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PubMed2003

Exercising animal models in inhalation toxicology: interactions with ozone and formaldehyde.

Exercise during exposure to inhaled toxicants increases inhaled dose rate and alters dose distribution within the respiratory tract, and exercise has long been recognized as a critical exposure variable. While modern inhalation exposure studies with human subjects routinely use an exercise protocol, most investigations with animal models are performed with resting subjects. Animal inhalation exposures under exercising conditions frequently induce respiratory toxic effects well beyond that expected from the simple increase in ventilation dose rate. Different classes of irritants can induce different reflex breathing patterns, and small mammals have different capacities for hypothermic or hyperthermic responses to rest or exercise exposure. Respiratory tract injury and breathing pattern responses of rats to upper and lower airway irritants ozone and formaldehyde were measured under conditions of rest and exercise to illustrate the complexities of comparison to human exposures. In addition to the exercise effects on dose and dose distribution and the possibility of hypo- or hyperthermic responses, exercise enhancement of inhalation injury may also be related to a combination of toxicant-induced disruption of the pulmonary epithelial permeability barrier and exercise-induced pulmonary capillary stress failure.

Animals↗

PubMed2004

A comparison of indoor air pollutants in Japan and Sweden: formaldehyde, nitrogen dioxide, and chlorinated volatile organic compounds.

Indoor and outdoor concentrations of formaldehyde (HCHO), nitrogen dioxide (NO2), and selected chlorinated volatile organic compounds (chlorinated VOC) were measured in 37 urban dwellings in Nagoya, Japan, and 27 urban dwellings in Uppsala, Sweden, using the same sampling procedures and analytical methods. Indoor as well as outdoor air concentrations of HCHO, NO2, and chlorinated VOC were significantly higher in Nagoya than in Uppsala (P<0.01), with the exception of tetrachlorocarbon in outdoor air. In Nagoya, HCHO and NO2 concentrations were significantly higher in modern concrete houses than in wooden houses and higher in newer (less than 10 years) than in older dwellings (P<0.01), possibly due to less natural ventilation and more emission sources in modern buildings. Dwellings heated with unvented combustion sources had significantly higher indoor concentrations of NO2 than those with clean heating (P<0.05). Moreover, dwellings with moth repellents containing p-dichlorobenzene had significantly higher indoor concentrations of p-dichlorobenzene (P<0.01). In conclusion, there appear to be differences between Nagoya and Uppsala with respect to both indoor and outdoor pollution levels of the measured pollutants. More indoor pollution sources could be identified in Nagoya than in Uppsala, including construction and interior materials emitting VOC, use of unvented combustion space heaters, and moth repellents containing p-dichlorobenzene.

Air Pollutants↗

PubMed1990

Chronic respiratory effects of indoor formaldehyde exposure.

The relation of chronic respiratory symptoms and pulmonary function to formaldehyde (HCHO) in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. HCHO measurements were made with passive samplers during two 1-week periods. Data on chronic cough and phlegm, wheeze, attacks of breathlessness, and doctor diagnoses of chronic bronchitis and asthma were collected with self-completed questionnaires. Peak expiratory flow rates (PEFR) were obtained during the evenings and mornings for up to 14 consecutive days for each individual. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with HCHO levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR decreased linearly with HCHO exposure, with the estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children. The effects in asthmatic children exposed to HCHO below 50 ppb were greater than in healthy ones. The effects in adults were less evident: decrements in PEFR due to HCHO over 40 ppb were seen only in the morning, and mainly in smokers.

Adolescent↗

PubMed1987

Distribution of DNA and RNA content in the bone marrow and alveolar macrophages of rats after subchronic inhalation of formaldehyde.

The technique of flow cytometry was used to monitor the cell-cycle distribution of DNA and RNA in selected tissues of rats that were subchronically exposed to formaldehyde (HCHO) inhalation. Male Sprague-Dawley rats inhaled HCHO vapor concentrations of 0, 0.5, 3, or 15 ppm for 6 hr/day, 5 days/week, for up to 24 weeks. Simultaneous two-parameter measurements were made on a Phywe ICP 22 pulse cytophotometer by use of an acridine orange stain of the DNA and RNA of each cell sampled. No significant changes relative to the controls were determined in the percentage S and G2 + M phases of the DNA from sample tissues of the HCHO-exposed animals. Increases of 50 to 60% in the RNA content of G1 cells (RI) in the alveolar macrophages were seen after 1 week of exposure at all three HCHO doses. This effect was diminished after subchronic exposure. No HCHO-related effect was observed, though, in the RI of the rat bone marrow cells at any time point. However, the observed changes in RNA content were of rather limited magnitude relative to the cell-cycle perturbation induced by known cytotoxic agents in this and other flow cytometry studies. These modest and transient RI increases therefore probably did not reflect any significant effect on cell viability or cell proliferation in the affected tissues.

Administration, Inhalation↗

PubMed1987

A study of respiratory effects from exposure to 2.0 ppm formaldehyde in occupationally exposed workers.

It has been suggested that exposure to formaldehyde (FA) induces asthmatic symptomatology. We have previously studied healthy and asthmatic individuals and found that lung function was unaltered by controlled exposures to 2.0 ppm FA with and without mild exercise. Our present study extends these observations to a group of hospital laboratory workers routinely exposed to FA. Fifteen laboratory workers were exposed in double-blind, random sequence to 0 and 2 ppm FA for 40 min in an environmental chamber with temperature and relative humidity held constant at 23 degrees C and 50%, respectively. These exposures were repeated on two more occasions with a 10-min exercise regimen (450 kpm/min) after being in the chamber 5 min. In addition, a symptom diary and measurements of peak expiratory flow rate (PEFR) were recorded for 24 hr after exposure. Lung function remained unaltered for all 4 exposure days; e.g., mean FEV1.0 for the group did not change by more than 3% at any testing time on any exposure day. Also, there were no delayed obstructive changes as measured by PEFR recordings. Symptoms were mild and transient with unusual odor and eye irritation the most frequent complaint. No lower airway symptoms were reported. We conclude that this group of healthy laboratory workers did not experience any acute or delayed lung function changes from exposure to 2.0 ppm FA at rest and with exercise and that irritative symptoms were few.

Adult↗

PubMed1989

The influence of inhaled formaldehyde on rat lung cytochrome P450.

The effect of formaldehyde (HCHO) inhalation on total cytochrome P450 in the lungs of Sprague-Dawley rats was assessed after single and repeated exposures to 0, 0.5, 3, and 15 ppm HCHO. Whole-body exposures were conducted in dynamic, monitored exposure systems for 6 hr/day, 5 days/week, for periods of exposure of 1 day, 4 days, 12 weeks, or 24 weeks. Lung microsomal fractions were prepared and total protein and cytochrome P450 were measured 18 hr after the end of exposure at each time point. Two separate sets of exposure studies were conducted, thus duplicating all measurements for each dose group and at each time point. There were no detectable levels of total lung P450 in any of the rats that received a single 6-hr exposure to all three HCHO doses, while control lung P450 levels were similar to that found for 4-day and 12-week control rats. After 4 days of repeated exposures, however, there was a highly significant, reproducible, and dose-dependent increase in lung P450 levels relative to controls, with the 0.5, 3, and 15 ppm groups demonstrating 387, 1026, and 1123% of control values, respectively. Lung P450 levels remained elevated at all HCHO concentrations through 12 and 24 weeks of exposure, although the percentage difference between exposed and control rats continually dropped throughout the course of long-term repeated exposures. While HCHO-exposed rats did have decreased total body weight relative to controls, lung microsomal protein and lung weight of nearly all of the HCHO-exposed rats was not significantly different from the controls. The initial inactivation of lung P450 after a single HCHO exposure is apparently a transient phenomenon, with dose-dependent induction of the total P450 levels in the lung as the pattern of response to repeated exposures to inhaled HCHO.

Administration, Inhalation↗

PubMed1979

Gas chromatographic-mass spectrometric analysis of formaldehyde in ambient air using a sampling tube.

A gas chromatographic-mass spectrometric technique for the analysis of trace concentrations of formaldehyde in air is described. Molecular Sieve 13X was found to be an excellent adsorbent. The collected samples were thermally desorbed onto the analytical column (Porapak T) for separation, and quantified by mass fragmentography (m/e 29 and 30). Advantages of the technique include ppb sensitivity, selectivity and quantitative recovery. Experimental results are given for air samples in a rural area.

Air Pollutants↗

PubMed2002

Urea-formaldehyde resin monolith as a new packing material for affinity chromatography.

A urea-formaldehyde resin (UF) continuous bed has been prepared through in-situ condensation polymerization in a confined tube. The monolith is an agglomerate of 2-microm irregular particles. Nitrogen adsorption shows that the monolith has a bimodal pore size distribution. It has low resistance to flow. A dyed monolith is obtained through modification of the UF monolith with Cibacron blue F3GA. Although its dye concentration and dynamic capacity are low compared to Sepharose type affinity media, the dyed monolith can separate some proteins in the affinity mode of liquid chromatography.

Chromatography, Affinity↗

PubMed1989

Conservative treatment of renal allograft rupture with polyglactin 910 mesh and gelatin resorcin formaldehyde glue.

Renal-sparing treatment of spontaneous renal allograft rupture remains a surgical challenge, since profuse hemorrhage may result from these friable kidneys during surgical repair. A technique is proposed to achieve control of local bleeding with a synthetic glue (gelatin, resorcin and formaldehyde) and external compression with a polyglactin 910 absorbable mesh. We report 4 cases of spontaneous allograft rupture associated with rejection and bleeding was controlled in all 4. Three grafts were preserved with more than 1 year of followup. The other graft had to be removed for uncontrolled vascular rejection despite satisfactory control of renal fractures. Renal wrapping with external compression is proposed to improve results of conservative management of renal allograft rupture.

Adult↗

PubMed1998

Autoradiographic imaging of formaldehyde adducts in mice: possible relevance for vascular damage in diabetes.

The activity of semicarbazide-sensitive amine oxidase (SSAO) has been reported to be elevated in blood from diabetic patients. It has been suggested that the enzyme is involved in the development of complications such as retinopathies, nephropathies and neuropathies, which are associated with advanced diabetes, possibly by the formation of toxic metabolites. Under the influence of SSAO, methylamine is deaminated to formaldehyde which is known to react with various macromolecules. It has therefore been proposed that specific inhibition of SSAO could be of therapeutic value for treatment of diabetic patients. The present results provide evidence that treatment with an SSAO inhibitor potently reduces the levels of irreversible adducts. In this study, 14C-methylamine was given intraperitoneally to NMRI mice, and the tissue distribution of irreversibly bound methylamine metabolites was estimated by an autoradiographic method. Such radioactive residues occurred in high concentrations in the intestinal wall, brown adipose tissue, spleen and bone marrow. By inhibiting SSAO irreversibly with hydralazine before giving 14C-methylamine to the mice, it was possible to determine the resynthesis rate of SSAO in different tissues. A complete recovery of SSAO activity was seen in the intestinal wall after 6 days, whereas only about 60% was recovered in adipose tissue after 14 days. This suggests that factors controlling the synthesis of SSAO differ in these tissues, or that these tissues express different forms of enzymes.

Amine Oxidase (Copper-Containing)↗

PubMed2003

Adenovirus type 5 DNA-protein complexes from formaldehyde cross-linked cells early after infection.

We report here the properties of viral DNA-protein complexes that purify with cellular chromatin following formaldehyde cross-linking of intact cells early after infection. The cross-linked viral DNA fractionated into shear-sensitive (S) and shear- resistant (R) components that were separable by sedimentation, which allowed independent characterization. The R component had the density and sedimentation properties expected for DNA-protein complexes and contained intact viral DNA. It accounted for about 50% of the viral DNA recovered at 1.5 h after infection but less than 20% by 4.5 h. The proportion of R component was independent of multiplicity of infection, even at less than one particle per cell. Viral hexon and protein VII, but not protein VI, were detected in the fractions containing the R component. These properties are consistent with those of partially uncoated virions associated with the nuclear envelope. A substantial proportion of the S component viral DNA had the same density as cellular chromatin. Protein VII was the most abundant viral protein present in gradient fractions that contained the S component. Complexes containing USF transcription factor cross-linked to the adenovirus major late promoter were detected by viral chromatin immunoprecipitation of the fractions containing S component. The S component probably contained uncoated nuclear viral DNA that assembles into early viral transcription complexes.

Adenoviridae↗

PubMed1995

The effect of Ca-formaldehyde fixation on the activity of the reporter enzyme beta-glucuronidase (GUS) in transgenic tobacco.

The inhibition of beta-glucuronidase (GUS) activity by Ca-formaldehyde fixation was investigated in leaves of transgenic tobacco (Nicotiana tabacum L.) expressing the beta-glucuronidase uidA reporter gene from Escherichia coli. One-hour fixation of a free-floating leaf disc in a cold fixative decreased the activity of GUS by 60% as compared with the untreated control disc kept in a moist chamber. The inhibition was identical in the periphery and centre of the disc. Fixation including initial vacuum infiltration of the fixative led to almost complete inactivation of the enzyme. The incubation of discs in H2O, either with or without vacuum infiltration, did not lower GUS activity.

Calcium↗

PubMed1995

Immunohistochemical assessment of cell proliferation in plant tissues using formaldehyde-fixed paraffin-embedded material.

Cell proliferation in formaldehyde-fixed and wax-embedded sections of root tissues from Vicia faba beans was assessed by using a monoclonal antibody raised against the proliferating cell nuclear antigen (PCNA). Positive PCNA immunoreactivity was restricted to nuclei in known proliferating zones of the root. The immunoreactivity of cells in metaphase/anaphase of mitosis showed weaker PCNA immunoreactivity while nuclei in telophase showed no PCNA immunoreactivity indicating that this method is well suited to label proliferating cells in plant tissues.

Antibodies, Monoclonal↗

PubMed1978

Comparative formaldehyde-induced and glyoxylic acid-induced fluorescence histochemical studies on the intrinsic adrenergic innervation of the intestine and the liver of normal and vagotomized cats.

The inbuilt intrinsic adrenergic nervous apparatus of the intestine and liver of the cat was studied using 1. the formaldehyde-induced fluorescence histochemical method and 2. the glyoxylic acid-induced fluorescence histochemical method for serial microtome sections and whole mount tissue layers or smear preparations. In addition, the effect of I) total abdominal infra-diaphragmatic vagotomy with or without associated Finney-type gastro-duodenostomy and II) unilateral (left or right) and bilateral cervical vagotomy with or without tracheostomy on the intrinsic adrenergic innervation was tested. Fluorescing varicose axons, both "free" (i.e. unrelated to the blood vessels) and gathered to typical perivascular nerve plexuses were observed in all segments and all layers of the wall of the intestine. The density of the adrenergic innervation varied remarkably from an area to another, even in the same segment and tissue layer, which makes comparative estimations of the density of the innervation very difficult. However, the intrinsic adrenergic innervation of the circular muscle layer of the colon and the rectum seems to be consistently quite rich, and in the rectum, also the longitudinal muscle layer is relatively heavily innervated. It thus seems obvious that (in the cat) also the direct adrenergic innervation of the external smooth muscle layers is of considerable importance, specially in the rectum. In contrast, the results of the present study clearly indicate that the liver parenchyma (of the cat) is devoid of functional intrinsic adrenergic innervation. Vagotomies did not cause any changes in the intrinsic adrenergic innervation of the intestine and liver: even after complete vagotomy no reduction was observed in the number of fluorescing axons or in the intensity of the fluorescence. Consequently, the vagal contribution of adrenergic axons to the liver and the intestine must be negligible, at least in the cat. The use of the glyoxylic acid-induced fluorescence histochemical method and whole-mount tissue layers was found most suitable for mapping and comparative estimation of the density of the intrinsic adrenergic nerve net, and is therefore recommended for other similar or related studies.

Adrenergic Fibers↗

PubMed1990

Clinical and immunologic evaluation of 37 workers exposed to gaseous formaldehyde.

Thirty-seven workers exposed to formaldehyde (F) were evaluated to determine whether any of their respiratory or ocular symptoms were mediated by an immunologic response to F. Because there has never been a case of defined immunologically mediated respiratory or ocular disease as a result of exposure to gaseous F, we used clinical and immunologic criteria developed for immunologic respiratory diseases that result from inhalational exposure to trimellitic anhydride. A clinical assessment included review of a medical summary of history, physical examination, chest x-ray films, and pulmonary function studies. Serologic assessment was made with an ELISA for IgE and IgG to F human serum albumin. The final evaluation for immunologically mediated disease was based on both the clinical and serologic assessments. None of the workers had IgE or IgG antibody to F-human serum albumin or an immunologically mediated respiratory or ocular disease caused by F; however, some of the workers appeared to experience irritant symptoms caused by workplace exposure to F or other irritant chemicals.

Adult↗

PubMed1983

Innocuity testing of foot-and-mouth disease vaccines. I. Formaldehyde-inactivated alhydrogel vaccines.

Conditions that contribute to efficient innocuity testing of formaldehyde (FA)-inactivated alhydrogel vaccines were investigated. Under our conditions good yields of 146S antigen were obtained if the antigen was eluted by potassium phosphate buffer (pH 7.4) and concentrated by ultrafiltration. Non-inactivated virus added to the vaccine and adsorbed overnight could be recovered if residual FA was removed from the vaccine by washing the gel thoroughly with Frenkel culture medium before the addition of the virus. It was shown that the presence of high concentrations of inactivated virus in the concentrated eluate could prevent the detection of small amounts infectious virus in intradermolingual tests in cattle. This interference phenomenon was not found if (more susceptible) monolayers of foetal calf thyroid cells were used for the detection of virus. Intensive pre-washing of the gel with Frenkel culture medium, elution with potassium phosphate, concentration by ultrafiltration and the use of thyroid cells for the final detection of surviving virus is therefore advised for safety testing.

Animals↗

PubMed1989

Systemic distribution of 14C-labeled formaldehyde applied in the root canal following pulpectomy.

The systemic distribution of 14C-labeled formaldehyde which had been placed in the root canals of the canines of cats following pulpectomies was studied using liquid scintillation counting and wholebody autoradiographic technique. Radioactive 14C which had been placed in the canals was found in the plasma 30 min after the root canal procedure. The recovery of systemic 14C radioactivity increased with time. In addition, it seemed that approximately 3% of the dose placed in the teeth was excreted in the urine within 36 h. Whole-body autoradiograms indicated extensive concentration of 14C radioactivity in tissues other than those analyzed with the liquid scintillation technique.

Animals↗

PubMed1997

An optimal antigen retrieval method suitable for different antibodies on human brain tissue stored for several years in formaldehyde fixative.

In the last 5 years the microwave oven has become a widely accepted apparatus for retrieving all kinds of antigens that are masked by prolonged formaldehyde fixation. However, it has so far not been possible to obtain good results for all the antigens we were interested in with just one method. This study offers a solution for this problem. We tested Tris buffered saline (TBS) pH 8-10 in order to see whether a microwave (MW) pretreatment in a solution with a high pH works on the antigens that have our particular interest: MAP-2, non-phosphorylated part of the neurofilament (SMI-32, SMI-311), phosphorylated part of the neurofilament (SMI-312) and the calcium binding proteins Calbindin D28-K, Parvalbumin and Calretinin. Furthermore we checked whether or not a lower temperature of 90 degrees C (instead of boiling the tissue) could be used to achieve the same good staining results. These tests showed that an MW pretreatment in TBS pH 9.0 at full power (boiling) gave the best results. Pretreatment at a lower temperature gave also good results for most (but not all) antibodies when the irradiation time was prolonged to 30 min. The optimal antigen retrieval method also improved the quality of staining with an antibody against neuropeptide Y (NPY), for which, until now, no antigen retrieval appeared to be necessary, even after a long duration of fixation.

Adolescent↗