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Bronchial challenge with formaldehyde gas: lack of bronchoconstriction in 13 patients suspected of having formaldehyde-induced asthma.

We studied 13 selected patients with symptoms suggestive of asthma who suspected exposure to formaldehyde as a cause. These patients had a history of exposure to formaldehyde gas which either coincided with the onset of or aggravated their symptoms of asthma. The levels of exposure at their homes or at work ranged from 0.1 to 1.2 parts per million (ppm) of formaldehyde gas. The patients were tested with bronchial challenges of 0.1-, 1-, and 3-ppm concentrations of formaldehyde gas and randomly interspersed room-air placebos. The formaldehyde gas or placebo was delivered via a Dynacalibrator . The period of exposure to formaldehyde gas or placebo with each challenge was 20 minutes. Pulmonary function was measured before and for 24 hours after each bronchial challenge. No patient had a significantly greater decrease in the forced expiratory volume in 1 second after exposure to formaldehyde than after exposure to air. In no case were we able to substantiate that exposure to formaldehyde gas (3 ppm or less) was indeed causing or aggravating the asthmatic symptoms.

Adolescent↗

A method for quantification of formaldehyde in the presence of formaldehyde donors in skin-care products.

Reliable and uncomplicated methods for detection of free formaldehyde in products preserved with formaldehyde donors are desirable to decrease the risk of allergic contact dermatitis. The aim of this study was to develop a method that could be used in clinics and workplaces for quantification of free formaldehyde in products preserved with formaldehyde donors. The method developed is named the closed container diffusion (CCD) method. Formaldehyde in a sample is allowed to evaporate in a closed container and react with 2,4-dinitrophenylhydrazine coated on a glass fibre filter. The hydrazone formed is analyzed with HPLC. The method was tested on 3 different formaldehyde donors, imidazolidinyl urea, diazolidinyl urea and 2-bromo-2-nitropropane-1,3-diol, using 4 different cream bases. The results obtained with this method accord, with those obtained with the official method within the European Union (EU). The method is sensitive enough for analysis of patients' products and for control of labelled amounts of formaldehyde in technical products without solvent extraction. As a result of our studies, we observed a risk of exceeding the labelling limit for free formaldehyde in cosmetic products when using the highest amount of diazolidinyl urea allowed within the EU.

Dermatitis, Allergic Contact↗

Formaldehyde lacks genotoxicity in formaldehyde-hyperresistant strains of the yeast Saccharomyces cerevisiae.

Formaldehyde is a weak mutagen and recombinagen in wild type strains of Saccharomyces cerevisiae. Genotoxicity of formaldehyde is influenced by the activity of the SFA yeast gene. Yeast transformants containing multiple copies of the plasmid-contained SFA gene are hyperresistant to the chemical and grow in the presence of 5 mM formaldehyde, a concentration lethal for the wild type. The SFA-encoded protein mediates the degradation of formaldehyde and its activity is most probably responsible for the low or absent genotoxic effects in formaldehyde-treated cells. Multi-copy vectors containing the SFA gene are retained in yeast transformants growing in complex media supplemented with 5 mM formaldehyde. Cells harboring such multi-copy vectors may, therefore, be propagated in large batch cultures in undefined media in the presence of formaldehyde concentrations toxic to the wild type.

Drug Resistance↗

Demonstration of formaldehyde dehydrogenase activity in formaldehyde-resistant Enterobacteriaceae.

Clinical isolates of different Enterobacteriaceae strains and genetically modified variants which were resistant to the disinfectant formaldehyde were investigated. In cell-free extracts of all formaldehyde-resistant strains a glutathione-dependent formaldehyde dehydrogenase activity was demonstrated. In contrast cell extracts from formaldehyde sensitive strains did not show any formaldehyde dehydrogenase activity. The enzymatic degradation of formaldehyde seems to play an important role in formaldehyde resistance.

Aldehyde Oxidoreductases↗

Proallergens of formaldehyde applied in patch testing of formaldehyde contact allergy.

The ability of the nonliquid, nonvolatile proallergen of formaldehyde, N-hydroxymethylsuccinimide, to test for contact allergy to formaldehyde has been investigated by in vitro penetration studies in human epidermis. Compared with the standard test, 1% formaldehyde in water, N-hydroxymethylsuccinimide equal to 0.8 mg formaldehyde gave a similar penetration profile. This is explained by cleavage of N-hydroxymethylsuccinimide into formaldehyde and carrier (succinimide) by transepidermal water on the surface of the skin. Results were confirmed by a guinea pig maximazation test on animals sensitized to formaldehyde and in a preliminary clinical study on nine patients with known allergy to formaldehyde.

Administration, Cutaneous↗

Formaldehyde content of milk in goats fed formaldehyde-treated soybean oil-meal.

Formaldehyde is used in ruminant feeding for different purposes including the protection of dietary proteins from ruminal degradation. The formaldehyde content of milk of goats fed various levels of formaldehyde-treated soybean oil-meal has been determined by using a sensitive HPLC method. Results showed a significant linear correlation between ingested formaldehyde and formaldehyde concentration in milk. About 0.02% of ingested formaldehyde was excreted in milk, as free formaldehyde.

Animal Feed↗

ACTION OF FORMALDEHYDE ON MICROORGANISMS. III. BACTERICIDAL ACTION OF SUBLETHAL CONCENTRATIONS OF FORMALDEHYDE ON AEROBACTER AEROGENES.

Neely, W. Brock (The Dow Chemical Co., Midland, Mich.). Action of formaldehyde on microorganisms. III. Bactericidal action of sublethal concentrations of formaldehyde on Aerobacter aerogenes. J. Bacteriol. 86:445-448. 1963.-Bacteriostatic concentrations of formaldehyde were found to be bactericidal during the initial growth period. This bactericidal activity was due to the primary induction of unbalanced growth by formaldehyde. The subsequent formation of 1,3-thiazane-4-carboxylic acid prevented the synthesis of methionine. This dual activity of formaldehyde resulted in an inhibition of both nuclear and cytoplasmic syntheses, and created the normal bacteriostatic condition that has been observed before with sublethal concentrations of formaldehyde.

Anti-Bacterial Agents↗

Residual formaldehyde on plastic materials and medical equipment following low-temperature steam and formaldehyde sterilization.

We measured the amount of residual formaldehyde on 16 plastic materials and five medical devices following low-temperature steam and formaldehyde (LTSF) sterilization, based on the European Standard EN14180. The amounts of formaldehyde residue on the plastic materials were compared with that on a filter paper of similar dimensions. The amount of residual formaldehyde on polyamide 6, polyurethane, natural rubber and polyacetal was higher (21.9, 15.2, 3.0 and 2.1 times, respectively) than that on the filter paper. The amount of formaldehyde recovered from a breathing circuit, anaesthesia circuit, oxygen tubing, airway tube and tweezers was 260, 240, 594, 56 and 0 microg, respectively, following LTSF sterilization. Our results emphasize the need to verify the main material composing the medical equipment before LTSF sterilization, as the amount of formaldehyde retrieved following sterilization varies according to the material used for construction.

Cross Infection↗

Function of a glutathione-dependent formaldehyde dehydrogenase in Rhodobacter sphaeroides formaldehyde oxidation and assimilation.

Despite its reactivity with many biological molecules, formaldehyde can be commonly encountered by virtually all cells. The widespread existence of glutathione-dependent formaldehyde dehydrogenases (GSH-FDH) in procaryotes and eucaryotes suggests this enzyme plays a central and universal role in biological formaldehyde oxidation. This work sought to determine the role of GSH-FDH in the facultative phototrophic bacterium Rhodobacter sphaeroides. Growth phenotypes of wild-type and mutant cells, changes in enzyme specific activities, and the pattern of 13C-labeled compounds detected by NMR spectroscopy cumulatively suggest that R. sphaeroides GSH-FDH can play a critical role in formaldehyde metabolism under both photosynthetic and aerobic respiratory conditions. In photosynthetic cells, the data indicate that GSH-FDH generates reducing power, in the form of NADH, and one-carbon skeletons that are oxidized to carbon dioxide for subsequent assimilation by the Calvin-Benson-Bassham cycle. For example, use of methanol as a sole photosynthetic carbon source increases the specific activities of GSH-FDH, an NAD-dependent formate dehydrogenase, and the key Calvin-Benson-Bassham cycle enzyme, ribulose-1,5-bisphosphate carboxylase. This role of GSH-FDH is also supported by the pattern of [13C]formaldehyde oxidation products that accumulate in photosynthetic cells and the inability of defined GSH-FDH or Calvin cycle mutants to use methanol as a sole carbon source. Our data also suggest that GSH-FDH acts in formaldehyde dissimilation when aerobic respiratory cultures cometabolize methanol and succinate.

Aerobiosis↗

Formaldehyde exposure levels and serum antibodies to formaldehyde-human serum albumin of Korean medical students.

In our study, we estimated formaldehyde exposure levels of Korean medical students during their cadaver dissection practice hours. In addition, we examined the prevalence rates of formaldehyde-specific immunoglobulin E or immunoglobulin G antibodies and compared the results with the symptoms the students experienced as a result of formaldehyde exposure. There were 167 Korean medical students (i.e., subjects) aged 23.8+/-2.5 y (mean+/-standard deviation) and a control group of 67 premedical students aged 20.1+/-2.8 y (mean+/-standard deviation). Concentrations of formaldehyde in the cadaver dissection practice laboratory ranged from 0.194 to 11.245 mg/m3 (3.736+/-3.478 mg/m3 [mean+/-standard deviation]). Students reported by self-administered questionnaires that eye soreness (92.8%) and lacrimation (74.9%) were the most common symptoms they experienced during the laboratory sessions. One (0.6%) of the 167 medical students had a history of wheezing during dissection. Fourteen (8.4%) had specific immunoglobulin G antibody, but none had specific immunoglobulin E antibody. These results suggest that (a) Korean medical students are exposed to formaldehyde at a relatively high levels in their dissection practice hours, (b) specific immunoglobulin G is not related to adverse eye or respiratory symptoms, and (c) specific immunoglobulin E is rarely induced as a result of exposure to formaldehyde.

Antibodies↗

Release of formaldehyde and melamine from tableware made of melamine-formaldehyde resin.

The relationship between the concentrations of formaldehyde and melamine released into 4% acetic acid from dishes and bowls made of melamine-formaldehyde resin was determined. The average concentrations in the migration solution after the sample had been treated at 60, 80, and 95 degrees C for 30 min with 4% acetic acid were 0.0 +/- 0.1, 0.5 +/- 0.4 and 3.0 +/- 2.2 ppm, respectively for formaldehyde and 0.04 +/- 0.07, 0.21 +/- 0.20 and 1.19 +/- 1.18 ppm, respectively for melamine. The correlation between the concentrations of formaldehyde and melamine released at 95 degrees C was y=0.4858x-0.2728 (r=0.8860), where y is melamine concentration (ppm), x is formaldehyde concentration (ppm) and r is the correlation coefficient. The molar concentration ratios of formaldehyde to melamine (F/M ratio) were 15.4 +/- 11.6 at 80 degrees C and 14.9 +/- 10.1 at 95 degrees C. Hence the release of both migrants was affected by temperature but the F/M ratio was not affected. The release of both compounds was was increased on repetition of the migration test at 95 degrees C but their concentrations remained constant after the tenth and seventeenth repetitions of the treatment. During this period, the F/M ratio decreased according to the equation 1n y=-1.4344 1n x+3.7814 (r=-0.9984) for a sample before the tenth repetition of the treatment and remained between 1.7 and 1.9 after the twelfth repetition, where y is the F/M ratio and x is the number of repetitions of the treatment.

Acetates↗

The sodium cycle in methanogenesis. CO2 reduction to the formaldehyde level in methanogenic bacteria is driven by a primary electrochemical potential of Na+ generated by formaldehyde reduction to CH4.

CH4 formation from CO2 and H2 rather than from formaldehyde and H2 in methanogenic bacteria is inhibited by uncouplers, indicating that CO2 reduction to the formaldehyde level is energy-driven. We report here that in Methanosarcina barkeri the driving force is a primary electrochemical sodium potential (delta mu Na+) generated by formaldehyde reduction to CH4. This is concluded from the following findings. 1. CO2 reduction to CH4 was insensitive towards protonophores, when the Na+/H+ antiporter was inhibited; under these conditions delta mu Na+ was 120 mV (inside negative), whereas both delta mu H+ and the cellular ATP content were low. 2. CO2 reduction to CH4, rather than formaldehyde reduction, was sensitive towards Na+ ionophores, which dissipated delta mu Na+. 3. CO2 reduction to CH4, in the presence of protonophores and Na+/H+ antiport inhibitors, was coupled with the extrusion of 1-2 mol Na+/mol CH4, and formaldehyde reduction to CH4 was coupled with the extrusion of 3-4 mol Na+/mol CH4. Thus during CO2 reduction to the formaldehyde level 2-3 mol Na+ were consumed.

Amiloride↗

Biodegradation of formaldehyde by a formaldehyde-resistant bacterium isolated from seawater.

A formaldehyde-tolerant bacterium designated as a DM-2 strain was used to biodegrade formaldehyde. The cells, precultivated in the presence of 400 ppm of formaldehyde, were able to degrade formaldehyde in a minimal medium supplemented with up to 400 ppm of formaldehyde in the presence of 3% NaCl. The rate of formaldehyde degradation achieved in this study was 45 ppm/h when the DM-2 culture's optical density at 660 nm was 1.2.

Bacteria↗

[Effects of ventilation with defined formaldehyde concentrations on lung function and lung structures. Animal experiments on the noxiousness of formaldehyde residues after disinfection in the aseptor (author's transl)].

Having seen the development of fatal pneumonias in ventilated patients, the cause of which was assumed to be the presence of residual traces of formaldehyde in the air in the respirator Kilian and Haug showed in 1973 initial formaldehyde concentrations up to 0.2 ppm in the ventilatory air of respirators correctly disinfected in the Aseptor. To study the effects of formaldehyde on lung function and lung structures, 23 young pigs were automatically ventilated with defined formaldehyde concentrations during 6 hours. The concentrations used were 0.02 ppm, 0.2 ppm and 2.0 ppm (double of the maximum permissible concentration). We found no differences in lung function, as shown by compliance measurements and arterial blood gas analysis. No radiological differences were in the thorax. Histologically, there were only slight alterations in lung structure in the group ventilated with double the maximum permissible concentration of formaldehyde. We conclude that the disinfection of respirators using formaldehyde in the Aseptor will remain the method of choice.

Animals↗

ACTION OF FORMALDEHYDE ON MICROORGANISMS. I. CORRELATION OF ACTIVITY WITH FORMALDEHYDE METABOLISM.

Neely, W. Brock (The Dow Chemical Co., Midland, Mich.). Action of formaldehyde on microorganisms. I. Correlation of activity with formaldehyde metabolism. J. Bacteriol. 85:1028-1031. 1963.-The action of formaldehyde in concentrations sublethal for the culture appeared to be at least twofold. The first phase caused a drop in viability, followed by a second phase where bacteriostatic conditions existed. During both these intervals, formaldehyde was being metabolized. As soon as the organism had lowered the formaldehyde concentration to a critical level, the normal growth cycle was resumed, with a resultant increase in cell population.

Carbon Dioxide↗