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PubMed1999

Formaldehyde allergy: A follow-up study.

BACKGROUND: Formaldehyde is a commonly used preservative in cosmetic products, cleaning agents and industrial products, and sensitization to formaldehyde frequently occurs. OBJECTIVE: The aim of the study was to evaluate the effect of extensive information and exposure assessment of formaldehyde on the prognosis of eczema. METHODS: The present study was designed as a clinical follow-up study of formaldehyde-sensitive patients. 105 patients diagnosed as formaldehyde allergic in the period January 1 1990 to December 31 1994 were thoroughly informed about their allergy, and exposure assessment was performed as a formaldehyde analysis on the patients' products. RESULTS: At follow-up 1 to 5 years later, 57 patients accepted the invitation to attend the outpatient clinic for an interview and a skin examination by a dermatologist, and were also at this time asked to bring products to which they were currently exposed for formaldehyde analysis. Evaluated by reported number of eczema eruptions and from objective skin examination patients had generally improved from their first visit to the department. At follow-up, 38 of 49 patients bringing products for analysis were still exposed to formaldehyde, as assessed by formaldehyde analysis on their products. There was a trend that severe eczema was found more often in patients still exposed to formaldehyde, but this finding was not statistically significant. Thirty-seven patients reported that they "paid attention to their allergy" when buying and using cosmetics or consumer products. CONCLUSION: Patients who paid attention to their allergy had statistically significantly fewer eruptions than those who did not.

Adult↗
PubMed1989

Effects of formaldehyde gas on the respiratory tract of rhesus monkeys. Pathology and cell proliferation.

Formaldehyde is a nasal carcinogen in rats but it remains to be determined what cancer risk this chemical poses in humans. Molecular dosimetry studies of formaldehyde and cellular proliferative responses to formaldehyde-induced cytotoxicity have been studied in the rodent and are important components of the authors' ongoing research, which has now been extended to nonhuman primates, a species more analogous to humans. The present study was designed to characterize formaldehyde injury in the respiratory tract of nonhuman primates to provide a direct comparison to the toxic effects of formaldehyde in rodents. Groups of three rhesus monkeys were exposed to room air, or 6 ppm formaldehyde for 5 days per week for 1 or 6 weeks, and the respiratory tract was assessed for nature and extent of histologic responses, and changes in epithelial cell proliferation rate. Lesions were characterized by mild degeneration and early squamous metaplasia confined to specific regions of the transitional and respiratory epithelia of the nasal passages and the respiratory epithelium of the trachea and major bronchi. There was minimal progression of histologic changes between 1 and 6 weeks; however, the percent of nasal surface area affected significantly increased in the 6-week exposure group. Formaldehyde-induced lesions were associated with increases in cell proliferation rates up to 18-fold over controls, which remained significantly elevated after 6 weeks of exposure. Histologic lesions and increases in cell proliferation were most extensive in the nasal passages and were minimal in the lower airways, whereas the maxillary sinuses exhibited no evidence of a response to formaldehyde exposure. Based on the extent of lesions and cell proliferation data, it appears that the monkey is more sensitive than the rat to the acute and subacute effects of formaldehyde at 6 ppm. The absence of response in the maxillary sinuses in the monkey suggests that combining tumors of the nasal cavity and sinuses in epidemiologic studies may not be appropriate for formaldehyde cancer risk assessment. Results of this study also have provided important information for tissue sample site selection in the monkey respiratory tract for ongoing molecular dosimetry studies.

Animals↗
PubMed1987

[Determination of formaldehyde concentration in a low-pressure sterilizer].

Two methods are described in determining the concentration of Formaldehyde in the sterilisation chamber of a regular commercial sterilizer. The measurement and flow of the concentration is ascertained during a routine sterilization procedure. With regard to the biological efficiency test of the examined apparatus the stability of the active Formaldehyde concentration is controlled. The difficulty in the determination of the Formaldehyde in such sterilizers is due to the fact that samples must be taken at a reduced pressure of 200 mbar. We have developed two different sampling methods. By employing the first continual collection method Formaldehyde gas is drawn out of the sterilization chamber with a high vacuum pump and conveyed with hydrogen into a nickel catalysator, whereby Methane is formed. The determination of Methane is carried out with a flame ionisation detector (F.I.D.). The results of the F.I.D. method are between 10.1-10.8 mg Formaldehyde per litre of gas. It is possible to detect a slight, even reduction in the Formaldehyde concentration throughout a period of 90 min. With the second discontinual method of determination vacuum tubes are employed which are furnished with external magnetic valves for control. By opening the magnetic valves briefly during the pre-vacuum therewith causing loss of pressure, Formaldehyde gas can be collected in the vacuum tubes throughout the sterilization procedure. The determination of the samples extracted by the discontinual method is carried out spectrophotometrically using the p-Rosanilin method after Miksch et al. The second method of determination shows values of 9.0-9.8 mg/l (Sx = 0.8 mg/l). These results lie somewhat lower than those of the F.I.D. determination. The flow of the concentration during 90 min. shows an average reduction of 7.4% and matches exactly the curve which was obtained by the F.I.D. method. By measuring the Formaldehyde concentrations which goods are subjected to in normal sterilization procedure it is possible to examine the efficacy of Formaldehyde sterilizers under regular conditions. Only by quotation of the Formaldehyde concentration present is it possible to reproduce details on sterilization times of treated articles.

Calibration↗
PubMed1990

Mortality from lung cancer among workers employed in formaldehyde industries.

A historical cohort of 26,561 workers employed in ten facilities was assembled to evaluate cancer risks associated with exposure to formaldehyde. Historical exposures to formaldehyde by job, work area, plant, and calendar time were estimated using monitoring data available from participating plants, comments from long-term workers and company officials, exposure evaluations from walk-through surveys conducted by project industrial hygienists, and results from monitoring specifically performed for this project. A previous report of findings from this study noted a 30% excess mortality from lung cancer among wage workers. The relative risk for lung cancer (whether estimated by SMRs or SRRs) 20 or more years after first exposure did not generally rise with increasing exposure to formaldehyde. Various estimates of exposure were investigated including duration, intensity, peak, cumulative, and average, and by exposures lagged by 5, 10, 20, and 30 years. The excess did not appear to arise gradually, but emerged suddenly among workers whose total cumulative exposure was less than 0.1 ppm-years. Slightly positive, but nonsignificant, exposure-response associations between lung cancer and level of formaldehyde occurred in only a few out of a large number of comparisons (e.g., for persons hired before the start dates for the study and for workers also exposed to particulates). There was a lack of consistency among the various plants for risk of lung cancer, with six plants having elevated SMRs and four plants having deficits. Mortality from lung cancer was more strongly associated with exposure to other substances including phenol, melamine, urea, and wood dust than with exposure to formaldehyde. Workers exposed to formaldehyde without exposure to these substances did not experience an elevated mortality from lung cancer. The risk did not increase with cumulative levels of formaldehyde among those exposed to other substances and there was a slightly negative trend for those exposed to formaldehyde alone. Although some role for formaldehyde, particularly in association with other substances, in the excess of lung cancer seen among these workers cannot be ruled out, these findings suggest that exposure to phenol, melamine, urea, wood dust or other exposures also occurring in the area where these substances were used (i.e., production of resin and molding compounds) may play a more primary role. This association should be further evaluated in other studies that include workers from resin and molding compound operations.

Cohort Studies↗
PubMed2002

Dose response for formaldehyde-induced cytotoxicity in the human respiratory tract.

Human studies of the sensory irritant effects of formaldehyde are complicated by the subjective nature of some clinical endpoints. This limits the usefulness of such studies for quantitative noncancer risk assessment of airborne formaldehyde. Objective measures of the noncancer effects of formaldehyde, such as the rate of regenerative cellular proliferation (RCP) secondary to cytolethality, can be obtained from laboratory animals but present the challenge of interspecies extrapolation of the data. To the extent that uncertainties associated with this extrapolation can be reduced, however, dose-response data obtained in laboratory animals are a viable alternative to clinical studies. Here, we describe the extrapolation of dose-response data for RCP from F344 rats to humans. Rats inhaled formaldehyde (0, 0.7, 2.0, 6.0, 10, and 15 ppm) 6 h/day, 5 days/week for up to 2 years. The dose response for RCP was J-shaped, with the rates of RCP at 0.7 and 2.0 ppm below but not statistically different from control, while the rates at the higher concentrations were significantly greater than control. Both the raw J-shaped data and a hockey-stick-shaped curve fitted to the raw data were used for predicting the human dose response for RCP. Cells lining the nasal airways of F344 rats and rhesus monkeys are comparably sensitive to the cytolethal effects of inhaled formaldehyde, suggesting that the equivalent human cells are also likely to be comparably sensitive. Using this assumption, the challenge of rat-to-human extrapolation was reduced to accurate prediction of site-specific flux of formaldehyde from inhaled air into the tissue lining the human respiratory tract. A computational fluid dynamics model of air flow and gas transport in the human nasal airways was linked to a typical path model of the human lung to provide site-specific flux predictions throughout the respiratory tract. Since breathing rate affects formaldehyde dosimetry, cytotoxicity dose-response curves were predicted for three standard working levels. With the most vigorous working level, the lowest concentrations of formaldehyde predicted to exert any cytotoxic effects in humans were 1.0 and 0.6 ppm, for the J-shaped and hockey-stick-shaped RCP curves, respectively. The predicted levels of response at the lowest effect concentrations are smaller than can be measured clinically. Published literature showing that the cytotoxicity of inhaled formaldehyde is related to exposure level rather than to duration of exposure suggests that the present analysis is a reasonable basis for derivation of standards for continuous human exposure.

Animals↗
PubMed1980

New aspects on factors determining the sensitivity of the formaldehyde and glyoxylic acid fluorescence histochemical methods for monoamines.

The fluorophore and fluorescence yield from tryptamine and 3-methoxytyramine in histochemical protein models have been compared in the standard formaldehyde reaction, the acid-catalyzed formaldehyde reaction, the formaldehyde-ozone reaction, and the aluminum-formaldehyde reaction. In the standard formaldehyde reaction both the fluorophore and fluorescence yields are low. However, the other reactions give a dramatic increase in fluorescence intensity (18-20 times) from tryptamine and 3-methoxytyramine whereas only minor changes (up to 100% increase) in fluorophore yield are observed. It is concluded that the relative fluorescence intensity of each fluorophore molecule formed in the three modifications of the formaldehyde reaction is much higher than that of the molecules formed in the standard formaldehyde reaction. It has previously been demonstrated that the fluorophores formed from dopamine in the gaseous formaldehyde and glyoxylic acid reactions have a much higher (10 times) relative fluorescence intensity than the synthetic fluorophores. the prresent experiments show that if the histochemicl models are dissolved in buffer after the reaction and new models are made from this solution, the fluorescence intensity of the fluorophores formed in the reaction is drastically reduced and becomes comparable to that of the synthetic ones. The results of this and our previous studies indicate that hitherto unknown fluorescence enhancing mechanisms play a major role for the fluorescence yield, i.e. the sensitivity, in the various formaldehyde and glyoxylic acid methods. One possible explanation to the high relative fluorescence intensity of the fluorophores formed in the histochemical reactions could be an energy transfer between, e.g. the non-fluorescent intermediary reaction products (the tetrahydro derivatives) and the fluorophores (the dihydroisoquinolines and dihydro-beta-carbolines). Such an energy transfer is probably attenuated in the dissolved models, where th distances betweenm and orientations of the various molecules have been changed.

Dopamine↗
PubMed1995

Denaturation of fish proteins during frozen storage: role of formaldehyde.

Proteins of fish muscle undergo chemical and physical changes during frozen storage which may result in, under certain conditions (i.e. long periods of storage, poor freezing practices, temperature fluctuations, etc), loss of quality, reflected mainly by an unacceptable texture as well as an undesirable flavour, odour and colour. In frozen gadoid fish species, most of these changes are caused by the production of formaldehyde in the muscle. Formaldehyde is produced, along with dimethylamine, by the enzymatic reduction of trimethylamine oxide (TMAO). Many aspects of formaldehyde production by TMAO demethylase (TMAOase) have been studied throughout the last decade. In addition, different approaches have been used to investigate the effect of formaldehyde production on protein denaturation and the associated muscle textural changes. Some insight into the reaction between protein and formaldehyde has clarified the possible mechanism of formaldehyde-mediated denaturation. However, evidence of covalent bonding between proteins and formaldehyde, to form crosslinks, has not explained fully the changes observed in fish proteins during frozen storage. The study of cold-induced denaturation of proteins might give new clues for further investigation of the problem. The implications of formaldehyde in toxicological and nutritional issues is also reviewed, as general concern about the safety of food products is a growing field in food science. Finally, different approaches have been proposed to avoid the detrimental action of formaldehyde during frozen storage of gadoid fish; they are some of the practical applications of the knowledge acquired after years of study of different workers in the field.

Animals↗
PubMed1984

Formaldehyde inactivation of foot-and-mouth disease virus. Conditions for the preparation of safe vaccine.

The inactivation of foot-and-mouth disease virus by formaldehyde was studied under different conditions, both as free virus and (as in routine vaccine production) after adsorption of the virus to aluminium hydroxide gel (alhydrogel). In the latter case infectivity was monitored after elution of the virus from the gel by isopycnic ultracentrifugation of the virus-alhydrogel mixture in CsCl. By this method good virus recoveries were obtained. Adsorption of the virus to alhydrogel (without formaldehyde) did not reduce infectivity significantly. Both adsorbed and non-absorbed virus lost infectivity at a rate of about one log10 per day (at pH 8.5, 25 degrees C--no formaldehyde). Kinetics of formaldehyde inactivation of adsorbed and non-adsorbed virus were also identical, with a fast reduction in the initial phase (in case of O1 and A10-virus approximately one log10/hour). After this initial phase inactivation became linear and rather slow (for O1 and A10-virus 0.2 log10/hour). No "tailing-off" was observed. Under standard conditions (0.04 per cent formaldehyde, pH 8.5, 25 degrees C) CD-virus was inactivated approximately 1.5 times faster than O1 and A10-virus. At 4 degrees C the inactivation of the three strains continued at about one log10/day. Increased lactalbumin hydrolysate concentrations reduced the inactivation rate, especially at the formaldehyde concentration of 0.02 per cent, which was originally applied. Quaternary amines like Tris strongly inhibited formaldehyde activity. These findings might explain some data of others who observed "tailing off". Analysis of formaldehyde inactivated antigen by SDS-PAGE and electrofocusing showed that extensive cross-linking occurs especially of VP1, probably with other virus proteins but also with non-virus proteins from the medium. VP2 and VP3 are less affected. Cross-linking was enhanced when the virus had been adsorbed to alhydrogel during inactivation. Progressive cross-linking was observed during storage of the vaccine at 4 degrees C, which also indicated that inactivation continued at this temperature. These data show that formaldehyde inactivated adsorbate vaccines can be safe.

Amines↗
PubMed2002

Cofactor-dependent pathways of formaldehyde oxidation in methylotrophic bacteria.

Methylotrophic bacteria can grow on a number of substrates as energy source with only one carbon atom, such as methanol, methane, methylamine, and dichloromethane. These compounds are metabolized via the cytotoxin formaldehyde. The formaldehyde consumption pathways, especially the pathways for the oxidation of formaldehyde to CO(2) for energy metabolism, are a central and critical part of the metabolism of these aerobic bacteria. Principally, two main types of pathways for the conversion of formaldehyde to CO(2) have been described: (1) a cyclic pathway initiated by the condensation of formaldehyde with ribulose monophosphate, and (2) distinct linear pathways that involve a dye-linked formaldehyde dehydrogenase or C(1) unit conversion bound to the cofactors tetrahydrofolate (H(4)F), tetrahydromethanopterin (H(4)MPT), glutathione (GSH), or mycothiol (MySH). The pathways involving the four cofactors have in common the following sequence of events: the spontaneous or enzyme-catalyzed condensation of formaldehyde and the respective C(1) carrier, the oxidation of the cofactor-bound C(1) unit and its conversion to formate, and the oxidation of formate to CO(2). However, the H(4)MPT pathway is more complex and involves intermediates that were previously known solely from the energy metabolism of methanogenic archaea. The occurrence of the different formaldehyde oxidation pathways is not uniform among different methylotrophic bacteria. The pathways are in part also used by other organisms to provide C(1) units for biosynthetic reactions (e.g., H(4)F-dependent enzymes) or detoxification of formaldehyde (e.g., GSH-dependent enzymes).

Cysteine↗
PubMed1992

Structural determinants for alcohol substrates to be oxidized to formaldehyde by rat liver microsomes.

Glycerol can be oxidized to formaldehyde by rat liver microsomes and by cytochrome P450. The ability of other alcohols to be oxidized to formaldehyde was determined to evaluate the structural determinants of the alcohol which eventually lead to this production of formaldehyde. Monohydroxylated alcohols such as 1- or 2-propanol did not produce formaldehyde when incubated with NADPH and microsomes. Geminal diols such as 1,3-propanediol, 1,3-butanediol, or 1,4-butanediol also did not yield formaldehyde. However, vicinal diols such as 1,2-propanediol or 1,2-butanediol produced formaldehyde. With 1,2-propanediol, the residual two-carbon fragment was found to be acetaldehyde, while with 1,2-butanediol, the residual three-carbon fragment was propionaldehyde. Oxidation of 1,2-propanediol to formaldehyde plus acetaldehyde involved interaction with an oxidant derived from H2O2 plus nonheme iron, since production of the two aldehydic products was completely prevented by catalase or glutathione plus glutathione peroxidase and by chelators such as desferrioxamine or EDTA. The oxidant was not superoxide or hydroxyl radical. Product formation was fivefold lower when NADH replaced NADPH, and was inhibited by substrates, ligands, and inhibitors of cytochrome P450. A charged glycol such as alpha-glycerophosphate (but not the geminal beta-glycerophosphate) was readily oxidized to formaldehyde, suggesting that interaction of the glycol with the oxidant was occurring in solution and not in a hydrophobic environment. These results indicate that the carbon-carbon bond between 1,2-glycols can be cleaved by an oxidant derived from microsomal generated H2O2 and reduction of non-heme iron, with the subsequent production of formaldehyde plus an aldehyde with one less carbon than the initial glycol substrate.

Acetaldehyde↗
PubMed1986

Distribution, progression, and recovery of acute formaldehyde-induced inhibition of nasal mucociliary function in F-344 rats.

A previous report of inhalation exposure of F-344 rats to formaldehyde gas, using a whole-body exposure system, described the induction of regional inhibition of nasal mucociliary function, with a clear concentration-response relationship. A head-only exposure system was subsequently developed in order to facilitate the present study of reversibility of acute effects of formaldehyde on the nasal mucociliary apparatus. This study also included an examination of more extensive areas of the nose than those reported in the previous work. Male F-344 rats were exposed to 2 or 15 ppm formaldehyde gas for 10, 20, 45, or 90 min or 6 hr with recovery groups examined 1 hr after the end of the 90-min and 6-hr exposures. No effects were observed in rats exposed to 2 ppm formaldehyde. In rats exposed to 15 ppm, the extent of formaldehyde-induced inhibition of mucociliary function detected in specific regions of the nose was time dependent, with increasing areas of mucostasis and ciliastasis being induced during a 6-hr exposure period. A 1-hr room-air exposure, following exposure to 15 ppm formaldehyde, resulted in marked recovery of mucociliary function, indicating the value of a head-only exposure system for rapid examination of mucociliary function following exposure. Recovery of mucociliary function occurred especially in the more posterior areas of affected regions of the nose. However, in areas of recovery mucus flow rate was reduced compared to unexposed control rates, indicating incomplete recovery of function in these areas. Regions of formaldehyde-induced inhibition of mucociliary function correlated well with the previously reported distribution of formaldehyde-induced nasal squamous cell carcinomas, with the exception of effects on the medial aspect of the maxilloturbinate. These findings were considered to provide further support for the proposal that both regional exposure and local tissue susceptibility may be responsible for the distribution of formaldehyde-induced nasal squamous cell carcinomas. It was also postulated, on the basis of mucus flow patterns derived from control animals in this study, that flow relationships between nasal mucus and inspired air form a countercurrent system which may optimize clearance of inhaled air contaminants.

Animals↗
PubMed1986

Inhibition of CO2 production from aminopyrine or methanol by cyanamide or crotonaldehyde and the role of mitochondrial aldehyde dehydrogenase in formaldehyde oxidation.

Previous results have shown that cyanamide or crotonaldehyde are effective inhibitors of the oxidation of formaldehyde by the low-Km mitochondrial aldehyde dehydrogenase, but do not affect the activity of the glutathione-dependent formaldehyde dehydrogenase. These compounds were used to evaluate the enzyme pathways responsible for the oxidation of formaldehyde generated during the metabolism of aminopyrine or methanol by isolated hepatocytes. Both cyanamide and crotonaldehyde inhibited the production of 14CO2 from 14C-labeled aminopyrine by 30-40%. These agents caused an accumulation of formaldehyde which was identical to the loss in CO2 production, indicating that the inhibition of CO2 production reflected an inhibition of formaldehyde oxidation. The oxidation of methanol was stimulated by the addition of glyoxylic acid, which increases the rate of H2O2 generation. Crotonaldehyde inhibited CO2 production from methanol, but caused a corresponding increase in formaldehyde accumulation. The partial sensitivity of CO2 production to inhibition by cyanamide or crotonaldehyde suggests that both the mitochondrial aldehyde dehydrogenase and formaldehyde dehydrogenase contribute towards the metabolism of formaldehyde which is generated from mixed-function oxidase activity or from methanol, just as both enzyme systems contribute towards the metabolism of exogenously added formaldehyde.

Aldehyde Dehydrogenase↗
PubMed1987

Binding of formaldehyde to human and rat nasal mucus and bovine serum albumin.

The function of the nasal mucociliary apparatus, an important airway defense mechanism, is inhibited by inhaled formaldehyde. Nasal mucus, which contains significant concentrations of glycoprotein and soluble proteins, is an integral component of this system. This investigation addresses some reactions of formaldehyde with human and rat mucus in vitro in comparison with a model protein, bovine serum albumin. [14C]Formaldehyde was incubated with reconstituted preparations of human and rat nasal mucus or bovine serum albumin. Formaldehyde adducts, stabilized by sodium cyanoborohydride reduction to methylamines, were separated by Sepharose 2B gel filtration. [14C]Formaldehyde bound exclusively to one component of nasal mucus which had an elution volume identical to that of albumin. There was no detectable binding to the large molecular weight glycoproteins. The time course of reaction of formaldehyde to free amino groups was then measured using the fluorescamine technique. Formaldehyde binding was characterized by an initial fast phase (less than 2 min) followed by a slower phase which appeared to approach equilibrium (greater than 60 min). The rate of binding to human and rat nasal mucus was similar to albumin. Irreversible binding of formaldehyde to albumin was insignificant within the first 60 min indicating the reversibility of binding during this time. These data indicate that within the first 60 min, formaldehyde reacts rapidly and reversibly with nasal mucus and that it binds primarily to one component of nasal mucus. Gel filtration analysis suggests this component may be albumin although other low molecular weight proteins cannot be ruled out.

Amino Acids↗
PubMed2006

Mis-specified and non-robust mortality risk models for nasopharyngeal cancer in the National Cancer Institute formaldehyde worker cohort study.

An IARC (International Agency for Research on Cancer) working group categorized formaldehyde as a human carcinogen (Group 1) in 2004. A major component of the epidemiologic evidence evaluated by IARC to reach this decision was the analysis published by Hauptmann et al. [Hauptmann, M., Lubin, J. H., Stewart, P. A., Hayes, R. B., Blair, A. 2004. Mortality from solid cancers among workers in formaldehyde industries. Am. J. Epidemiol. 159, 1117-1130.] of the National Cancer Institute (NCI) historical cohort comprising industrial workers exposed to formaldehyde in 10 U.S. plants. The NCI authors emphasized the relationship found between highest formaldehyde peak exposure and death from nasopharyngeal cancer (NPC). We performed two additional types of re-analyses of the NCI cohort data with focus on peak exposure and NPC mortality. The analyses were aimed at (1) investigating whether the model specification chosen by Hauptmann et al. (2004) was appropriate (interaction assessment) and (2) exploring the degree of instability of the risk estimates for NPC in relation to highest peak exposure (sensitivity analysis). Hauptmann et al. (2004) failed to account for an important interaction structure between plant group and the exposure variable that prohibits a generalization of formaldehyde effects within the NCI cohort and, in particular, beyond the NCI cohort. In addition, our sensitivity analysis demonstrates considerable uncertainties in the risk estimates and points convincingly to instability problems particularly related to Plant 1. Even a simple sensitivity model taking only one additional death into account produced a variation of the risk estimates beyond the instability conveyed by standard confidence intervals. The results of our current reanalysis of the NCI study do not support NCI's suggestion of a causal association with formaldehyde exposure and nasopharyngeal cancer. The decision by the IARC working group to reclassify formaldehyde as a Group 1 substance was clearly premature considering: (1) the missing evidence of an NPC excess from the large British and NIOSH cohort studies; (2) the absence of an association with formaldehyde and NPC in the independent and expanded study of Plant 1; and (3) the mis-specified and non-robust internal analysis of the NCI cohort study brought to light in our current re-analysis. Thus, the 2004 IARC decision to reclassify formaldehyde as a Group 1 substance should be reconsidered.

Adenocarcinoma↗
PubMed1989

Quantitative risk approaches for formaldehyde.

Formaldehyde presents unique data that highlight significant issues in the extrapolation of animal studies to human risk assessments. Formaldehyde causes rare nasal cancer in rats at 15 ppm, but not at lower levels of 2 ppm and 0.5 ppm in the range of human exposures. Mice and hamster studies even at high levels have results similar to low dose rats. Higginson et al. reviewed the human epidemiology studies and concluded that no excess cancer risk was observed; and if a risk exists, it is very low. Formaldehyde is a natural metabolite--the human body turns over 51 g/day. Cells, therefore, have detoxification and other defence mechanisms to formaldehyde. Recent CIIT biomechanism results elucidate these factors. These data raise two issues: First, the appropriateness of linear quantitative risk methodology given the non-linear nature of the biological data. Either a non-linear (threshold) statistical model or NOEL approach are appropriate risk assessment techniques for formaldehyde. Second, the rare nasal cancer observed in rats also occurs in control animals. A comparison of relative risk between background and low formaldehyde exposures has been calculated for both groups. Non-linear (MLE) 5 stage multistage models estimate 0 per million risk from both background and 1 ppm of formaldehyde exposure. Linear or upperbound (95%) estimates are 7,200/million from background and 5,000/million from 1 ppm formaldehyde. These estimates have a significant impact on formaldehyde regulatory programs for warning labels and "safe" exposure levels.

Environmental Pollutants↗
PubMed1986

Characterization of particleboard aerosol--size distribution and formaldehyde content.

Health hazards unique to particleboard include the generation of urea-formaldehyde resin bound in wood aerosol and release of formaldehyde gas that can be inhaled by the worker. A particleboard aerosol was generated by a sanding process and collected under laboratory conditions that determined the particle size distribution and formaldehyde content. Three side-by-side Marple 296 personal cascade impactors with midget impingers attached downstream collected particleboard aerosol and gaseous formaldehyde for ten sample runs. Gravimetric analysis quantified the collected aerosol mass, and chromotropic acid/spectrophotometric analytical methods were employed for formaldehyde content in particleboard aerosol and gaseous formaldehyde liberated from sanded particleboard. Significant variations (p less than .005) were observed for the particleboard mass and gaseous formaldehyde collected between sample runs. No significant differences (alpha = .05) were observed for the aerosol size distribution determined and formaldehyde content in particleboard aerosol per unit mass for sampling trials. The overall MMAD of particleboard aerosol was 8.26 microns AED with a sigma g of 2.01. A predictive model was derived for determining the expected formaldehyde content (microgram) by particleboard aerosol mass (mg) collected and particulate size (micron AED).

Aerosols↗
PubMed1986

Mitigation of residential formaldehyde contamination by indoor climate control.

The effectiveness of indoor climate as a mitigation measure for indoor formaldehyde contamination was studied in a mobile home. The effects of nine indoor climate regimes on formaldehyde levels were evaluated for the temperature and humidity ranges of 20 degrees C to 30 degrees C and 30% RH to 70% RH. Formaldehyde levels at the lowest combination of temperature and relative humidity (20 degrees C, 30% RH) were only 20% of those measured at the highest combination of temperature and relative humidity (30 degrees C, 70% RH) evaluated. Reducing temperature alone (from 30 degrees C to 20 degrees C) was shown to result in an approximate 70% reduction in formaldehyde levels. Reducing relative humidity alone (from 70% to 30%) resulted in an approximate 40% reduction in formaldehyde levels. A high linear correlation was observed between formaldehyde levels and temperature and between formaldehyde levels and relative humidity. Analysis of energy consumption and associated costs indicated that temperature reduction from 25 degrees C to 20 degrees C during the cooling season would increase energy usage costs by about 20%; temperature reduction in the heating season would result in both reduced formaldehyde levels and reduced energy costs. Although effective, humidity control--particularly to 30% under summertime conditions--appears to be prohibitively costly. The relationship between temperature and formaldehyde levels suggests that climate control also may be appropriate for reducing indoor levels of other continuously generated contaminants.

Environmental Exposure↗
PubMed1984

Treatment of dietary casein with formaldehyde reduces its hypercholesterolemic effect in rabbits.

Rabbits were fed cholesterol-free, semipurified diets containing 42% (wt/wt) casein or 21% casein plus one of the following nitrogen sources: soy isolate, amino acid mixture simulating casein, amino acid mixture simulating soy isolate, formaldehyde-treated casein or formaldehyde-treated soy isolate. Two additional groups of rabbits were fed the 42% casein diet and the diet containing casein plus soy isolate to which 0.4% (wt/wt) pure formaldehyde was added, this amount being identical to the amount of formaldehyde present in the diets with formaldehyde-treated proteins. Growth was somewhat reduced on the three diets containing 42% casein. The diet containing 42% casein to which no formaldehyde had been added induced severe hypercholesterolemia, the level of serum cholesterol after 8 weeks being about 10 mmol/L. The hypercholesterolemia was markedly reduced by the replacement of half of the casein by soy isolate, formaldehyde-treated soy isolate or formaldehyde-treated casein. No significant reduction of the concentration of serum cholesterol was seen when half of the 42% casein was replaced by an amino acid mixture imitating either casein or soy isolate. Formaldehyde per se did not significantly influence the level of serum cholesterol. We conclude that the differential tertiary structure of intact casein and soy isolate is an important factor in determining the cholesterolemic responses in rabbits to these proteins.

Animals↗