A cross-sectional study of human symptomatology and residential formaldehyde concentrations

The cross-sectional study was performed to quantify the prevalence of symtomatology in residents of mobile homes as a function of indoor formaldehyde concentration. Formaldehyde concentrations were monitored for a seven hour period with an automated wet-chemical colorimetric analyzer. The health status of family members was ascertained by administration of questionnaires and physical exams. This is the first investigation to perform clinical assessments on residents undergoing concurrent exposure assessment in the home.^ Only 22.8% of households eligible for participation chose to cooperate. Monitoring data and health evaluations were obtained from 155 households in four Texas counties. A total of 428 residents (86.1%) were available for examination during the sampling hours. The study population included 45 infants, 126 children, and 257 adults.^ Formaldehyde concentration was not found to be significantly associated with increased risks for symptoms and signs of ocular irritation, dermal anomalies, or malaise. Three associations were identified that warrant further investigation. The relative odds associated with a doubling of formaldehyde concentration was significantly associated with parenchymal rales in adults and children. However, risk was modified by log respirable suspended particulate concentrations. Due to the presence of modification by a continuous variable, prevalence odds ratios (POR) and 95% confidence intervals (95% CI) for these associations are presented in tables. A doubling of formaldehyde concentration was also associated with an increased risk of perceived tightness in the chest in adults. Prevalence odds ratios are presented in a table due to effect modification by the average number of hours spent indoors on weekdays. Furthermore, a doubling of formaldehyde concentration was associated with an increased risk of drowsiness in children (POR = 2.60; 95% CI 1.04-6.51) and adults (POR = 1.94; 95% CI 1.20-3.14). ^

SYSTEMIC TOXICITY IN RODENTS FOLLOWING ACUTE AND SUBCHRONIC INHALATION OF FORMALDEHYDE (FLOW CYTOMETRY, CELL CYCLE KINETICS, ALKALINE ELUTION)

Systemic toxicity was evaluated in Sprague-Dawley (SD) rats and A-strain mice exposed to HCHO inhalation at 0, 0.5, 3, or 15 ppm for six hours/day, five days/week for up to 24 weeks. Toxicity was measured by flow cytometry to detect changes in cell cycle RNA and DNA content and by alkaline elution to detect DNA protein cross-link (DPC) formation.^ A G(,2)M block was detected in SD rat marrow following one week of exposure to 0.5, 3, or 15 ppm HCHO, but this block did not persist. No effect was noticed in mouse marrow. Only a minimal increase in RNA content was detected in rat or mouse marrow while exfoliated lung cells showed a significant increase in RNA activity after one week of exposure.^ Acute exposure in SD rats for four hours/day for one or three days at 150 ppm showed an increase in RNA activity in exfoliated lung cells but not in the marrow after one day. On the third day, dead cells were detected in exfoliated lung cells.^ In alkaline elution studies, no DPC were detected in marrow of SD rats after 24 weeks exposure up to 15 ppm. During acute exposures, a dose response relationship was detected in SD rat exfoliated lung cells which yielded cross-linking factors of 0.954, 1.237, and 1.417 following a four hour exposure to 15, 50, or 150 ppm, respectively. No DPC were detected in the marrow at 150 ppm. In vitro exposures to HCHO of CHO and SHE cells and rat marrow cells revealed the production of DPC and DNA-DNA cross-links.^ Cytoxan treatment of SD rats was used to provide positive controls for flow cytometry and alkaline elution. A drastic reduction in RNA content and cycling cells occurred one day following treatment. After four days, RNA content was greatly increased; and on day eleven the marrow had regenerated. DPCs were detected in both the marrow and the exfoliated lung cells.^ The lack of significant responses in SD rats and A-strain mice below 15 ppm HCHO is explainable by host defense mechanisms. Apparently, the mucociliary apparatus and enzymatic detoxification are sufficient to reduce systemic toxicity to low level concentrations of formaldehyde. ^

RESPIRATORY COMPENSATION MECHANISMS IN THE UPPER AND LOWER RESPIRATORY TRACTS OF AN ANIMAL MODEL AFTER SUBCHRONIC INHALATION EXPOSURE TO FORMALDEHYDE: IMPLICATIONS FOR TOXICOLOGY RISK ASSESSMENT (DEPOSITION, DOSE RECEIVED, RESPONSE)

The potential for significant human populations to experience long-term inhalation of formaldehyde and reports of symptomatology due to this exposure has led to a considerable interest in the toxicologic assessment of risk from subchronic formaldehyde exposures using animal models. Since formaldehyde inhalation depresses certain respiratory parameters in addition to its other forms of toxicity, there is a potential for the alteration of the actual dose received by the exposed individual (and the resulting toxicity) due to this respiratory effect. The respiratory responses to formaldehyde inhalation and the subsequent pattern of deposition were therefore investigated in animals that had received subchronic exposure to the compound, and the potential for changes in the formaldehyde dose received due to long-term inhalation evaluated. Male Sprague-Dawley rats were exposed to either 0, 0.5, 3, or 15 ppm formaldehyde for 6 hours/day, 5 days/week for up to 6 months. The patterns of respiratory response, deposition and the compensation mechanisms involved were then determined in a series of formaldehyde test challenges to both the upper and to the lower respiratory tracts in separate groups of subchronically exposed animals and age-specific controls (four concentration groups, two time points). In both the control and pre-exposed animals, there was a characteristic recovery of respiratory parameters initially depressed by formaldehyde inhalation to at or approaching pre-exposure levels within 10 minutes of the initiation of exposure. Also, formaldehyde deposition was found to remain very high in the upper and lower tracts after long-term exposure. Therefore, there was probably little subsequent effect on the dose received by the exposed individual that was attributable to the repeated exposures. There was a diminished initial minute volume response in test challenges of both the upper and lower tracts of animals that had received at least 16 weeks of exposure to 15 ppm, with compensatory increases in tidal volume in the upper tract and respiratory rate in the lower tract. However, this dose-related effect was probably not relevant to human risk estimation because this formaldehyde dose is in excess of that experienced by human populations. ^

AN INVESTIGATION OF THE EFFECT OF FORMALDEHYDE SPECIES ON ENVIRONMENTAL MEASUREMENT METHODS UNDER AMBIENT CONDITIONS

Species variations in formaldehyde solutions and gases were investigated by means of infrared spectral analysis. Double beam infrared spectrometry in conjunction with sodium chloride wafer technique and solvent compensation technique were employed. Formaldehyde species in various solutions were investigated. Formalin 37% was stable for many months. Refrigeration had no effects on its stability. Spectral changes were detected in 1000 ppm formaldehyde solutions. The absorbances of very diluted solutions up to 100 ppm were lower than the detection limit of the instruments. Solvent compensation improved resolution, but was associated with an observed lack of repeatability. Formaldehyde species in animal chambers containing animals and in mobile home air were analyzed with the infrared spectrophotometer equipped with a 10 cm gas cell. Spectra were not different from the spectrum of clean air. A portable single beam infrared spectrometer with a 20 meter pathlength was used for reinvestigation. Indoor formaldehyde could not be detected in the spectral; conversely, an absorption peak at 3.58 microns was found in the spectra of 3 and 15 ppm formaldehyde gas in animal chambers. This peak did not appear in the spectrum of the control chamber. Because of concerns over measurement bias among various analytical methods for formaldehyde, side-by-side comparisons were conducted in both laboratory and field measurements. The chromotropic acid method with water and 1% sodium bisulfite as collection media, the pararosaniline method, and a single beam infrared spectrometer were compared. Measurement bias was elucidated and the extent of the effects of temperature and humidity was also determined. The problems associated with related methods were discussed. ^

Pea formaldehyde-active class III alcohol dehydrogenase: common derivation of the plant and animal forms but not of the corresponding ethanol-active forms (classes I and P).

A plant class III alcohol dehydrogenase (or glutathione-dependent formaldehyde dehydrogenase) has been characterized. The enzyme is a typical class III member with enzymatic parameters and substrate specificity closely related to those of already established animal forms. Km values with the pea enzyme are 6.5 microM for NAD+, 2 microM for S-hydroxymethylglutathione, and 840 microM for octanol versus 9, 4, and 1200 microM, respectively, with the human enzyme. Structurally, the pea/human class III enzymes are closely related, exhibiting a residue identity of 69% and with only 3 of 23 residues differing among those often considered in substrate and coenzyme binding. In contrast, the corresponding ethanol-active enzymes, the long-known human liver and pea alcohol dehydrogenases, differ more (47% residue identities) and are also in functionally important active site segments, with 12 of the 23 positions exchanged, including no less than 7 at the usually much conserved coenzyme-binding segment. These differences affect functionally important residues that are often class-distinguishing, such as those at positions 48, 51, and 115, where the plant ethanol-active forms resemble class III (Thr, Tyr, and Arg, respectively) rather than the animal ethanol-active class I forms (typically Ser, His, and Asp, respectively). Calculations of phylogenetic trees support the conclusions from functional residues in subgrouping plant ethanol-active dehydrogenases and the animal ethanol-active enzymes (class I) as separate descendants from the class III line. It appears that the classical plant alcohol dehydrogenases (now called class P) have a duplicatory origin separate from that of the animal class I enzymes and therefore a paralogous relationship with functional convergence of their alcohol substrate specificity. Combined, the results establish the conserved nature of class III also in plants, and contribute to the molecular and functional understanding of alcohol dehydrogenases by defining two branches of plant enzymes into the system.

Formaldehyde : questions concerning potential health problems.

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Urea formaldehyde foam insulation.

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Simultaneous chemical reaction and distillation of formaldehyde

The thesis is concerned with the development and testing of a mathematical model of a distillation process in which the components react chemically. The formaldehyde-methanol-water system was selected and only the reversible reactions between formaldehyde and water giving methylene glycol and between formaldehyde and methanol producing hemiformal were assumed to occur under the distillation conditions. Accordingly the system has been treated as a five component system. The vapour-liquid equilibrium calculations were performed by solving iteratively the thermodynamic relationships expressing the phase equilibria with the stoichiometric equations expressing the chemical equilibria. Using optimisation techniques, the Wilson single parameters and Henry's constants were calculated for binary systems containing formaldehyde which was assumed to be a supercritical component whilst Wilson binary parameters were calculated for the remaining binary systems. Thus the phase equilibria for the formaldehyde system could be calculated using these parameters and good accuracy was obtained when calculated values were compared with experimental values. The distillation process was modelled using the mass and energy balance equations together with the phase equilibria calculations. The plate efficiencies were obtained from a modified A.I.Ch.E. Bubble Tray method. The resulting equations were solved by an iterative plate to plate calculation based on the Newton Raphson method. Experiments were carried out in a 76mm I.D., eight sieve plate distillation column and the results were compared with the mathematical model calculations. Overall, good agreement was obtained but some discrepancies were observed in the concentration profiles and these may have been caused by the effect of limited physical property data and a limited understanding of the reactions mechanism. The model equations were solved in the form of modular computer programs. Although they were written to describe the steady state distillation with simultaneous chemical reaction of the formaldehyde system, the approach used may be of wider application.

Production of phenol-formaldehyde resin composites

The main objective of this work was to examlne the various stages of the production of industrial laminates based on phenol-formaldehyde resins, with a view of suggesting ways of improving the process economics and/or the physical properties of the final product. Aspects of impregnation, drying, and lamination were investigated. The resins used in all experiments were ammonia-catalysed. Work was concentrated on the lamination stage since this is a labour intensive activity. Paper-phenolic lay-ups were characterised in terms of the temperatures experienced during cure, and a shorter cure-cycle is proposed, utilising the exothermic heat produced during pressing of 25.5 mm thick lay-ups. Significant savings in production costs and improvements in some of the physical properties have been achieved. In particular, water absorption has been reduced by 43-61%. Work on the drying stage has shown that rapid heating of the wet impregnated substrate results in resin solids losses. Drying at lower temperatures by reducing the driving force leads to more resin (up to 6.5%) being retained by the prepregs and therefore more effective use of an expensive raw material. The impregnation work has indicated that residence times above 6 seconds in the varnish bath enhance the insulation resistance of the final product, possibly due to improved resin distribution and reduction in water absorption. In addition, a novel process which involves production of laminates by in situ polymerisation of the phenolic resin on the substrate has been examined. Such a process would eliminate the solvent recovery plant - a necessary stage in current industrial processes. In situ polymerisation has been shown to be chemically feasible.

Study on synthetic and bio-based phenol-formaldehyde adhesives for the wood-based industry

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Influence of serum levels of vitamins A, D, and E as well as vitamin D receptor polymorphisms on micronucleus frequencies and other biomarkers of genotoxicity in workers exposed to formaldehyde

Background/Aim: Formaldehyde is classified as carcinogenic to humans, making it a major concern, particularly in occupational settings. Fat-soluble vitamins, such as vitamins A, D, and E, are documented as antigenotoxic and antimutagenic and also correlate with the cell antioxidant potential. This study investigates the influence of these vitamins on genotoxicity biomarkers of formaldehyde-exposed hospital workers. Methods: The target population were hospital workers exposed to formaldehyde (n = 55). Controls were nonexposed individuals (n = 80). The most used genotoxicity biomarkers were the cytokinesis-block micronucleus assay for lymphocytes and the micronucleus test for exfoliated buccal cells. Vitamins A and E were determined by high-performance liquid chromatography with a diode array detector (HPLC-DAD) and vitamin D receptor (VDR) polymorphisms by real-time PCR. Results: Significant correlations were found between genotoxicity biomarkers and between vitamins A and E in controls. Multiple regression showed that vitamin A was significantly associated with a higher mean of nucleoplasmic bridges (p < 0.001), and vitamin E was significantly associated with a decreased frequency of nuclear buds (p = 0.045) in the exposed group. No effect of vitamin D was observed. The VDRBsmI TT genotype carriers presented higher means of all the genotoxicity biomarkers; however, we found no significant associations. Conclusions: The study suggests that vitamin levels may modulate direct signs of genotoxicity.