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PubMed2000

Retrospective diagnosis of diphtheria by detection of the Corynebacterium diphtheriae tox gene in a formaldehyde-fixed throat swab using PCR and sequencing analysis.

The tox gene of Corynebacterium diphtheriae was detected in a formaldehyde-fixed throat swab taken from a 68-year-old man who was reported to have died of suffocation due to a pharyngeal tumor. DNA templates prepared from bacterial cells fixed with 10% formaldehyde were subjected to a PCR analysis with tox gene-specific PCR primers. The resultant 112-nucleotide-long PCR product was sequenced using a dye terminator method, and an expected 57-nucleotide-long internal sequence of the tox gene was detected. This method is applicable for retrospective diagnosis in diphtheria cases in which only a formaldehyde-fixed clinical sample is available.

Base Sequence↗

PubMed2005

Induction of humoral immune responses following vaccination with envelope-containing, formaldehyde-treated, thermally inactivated human immunodeficiency virus type 1.

The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.

AIDS Vaccines↗

PubMed1991

Malignant melanomas of the nasal cavity after occupational exposure to formaldehyde.

Formaldehyde is a well known nasal carcinogen in rodents, but so far there has been no convincing evidence that workers occupationally exposed to formaldehyde have an increased risk of nasal cancer. In this study three cases of malignant melanoma of the nasal mucosa in persons occupationally exposed to formaldehyde for a long time are presented. The occurrence of such a rare tumour in patients with significant exposure to a known carcinogen warrants further investigation.

Aged↗

PubMed1993

Sporocidal properties of peracetic acid and hydrogen peroxide, alone and in combination, in comparison with chlorine and formaldehyde for ultrafiltration membrane disinfection.

The sporocidal properties of peracetic acid, hydrogen peroxide, chlorine, and formaldehyde were compared in vitro using a dilution-neutralization micromethod. A combination of peracetic acid and hydrogen peroxide was also tested to assess their interactions. The activities of these agents, which are widely used as disinfectants, were evaluated against Bacillus spore isolates found on stored membranes and collection cultures. Peracetic acid and chlorine exhibited an excellent antimicrobial activity, with a destruction of 10(5) spores/mL after 5 min of contact. Generally the effects of the biocides tested were time dependent. The sporocidal activities of hydrogen peroxide and formaldehyde were the lowest. The combination of peracetic acid and hydrogen peroxide, tested by a checkerboard micromethod, was found to be synergistic. The minimal sporocidal concentration (MSC) was established in terms of time for each biocide. The lowest MSC values for peracetic acid, hydrogen peroxide, chlorine, and formaldehyde were 168-336 ppm (1-2 h of contact), 5625-11250 ppm (5-7 h), 168-336 ppm (2-3 h), and 1875-3750 ppm (5-30 min), respectively. The MSC of a biocide combination of peracetic acid and hydrogen peroxide showed that synergy was maintained with increasing contact time and that the MSC could be reduced by two to eight times when compared with those of the biocides alone. Optimal concentrations and contact times of those chemicals that were promising in vitro were then tested for their ability to disinfect ultrafiltration membranes. The sporocidal activities of peroxide compounds and chlorine were confirmed and the synergism between peracetic acid and hydrogen peroxide was also maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus↗

PubMed1983

Antibodies to indolealkylamines II: site of conjugation of melatonin to protein using formaldehyde.

The site of coupling on the hapten was investigated for melatonin, formaldehyde, and protein conjugates. Model reactions of glycine ethyl ester and piperidine with formaldehyde and melatonin suggested that coupling first occurred through the indole nitrogen and then a stable bond was formed at C-2. Cross-reaction studies of antisera stimulated by melatonin, formaldehyde, and protein conjugates support the hypothesis that C-2 is the site of conjugation of melatonin to protein.

Animals↗

PubMed1987

Acute response to 3.0 ppm formaldehyde in exercising healthy nonsmokers and asthmatics.

Formaldehyde is an ubiquitous industrial and indoor air pollutant to which millions are daily exposed. Because of the paucity of scientific data concerning the inhalation toxicity of this compound in humans, we determined the symptoms and alterations in pulmonary function resulting from inhalation for 1 h of 3 parts per million formaldehyde in a controlled environmental chamber. The protocol consisted of randomized exposure of each subject to clean air or 3.0 ppm HCHO on 2 separate days. Twenty-two healthy normal subjects engaged in intermittent heavy exercise (VE = 65 L/min) and 16 asthmatic subjects performed intermittent moderate exercise (VE = 37 L/min). Symptoms and pulmonary function were assessed during the time course of exposure; nonspecific airway reactivity was assessed after exposure. Both groups exhibited similar, significant (p less than 0.01) increases in perceived odor, nose/throat irritation, and eye irritation throughout the exposure. The normal group had the following statistically significant (p less than 0.02) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air: 3.8% in FEV1, 2.6% in FVC, and 2.8% in FEV3. The asthmatic group showed no statistically significant decrements in pulmonary function. Five of 38 subjects studied had decrements in FEV1 greater than 10%. In conclusion, acute exposure to 3 ppm HCHO produced: consistent irritant symptoms in both normal and asthmatic subjects, small decreases in pulmonary function in normal subjects engaging in heavy exercise, and clinically significant responses (defined here as decrements in FEU1 greater than 10) in 13% of the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1980

Calibrant solutions for continuous-flow urate analysis: interference by formaldehyde.

The use of formaldehyde to preserve aqueous urate calibration solutions has been recommended since 1913, but it interferes in some commonly used methods. At a pH below 8.5 formaldehyde affects the rate of dialysis of urate in Technicon AutoAnalyzer systems. This effect has been studied by variation of the pH at which dialysis takes place. The interference is attributed to the formation of pH-dependent addition products between uric acid and formaldehyde, which have been examined by thin-layer chromatography and mass spectrometry. Recovery experiments on protein-containing solutions show that a purely aqueous urate calibrant solution is satisfactory for use in AutoAnalyzer systems.

Autoanalysis↗

PubMedDate not supplied

A brief review of formaldehyde carcinogenesis in relation to rat nasal pathology and human health risk assessment.

The 1980 report that inhaled formaldehyde induced nasal squamous cell carcinomas in rats had a significant societal impact and resulted in extensive research in the fields of rodent nasal pathology and human cancer risk assessment. This article presents an overview of the evolution of these events. It is concluded that the nasal passages of humans and rats are fundamentally identical biological target organs. Nevertheless, in the case of human health risk assessment, minor differences between these species may be critically important. Special attention should be paid to interspecies differences in nasal dosimetry and local metabolism; thus, chemical toxicity data derived from rats require careful interpretation when used for human risk assessments. In the case of formaldehyde, it is recommended that low-concentration (< or = 2 ppm airborne exposure) extrapolation, where no tissue damage is observed, be uncoupled from the responses at high concentrations (> or = 6 ppm), where epithelial degeneration, regenerative cell replication, and inflammation appear to be essential driving forces in formaldehyde carcinogenesis. The presence of treatment-related nasal lesions in rats following exposure to chemicals should always be treated as an indication of a potential human health risk, whether exposure is by the inhalation, oral, or dermal route.

Animals↗

PubMed1977

Interaction of polyanions with basic fuchsin and formaldehyde.

Basic fuchsin and formaldehyde react readily with a number of polyanions in aqueous solutions. Deoxyribonucleic acid, ribonucleic acid, several synthetic polynucleotides and polyvinylsulfate all convert buffered solutions of basic fuchsin and formaldehyde from a magenta to a purple color at ambient temperature. The formation of product is maximal in about 20 min and the resulting complexes are stable enough to be isolated by gel filtration. Microgram amounts of polyanion suffice to produce the color changes and the spectral shifts vary with the type of polyanion. These results are interpreted to indicate that polymerization of basic fuchsin and formaldehyde is an essential aspect of color formation.

Chromatography, Gel↗

PubMed1991

Effects of formaldehyde fixation on protein secondary structure: a calorimetric and infrared spectroscopic investigation.

We investigated the effects of formaldehyde fixation on the secondary structure of isolated proteins (bovine serum albumin, ribonuclease A, and hemoglobin) using high-sensitivity differential scanning calorimetry and Fourier transform infrared spectroscopy. Whereas thermograms obtained by scanning calorimetry on unfixed purified proteins demonstrated denaturation transitions in the 70-90 degrees C temperature range, the thermograms showed no denaturation transitions in this temperature range when the proteins had been placed in formaldehyde solutions. Thus, fixation destroyed the denaturation transition of bovine serum albumin, ribonuclease A, and hemoglobin. Infrared spectra obtained on the unfixed and fixed proteins were essentially identical. This demonstrates that the "fixed" proteins retain the secondary structure present before fixation. We therefore conclude that the cross-linking of proteins that occurs in the process of formaldehyde fixation "locks in" the secondary structure of these protein molecules.

Calorimetry, Differential Scanning↗

PubMed1999

Acute airway effects of formaldehyde and ozone in BALB/c mice.

1. Concentration and time-effect relationships of formaldehyde and ozone on the airways were investigated in BALB/c mice. The effects were obtained by continuous monitoring of the respiratory rate, tidal volume, expiratory flow rate, time of inspiration, time of expiration, and respiratory patterns. 2. With concentrations up to 4 p.p.m., formaldehyde showed mainly sensory irritation effects of the upper airways that decrease the respiratory rate from a trigeminal reflex. The no-effect level (NOEL) was about 0.3 p.p.m. This value is close to the human NOEL, which is about 0.08 p.p.m. 3. Ozone caused rapid, shallow breathing in BALB/c mice. Later on, the respiratory rate decreased due to another vagal response that indicated an incipient lung oedema. The NOEL in mice was about 1 p.p.m. during 30 min of ozone exposure. No major effect occurs in resting humans at about 0.4 p.p.m. 4. Thus, the upper airway irritant, formaldehyde, and the deep lung irritant, ozone, showed the same types of respiratory effects in humans and in BALB/c mice. Also, the sensitivity was nearly identical. Continuous monitoring of respiratory effects in BALB/c mice, therefore, may be a valuable method for the study of effects of other environmental pollutants, which, however, should be confirmed in further studies.

Animals↗

PubMed1980

The effects of glutaraldehyde and formaldehyde fixation on the retention and subcellular location of [3H]5-hydroxytryptamine in rabbit platelets: a study using liquid scintillation counting and E.M. autoradiography.

The retention and loss of [3H]5-hydroxytryptamine (5-HT) from rabbit platelets during fixation was studied using liquid scintillation counting and quantitative electron-microscopic autoradiography. The results were at variance with previously reported data on human platelets. Following treatment of the platelets with either 2.0% formaldehyde or 2.5% glutaraldehyde for 2 min or 1 h it was found that a significantly increased proportion of the radioactivity was lost from treated as compared with untreated platelets. Using a method of analysis which accounts for cross-scatter of decay particles between cell compartments, electron-microscopic autoradiography revealed that 50% of the radioactivity following incubation of platelets with [3H]5-HT was associated with dense bodies and 30% in the cytoplasm when fixation was in formaldehyde or glutaraldehyde. The only major difference in the labelling pattern was that whereas glutaraldehyde appeared to retain no activity in the surface connected system the latter contained 12% of total retained activity following fixation with formaldehyde.

Aldehydes↗

PubMed2005

Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate.

PURPOSE: It has been claimed that oral creatine supplementation might have potential cytotoxic effects on healthy consumers by increasing the production of methylamine and formaldehyde. Despite this allegation, there has been no scientific evidence obtained in humans to sustain or disprove such a detrimental effect of this widely used ergogenic substance. METHODS: Twenty young healthy men ingested 21 g of creatine monohydrate daily for 14 consecutive days. Venous blood samples and 24-h urine were collected before and after the 14th day of supplementation. Creatine and creatinine were analyzed in plasma and urine, and methylamine, formaldehyde, and formate were determined in 24-h urine samples. RESULTS: Oral creatine supplementation increased plasma creatine content 7.2-fold (P < 0.001) and urine output 141-fold (P < 0.001) with no effect on creatinine levels. Twenty-four-hour urine excretion of methylamine and formaldehyde increased, respectively, 9.2-fold (P = 0.001) and 4.5-fold (P = 0.002) after creatine feeding, with no increase in urinary albumin output (9.78 +/- 1.93 mg x 24 h(-1) before, 6.97 +/- 1.15 mg x 24 h(-1) creatine feeding). CONCLUSION: This investigation shows that short-term, high-dose oral creatine supplementation enhances the excretion of potential cytotoxic compounds, but does not have any detrimental effects on kidney permeability. This provides indirect evidence of the absence of microangiopathy in renal glomeruli.

Administration, Oral↗

PubMed2003

Formaldehyde-induced shrinkage of rat thymocytes.

To test the possibility that micromolar formaldehyde, a metabolite of methanol derived from aspartame, exerts cytotoxicity, its effect on rat thymocytes was examined under the in vitro condition using a flow cytometer. Incubation of thymocytes with formaldehyde at 100 micro M or more for 24 h significantly increased the populations of shrunken cells and cells with hypodiploid DNA. The peak blood concentration of methanol in human subjects administered abuse doses of aspartame has been reported to exceed 2 mg/dL (625 micro M). It would increase the population of thymocytes undergoing apoptosis if formaldehyde at 100 micro M or more appears in the blood after administration of aspartame.

Animals↗

PubMed2006

A novel type of formaldehyde-oxidizing enzyme from the membrane of Acetobacter sp. SKU 14.

Membrane-bound NADP-independent formaldehyde-oxidizing enzyme was purified to homogeneity from the membrane of Acetobacter sp. SKU 14 isolated in Thailand. The enzyme was solubilized from the membrane fraction of glycerol-grown cells with 1% Tween 20 at pH 2.85, and purified to homogeneity through the steps of column chromatographies on DEAE-Sephadex A-50 and Q-Sepharose in the presence of 0.1% Tween 20 and 0.1% Triton X-100. The enzyme purified together with a cytochrome c showed a single protein band on native-PAGE, and was dissociated into three different subunits upon SDS-PAGE with molecular masses of 78 kDa, 55 kDa, and 18 kDa. The purified enzyme was finally characterized as a quinoprotein alcohol dehydrogenase (QADH), and this is the first indication that QADH highly oxidizes formaldehyde. The substrate specificity of the enzyme was found to be broad toward aldehydes and alcohols, and alcohols, especially n-butanol, n-propanol, and ethanol, were oxidized more rapidly than formaldehyde.

Acetobacter↗

PubMed2005

Meeting report: summary of IARC monographs on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol.

An international, interdisciplinary working group of expert scientists met in June 2004 to develop IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol. Each IARC Monograph includes a critical review of the pertinent scientific literature and an evaluation of an agent's potential to cause cancer in humans. After a thorough discussion of the epidemiologic, experimental, and other relevant data, the working group concluded that formaldehyde is carcinogenic to humans, based on sufficient evidence in humans and in experimental animals. In the epidemiologic studies, there was sufficient evidence that formaldehyde causes nasopharyngeal cancer, "strong but not sufficient" evidence of leukemia, and limited evidence of sinonasal cancer. The working group also concluded that 2-butoxyethanol and 1-tert-butoxy-2-propanol are not classifiable as to their carcinogenicity to humans, each having limited evidence in experimental animals and inadequate evidence in humans. These three evaluations and the supporting data will be published as Volume 88 of the IARC Monographs.

Animals↗

PubMed2005

Strategies for formaldehyde detection in flames and engines using a single-mode Nd:YAG/OPO laser system.

This paper presents technical developments for the detection of formaldehyde (CH2O) using laser-induced fluorescence. The easily accessible third harmonic of the Nd:YAG laser at 355 nm was used for excitation of formaldehyde. In order to investigate potential background fluorescence, e.g., from large molecules such as polyaromatic hydrocarbons, special attention was paid to investigating the possibility of scanning the wavelength of a single-mode Nd:YAG laser under the gain profile, approximately 3 cm(-1), on and off resonance. Furthermore, a technique for simultaneous detection of formaldehyde and OH using one laser system is presented. The single-mode Nd: YAG laser at 355 nm in combination with an optical parametric oscillator (OPO) laser tuned to 283 nm was used for simultaneous two-dimensional imaging of both species using one charge-coupled device (CCD) detector equipped with a dual filter image separator. The techniques are demonstrated with measurements in laboratory flames and the combined measurements are also demonstrated in an engine.

Formaldehyde↗

PubMed2005

Flux analysis uncovers key role of functional redundancy in formaldehyde metabolism.

Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and (14)C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.

Deuterium↗