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Air formaldehyde and solvent concentrations during surface coating with acid-curing lacquers and paints in the woodworking and furniture industry.

An investigation of contemporary exposure to formaldehyde and organic solvents has been carried out during surface coating with acid-curing lacquers and paints in the Norwegian woodworking and furniture industry over a period of 3 years. The investigation covered 27 factories of different sizes and with different types of production, and totally 557 parallel formaldehyde and solvent samples were collected. The formaldehyde concentration (geometric mean) was 0.15 ppm (range 0.01-1.48 ppm) with about 10% of the samples exceeding the Norwegian occupational exposure limit of 0.5 ppm. The solvent concentration as additive effect (geometric mean) was 0.13 (range 0.0004-5.08) and about 5% of the samples exceeded the Norwegian occupational exposure limit. The most frequently occurring solvents from acid-curing lacquers were n-butyl acetate, ethanol, ethyl acetate and 1-butanol, which were found in 88-98% of the samples. Toluene, n-butyl acetate and 1-butanol were the only solvents with maximum concentrations exceeding their respective occupational exposure limits. Curtain painting machine operators were exposed to the highest concentrations of both formaldehyde (geometric mean 0.51 ppm, range 0.08-1.48 ppm) and organic solvents (additive effect, geometric mean 1.18, range 0.02-5.08). Other painting application work tasks such as automatic and manual spray-painting, manual painting and dip painting, showed on average considerably lower concentrations of both formaldehyde (geometric means 0.07-0.16 ppm) and organic solvents (additive effect, geometric mean 0.02-0.18). Non-painting work tasks also displayed moderate concentrations of formaldehyde (geometric means 0.11-0.17 ppm) and organic solvents (additive effect, geometric mean 0.04-0.07).

Acids↗

Formaldehyde release from root-canal sealers: influence of method.

AIM: To examine formaldehyde release from three different root-canal sealers: one phenol resin, one epoxy resin and one paraformaldehyde containing zinc oxide eugenol cement. METHODOLOGY: Formaldehyde was measured from freshly mixed material and from specimens allowed to set for 2 days or 2 weeks. Different mixing ratios and sample sizes were tested. Analysis was performed by reacting formaldehyde with acetylacetone and ammonia to form diacetyldihydrolutidine, which was revealed by spectrophotometry. RESULTS: Analysis revealed that mixing ratio, time after mixing and surface:weight ratios of specimens had different influences on the formaldehyde release from different materials. CONCLUSIONS: From the results of this study it is difficult to define a standardized in-vitro test that can be applied universally for the definitive determination of formaldehyde release from endodontic sealers. Prediction of in-vivo formaldehyde release from endodontic sealers is difficult.

Epoxy Resins↗

Formaldehyde kills spores of Bacillus subtilis by DNA damage and small, acid-soluble spore proteins of the alpha/beta-type protect spores against this DNA damage.

Killing of wild-type spores of Bacillus subtilis with formaldehyde also caused significant mutagenesis; spores (termed alpha-beta-) lacking the two major alpha/beta-type small, acid-soluble spore proteins (SASP) were more sensitive to both formaldehyde killing and mutagenesis. A recA mutation sensitized both wild-type and alpha-beta- spores to formaldehyde treatment, which caused significant expression of a recA-lacZ fusion when the treated spores germinated. Formaldehyde also caused protein-DNA cross-linking in both wild-type and alpha-beta- spores. These results indicate that: (i) formaldehyde kills B. subtilis spores at least in part by DNA damage and (b) alpha/beta-type SASP protect against spore killing by formaldehyde, presumably by protecting spore DNA.

Bacillus subtilis↗

Formaldehyde application for haemorrhagic radiation-induced proctitis: a clinical and histological study.

OBJECTIVES: Haemorrhagic radiation-induced proctitis is a serious complication of radiotherapy of pelvic organs. In severe cases, massive haemorrhage may necessitate hospitalization and repeated transfusions. Application of formaldehyde under direct vision is one of the most efficient treatments. The aim of this study was to evaluate the results of this treatment as well as the histological changes induced by formaldehyde on the rectal mucosa. MATERIAL AND METHODS: From January 1991 to September 2001, 13 patients who presented a haemorrhagic radiation-induced proctitis have been treated in our outpatient clinic with 4% formaldehyde cotton soaked applications. They were followed up to one year after the treatment. Endoscopic biopsies were performed before, immediately after the application, 1 month later, as well as at the one-year follow-up. RESULTS: In eight cases bleeding stopped after the first application. In two patients a second application was necessary to control the haemorrhage and in two other patients bleeding ceased definitively after the fourth application. Follow-up evaluation at 12 months showed no sign of acute proctitis or rebleeding. One asymptomatic patient had a mild stenosis of the rectum. Baseline biopsies showed signs of acute inflammation. Those performed after the application of formaldehyde showed fresh thromboses of the vessels of the mucosa. Biopsies at 1 month and 1 year showed only chronic changes secondary to the radiotherapy. CONCLUSION: Local application of 4% formaldehyde for the treatment of haemorrhagic radiation-induced proctitis gives good results, is well tolerated and easy to perform. Formaldehyde applied selectively causes thromboses of the bleeding vessels, without deep lesions or extended necrosis.

Aged↗

Digestibility of casein, formaldehyde-treated casein and soya-bean protein in relation to their effects on serum cholesterol in rabbits.

Adult male rabbits were fed on semi-purified diets containing soya-bean protein isolate, casein or formaldehyde-treated casein as the protein source and 1 g cholesterol and 5 g of the non-absorbable marker chronic oxide/kg diet. The concentration of cholesterol in serum and in liver was increased on both the casein and formaldehyde-treated-casein diets. Excretion of bile acids and their concentration in faeces were lower in rabbits fed on casein or formaldehyde-treated casein when compared with rabbits fed on soya-bean protein. Apparent digestibility of nitrogen was lowest when formaldehyde-treated casein was fed, and highest on the casein diet. In rabbits fed on casein treated with formaldehyde, higher proportions of N were found in the water-soluble and trichloroacetic acid-insoluble protein fractions of the gastrointestinal tract contents compared with rabbits on the other two diets. Absorption of phosphate from the gastrointestinal tract was higher in rabbits fed on casein than in rabbits fed on soya-bean protein or formaldehyde-treated casein. The results indicate that, in rabbits, protein digestibility may not be an important determinant of serum cholesterol.

Animals↗

Short-term effects of formaldehyde on peak expiratory flow and irritant symptoms.

The authors studied the respiratory effects of formaldehyde exposure among students who dissected cadavers in a gross anatomy laboratory. Peak expiratory flow and respiratory symptoms were measured before and after each weekly laboratory session. Each of 38 students was exposed to formaldehyde for 2.5 hr/wk for 14 wk. Individual, daily formaldehyde measurements averaged 1.1 ppm (standard deviation = 0.56 ppm). Multivariate models demonstrated two different time scales of effect of formaldehyde on peak expiratory flow: (1) exposure during the previous 2.5 hr reduced peak expiratory flow by -1.0% per ppm, and (2) average exposure during all preceding weeks reduced peak expiratory flow by an additional -0.5% per ppm of formaldehyde. However, the short-term exposure effect was diminished during the first 4 wk, suggesting at least partial acclimatization. Symptom reporting was also associated with exposure during the previous 2.5 hr, and similar evidence of acclimatization was observed. These results suggest that there are two different time scales of response to formaldehyde, and they emphasize the need for longitudinal studies, characterized by quantitative exposure characterization, and frequent measurements of outcome.

Acclimatization↗

Formaldehyde exposure in nonoccupational environments.

Free formaldehyde may be released from wood products and foam insulation where urea-formaldehyde resins have been used. From January, 1978 to November, 1979, 100 structures were investigated by the Wisconsin Division of Health after receiving complaints of health problems from occupants. Air samples were collected in midget impingers and analyzed for formaldehyde content by the chromotropic acid procedure. Health information was obtained from the occupants via questionnaires. Mean formaldehyde concentration observed ranged from below the limit of detection to 3.68 ppm. Eye irritation, burning eyes, runny nose, dry or sore throat, headache, and cough were the primary symptoms which were reported by the occupants. Statistically significant associations were seen between formaldehyde levels and age of home/building materials. Observations presented suggest nonoccupational, indoor environmental exposure to formaldehyde is significant and may reach levels which exceed occupational exposure standards.

Adolescent↗

Survey of the migration of melamine and formaldehyde from melamine food contact articles available on the UK market.

The migration of melamine and formaldehyde, monomers used in the production of melamine-ware food contact articles, has been determined from 50 retail articles purchased in the UK. The food simulant 3% aqueous acetic acid was used as this is the most aggressive simulant towards melamine plastics. The test conditions used were repeated exposure to the simulant for 2 hours at 70 degrees C, since the articles were all intended for general use including contact with hot foods and beverages. Melamine migrated from 43 of the 50 samples tested and formaldehyde migrated from all 50 samples. Directive 2002/72/EC specifies migration limits for both of these monomers in foods and food simulants. Melamine is restricted by a specific migration limit (SML) of 30 mg/kg (equivalent to 5 mg/dm(2)) and formaldehyde, along with hexamethylenetetramine expressed as formaldehyde, is restricted by a total (T) SML(T) of 15 mg/kg (equivalent to 2.5 mg/dm(2)). In all cases the migration of melamine was much lower than the SML for this monomer. The migration of formaldehyde exceeded the SML(T) for 5 of the 50 samples tested. The failure to comply with the SML(T) was accompanied by a number of visible surface effects including discolouration and/or pitting of the simulant contact surface and cracking of the articles. Similar surface effects were observed when one of the samples was exposed to fruit juice which confirmed the suitability of the exposure conditions and 3% acetic acid as a simulant for the articles tested. The ratio of specific migration to overall migration was consistent with, but did not prove, the hypothesis that high formaldehyde migration could be due to the use of excessive hexamethylenetetramine in the polymer formulation. All illegal products were voluntarily removed from the market by the product suppliers.

Acetic Acid↗

A distributed-parameter model for formaldehyde uptake and disposition in the rat nasal lining.

DNA-protein cross-links (DPX) serve as a dosimeter for inhaled formaldehyde and are associated with tumor induction in rat nasal passages after chronic exposure to 6 ppm and above. To determine the role of epithelium-specific morphometry in formaldehyde-induced patterns of injury, we developed a mathematical model that links airflow-driven formaldehyde uptake with DPX formation in regions of the rat nose with high and low tumor incidence. A three-dimensional, anatomically accurate computational fluid dynamics model of rat nasal airflow and inhaled gas uptake was integrated with a physiologically based mathematical model incorporating tissue thickness, formaldehyde diffusion, its removal by enzymatic and nonenzymatic processes, and DNA distribution in the nasal mucosa to predict DPX formation. The model implicitly incorporates the reversible conversion of formaldehyde to methylene glycol. Where possible, parameter values were taken from the literature or estimated using published correlations. The Michaelis-Menten kinetic constants Vmax and Km, as well as a first-order constant for formaldehyde removal, were left as fitted parameters. The resultant model fit to the experimentally measured DPX in the high- and low-tumor-incidence regions of the rat nasal passages was very good. Sensitivity analysis indicates that among the fitted parameters, model fits are most sensitive to Vmax and that predictions were sensitive to changes in tissue thickness when all other parameters are held constant. The model structure facilitates extrapolation to primates and humans and application to other soluble, reactive gases.

Administration, Inhalation↗

Bioavailability in rabbits of formaldehyde from durable-press textiles.

Carbon-14-labeled formaldehyde was used per se, or was used in the synthesis of dimethyloldihydroxyethyleneurea (DMDHEU), which was incorporated into cotton or cotton/polyester blend fabric. Patches of the fabric containing known quantities of radioactive DMDHEU were applied to the backs of New Zealand White rabbits for periods up to 48 h. The rabbits were placed in specially constructed metabolism chambers designed to prevent either inhalation of volatile material emanating from the fabric or interference of any volatile material from the fabric with trapping of expired carbon dioxide. The results of the studies indicate that aqueous formaldehyde covered with a latex barrier is absorbed and retained in the layers of skin in direct contact with the formaldehyde. Approximately 65% of a dose of [14C] formaldehyde was recovered in skin 4 h after application. Skin samples from the backs of rabbits to which durable-press fabric prepared from radiolabeled DMDHEU had been applied were found to have 0.09-2.61% of the total 14C contained in the cloth patches. The levels of radioactivity recovered from the skin varied with degree of occlusion of the cloth, presence or absence of perspiration, type of synthesis used for the preparation of DMDHEU, and whether cotton or cotton/polyester blend fabric was used. Other tissues and organs had only low levels of radioactivity. Injected [14C] formaldehyde was rapidly expired as 14CO2 (28.6% of the dose within 4 h; 37.0% within 48 h). Metabolism and distribution of formaldehyde was found to be dependent on route of administration: i.e., topical application resulted in high skin levels, whereas intravenous injection led to rapid pulmonary and renal excretion and retention of radioactivity in liver, kidney, and blood.

Animals↗

Exposure to formaldehyde among animal health students.

The objective of the present study was to evaluate the exposure to formaldehyde in 2 groups each with 18 students in animal health technology from two different training centers (TC) during a 3-hour weekly laboratory session in biology. Personal sampling during the session was done with passive bubblers for formaldehyde. The analysis of formaldehyde was done by visible absorption spectrometry according to NIOSH method 3500. The students in TC 1 were exposed to formaldehyde levels ranging from less than 0.11 to 0.76 mg/m3 with an average at 0.25 mg/m3 during the 3-hour biology laboratory. The students in TC 2 were exposed to higher concentrations of formaldehyde ranging from 0.26 to 1.2 mg/m3 with an average at 0.632 mg/m3. The results of the survey indicate that the students in both centers were exposed to a notable amount of formaldehyde vapor, at a level that is above the threshold limit value.

Adult↗

Role of formaldehyde hydrazone and catalase in hydrazine-induced methylation of DNA guanine.

Hydrazine is acutely neurotoxic, hepatotoxic and nephrotoxic; it is also carcinogenic to liver and lung in rodents. Administration of hydrazine results in formation of 7-methylguanine and O6-methylguanine in target organ DNA of rats, mice, hamsters and guinea-pigs. It has been suggested that hydrazine reacts with endogenous formaldehyde to form a condensation product which could be metabolized to a methylating agent. Solutions of 0.50 mM hydrazine and formaldehyde have, upon mixing, NMR spectra (300 MHz) consistent with the formation of formaldehyde hydrazone but not other possible condensation products such as tetraformyltriazine or formaldehyde azine. These same solutions evidencing hydrazone formation, when incubated in an in vitro system containing post-mitochondrial (S9), microsomal, cytosolic or mitochondrial cell fractions, resulted in the methylation of DNA guanine; S9 was the most active fraction. Neither the P-450 monooxygenase nor flavin monooxygenase systems appeared to be important in hydrazine/formaldehyde-induced methylation of DNA. However, sodium azide, cyanamide and carbon monoxide all inhibited S9-supported DNA methylation. Bovine liver catalase, a heme-containing cytochrome, readily transformed hydrazine/formaldehyde to a methylating agent. The data support formation of formaldehyde hydrazone as the condensation product of hydrazine and formaldehyde which is rapidly transformed in various liver cell fractions, perhaps by catalase and/or catalase-like enzymes, to a methylating agent.

Amines↗

Extended follow-up of a cohort of british chemical workers exposed to formaldehyde.

BACKGROUND: Formaldehyde is mutagenic and, when inhaled at high concentrations, carcinogenic in rats. Some epidemiologic studies have linked occupational exposure to formaldehyde with cancers of the nose, nasopharynx, and lung, but the evidence for human carcinogenicity has been inconsistent and requires clarification. METHODS: We extended by 11 years the follow-up of an existing cohort of 14 014 men employed after 1937 at six British factories where formaldehyde was produced or used. Subjects had been identified from employment records, and their jobs had been classified for potential exposure to formaldehyde. Standardized mortality ratios (SMRs) were derived using the person-years method and were compared with the expected numbers of deaths for the national population. RESULTS: During follow-up through December 31, 2000, 5185 deaths were recorded, including two from sino-nasal cancer (2.3 expected) and one from nasopharyngeal cancer (2.0 expected). Relative to the national population, mortality from lung cancer was increased among those who worked with formaldehyde, particularly in men in the highest of four estimated exposure categories (>2 ppm) (SMR = 1.58, 95% confidence interval = 1.40 to 1.78), and the increase persisted after adjustment for local geographic variations in mortality (SMR = 1.28, 95% confidence interval = 1.13 to 1.44). However, there was a statistically nonsignificant decrease in the risk of death from lung cancer with duration of high exposure (P(trend) =.18), and this risk showed no trend with time since first high exposure (P(trend) =.99). CONCLUSIONS: The evidence for human carcinogenicity of formaldehyde remains unconvincing. Although a small effect on sino-nasal or nasopharyngeal cancer cannot be ruled out, a possible increase in the risk of lung cancer is a greater concern.

Adult↗

Dosimetry modeling of inhaled formaldehyde: comparisons of local flux predictions in the rat, monkey, and human nasal passages.

Formaldehyde-induced nasal squamous cell carcinomas in rats and squamous metaplasia in rats and rhesus monkeys occur in specific regions of the nose with species-specific distribution patterns. Experimental approaches addressing local differences in formaldehyde uptake patterns and dose are limited by the resolution of dissection techniques used to obtain tissue samples and the rapid metabolism of absorbed formaldehyde in the nasal mucosa. Anatomically accurate, 3-dimensional computational fluid dynamics models of F344 rat, rhesus monkey, and human nasal passages were used to estimate and compare regional inhaled formaldehyde uptake patterns predicted among these species. Maximum flux values, averaged over a breath, in nonsquamous epithelium were estimated to be 2620, 4492, and 2082 pmol/(mm(2)-h-ppm) in the rat, monkey, and human respectively. Flux values predicted in sites where cell proliferation rates were measured as similar in rats and monkeys were also similar, as were fluxes predicted in a region of high tumor incidence in the rat nose and the anterior portion of the human nose. Regional formaldehyde flux estimates are directly applicable to clonal growth modeling of formaldehyde carcinogenesis to help reduce uncertainty in human cancer risk estimates.

Animals↗

Biologically motivated computational modeling of formaldehyde carcinogenicity in the F344 rat.

Formaldehyde inhalation at 6 ppm and above causes nasal squamous cell carcinoma (SCC) in F344 rats. The human health implications of this effect are of significant interest since human exposure to environmental formaldehyde is widespread, though at lower concentrations than those that cause cancer in rats. In this article, which is part of a larger effort to predict the human cancer risks of inhaled formaldehyde, we describe biologically motivated quantitative modeling of the exposure-tumor response continuum in the rat. An anatomically realistic, three-dimensional fluid dynamics model of the F344 rat nasal airways was used to predict site-specific flux of formaldehyde from inhaled air into tissue, since both SCC and preneoplastic lesions develop in a characteristic site-specific pattern. Flux into tissue was used as a dose metric for two modes of action, direct mutagenicity and cytolethality-regenerative cellular proliferation (CRCP), which in turn were linked to key parameters of a two-stage clonal growth model. The direct mutagenicity mode of action was represented by a low dose linear dose-response model of DNA-protein cross-link (DPX) formation. An empirical J-shaped dose-response model and a threshold model fit to the empirical data were used for CRCP. In the clonal growth model, the probability of mutation per cell generation was a function of the tissue concentration of DPX while the rate of cell division was calculated from the CRCP data. Maximum likelihood methods were used to estimate parameter values. Survivor (a nontumor outcome) and tumor data for controls from the National Toxicology Program database and from two formaldehyde inhalation bioassays were used for likelihood calculations. The J-shaped dose-response for CRCP provided a better description of the SCC data than did the threshold model. Sensitivity analyses indicated that the rodent tumor response is due to the CRCP mode of action, with the directly mutagenic pathway having little, if any, influence. When evaluated in light of modeling and database uncertainties, particularly the specification of the clonal growth model and the dose-response data for CRCP, this work provides suggestive though not definitive evidence for a J-shaped dose-response for formaldehyde-mediated nasal SCC in the F344 rat.

Administration, Inhalation↗

Formaldehyde in reusable protective gloves.

Due to the clinical findings in a single patient's case, formaldehyde was suspected to be present in clinically relevant levels in reusable protective gloves. Therefore, 9 types of gloves were investigated with the semi-quantitative chromotropic acid method. It was found that 6/9 gloves emitted some formaldehyde and that 4/9 gloves emitted > or =40 microg of formaldehyde. Most of the formaldehyde was found on the inside of the gloves. To get an indication of the clinical relevance, a comparison with a protective cream declared to contain the formaldehyde-releasing agent diazolidinyl urea was performed by comparing areas of gloves with areas of cream layers with thickness 1-2 mg/cm(2). It was found that the amounts of formaldehyde emitted from the gloves might be in the same range as emitted from a layer of cream.

Adult↗

The role of formaldehyde in the formation of haemodialysis-associated anti-N-like antibodies.

In the sera of 68 (20.9%) of 325 haemodialysis patients, a specific cold agglutinin, cross-reacting with anti-N, was detected. Each patient showing this anti-N-like antibody used a formaldehyde-sterilized dialyser. By contrast, the antibody was not found in any of the 73 patients using a non-formaldehyde-sterilized dialyser. The results of transfusion experiments indicate an in vivo haemolytic activity of the antibody. In vitro, formaldehyde pretreatment of erythrocytes increased the agglutinability of the cells by the anti-N-like antibody. This effect could be prevented when the MN receptor of the red cells was exposed to neuraminidase. Trace quantities of formaldehyde inevitably enter the patient during dialysis when a formaldehyde-sterilized dialyser is used. It is postulated that this in vivo formaldehyde exposure might interact with the MN receptor of the red cells, rendering it immunogenic, and thus induce the formation of the haemodialysis-associated anti-N-like antibody.

Antibody Specificity↗

Electron-transport-driven sodium extrusion during methanogenesis from formaldehyde and molecular hydrogen by Methanosarcina barkeri.

Methanogenesis from formaldehyde or formaldehyde + H2, as carried out by Methanosarcina barkeri, was strictly dependent on sodium ions whereas methane formation from methanol + H2 or methanol + formaldehyde was Na+-independent. This indicates that the reduction of formaldehyde to the formal redox level of methanol exhibits a Na+ requirement. During methanogenesis from formaldehyde, a delta pNa in the range of -62 mV to -80 mV was generated by means of a primary, electron-transport-driven sodium pump. This could be concluded from the following results obtained on cell suspensions of M. barkeri. 1. The addition of proton conductors or inhibitors of the Na+/H+ antiporter had no effect on sodium extrusion. 2. During methanogenesis from formaldehyde + H2 a delta psi of -60 mV to -70 mV was generated even in the presence of proton conductors. 3. ATPase inhibitors, applied in the presence of proton conductors, had no effect on primary sodium extrusion or generation of a delta psi. Evidence for a Na+-translocating ATPase could not be obtained.

Adenosine Triphosphate↗