruits and vegetables, in the order of parts per million), or as a result of its use as a food additive. The use of FA and its derivative, hexamethylenetetramine (HMT), which gradually decomposes to FA under acidic conditions as antimicrobial agents in food, raises questions about their potential chronic oral toxicity. Furthermore, since FA is a very reactive compound and reacts with different macromolecules such as proteins and nucleic acids, the safety evaluation of FA as a cheese additive must take into account the toxicity of the reaction products between FA and milk components. Biochemical aspects, acute and short-term toxicity studies including mutagenicity, multigeneration, and reproduction studies, long-term carcinogenicity studies after oral administration of FA and HMT are reviewed in this paper. The results of these studies indicate that repeated oral exposure of a relatively large amount of FA that could overwhelm the normal metabolic capacity of animals to convert FA into formiate, CO2, and water produces histopathological gastric changes. This paper correlates the hazard caused by the exposure to low levels of FA, as far as its carcinogenic potential by oral route is concerned per se or regarding its use as a food additive. Based on the evidence that FA is formed naturally in food and is a normal mammalian metabolite and that a threshold for carcinogenicity exists both after exposure by inhalation and oral administration, it may be deduced that FA is not carcinogenic at low levels of exposure.

Administration, Oral↗

Kinetic studies of formaldehyde binding in tissue.

Specimens of rabbit liver were fixed for various periods up to 6 days in buffered 14C-formaldehyde. Binding of the isotope reached a plateau after fixation for approximately 24 hr; the half-maximal binding level was reached after approximately 100 min. Formaldehyde binding at 37 C was faster than at 25 C, and faster at pH 7.0 than at pH 4.0. During rinsing of the fixed tissue in water for up to 26 days there was a progressive decrease in isotope content to 10-20% of the pre-rinse level, indicating that formaldehyde fixation is a reversible process.

Animals↗

Effectiveness of acetic acid and formaldehyde for preventing protein degradation in the rumen.

Six rumen cannulated steers were in a replicated 3 X 3 Latin square arrangement to investigate degradability in the rumen of dry matter and crude protein from soybean meal that was untreated or treated with either 8% acetic acid or .3% formaldehyde. Polyester bags containing the soybean meals were suspended in the rumen of each steer and removed after 1, 2, 4, 8, 12, 16, and 24 h to calculate degradation rates. Soybean meals remaining in the polyester bags after 12 h of rumen exposure were collected and referred to as residues. Postruminal digestion was stimulated by incubating 200 mg of soybean meal residues with pepsin and pancreatin. Formaldehyde treatment of soybean meal was more effective than acetic acid treatment in preventing ruminal degradation of dry matter and crude protein under these experimental conditions. However, soybean meal treated with acetic acid and remaining in polyester bags after 12 h of ruminal exposure released a larger quantity of alpha-amino nitrogen during in vitro incubation with pepsin and pancreatin than did residue of soybean meal treated with formaldehyde. Acetic acid may prove to be an effective agent for increasing the supply of absorbable dietary amino acids.

Acetates↗

Effects of ruminal exposure on the amino acid profile of heated and formaldehyde-treated soybean meal.

Rumen cannulated Holstein steers, fed corn silage and a corn-soybean grain mixture twice a day, were used to compare the effectiveness of heat and formaldehyde treatments in preserving the amino acid profile of soybean meal exposed to ruminal fermentation for 12 h. Formaldehyde treatments were 0, .3, .6, and .9 g/100 g soybean meal. Defatted soybean flakes treated at 250, 250, 215, and 180 degrees C for 30, 20, 20, and 25 min, respectively, and unheated soybean meal comprised the heat treatments. The in situ polyester bag technique was used to obtain estimates of ruminal degradation of the treated and untreated soybean meals and to obtain undegraded residues from the soybean meals following 12 h of rumen exposure. Diaminopimelic acid was used to assess the extent of bacterial contamination. Significant amounts of apparent diaminopimelic acid were detected in unexposed samples (2.0 to 7.6% of soybean nitrogen) and in residues (4.8 to 12.7% of residue nitrogen). Significant differences in amino acid contents were detected between untreated and heat-treated soybean meals and their respective residues. Formaldehyde treatment was effective in preserving the original amino acid profile of soybean meal.

Amino Acids↗

Allergic contact dermatitis from formaldehyde in a liquid soap.

A case is reported of a 74-year-old white man who developed generalized allergic contact dermatitis from formaldehyde present in a liquid soap. The patient had a 2+ positive patch test reaction to formaldehyde, which was present as a preservative in the soap at 0.1% concentration. His dermatitis cleared when he switched to a nonformaldehyde-containing bar soap. The cause of the contact dermatitis was covert to both physician and patient before patch testing. Since registration with the Food and Drug Administration of formaldehyde-containing soaps is voluntary, it is likely that there are more soaps on the market than the six registered as of June 1988.

Aged↗

Effect of an ultraviolet light-activated coating material on reduction of the leaching of methyl methacrylate and formaldehyde from denture acrylic resins.

Effect of glazing with an ultraviolet light-activated coating material on reduction of the leaching of methyl methacrylate and formaldehyde from denture acrylic resins was quantitatively evaluated. Disks prepared from auto-polymerized resins were painted with the material and radiated with ultraviolet light. The disks were immersed in artificial saliva and the concentrations of methyl methacrylate and formaldehyde leached were determined by high-performance liquid chromatography and flow injection analysis. Compared to untreated controls, the glaze significantly decreased concentrations of both leachable substances. Treatment with an ultraviolet light-activated coating material is effective in suppressing the leaching of methyl methacrylate and formaldehyde from acrylic resins as well as in smoothing the denture surfaces.

Acrylic Resins↗

Observations on a formaldehyde low-temperature steam sterilizer.

In Finnish hospitals, heat labile equipment is mostly sterilized by ethylene oxide (EO) gas. Formaldehyde sterilizers are rarely used. We have tested a new commercial autoclave constructed exclusively for formaldehyde and low-temperature steam (F-LTS) sterilization, offering a potentially safer and cheaper method of sterilization. Both the sterilizing efficacy of the apparatus and the levels of formaldehyde in the processed materials were studied.

Equipment and Supplies, Hospital↗

Drought stress, peroxidase activity and formaldehyde metabolism in bean plants.

In our investigations we have studied the changes of total peroxidase and isozyme activities, peroxidase isozyme pattern and the level of endogenous formaldehyde and trigonelline. We have examined the effect of drought stress resulted by Carbowax treatment (2, 5, 7, 10%) of two different snap bean (Phaseolus vulgaris L.) genotypes [drought tolerant (T) and drought sensitive (S)]. There were no detectable differences in the peroxidase isozyme patterns but the total peroxidase activity was increased. We have found similar steep enhancement in the peroxidase activities of one of three peroxidase fractions while the increase in the other isozyme fractions was not so significant in the two genotypes. Increasing peroxidase activities and changes in the amount of endogenous formaldehyde and trigonelline were detectable with increasing Carbowax treatment in both genotypes, but in different ways. According to our experiments, the total peroxidase and some isozyme activity correlated with the concentration of endogenous formaldehyde and trigonelline, playing an important role during drought stress.

Chromatography, High Pressure Liquid↗

Formaldehyde generation by N-demethylation.

Microsomal oxidation of exogenic compounds yields efferent metabolites with small molecular size. N-demethylation results in formaldehyde generation in addition to the nor-compound. Interesting changes in the level of formaldehyde elimination were observed after a single dose of either ( )-deprenyl or (+)-deprenyl. Urine elimination of the generated formaldehyde was determined using thin-layer chromatography after derivatization with dimedone.

Formaldehyde↗

Changes in formaldehyde contents of germinating acorns of Quercus cerris L. under low temperature stress conditions.

Acorns of Quercus cerris L., after saturation with water and storage at -20 degrees C, were studied for changes in their contents of endogenous formaldehyde and its potential precursor and generator compounds. For the measurement of formaldehyde, after conversion to formaldemethone and some methyl acceptor and donor substances, high performance liquid chromatography (HPLC) were used. First, the amount of formaldehyde was drastically decreased. Having reached a minimum value within three to five days of the beginning of low temperature storage, a higher steady-state than the control acorns was recorded. Trigonelline and gamma-amino-butyric acid in seedleaf extracts were identified by matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS).

Chromatography, High Pressure Liquid↗