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Antigens of Bordetella pertussis. IV. Effect of heat, merthiolate, and formaldehyde on histamine-sensitizing factor and protective activity of soluble extracts from Bordetella pertussi.s.

Munoz, J. (Rocky Mountain Laboratory, Hamilton, Mont.), and B. M. Hestekin. Antigens of Bordetella pertussis. IV. Effect of heat, Merthiolate, and formaldehyde on histamine-sensitizing factor and protective activity of soluble extracts from Bordetella pertussis. J. Bacteriol. 91:2175-2179. 1966.-Both histamine-sensitizing and protective activities of soluble preparations from Bordetella pertussis cells are destroyed by heating at 80 C for 0.5 hr. The histamine-sensitizing activity appeared to be more susceptible to inactivation by heat than the protective activity. Formaldehyde in a final concentration of 0.5% rapidly diminished the histamine-sensitizing ability of saline extract (SE) held at 37 C. The protective activity was clearly more resistant to inactivation by formaldehyde at similar temperature. The inactivating action of formaldehyde was slower when the concentration of SE was increased or when the mixture was kept at 2 to 5 C. Merthiolate in a final concentration of 1:10,000 had no demonstrable deleterious effects on either protective or histamine-sensitizing activity of SE.

Animals↗

Release of formaldehyde from polynoxylin and noxythiolin.

Polynoxylin and noxythiolin (Anaflex and Noxyflex) have been recommended for the treatment of certain bacterial infections. Both compounds were shown to release formaldehyde. Detailed studies with noxythiolin showed that it decomposed in solution to liberate most of its formaldehyde, and that solutions of formaldehyde of the appropriate strength gave zones of inhibition on seeded plates comparable in size with those given by noxythiolin. It is suggested that the effects observed with these compounds are caused by the formaldehyde released.

Anti-Infective Agents, Local↗

Formaldehyde in pathology departments.

Toxic effects of formaldehyde in humans are discussed in relation to occupational exposure and tolerance to this agent. Carcinogenic and mutagenic properties of formaldehyde have been reported in animals and this has led to concern about a possible role in human cancer. The current state of affairs is reviewed in the light of a lack of direct evidence linking formaldehyde with cancer in man and in relation to recommended exposure levels. It is important to employ effective means of containment and practical methods for reducing exposure to formaldehyde in pathology departments and post-mortem rooms are described.

Adult↗

Formaldehyde and the risk of squamous cell carcinoma of the sinonasal cavities.

A study of 759 histologically verified cancers of the nasal cavity (287 cases), paranasal sinuses (179 cases), and nasopharynx (293 cases) and 2465 cancer controls diagnosed in Denmark between 1970 and 1982 was conducted to investigate the importance of occupational exposure to formaldehyde. Information on job history for cases and controls was derived from a national data linkage system and exposure to formaldehyde and wood dust was assessed by industrial hygienists unaware of the case-control status of the patients. The exposure rates for formaldehyde among male and female controls were 4.2% and 0.1%, respectively. After proper adjustment for contemporary wood dust exposure, relative risks of 2.3 (95% CI = 0.9-5.8) for squamous cell carcinoma and 2.2 (95% CI = 0.7-7.2) for adenocarcinoma of the nasal cavity and paranasal sinuses were detected among men who have ever been exposed to formaldehyde in their job compared with those never exposed. The introduction of a 10 year latency period did not change the risk estimates substantially. It was considered unlikely that the results were due to bias or misclassification of exposure although the effect of chance could not be excluded.

Adenocarcinoma↗

A cohort study of workers exposed to formaldehyde in the British chemical industry: an update.

A cohort study of workers exposed to formaldehyde in the British chemical industry in any one of six factories has been extended after the earlier published report in 1984. A further eight years of follow up to the end of 1989 have been included for the originally reported 7660 workers first employed before 1965, and a first follow up to the same date has been carried out for 6357 workers first employed since 1964. Extensive checking of the database has taken place including records at the factories, the MRC Environmental Epidemiology Unit, and the National Health Service Central Register. The updated findings include one death from nasal cancer compared with 1.7 expected in this number of men during the follow up period--which gives no support to the original hypothesis based on animal experimental data that formaldehyde may be a nasal carcinogen in humans. There have been no cases of nasopharyngeal cancer in the cohort compared with an estimated 1.3 expected--which gives no support to the findings in a similarly designed study in the United States of an excess of cancers of the nasopharynx associated with exposure to formaldehyde. There has been a slight excess of about 12% for lung cancer with 402 deaths compared with about 359 expected. This is similar to that found in the United States study, but higher than we reported earlier before the checking procedures and extended follow up. Further analysis gives no definitive indication of this excess of lung cancer being clearly related to formaldehyde exposure, and the increase is within that generally thought consistent with possible confounding effects of cigarette smoking (although no data are available on this point).

Chemical Industry↗

Asthmatic symptoms and volatile organic compounds, formaldehyde, and carbon dioxide in dwellings.

OBJECTIVES: As a part of the worldwide European Community respiratory health survey, possible relations between symptoms of asthma, building characteristics, and indoor concentration of volatile organic compounds (VOCs) in dwellings were studied. METHODS: The study comprised 88 subjects, aged 20-45 years, from the general population in Uppsala, a mid-Swedish urban community, selected by stratified random sampling. Room temperature, air humidity, respirable dust, carbon dioxide (CO2), VOCs, formaldehyde, and house dust mites were measured in the homes of the subjects. They underwent a structured interview, spirometry, peak expiratory flow (PEF) measurements at home, methacholine provocation test for bronchial hyperresponsiveness, and skin prick tests. In addition, serum concentration of eosinophilic cationic protein (S-ECP), blood eosinophil count, and total immunoglobulin E (S-IgE) were measured. RESULTS: Symptoms related to asthma were more common in dwellings with house dust mites, and visible signs of dampness or microbial growth in the building. Significant relations were also found between nocturnal breathlessness and presence of wall to wall carpets, and indoor concentration of CO2, formaldehyde, and VOCs. The formaldehyde concentration exceeded the Swedish limit value for dwellings (100 micrograms/m3) in one building, and CO2 exceeded the recommended limit value of 1000 ppm in 26% of the dwellings, showing insufficient outdoor air supply. Bronchial hyperresponsiveness was related to indoor concentration of limonene, the most prevalent terpene. Variability in PEF was related to two other terpenes; alpha-pinen and delta-karen. CONCLUSION: Our results suggest that indoor VOCs and formaldehyde may cause asthma-like symptoms. There is a need to increase the outdoor air supply in many dwelling, and wall to wall carpeting and dampness in the building should be avoided. Improved indoor environment can also be achieved by selecting building materials, building construction, and indoor activities on the principle that the emission of volatile organic compounds should be as low as reasonably achievable, to minimise symptoms related to asthma due to indoor air pollution.

Adult↗

Laryngeal and hypopharyngeal cancers and occupational exposure to formaldehyde and various dusts: a case-control study in France.

OBJECTIVES: A case-control study was conducted in France to assess possible associations between occupational exposures and squamous cell carcinomas of the larynx and hypopharynx. METHODS: The study was restricted to men, and included 201 hypopharyngeal cancers, 296 laryngeal cancers, and 296 controls (patients with other tumour sites). Detailed information on smoking, alcohol consumption, and lifetime occupational history was collected. Occupational exposure to seven substances (formaldehyde, leather dust, wood dust, flour dust, coal dust, silica dust, and textile dust) was assessed with a job exposure matrix. Exposure variables used in the analysis were probability, duration, and cumulative level of exposure. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were estimated by unconditional logistic regression, and were adjusted for major confounding factors (age, smoking, alcohol, and when relevant other occupational exposures). RESULTS: Hypopharyngeal cancer was found to be associated with exposure to coal dust (OR 2.31, 95% CI 1.21 to 4.40), with a significant rise in risk with probability (p<0.005 for trend) and level (p<0.007 for trend) of exposure. Exposure to coal dust was also associated with an increased risk of laryngeal cancer (OR 1.67, 95% CI 0.92 to 3.02), but no dose-response pattern was found. A significant relation, limited to hypopharyngeal cancer, was found with the probability of exposure to formaldehyde (p<0.005 for trend), with a fourfold risk for the highest category (OR 3.78, 95% CI 1.50 to 9.49). When subjects exposed to formaldehyde with a low probability were excluded, the risk also increased with duration (p<0.04) and cumulative level of exposure (p<0.14). No significant association was found for any other substance. CONCLUSION: These results indicate that exposure to formaldehyde and coal dust may increase the risk of hypopharyngeal cancer.

Aged↗

Improved utilization of tissue blocks for electron microscopy. Effect of various concentrations of formaldehyde and glutaraldehyde.

Liver tissue from miniature pig fetuses was immersion-fixed in fixative mixtures with various concentrations of formaldehyde and glutaraldehyde. The preservation quality of hepatocytes was evaluated ultrastructurally in a peripheral zone (30--130 micron below the surface) and a central zone (500 micron below the surface). In the peripheral zone the best preservation was obtained with a fixative mixture containing 2% formaldehyde and 2% glutaraldehyde and in the central zone with a fixative mixture containing 8% formaldehyde and 8% glutaraldehyde. It is concluded that a better utilization of fairly large tissue blocks for ultrastructural investigation can be obtained by division of the block and subsequent fixation in fixatives containing various concentrations of formaldehyde and glutaraldehyde.

Aldehydes↗

Control of autofluorescence of archival formaldehyde-fixed, paraffin-embedded tissue in confocal laser scanning microscopy (CLSM).

Confocal laser scanning microscopy (CLSM) offers the advantage of quasi-theoretical resolution due to absence of interference with out-of-focus light. Prerequisites include minimal tissue autofluorescence, either intrinsic or induced by fixation and tissue processing, and minimal background fluorescence due to nonspecific binding of the fluorescent label. To eliminate or reduce autofluorescence, three different reagents, ammonia-ethanol, sodium borohydride, and Sudan Black B were tested on paraffin sections of archival formaldehyde-fixed tissue. Paraffin sections of biopsy specimens of human bone marrow, myocardium, and of bovine cartilage were compared by CLSM at 488-nm, 568-nm and 647-nm wavelengths with bone marrow frozen sections fixed either with formaldehyde or with glutaraldehyde. Autofluorescence of untreated sections related to both the specific type of tissue and to the tissue processing technique, including fixation. The reagents' effects also depended on the type of tissue and technique of tissue processing, including fixation, and so did the efficiency of the reagents tested. Therefore, no general recipe for the control of autofluorescence could be delineated. Ammonia-ethanol proved most efficient in archival bone marrow sections. Sudan Black B performed best on myocardium, and the combination of all three reagents proved most efficient on paraffin sections of cartilage and on frozen sections fixed in formaldehyde or glutaraldehyde. Sodium borohydride was required for the reduction of unwanted fluorescence in glutaraldehyde-fixed tissue. In formaldehyde-fixed tissue, however, sodium borohydride induced brilliant autofluorescence in erythrocytes that otherwise remained inconspicuous. Ammonia-ethanol is believed to reduce autofluorescence by improving the extraction of fluorescent molecules and by inactivating pH-sensitive fluorochromes. The efficiency of borohydride is related to its capacity of reducing aldehyde and keto-groups, thus changing the fluorescence of tissue constituents and especially of glutaraldehyde-derived condensates. Sudan Black B is suggested to mask fluorescent tissue components.

Ammonia↗

Formaldehyde-hydrochloric acid treatment. A fluorescence histochemical method for the demonstration of tryptophan residues in peptides and proteins.

Treatment with formaldehyde gas and HCl vapor, simultaneously or in sequence, induces fluorescence with indoles, including tryptophan residues of peptides, as is evident from studies on protein droplet models. Among cells that display intense formaldehyde-HCl-induced fluorescence are pancreatic exocrine cells, gastric chief cells, Paneth cells and enterochromaffin cells. Peptide hormone-producing cells that can be visualized by the formaldehyde-HCl treatment include gastrin cells and glucagon cells. The simultaneous procedure has proved superior to the sequential procedure. Simultaneous formaldehyde-HCl treatment appears to be a useful method for the demonstration of tryptophan residues of peptides and proteins. It seems more sensitive than previously described indole methods.

Animals↗

Occupational asthma caused by cedar urea formaldehyde particle board.

Two carpenters developed asthma and rhinitis related to occupational exposure to a cedar urea formaldehyde (CUF) particle board. One patient developed nasal and chest symptoms and an equivocal early asthmatic response after CUF sawdust exposure, but not after spruce or western red cedar sawdust exposure; possible late asthmatic response may have been inhibited by beclomethasone treatment. The other patient developed marked nasal and chest symptoms and a dual asthmatic response after CUF exposure, but not after spruce or cedar exposure. Both patients developed increased bronchial responsiveness to inhaled histamine, which persisted for at least six days in the first patient, and which was associated with increased asthmatic symptoms of days' to weeks' duration in both. A previously unexposed asthmatic patient, with more markedly hyperreactive bronchi, developed no symptoms, no change on spirometric testing, and no change in histamine response after CUF exposure. Specific IgE antibodies directed against formaldehyde-human serum albumin conjugate could not be demonstrated using the radioallergosorbent test. This investigation documents the occurrence of occupational asthma caused by urea formaldehyde used as a bonding agent in particle boards. Absence of a response in a previously unexposed, more severe asthmatic patient suggests specific sensitization to some component of the urea formaldehyde resin complex had developed.

Asthma↗

An autometallographic technique for myelin staining in formaldehyde-fixed tissue.

A new autometallographic (AMG) technique for staining myelin in formaldehyde- or paraformaldehyde- (PFA) fixed tissue is presented. The tissue sections were exposed to AMG development without prior treatment with silver salts. The method was examined on PFA-fixed tissue from mouse, rat, pig, and formaldehyde-fixed human autopsy material. Samples from brain, spinal cord, cranial, and spinal nerves were either cut on a vibratome, frozen and cryostat sectioned, or embedded and microtome sectioned, before AMG development and counterstaining. The AMG-myelin technique results in a specific black/dark-brown staining of myelin in all parts of the CNS and PNS. It works on all species examined, independent of the histological preparation techniques applied. The AMG staining is stable, stays unchanged through decades, allows counterstaining, and has previously been used with immunohistochemical techniques. On perfusion-fixed tissue the technique works without further fixation, but the intensity of the AMG-myelin staining is increased by increased postfixation time. Additionally, immersion fixation has to last for days depending on the size of the tissue block in order to obtain proper myelin staining. The most feasible explanation of the chemical events underlying the AMG-myelin technique is that nano-sized clusters of metallic silver are formed in the myelin as a result of chemical bounds with reducing capacity, exposed or created by the formaldehyde molecule. The AMG method is simple to perform and as specific as the conventional osmium and luxol fast blue stainings. The present technique is thus an effective, simple, inexpensive, and quick myelin staining method of formaldehyde- or PFA-fixed tissue.

Animals↗

Motility and eosin uptake of formaldehyde-treated ram spermatozoa.

A concentration of 0.005% formaldehyde in phosphate-buffered saline (PBS) achieved complete immobilization of ram spermatozoa while also yielding good recovery of sperm motility after removal by washing. At a higher formaldehyde concentration (0.01%) recovery rate declined with increasing dilution rate. Incubation of spermatozoa in PBS containing 0.005% formaldehyde beyond 6 h at 5, 15 or 25 degrees C resulted in poor recovery rates. Of the incubation temperatures, eosin uptake was lowest at 25 degrees C. During 4 h post-wash incubation at 30 degrees C sperm motility was significantly (P less than 0.001) affected by pre-wash formaldehyde concentration which had no effect on the proportion of eosinophilic spermatozoa.

Alkaline Phosphatase↗

Rumen fermentation and starch degradation by Holstein steers fed sodium-hydroxide- or formaldehyde-treated wheat.

The authors investigated the effect of feeding 2% sodium-hydroxide-treated (as-fed basis) or 2% formaldehyde-treated (crude protein basis) wheat to rumen-, duodenal- and ileocaecal-cannulated Holstein steers on rumen fermentation and ruminal and postruminal starch degradation. Feeding 2 kg/day wheat treated with sodium hydroxide (NaOH) or formaldehyde did not affect negatively the main parameters of rumen fermentation, i.e. pH, short-chain fatty acid (SCFA) production, and microbial activity. Fibre degradation in the rumen was significantly improved when NaOH-treated wheat was fed. The in vivo experiments demonstrated that feeding NaOH- and formaldehyde-treated wheat to steers significantly increased the amount of starch that reached the small intestine. The amount of starch that entered the duodenum increased by 57% and 75% when steers were fed NaOH- and formaldehyde-treated wheat compared to the control phase, respectively. This higher quantity of starch was digested and absorbed, which can provide an increased glucose supply to the animals.

Animal Feed↗

Formaldehyde exposures from tobacco smoke: a review.

Reports of formaldehyde levels in mainstream, sidestream, and environmental tobacco smoke from nine studies are reviewed. Considerable disparity exists between formaldehyde production rates determined from mainstream-sidestream studies and those reporting levels in environmental tobacco smoke. Tobacco smoke does not appear to increase vapor-phase formaldehyde levels significantly in indoor environments, but formaldehyde exposure in mainstream smoke may pose a risk of upper respiratory system cancer and increase the risk of cancer in smokers.

Environmental Exposure↗

Flow-injection chemiluminescence determination of formaldehyde with a bromate-rhodamine 6G system.

In this paper, a novel flow-injection chemiluminescence (CL) system for the determination of formaldehyde is described. It is based on a strong enhance effect of formaldehyde on the weak CL emission of the reaction between potassium bromate and rhodamine 6G in a sulfuric acid medium. A possible mechanism for this CL reaction is proposed. A CL calibration graph was linear in the range of 0.8 - 200 microg l(-1) and the detection limit was 0.3 microg l(-1) (3sigma). The relative standard deviation was less than 3% for 10 microg l(-1) formaldehyde (n = 11). The method has been applied to determine formaldehyde in the air samples.

Air Pollution↗

Changes in conformation of human neuronal tau during denaturation in formaldehyde solution.

Human neuronal tau was incubated in formaldehyde solution at low concentrations and the intensity of light scattering of tau-40 solution at 480 nm increased markedly. Then potassium iodide was used to quench the intrinsic fluorescence of tau. The fluorescent quenching constants decreased as formaldehyde concentrations increased. 8-anilino-1-naphthalenesulfonic acid (ANS) binding assay showed that a putative hydrophobic core formed in tau polymers during incubation with formaldehyde. Native tau was hydrolyzed by immobilized earthworm fibrinolytic enzyme-II (EFE-II), producing a digested fragment (36-37 kDa). However, formaldehyde-treated tau could not be digested under the same conditions, suggesting that aggregated protein was relatively rigidly deposited.

Anilino Naphthalenesulfonates↗

Nitrogen metabolism of growing lambs fed coastal bermudagrass as influenced by formaldehyde treatment and glucose.

Six abomasally-cannulated wethers (average initial weight 18 kg) were used in a split 3 X 3 Latin square design experiment with a crossover to determine effects of glucose (G) administered orally (O) or infused (I) into the abomasum on nitrogen metabolism and forage fiber digestion. Basal diets were Coastal bermudagrass (CBG) or CBG treated with 1% formaldehyde (F-CBG). Individual treatments were: (1) CBG, (3) CBG + G(O), (3) CBG + G(I), (4) F-CBG, (5) F-CBG + G(O) and (6) F-CBG + G(I). Nitrogen balance was 3.67, 4.86, 4.80, 5.04, 5.73 and 6.04 g/day and urinary N was 6.50, 4.10, 4.42, 5.25, 3.26 and 3.00 g/day for treatments 1,2,3,4,5 and 6, respectively. Nitrogen balance was increased and urinary nitrogen decreased (P < .005) by formaldehyde treatment and addition of G. Crude protein digested was decreased (P < .005) by G but was unaffected by formaldehyde (P > .05). Concentration of essential amino acids in plasma was decreased by addition of G (P < .005). Digestion of cellulose and hemicellulose was decreased by G (P < .005) administered orally but was unaffected by G infusion or formaldehyde treatment. Addition of G thus increased the overall efficiency of nitrogen and energy utilization.

Animals↗