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Formaldehyde reactions in dark clouds.

The low-pressure reactions of formaldehyde (H2CO) with D+, D2+, D3+, and He+ have been studied by the ion cyclotron resonance technique. These reactions are potential loss processes for formaldehyde in cores of dark interstellar clouds. The deuterated reactants, which are easier to study experimentally, represent direct analogs for protons. Rate coefficients and branching ratios of product channels have been measured. Charge transfer is observed to be the dominant reaction of H2CO with D+, D2+, and He+ ions. Only the D3+ reaction exhibits a proton transfer channel. All reactions proceed at rate coefficients near the collision limit. Proton-deuteron exchange reactions were found to be inefficient processes in the formaldehyde system.

Cyclotrons↗

Statistical modelling of formaldehyde occupational exposure levels in French industries, 1986-2003.

Occupational exposure databanks (OEDBs) have been cited as sources of exposure data for exposure surveillance and exposure assessment in epidemiology. In 2003, an extract was made from COLCHIC, the French national OEDB, of all concentrations of formaldehyde. The data were analysed with extended linear mixed-effects models in order to identify influent variables and elaborate a multi-sector picture of formaldehyde exposures. Respectively, 1401 and 1448 personal and area concentrations were available for the analysis. The fixed effects of the personal and area models explained, respectively, 57 and 53% of the total variance. Personal concentrations were related to the sampling duration (short-term higher than TWA levels), decreased with the year of sampling (-9% per year) and were higher when local exhaust ventilation was present. Personal levels taken during planned visits and for occupational illness notification purpose were consistently lower than those taken during ventilation modification programmes or because the hygienist suspected the presence of significant risk or exposure. Area concentrations were related to the sampling duration (short-term higher than TWA levels), and decreased with the year of sampling (-7% per year) and when the measurement sampling flow increased. Significant within-facility (correlation coefficient 0.4-0.5) and within-sampling campaign correlation (correlation coefficient 0.8) was found for both area and personal data. The industry/task classification appeared to have the greatest influence on exposure variability while the sample duration and the sampling flow were significant in some cases. Estimates made from the models for year 2002 showed elevated formaldehyde exposure in the fields of anatomopathological and biological analyses, operation of gluing machinery in the wood industry, operation and monitoring of mixers in the pharmaceutical industry, and garages and warehouses in urban transit authorities.

Air Pollutants, Occupational↗

Formaldehyde and hexamethylenetetramine in Styles' cell transformation assay.

A dose-dependent increase in the transformation rate in Styles' cell transformation assay using BHK-21/cl.13 cells was observed after exposure to formaldehyde and hexamethylenetetramine. The toxic and transforming effect was equal after exposure to 20 micrograms/ml of formaldehyde or 1000 micrograms/ml of hexamethylenetetramine which is slowly hydrolysed in aqueous solution to form ammonia and formaldehyde.

Animals↗

Detection of traces of formaldehyde in pure air by gas chromatography and helium ionization detection.

The sensitive helium ionization detector (HID) was used for the direct determination of ppm to ppb levels of formaldehyde in air. Two methods to generate formaldehyde in an air stream were evaluated. The first method utilized a paraformaldehyde permeation tube and the second utilized a motor driven syringe and a dilute solution of formaldehyde. The two methods were evaluated using gas chromatography with HID and spectrophotometry. The paraformaldehyde permeation tube generates only about 60% of the theoretical value, while the motor driven syringe was accurate for levels below 2 ppm; however, at a concentration of 13 ppm or above, oligomers or other chemical forms of CH2O are formed to decrease the concentration of gaseous CH2O produced.

Air↗

The production of amitriptyline from nortriptyline in formaldehyde-containing solutions.

The stability of nortriptyline in aqueous solutions containing various concentrations of formaldehyde was investigated. Amitriptyline, as a reaction product, was determined by gas chromatography/mass spectrometry (GC/MS) in these experiments. Factors that may contribute to this phenomenon, including pH, formaldehyde concentration, and incubation time were evaluated. At 40% (v/v) formaldehyde concentration and pH 4, there was a 68% decrease in nortriptyline concentration along with a concomitant formation of amitriptyline after 24 h. The N-methylated product was responsible for 48% of the total tricyclic drug present. The data also clearly indicate that the formation of amitriptyline is favored at elevated pH.

Amitriptyline↗

Micronuclei and nuclear anomalies induced in the gastro-intestinal epithelium of rats treated with formaldehyde.

The induction of micronuclei and nuclear anomalies in cells of the gastro-intestinal epithelium of rats treated per os with formaldehyde (200 mg/kg) was assessed in comparison with N-methyl-N'-nitro-N-nitrosoguanidine as a positive standard. Formaldehyde and N-methyl-N'-nitro-N-nitrosoguanidine both increased micronuclei and nuclear anomalies in almost all tissues analysed (stomach, duodenum, ileum and colon) though with different patterns and to different extents, reflecting different potency and specificity of target. In the case of formaldehyde these effects were observed in conjunction with signs of severe local irritation. This assay can be employed to detect the genotoxic potential of chemicals in vivo directly on target cells in the proximity of the administration site, thus reducing the likelihood of false-negative results.

Animals↗

Formaldehyde is a bacterial mutagen in a range of Salmonella and Escherichia indicator strains.

Formaldehyde was examined for bacterial mutagenicity using Escherichia coli WP2(pKM101) and WP2uvrA(pKM101), and Salmonella typhimurium TA1535, TA1537, TA1538, TA98, TA100 and TA102, in the absence of any exogenous source of metabolic activation. Using pre-incubation exposure, clear mutagenicity was seen for TA98, TA100 and TA102, and both E. coli strains. In standard plate-incorporation assays, consistent mutagenicity was seen only for TA100 and WP2uvrA(pKM101). No evidence of mutagenicity was seen for TA1535, TA1537 or TA1538 using either method of exposure. These data confirm the enhanced ability of the pre-incubation method to detect the mutagenicity of formaldehyde both quantitatively, as expressed by numbers of revertant colonies, and qualitatively, in terms of the range of indicator strains reverted. The relatively greater sensitivity of the pre-incubation assay is probably due to better containment of a volatile agent and/or lack of interaction with agar during the initial period of exposure. The findings are consistent with the suggestion that formaldehyde induces lesions in bacteria which are, at least to some extent, excision-repairable, and indicate that the presence of the R-factor plasmid may be required for the expression of its mutagenicity in excision repair-deficient Salmonella.

Dose-Response Relationship, Drug↗

Dosimetry modeling of inhaled formaldehyde: binning nasal flux predictions for quantitative risk assessment.

Interspecies extrapolations of tissue dose and tumor response have been a significant source of uncertainty in formaldehyde cancer risk assessment. The ability to account for species-specific variation of dose within the nasal passages would reduce this uncertainty. Three-dimensional, anatomically realistic, computational fluid dynamics (CFD) models of nasal airflow and formaldehyde gas transport in the F344 rat, rhesus monkey, and human were used to predict local patterns of wall mass flux (pmol/[mm(2)-h-ppm]). The nasal surface of each species was partitioned by flux into smaller regions (flux bins), each characterized by surface area and an average flux value. Rat and monkey flux bins were predicted for steady-state inspiratory airflow rates corresponding to the estimated minute volume for each species. Human flux bins were predicted for steady-state inspiratory airflow at 7.4, 15, 18, 25.8, 31.8, and 37 l/min and were extrapolated to 46 and 50 l/min. Flux values higher than half the maximum flux value (flux median) were predicted for nearly 20% of human nasal surfaces at 15 l/min, whereas only 5% of rat and less than 1% of monkey nasal surfaces were associated with fluxes higher than flux medians at 0.576 l/min and 4.8 l/min, respectively. Human nasal flux patterns shifted distally and uptake percentage decreased as inspiratory flow rate increased. Flux binning captures anatomical effects on flux and is thereby a basis for describing the effects of anatomy and airflow on local tissue disposition and distributions of tissue response. Formaldehyde risk models that incorporate flux binning derived from anatomically realistic CFD models will have significantly reduced uncertainty compared with risk estimates based on default methods.

Animals↗

Dose to the cell nucleus from exposure to tritiated pump oil or formaldehyde.

A Monte Carlo simulation of tritium decays in a cell composed of two parts, a nucleus and surrounding cytoplasm, was developed to evaluate the beta-radiation dose to the nucleus. A dose modifying factor (DMF), which is a ratio of the average nuclear dose to the whole-tissue dose, after skin-contact exposure of rats to tritiated pump oil or tritiated formaldehyde was estimated. Biokinetic data characterizing the retention of tritium in liver were available in the form of tritium-specific activities and biological half-times for tritiated water and five macromolecular species (DNA, RNA, acid-soluble fraction, acid-insoluble protein, and lipids). The spatial distribution of tissue-free water and macromolecular species in the nucleus and cytoplasm of rat liver cells was based on published data. In the case of exposure to tritiated pump oil, tritium incorporated into lipids provides the largest percentage (60%) of the absorbed dose to the nucleus. For the tritiated-formaldehyde exposure, the tritium dose to the nucleus is overwhelmingly contributed by tritiated water (58%) and in acid-insoluble proteins (40%). For both these tritiated organic exposures, the tritium-labeled DNA has a negligible effect on the DMF. The DMF for the tritiated pump oil and formaldehyde exposures was estimated as 0.81 and 1.05, respectively: the DMF of both exposures was close to unity. Given the other uncertainties in tritium dosimetry, our results suggest that for these skin-contact exposures a uniform distribution of tritium in tissue is an adequate assumption for dosimetry.

Animals↗

Health effects of low-level exposure to formaldehyde.

Twenty-one subjects exposed to formaldehyde (at levels between 0.12 and 1.6 parts per million [ppm]) in two mobile trailers and the remaining 18 unexposed workers of the same workforce were examined by questionnaire and spirometry. Symptoms of eye and throat irritation and increased headache and fatigue were significantly more common among the exposed group than the comparison group. Irritation of the nose, chest tightness, and shortness of breath were also more common among the exposed. Spirometry revealed no decrease in ventilatory function among the exposed workers. The significant increase in frequency of individuals with symptoms indicated an adverse health effect from exposure to formaldehyde at levels between 0.12 and 1.6 ppm. This may have implications regarding the adequacy of the US permissible exposure limit value and suggests the need for further examination of the health effects of formaldehyde in the nonoccupational environment.

Adult↗

An updated meta-analysis of formaldehyde exposure and upper respiratory tract cancers.

In this study, we summarize 47 epidemiologic studies related to formaldehyde exposure and use meta-analytic techniques to assess findings for cancers of the lung, nose/nasal sinuses, and nasopharynx. Our analyses indicate that workers with formaldehyde exposure have essentially null findings for lung cancer and a slight deficit of sinonasal cancer. Nasopharyngeal cancer rates were elevated moderately in a minority of studies. Most studies, however, did not find any nasopharyngeal cancers, and many failed to report their findings. After correcting for underreporting, we found a meta relative risk of 1.0 for cohort studies. Case-control studies had a meta relative risk of 1.3. Our review of the exposure literature indicated that the nasopharyngeal cancer case-control studies represented much lower and less certain exposures than the cohort studies. We conclude that the available studies do not support a causal relation between formaldehyde exposure and nasopharyngeal cancer. This conclusion conflicts with conclusions from two previous meta-analyses, primarily because of our consideration of unreported data.

Carcinogens, Environmental↗

Analysis of two formaldehyde oxidation pathways in Methylobacillus flagellatus KT, a ribulose monophosphate cycle methylotroph.

The roles of cyclic formaldehyde oxidation via 6-phosphogluconate dehydrogenase and linear oxidation via the tetrahydromethanopterin (H4MPT)-linked pathway were assessed in an obligate methylotroph, Methylobacillus flagellatus KT, by cloning, sequencing and mutating two chromosomal regions containing genes encoding enzymes specifically involved in these pathways: 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase and methenyl H4MPT cyclohydrolase (gndA, zwf and mch). No null mutants were obtained in gndA or zwf, implying that the cyclic oxidation of formaldehyde is required for C1 metabolism in this obligate methylotroph, probably as the main energy-generating pathway. In contrast, null mutants were generated in mch, indicating that the H4MPT-linked pathway is dispensable. These mutants showed enhanced sensitivity to formaldehyde, suggesting that this pathway plays a secondary physiological role in this methylotroph. This function is in contrast to Methylobacterium extorquens AM1, in which the H4MPT-linked pathway is essential.

Cloning, Molecular↗

The action of formaldehyde on staphylococcal delta haemolysin.

Native staphylococcal delta haemolysin was poorly immunogenic in the mouse. After treatment with formaldehyde at pH 5 or pH 7.5, haemolytic activity was rapidly lost but antigenic reactivity retained and, at pH 5, immunogenicity was enhanced. Treatment of the haemolysin with formaldehyde at pH 9.5 reduced haemolytic activity by 97% but did not enhance immunogenicity. There was no evidence of polymerisation of formaldehyde-treated delta haemolysin, and the enhanced immunogenicity was considered to be partly due to a reduced affinity for phospholipids.

Animals↗

Allergy in chronic haemodialysis. 1. Double-blind intravenous challenge with formaldehyde.

Patients undergoing chronic haemodialysis are often exposed to formaldehyde formaldehyde (F) has been reported to cause IgE-mediated anaphylactic shock. Many other patients reported pruritus or anaphylaxis-like symptoms when dialysed with F-sterilized dialysers. Ten patients presenting such symptoms were compared with five control subjects. Intravenous double-blind challenges were performed on six consecutive occasions, with capillary flow dialysers sterilized with or without F. Dialysis was performed by an investigator who was not aware of the sterilization procedure. Among the ten F-sensitive patients, five had symptoms with F-sterilized dialysers and no symptoms with new dialysers, sterilized by ethylene oxide and free of F. Symptoms included pruritus and hypotension. These five patients were subsequently dialysed with new dialysers, not sterilized with F, and symptoms subsided. The five other patients had inconclusive challenges. The five control subjects had no symptoms during challenges. Skin-prick tests with F showed that only one of the five patients who had symptoms with F-dialysers had a strongly positive prick test. RAST to F was titrated with HSA-discs but it was negative in all patients and control subjects. Formaldehyde was shown to cause symptoms in some patients under chronic haemodialysis but an IgE-mediated mechanism was not demonstrated.

Adult↗

Monitoring the efficacy of steam and formaldehyde treatment of naturally Salmonella-infected layer houses.

AIMS: To monitor if a temperature-humidity-time treatment found to be effective in eliminating Salmonella in laboratory trials (Gradel et al. 2003) was efficient against Salmonella in naturally infected layer houses. METHODS AND RESULTS: Six layer houses with natural Salmonella infections were steam treated in a download period, aiming at >or=60 degrees C and 100% relative humidity (RH) during a 24-h period, with or without the addition of 30 ppm formaldehyde. In addition, two control layer houses were disinfected chemically. Salmonella samples taken from predetermined sites before and after treatment were tested qualitatively for Salmonella and coliforms. Samples with indicator bacteria (feed inoculated with Escherichia coli or Enterococcus faecalis and faeces with naturally occurring E. coli and enterococci) were placed during steam-treatment at 12 sites in each house (where the temperature was logged at 5-min intervals) and tested for surviving bacteria. Generally, the field test results confirmed the results of laboratory tests, especially when 30 ppm formaldehyde was added to the steam. In well-sealed houses, the recommended temperature-humidity-time scheme was accomplished at a minimum of 10 cm above floor level within 1 h. CONCLUSIONS: A steam treatment of >or=60 degrees C and 100% RH during a 24-h period with the addition of 30 ppm formaldehyde at the beginning of the process is recommended for eliminating Salmonella from naturally infected poultry layer houses. SIGNIFICANCE AND IMPACT OF THE STUDY: A specific recommendation for the elimination of Salmonella in poultry houses can be given.

Animals↗

Formaldehyde and glutaraldehyde in the fixation of chromatin for electron microscopy.

Glutaraldehyde and formaldehyde have been used to fix chromatin core particles for electron microscopy. Glutaraldehyde crosslinks protein only, whereas formaldehyde crosslinks protein and DNA. This is confirmed by the observation that the detergents sodium dodecyl sulphate, Sarkosyl NL 35 and benzylalkyldimethyl ammonium chloride separate the DNA from the protein in the case of glutaraldehyde fixed core particles but not in the case of formaldehyde fixed core particles. The fixative used in the preparation must therefore be considered as a further variable when evaluating electron microscopic images of chromatin.

Aldehydes↗

Dentine hypersensitivity. I. Effects produced by the uptake in vitro of metal ions, fluoride and formaldehyde onto dentine.

Dentine has been shown to possess affinity for a large number of varied compounds, many of which have been shown effective in clinical trials, for the treatment of dentine hypersensitivity. The mode of action of these compounds is unclear. The aim of this study was to investigate the uptake of metal ions, fluoride and formaldehyde in solution onto dentine in vitro and determine whether therapeutic effects could be mediated through occlusion of dentinal tubules. Etched dentine sections were exposed for 1 h to 1000 ppm solutions of fluoride and metal salts. Levels of fluoride and respective metals could be extracted and measured from the specimens. Saliva pretreatment had a variable but small effect on uptake of each ion, but post treatment washings reduced all levels of retained fluoride and metals. X-ray microanalysis indicated surface or immediate subsurface deposits of metals. However, surface changes were only consistently produced by zinc and more particularly tin salts. Both zinc and tin salts produced covering or obturation of tubules. The surface effects of zinc could largely be reversed by washing, but not those of tin. Formaldehyde alone or in the presence of saliva produced no effects. A 4-week study involving twice daily exposure of specimens to saliva and fluoride, metals or formaldehyde yielded essentially the same results. It is unlikely that, except for tin, the compounds tested achieve their apparent clinical effects mediated by direct occlusion of dentinal tubules.

Calcium↗

Absence of specific IgE antibodies in allergic contact sensitivity to formaldehyde.

Immunologic reactions are customarily divided into two broad categories, cell-mediated and antibody-mediated. An interplay between these two pathogenetic principles is indicated by reactions such as cutaneous basophil hypersensitivity, late-phase reaction, and cutaneous lesions indistinguishable from regular allergic contact dermatitis lesions after sensitization with IgE antibodies against certain haptens. In the present study, 23 patients with a history of a positive epicutaneous test to formaldehyde participated. On retest, 15 showed a positive reaction. Eight patients were Phadiatop positive, indicating an atopic diathesis, and eight had a history of or ongoing atopic dermatitis. On RAST test, only two, nonatopic patients had specific IgE antibodies to formaldehyde. In the cellular infiltrates of biopsies from epicutaneous test sites, cells reactive with monoclonal antibodies against IgE were found in positive and negative formalin tests, both in atopics and nonatopics, as well as in control biopsies from nonlesional skin. Double immunofluorescence staining experiments showed that IgE occurred on Langerhans' cells. The proportion of IgE-positive cells correlated to the level of serum IgE, but not to atopy. These cells were also found both in the epidermis and in the dermis in nonatopic patients. ICAM-1 occurred on keratinocytes in all patient groups. This study does not support the hypothesis that specific IgE antibodies are active in the pathogenesis of contact sensitivity to formaldehyde either in atopic or in nonatopic patients.

Biopsy↗