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PubMed1986

A laboratory evaluation of two methods for measuring low levels of formaldehyde in indoor air.

Two methods for measuring formaldehyde at ppb levels--the modified pararosaniline (PRA) and the modified chromotropic acid (CTA)--were evaluated in a laboratory study. A dynamic double dilution system was used to generate controlled test atmospheres of formaldehyde by the catalytic depolymerization of trioxane. Impinger samples were collected from the sampling manifold and analyzed accordingly. Both methods demonstrated good precision (3.5% for the PRA and 3.4% for the CTA) but differed in accuracy and collection efficiency. Accuracy was 87.7 +/- 7.5% for the PRA and 92.5 +/- 4.2% for the CTA, while collection efficiency was 91.9 +/- 6.9% and 98.7 +/- 4.7% respectively. These differences were mainly due to the use of 1% NaHSO3 as the absorbing solution in the CTA method. Additionally, the NaHSO3 solution has the advantage of long sample preservation, making the modified CTA the method of choice in most non-industrial indoor air sampling situations.

Air Pollutants, Occupational↗
PubMed1960

Electron microscopy of retinal photoreceptors. The use of chromation following formaldehyde fixation as a complementary technique to osmium tetroxide fixation.

The fine structure of the cone and rod outer segments of the toad was studied under the electron microscope after fixation in osmium tetroxide and fixation in formaldehyde followed by chromation. In the OsO(4)-fixed specimens, the rod outer segment appears to be built of a stack of lobulated flattened sacs, each of which is made of two membranes of about 40 A separated by an innerspace of about 30 A. The distance between the rod sacs is about 50 A. The sacs in the cone outer segment are originated by the folding of a continuous membrane. The thickness of the membranes and width of the spaces between the cone sacs is the same as in rod, but the sac innerspace is slightly narrower in the cone ( approximately 20 A). After fixation in formaldehyde and chromation, two different dense lines (l(1) and l(2)) separated by spaces of less density appear. One of the lines, l(1), has a thickness of 70 A and is less dense than the other, l(2), which is 30 A thick. The correlation of the patterns obtained with both fixatives is considered and two possible interpretations are given. The possibility that l(2) is related to a soluble phospholipid component is discussed. It is suggested that the outer segments have a paracrystallin organization similar to that found in myelin.

Animals↗
PubMed1995

Effect of captopril on ocular irritative response to topical neutral formaldehyde and YAG-laser capsulotomy in the rabbit.

Angiotensin converting enzyme (ACE) -inhibitors inhibit degradation of inflammatory mediators substance P (SP) and bradykinin, which may further stimulate the synthesis of prostaglandins. The resulting increase in inflammatory mediators in tissues is suggested to be the reason for the dry cough, involving sensory C-fiber activation, among patients receiving ACE-inhibitor therapy. In the present study, the effect of an ACE-inhibitor, captopril, on ocular irritative responses was studied in the rabbit. Intravenous captopril decreased markedly the blood pressure and the intraocular pressure (IOP) modestly. Topical neutral formaldehyde elicits an irritative response in the eye mediated through sensory neuropeptides SP and calcitonin gene-related peptide (CGRP). Following topical neutral formaldehyde, the increase in IOP and breakdown of the blood-aqueous barrier were inhibited by captopril, while miosis was not affected. Cyclic AMP (cAMP) content in the aqueous humour was increased by captopril, and this increase was inhibited by indomethacin. Following YAG-laser anterior capsulotomy, captopril inhibited the increase in IOP, breakdown of the blood-aqueous barrier and miosis. The present study demonstrates that use of short-term administration of captopril prior to sensory nerve stimulation or YAG laser anterior capsulotomy does not enhance the ocular responses to these stimuli in the rabbit. In the present study, captopril inhibited these responses, at least partly by decreasing the blood pressure.

Administration, Topical↗
PubMed1996

Intraocular effects of ruthenium red in responses to compound 48/80 and topical formaldehyde in rabbit.

We have previously shown the presence and localization of mast cells and the intraocular effects of compound 48/80 in the rabbit eye. In the present study we have evaluated the mechanism of action of compound 48/80 using ruthenium red as a blocker of sensory axon reflexes in the rabbit eye and by measuring the intraocular pressure (IOP), the pupil size, the blood pressure, the protein and cAMP content in the aqueous humour. Topical neutral formaldehyde was used as a topical inducer of neuronally mediated response in a separate series of experiment. Intracamerally-injected ruthenium red suppressed the compound 48/80-induced elevation intraocular pressure and prevented miosis, while having little if any effect on the breakdown of the blood-aqueous barrier and on the increase in the cAMP concentration in aqueous humour. Ruthenium red also inhibited the irritative response in eyes treated with topical 1% formaldehyde. As the blood-aqueous barrier in the rabbit is an extremely sensitive system higher doses of ruthenium red causes damage of the barrier in the ruthenium red treated eyes. The results demonstrate that compound 48/80 not only has a mast cell degranulating effect but also a sensory nerve- stimulating effect.

Administration, Topical↗
PubMed2000

Nasopharyngeal carcinoma in Malaysian Chinese: occupational exposures to particles, formaldehyde and heat.

BACKGROUND: During 1990-1992, 282 Chinese residents of Selangor and the Federal Territory, Malaysia with histologically confirmed nasopharyngeal carcinoma (NPC) were interviewed about occupational history, diet, alcohol consumption, and tobacco use, as were an equal number of Malaysian Chinese population controls, pair-matched to cases by age and sex. METHODS: Exposures to 20 kinds of workplace substances, solar and industrial heat, and cigarette smoke, were analysed by univariate and multivariate methods. RESULTS: Nasopharyngeal carcinoma was associated with occupational exposures to construction, metal and wood dusts; motor fuel and oil; paints and varnishes; certain other chemicals; industrial heat; solar heat from outdoor occupations; certain smokes; cigarette smoking; and childhood exposure to parental smoking. After adjustment for risk from diet and cigarette smoke, only wood dust (OR = 2.36; 95% CI : 1.33- 4.19), and industrial heat (OR = 2.21; 95% CI : 1.12-4.33) remained clearly associated. Wood dust remained statistically significant after further adjustment for social class. No significant crude or adjusted association was found between NPC and formaldehyde (adjusted OR = 0.71; 95% CI : 0.34-1.43). CONCLUSIONS: This study supports previous findings that some occupational inhalants are risk factors for NPC. The statistical effect of wood dust remained substantial after adjustment for diet, cigarette smoke, and social class. Intense industrial heat emerged as a previously unreported risk factor, statistically significant even after adjustment for diet and cigarette smoke. No association was found between NPC and formaldehyde.

Adult↗
PubMed1975

Immunogenicity of formaldehyde-inactivated enterotoxins A and C1 of Staphylococcus aureus.

Quantitative precipitation of antisera specific for native enterotoxin revealed that 70% and 60%, respectively, of the antigenic determinants of enterotoxins A and C1 of Staphylococcus aureus were inactivated by formaldehyde at pH 5.0 or 7.5 contained large polymers (excluded by Sepharose 2B) and induced strong humoral immune responses in rhesus monkeys. Enterotoxin A inactivated at pH 5.0 or 7.5 was composed mostly of small polymers (excluded by Sephadex G-100 but included by Sepharose 2B); it provoked a poor immune response in monkeys (about equivalent to the response obtained with weakly reactive toxin inactivated at alkaline pH). It was concluded that potent enterotoxoids were formed by extensive cross-linking of enterotoxin C1 into large polymers in acidic or neutral formaldehyde solution.

Animals↗
PubMed2005

Reciprocal fusions of two genes in the formaldehyde detoxification pathway in ciliates and diatoms.

During the course of a pilot genome project for the ciliate Oxytricha trifallax, we discovered a fusion gene never before described in any taxa. This gene, FSF1, encodes a putative fusion protein comprising an entire formaldehyde dehydrogenase (FALDH) homolog at one end and an S-formylglutathione hydrolase (SFGH) homolog at the other, two proteins that catalyze serial steps in the formaldehyde detoxification pathway. We confirmed the presence of the Oxytricha fusion gene in vivo and detected transcripts of the full-length fusion gene. A survey of other large-scale sequencing projects revealed a similar fusion protein in a distantly related ciliate, Tetrahymena thermophila, and a possible fusion of these two genes in the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana, but in the reverse order, with the SFGH domain encoded upstream of the FALDH domain. Orthologs of these fusion proteins may be widespread within the ciliates and diatoms.

Amino Acid Sequence↗
PubMed1982

N-Sulfomethylation of guanine, adenine and cytosine with formaldehyde-bisulfite. A selective modification of guanine in DNA.

When guanine-, adenine- and cytosine-nucleosides and nucleotides were treated with formaldehyde and then with bisulfite, stable N-sulfomethyl compounds were formed. N2-Sulfomethylguanine, N6-sulfomethyladenine, N4-sulfomthylcytosine and N6-sulfomethyl-9-beta-D-arabinofuranosyladenine were isolated as crystals and characterized. A guanine-specific sulfomethylation was brought about by treatment and denatured single-stranded DNA with formaldehyde and then with bisulfite at pH 7 and 4 degrees C. Since native double-stranded DNA was not modified by this treatment, this new method of modification is expected to be useful as a conformational probe for polynucleotides.

Adenine↗
PubMed1997

Chromatin structure and methylation of rat rRNA genes studied by formaldehyde fixation and psoralen cross-linking.

By using formaldehyde cross-linking of histones to DNA and gel retardation assays we show that formaldehyde fixation, similar to previously established psoralen photocross-linking, discriminates between nucleosome- packed (inactive) and nucleosome-free (active) fractions of ribosomal RNA genes. By both cross-linking techniques we were able to purify fragments from agarose gels, corresponding to coding, enhancer and promoter sequences of rRNA genes, which were further investigated with respect to DNA methylation. This approach allows us to analyse independently and in detail methylation patterns of active and inactive rRNA gene copies by the combination of Hpa II and Msp I restriction enzymes. We found CpG methylation mainly present in enhancer and promoter regions of inactive rRNA gene copies. The methylation of one single Hpa II site, located in the promoter region, showed particularly strong correlation with the transcriptional activity.

Animals↗
PubMed1992

Formaldehyde.

In 1979 formaldehyde was projected into the toxicological limelight when Kerns and his group from the American Chemical Industry Institute of Toxicology (CIIT) released preliminary results of an inhalation study on male and female rats. Those animals exposed to 14.3 p.p.m. for 8 h/day and 5 days/week for up to 2 years showed the development of squamous cell carcinomas in a high proportion (55 per cent) of the animals. Rats similarly exposed to 5.6 p.p.m. were slightly affected with 0.85 per cent producing tumours. The next 10 years became a frenzy of activity by toxicologists, epidemiologists and industry groups, all striving to answer the question: 'Is formaldehyde a human carcinogen?'. This paper will attempt to examine the extent to which the question has been answered. It will consider how the industry responded to the initial shock finding and review the subsequent accumulation of animal and human data. It will also address the regulatory position and compare the steps taken in different countries to control the risk, and again consider how industry has responded to such regulatory forces. This review will necessarily only be able to cover the main issues and major conclusions as the extent of the subject is enormous. There are, however, a number of comprehensive texts on the subject should more information be required.

Animals↗
PubMed1984

Woodstoves, formaldehyde, and respiratory disease.

Telephone interviews were completed in Western Massachusetts in April 1983 for 399 households (91.5 per cent) in a random sample of households with elementary school children. Woodstoves were used in 64.7 per cent of the homes, but such use was not associated with acute respiratory illness. However, formaldehyde exposure was significantly related, with a risk ratio of 2.4 (95 per cent confidence interval 1.7-3.4). New construction/remodeling and new upholstered furniture had additive effects. Neither woodstove use nor formaldehyde exposure were significantly associated with asthma, chronic bronchitis, or allergies.

Asthma↗
PubMed1990

Correlation between different measures of occupational exposure to formaldehyde.

Data on exposure to formaldehyde from a cohort study of 26,561 workers first employed between 1934 and 1965 in 10 US plants producing or using formaldehyde were used to compare the classification of workers by different estimates of exposure, including duration of employment, duration of exposure, level for job with highest 8-hour time-weighted average exposure, estimated highest peak exposure, cumulative exposure, and average exposure. Measures of duration (employment and exposure) were highly correlated, as were average exposure and highest 8-hour time-weighted average exposure. Moderate correlations were seen between cumulative exposure and either average, highest 8-hour time-weighted average exposure, peak, or duration of exposure, between average and peak exposure, and between highest job and peak exposure. Average exposure, however, showed little correlation with duration of employment, duration of exposure, or peak exposures. The degree of similarity of these estimates of exposure also varied by plant. These results indicate that various measures of exposure rank subjects differently along an exposure gradient and that selection of an inappropriate measure could mute exposure-response gradients. Investigators should use several exposure measures in analyses whenever the mechanism of action is poorly understood in order to avoid false-negative findings.

Environmental Exposure↗
PubMed2001

Dosimetry modeling of inhaled formaldehyde: the human respiratory tract.

Formaldehyde (HCHO), which has been shown to be a nasal carcinogen in rats and mice, is used widely and extensively in various manufacturing processes. Studies in rhesus monkeys suggest that the lower respiratory tract may be at risk and some epidemiologic studies have reported an increase in lung cancer associated with HCHO; other studies have not. Thus, an assessment of possible human risk to HCHO exposure based on dosimetry information throughout the respiratory tract (RT) is desirable. To obtain dosimetry estimates for a risk assessment, two types of models were used. The first model (which is the subject of another investigation) used computational fluid dynamics (CFD) to estimate local fluxes in a 3-dimensional model of the nasal region. The subject of the present investigation (the second model) applied a 1-dimensional equation of mass transport to each generation of an adult human symmetric, bifurcating Weibel-type RT anatomical model, augmented by an upper respiratory tract. The two types of modeling approaches were made consistent by requiring that the 1-dimensional version of the nasal passages have the same inspiratory air-flow rate and uptake during inspiration as the CFD simulations for 4 daily human activity levels. Results obtained include the following: (1) More than 95% of the inhaled HCHO is predicted to be retained by the RT. (2) The CFD predictions for inspiration, modified to account for the difference in inspiration and complete breath times, are a good approximation to uptake in the nasal airways during a single breath. (3) In the lower respiratory tract, flux is predicted to increase for several generations and then decrease rapidly. (4) Compared to first pulmonary region generation fluxes, the first few tracheobronchial generations fluxes are over 1000 times larger. Further, there is essentially no flux in the alveolar sacs. (5) Predicted fluxes based on the 1-dimensional model are presented that can be used in a biologically based dose-response model for human carcinogenesis. Use of these fluxes will reduce uncertainty in a risk assessment for formaldehyde carcinogenicity.

Animals↗
PubMed2003

Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde.

Statistical analyses of nonmonotonic dose-response curves are proposed, experimental designs to detect low-dose effects of J-shaped curves are suggested, and sample sizes are provided. For quantal data such as cancer incidence rates, much larger numbers of animals are required than for continuous data such as biomarker measurements. For example, 155 animals per dose group are required to have at least an 80% chance of detecting a decrease from a 20% incidence in controls to an incidence of 10% at a low dose. For a continuous measurement, only 14 animals per group are required to have at least an 80% chance of detecting a change of the mean by one standard deviation of the control group. Experimental designs based on three dose groups plus controls are discussed to detect nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose that produces a response equal to the average response in the controls. Cell proliferation data in the nasal respiratory epithelium of rats exposed to formaldehyde by inhalation are used to illustrate the statistical procedures. Statistically significant departures from a monotonic dose response were obtained for time-weighted average labeling indices with an estimated ZED at a formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is concluded that demonstration of a statistically significant bi-phasic dose-response curve, together with estimation of the resulting ZED, could serve as a point-of departure in establishing a reference dose for low-dose risk assessment.

Administration, Inhalation↗
PubMed2000

Anaphylactic shock during endodontic treatment due to allergy to formaldehyde in a root canal sealant.

A 41-yr-old patient experienced an anaphylactic shock reaction caused by formaldehyde in a root canal sealant during endodontic treatment. The clinical events, positive skin tests, and a high level of immunoglobin E to formalin RAST (class 4) suggest the involvement of immunoglobin E-dependent mechanisms toward formaldehyde. This very infrequent observation in endodontic therapy focuses attention on the different pathological manifestations related to formalin, their mechanisms, and the prevention possibilities in dentistry.

Adult↗
PubMed2003

Incidence of flare-ups and evaluation of quality after retreatment of resorcinol-formaldehyde resin ("Russian Red Cement") endodontic therapy.

The purpose of this retrospective study was to evaluate the quality of treatment and incidence of flare-ups when teeth with resorcinol-formaldehyde resin are retreated in a postgraduate endodontic clinic. Fifty-eight cases were included in this study. Obturated and unfilled canal space was measured on radiographs. Forty-eight percent of the total canal space was filled before retreatment; 90% was filled after retreatment. After retreatment, obturations were rated as optimal in 59%, improved in 33%, unchanged in 6%, and worse in 2%. Seven patients (12%) had postretreatment flare-ups. Data were statistically analyzed using the Cochran-Armitage Test for Discrete Variables. No statistical difference in the incidence of flare-ups was found in teeth that before treatment had more than half the canal space filled compared to teeth with less than half, cases with pre-existing periradicular radiolucencies compared to cases with normal periradicular appearance, symptomatic cases compared to asymptomatic cases, or cases with optimal fillings after retreatment compared to less than optimal cases. It was concluded that teeth with resorcinol-formaldehyde fillings might be retreated with a good prognosis for improving the radiographic quality, but a higher than normal incidence of flare-ups may occur.

Acute Disease↗
PubMed1996

Detection of Mycobacterium tuberculosis in formaldehyde solution-fixed, paraffin-embedded tissue by polymerase chain reaction in Pott's disease.

STUDY DESIGN: Twenty-five formaldehyde solution-fixed, paraffin-embedded tissue blocks from vertebral biopsy specimen materials with presumptive diagnosis of tuberculous spondylitis and nonspecific vertebral osteomyelitis were studied. OBJECTIVES: To evaluate the sensitivity and specificity of polymerase chain reaction in detecting Mycobacterium tuberculosis in formaldehyde solution-fixed, paraffin-embedded tissue samples from histologically proved tuberculous spondylitis. SUMMARY OF BACKGROUND DATA: Diagnosis of a mycobacterial infection is a long and tedious process; because of the slow growth rate of mycobacteria on solid media, identification and antibiotic sensitivity testing can take up to 10 weeks, but the sensitivity of culture can be as low as 50%. Direct microscopy is insensitive because clinical samples may contain only few organisms. Recently, polymerase chain reaction has been applied in the rapid amplification and identification of many organisms, including mycobacteria. METHODS: The DNAs were extracted from 25 paraffin-embedded tissue blocks. An insertion element IS 6110 (Integrated DNA Tec. Inc., Corrallville, IA), a DNA sequence unique to Mycobacterium complex (M. tuberculosis and the subspecies Mycobacterium bovis), was amplified by polymerase chain reaction. Polymerase chain reaction results were compared with those of Mycobacterium culture, acid-fast bacilli staining, and histologic findings. RESULTS: Polymerase chain reaction was positive in 18 cases of 19 tuberculous spondylitis. Three of the polymerase chain reaction test results were positive with concomitant negative culture and positive acid-fast bacilli staining. There were six chronic nonspecific infections, and polymerase chain reaction results were negative in five cases; in the single positive case, DNA amplification results remained positive even after three repeated tests. CONCLUSION: Polymerase chain reaction has a sensitivity of 94.7%, specificity of 83.3%, positive predictive value of 94.7%, and a negative predictive value of 83.3%. Accuracy was calculated as 92%.

Fixatives↗
PubMed1984

The mortality of Ontario undertakers and a review of formaldehyde-related mortality studies.

In a study of the mortality of Ontario undertakers, a cohort of 1,477 men first licensed during 1928 through 1957 was followed up until the end of 1977. Numbers of observed and expected deaths were determined for the period 1950 through 1977, using mortality rates of Ontario men as the standard. In all, 319 persons had died, compared with 322 expected. Ontario undertakers were not at increased risk of death from cancers at sites of contact with formaldehyde. Cirrhosis of the liver (standardized mortality ratio, 238) and chronic rheumatic heart disease (standardized mortality ratio, 199) were the only causes of death found to be significantly in excess. The data are discussed in the context of current epidemiologic information on the mortality experience of persons exposed to formaldehyde.

Adult↗