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PubMed1979

A steady-state-kinetic model for formaldehyde dehydrogenase from human liver. A mechanism involving NAD+ and the hemimercaptal adduct of glutathione and formaldehyde as substrates and free glutathione as an allosteric activator of the enzyme.

The steady-state kinetics of formaldehyde dehydrogenase from human liver have been explored. Non-linearities were obtained in v-versus-v[S] plots. It was necessary and sufficient to consider two reactants of the equilibrium mixture of formaldehyde, glutathione and their hemimercaptal adduct for a complete description of the kinetics. A random sequential reaction scheme is proposed in which adduct and beta-NAD+ are the substrates. In addition, glutathione can bind to an allosteric regulatory site and only the glutathione-containing enzyme is considered productive. Various alternative reaction models were examined but no simple alterative was superior to the model chosen. The discrimination was largely based on results of non-linear regression analysis. Several S-substituted glutathione derivatives were tested as activators or inhibitors of the enzyme, but all were without effect. Thio-NAD+, nicotinamide--hypoxanthine dinucleotide and 3-acetylpyridine-adenine dinucleotide could substitute for beta-NAD+ as the nucleotide substrate. alpha-NAD+ and ADP-ribose were competitive inhibitors with respect to beta-NAD+ and non-competitive with glutathione and the adduct. When used simultaneously, the inhibitors were linear competitive versus each other, indicating a single nucleotide-binding site or, if more than one, non-co-operative binding sites.

Aldehyde Oxidoreductases↗
PubMed1995

Biological indicators for low temperature steam and formaldehyde sterilization: the effect of defined media on sporulation, growth index and formaldehyde resistance of spores of Bacillus stearothermophilus strains.

Preliminary screening was carried out on spores of 29 strains of Bacillus stearothermophilus to determine their potential as biological indicator organisms for low temperature steam and formaldehyde sterilization. Each strain was sporulated on four chemically defined media. Fourteen strains produced satisfactory sporulation on one or more of the media but there was considerable variation in the extent of sporulation. The growth index of the spores, which was dependent on both the strain of organism and the sporulation medium, ranged from 1% to 90%. The spores were appraised on the basis of their resistance to inactivation by 0.5% w/v formaldehyde in aqueous solution at 70 degrees C. The survivor curves obtained could be characterized into five types on the basis of the shape of the curve. Only five strains of Bacillus stearothermophilus produced spores with the characteristics of high resistance, linear semi-logarithmic survivor curve and high growth index that would be required of a potential biological indicator organism.

Culture Media↗
PubMed1988

Epidemiology of chronic occupational exposure to formaldehyde: report of the Ad Hoc Panel on Health Aspects of Formaldehyde. Universities Associated for Research and Education in Pathology, Inc.

An independent, international panel of scientists reviewed and evaluated the relevant literature on occupational and environmental exposure to formaldehyde and subsequent epidemiology of cancer in exposed populations. Studies of topical sites (respiratory tract and skin) were considered separately from non-topical sites (other major organ systems) and individual assessments were made of evidence of site-specific cancer risk within the broader categories. In addition to the studies per se, the Panel also took into account critiques and reviews of the published reports. The Panel concluded that: 1) for no malignancy in man is there convincing evidence of a relationship with formaldehyde exposure and 2) furthermore, that if a relationship does exist, the excess risk, in absolute terms, must be small. An apparent lack of consistency among the studies in site-specific cancer risk and uncertainty resulting from unresolved confounding by known risk factors were identified by the Panel as significant obstacles to more definitive conclusions.

Epidemiologic Methods↗
PubMed1989

Disinfection with gaseous formaldehyde. First Part: Bactericidal and sporicidal effectiveness of formaldehyde with and without formation of a condensing layer.

Suspensions of Staphylococcus aureus ATCC 6538, Streptococcus faecium ATCC 6057, and of spores of Bacillus subtilis var. niger DSM 675 dried on polished stainless steel carriers were exposed in a model chamber to 3.2 mg HCHO l-1 air at temperatures of 20, 25, 30, 35 and 40 degrees C and the kinetics of their inactivation were determined by successive colony counting during the exposures. The HCHO treatment was carried out once with the formation of a condensing layer on the carriers and once without recondensation, at a RH of about 90%. In both procedures the cells or spores were suspended and dried in saline peptone water and additionally, in the case of the exposure without condensate layer, suspended in peptone water only. For S. aureus and S. faecium, significant differences between the two processes were only observed at 20 degrees C, whereby S. aureus showed for example a D-value of 14.8 minutes and after an exposure with condensate a D-value of 28.1 min. However at higher temperatures the effectiveness of HCHO in gaseous or condensate form was rather similar. At 35 degrees C the D-values after exposure to HCHO in condensate and gaseous form was for S. aureus 4.1 min and 5.9 min respectively, whereas after treatment at 40 degrees C D-values of 3.2 min and 3.8 min respectively were determined. At 35 and 40 degrees C D-values for S. aureus suspended in peptone water and exposed to gaseous HCHO were 50% lower than when suspended in saline peptone water. At lower exposure temperatures large differences were not registered. For the B. subtilis spores exposure to formaldehyde without condensation showed D-values of 34.8 and 5.6 min at 20 and 40 degrees C respectively. These are 8- and 4-fold lower than those of a corresponding exposure with a condensing layer. No D-value differences were observed for spores suspended and dried in saline peptone water or in peptone water after exposures to gaseous formaldehyde.

Aerosols↗
PubMedDate not supplied

[Interaction of formaldehyde with nucleic acids and their structural components in the presence of amines. II. Structure of adenine derivatives formed in the reaction with formaldehyde and primary amine].

Two products of modified adenine have been isolated from reaction of adenine with a mixture of formaldehyde and methylamine; their structures have been demonstrated by UV, 1H NMR and mass spectra data. The formal scheme of reaction can be described as simultaneous or sequential cycloaddition of dimethylol derivatives of methylamine to two reaction's positions of the adenine residue. This results in the formation of a new partly or completely hydrogenated six-membered 1,3,5-triazine cycle which has the atoms of adenine nitrogen in its 1,3-positions and nitrogen of methylamine in 5-position. This is used as a model for discussing the peculiarities of DNA-formaldehyde interaction in the presence of amine.

Adenine↗
PubMed1983

[Detection and determination of protein-bound formaldehyde. II. Improved recovery of formaldehyde by reduction with sodium cyanoborohydride (NaCNBH3)].

When using NaCNBH3 as a reductant, it is possible to recover 70% of added formaldehyde in foods--in this skim milk powder. Formaldehyde is attached to the epsilon-Aminogroups of lysine and is detected after reduction in form of N epsilon-methyllysine in an automated amino acid analyzer system. After addition of N alpha-acetyllysine the reduction is carried out by incubating the skim milk powder at 70 degrees C for 1 h. The best combination of pH, concentration of reductant, time and temperature of incubation is described.

Amino Acids↗
PubMed1997

Dichloromethane metabolism to formaldehyde and reaction of formaldehyde with nucleic acids in hepatocytes of rodents and humans with and without glutathione S-transferase T1 and M1 genes.

Metabolism of dichloromethane (DCM) to formaldehyde (HCHO) via a glutathione S-transferase (GST) pathway is thought to be required for its carcinogenic effects in B6C3F1 mice. In humans, this reaction is catalyzed primarily by the protein product of the gene GSTT1, a member of the Theta class of GST, and perhaps to a small extent by the protein product of the gene GSTM1. Humans are polymorphic with respect to both genes. Since HCHO may bind to both DNA and RNA forming DNA-protein crosslinks (DPX) and RNA-formaldehyde adducts (RFA), respectively, these products were determined in isolated hepatocytes from B6C3F1 mice, F344 rats, Syrian golden hamsters, and humans to compare species with respect to the production of HCHO from DCM and its reaction with nucleic acids. Only mouse hepatocytes formed detectable amounts of DPX, the quantities of which corresponded well with quantities of DPX formed in the livers of mice exposed to DCM in vivo [Casanova, M., Conolly, R.B., and Heck, H. d'A. (1996). Fundam. Appl. Toxicol. 31, 103-116]. Hepatocytes from all rodent species and from humans with functional GSTT1 and GSTM1 genes formed RFA. No RFA were detected in human cells lacking these genes. Yields of RFA in hepatocytes of mice were 4-fold higher than in those of rats, 7-fold higher than in those of humans, and 14-fold higher than in those of hamsters. The RFA:DPX ratio in mouse hepatocytes incubated with DCM was approximately 9.0 +/- 1.4, but it was 1.1 +/- 0.3 when HCHO was added directly to the medium, indicating that HCHO generated internally from DCM is not equivalent to that added externally to cells and that it may occupy separate pools. DPX were not detected in human hepatocytes even at concentrations equivalent to an in vivo exposure of 10,000 ppm; however, the possibility that very small amounts of DPX were produced from DCM cannot be excluded, since HCHO was formed in human cells. Maximal amounts of DPXliver that might be formed in humans were predicted from the amounts in mice and the relative amounts of RFA in hepatocytes of both species. With predicted DPXliver as the dosimeter, the unit risk, the upper 95% confidence limit on the cancer risk, and the margin of exposure were calculated at several concentrations using the linearized multistage and benchmark dose methods. Since the actual delivered dose is smaller than that predicted, the results suggest that DCM poses at most a very low risk of liver cancer to humans.

Animals↗
PubMed1991

Serum IgE and IgG to formaldehyde-human serum albumin: lack of relation to gaseous formaldehyde exposure and symptoms.

Fifty-five subjects were studied to determine if the presence of IgE or IgG antibodies to formaldehyde (F)-human serum albumin (HSA) was associated with exposure to gaseous F or with respiratory or conjunctival symptoms from such exposure. The study population included cohorts exposed to F in the workplace, smokers, and normal subjects. IgE antibody specific for F-HSA was detected by ELISA in three subjects; immediate-type skin testing was negative in two of these subjects, and not interpretable because of dermatographism in one subject. One of these subjects had a history of respiratory symptoms when the subject was working in a histology laboratory that contained ambient F and xylene; a respiratory challenge with F at concentrations of up to 2 ppm failed to produce respiratory symptoms or significant changes in pulmonary function. Serum from the three subjects with IgE to F-HSA by ELISA failed to passively transfer skin reactivity to F-HSA to rhesus monkey recipients. These three subjects and two other subjects had IgG to F-HSA by ELISA, although this was of generally low titer. We could not define a relationship between the presence of antibodies and (1) a history of F exposure or (2) a history of adverse respiratory or conjunctival symptoms from F. This study is a continuum of 5 years of study in our laboratory attempting to define allergy to gaseous F, and the current study does not support an immunologic basis for respiratory or conjunctival symptoms from gaseous F exposure. Based on the findings of this and our other studies, it is possible that clinical IgE-mediated allergy to gaseous F does not exist, or if it does exist, it is extremely rare.

Adult↗
PubMed2004

Formaldehyde-induced DNA adducts as biomarkers of in vitro human nasal epithelial cell exposure to formaldehyde.

Formaldehyde (FA) is a mutagen that, at high concentrations and long durations, has been reported to cause nasal cancer in rats and in some humans. The level of FA-induced modified DNA in nasal cells should serve as a biomarker of FA exposure and effect. In the present study, a high-performance liquid chromatography (HPLC)-ultraviolet (UV) method at 254 nm was developed and optimized to detect and quantify hydroxymethyldeoxynucleosides after the isolated DNA in exposed human nasal epithelial cells (HNEC) was enzymically digested. Normal and modified deoxynucleosides were successfully resolved from one another and from tissue and enzyme blank interferences. The viability of HNEC exposed to FA in solution for 24 h decreased, and there was a linear dose response between % nonviability and FA dose from 10 to 500 microg/mL. Amounts of 18.0 +/- 1.5 pmol N6-dA and 12.0 +/- 1.2 pmol N2-dG derivatives were determined in a 10 microL injection after 1.4 x 10(7) HNEC (106 microg DNA) were exposed to 500 microg/mL in solution. The respective tissue concentrations in pmol hydroxymethyldeoxynucleoside/mg DNA were 170 +/- 14 and 113 +/- 11. The lower quantifiable limits were about 97 and 88 pmol/mg DNA, respectively. Diffusive exposure of HNEC to air FA up to 100 ppm (v/v) for 24 h did not produce quantifiable hydroxymethylnucleosides. FA-modified deoxynucleosides may be useful biomarkers for FA exposure in biological monitoring samples taken by nasal lavage or brush biopsy.

Animals↗
PubMed2001

Exposure to repeated low-level formaldehyde in rats increases basal corticosterone levels and enhances the corticosterone response to subsequent formaldehyde.

Low-level exposure to volatile organic compounds may produce symptoms in humans reporting multiple chemical sensitivity (MCS) through altered hypothalamic-pituitary-adrenal (HPA) axis functioning. We determined whether repeated formaldehyde (Form) exposure would alter corticosterone (CORT) levels in a rat model of MCS. Male Sprague-Dawley rats were given acute chamber exposures to Air or Form (0.7 or 2.4 ppm), and trunk blood was collected 20 or 60 min later. All groups showed increased CORT levels above naïve basal levels at 20 min and a return to baseline by 60 min, with no differences between treatment groups. The second experiment examined the effect of repeated Form exposure (1 h/day x 5 days/week x 2 or 4 weeks) on basal CORT levels and after a final challenge. Basal CORT was increased above naïve values after 2 week exposure to Air or 0.7 ppm Form. By 4 week, CORT levels in the Air group returned to naïve values, but remained elevated in the 0.7 ppm Form group. There were no differences in basal CORT levels among either 2.4 ppm exposed groups. After a final Air or Form challenge, the 2 and 4 week Air and 0.7 ppm Form groups had elevated CORT levels similar to their acute response, while the 2 and 4 week 2.4 ppm Form groups had elevated CORT levels compared to their acute response, indicating enhanced reactivity of the HPA axis to subsequent Form. These findings suggest that altered HPA axis functioning occurs after repeated low-level Form exposure, and may have implications for mechanisms mediating MCS in humans.

Animals↗
PubMed1978

Observations on the effects of formaldehyde on cockroaches and their flora: I. Survival of vaccinia virus-infected cockroaches during fumigation with formaldehyde.

In these studies it is shown that the common "British" and "American" adult cockroaches can survive exposure to formaldehyde fumigation carried out at double the strength and for four times as long as is recommended for disinfection of rooms. It is further reported that vaccinia virus ingested prior to the fumigation survives in the cockroach gut and may be excreted up to 5 days later. Since cockroaches are ubiquitous and are to be found in most hospitals, laboratories and animal houses, these findings should be considered whenever fumigation is called for.

Animals↗
PubMed1978

Observations on the effects of formaldehyde on cockroaches and their flora: II. Prolonged survival of cockroaches drinking formaldehyde or glutaraldehyde solutions.

Adult cockroaches were found to survive up to 22 weeks when provided with 1% Formalin (0.4% formaldehyde) in lieu of drinking water. Given 4% Formalin or 2% glutaraldehyde they survived up to 41 days. During the experiments eggs were laid and hatched and the offspring continued to grow. Combined with surface disinfection, this may hold out a simple method of rendering adult cockroaches gnotobiotic or even axenic.

Animals↗
PubMedDate not supplied

Evidence for formaldehyde antibodies and altered cellular immunity in subjects exposed to formaldehyde in mobile homes.

Eight symptomatic individuals chronically exposed to indoor formaldehyde (HCHO) at low concentrations (0.07-0.55 ppm) were compared to 8 nonexposed subjects with respect to: (1) presence of IgG and IgE antibodies to HCHO conjugated to human serum albumin (F-HSA); (2) the percentage of venous blood T and B cells by E and EAC-rosetting; and (3) the ability of T and B cells to undergo mitogen (PHA, PWM) stimulated blastogenesis as measured by the incorporation of tritiated thymidine. Anti-F-HSA IgG, but no IgE, antibodies were detected in the sera of the 8 exposed subjects; none were found in 7 of the unexposed controls. T lymphocytes were decreased in the exposed (48 +/- 11.5%) compared to the control (65.9 +/- 4.97%) subjects (p greater than .001 less than .01). B cells were 12.6 +/- 1.6% (HCHO group) and 14.75 +/- 2.1% (controls) (p greater than .02 less than .05). The incorporation of labeled thymidine by T cells (PHA) was decreased: 17,882 +/- 2,293 cpm (HCHO group) and 28,576 +/- 3,807 cpm (p greater than .001 less than .01). T and B cell blastogenesis (PWM) was 9,698 +/- 1,441 cpm (HCHO group) and 11,279 +/- 1,711 (controls) (p greater than .05 less than .1). Exposure to HCHO appears to stimulate IgG antibodies to F-HSA and decrease the proportion of peripheral T cells.

Adult↗
PubMed1986

Human antibodies against formaldehyde-human serum albumin conjugates or human serum albumin in individuals exposed to formaldehyde.

Sera from patients undergoing hemodialysis with formaldehyde (F)-sterilized dialyzers were studied to determine if antibodies against F conjugated to human serum albumin (HSA) could be detected. F-human serum albumin (F-HSA) conjugates were prepared using ratios of F to HSA that did not precipitate the HSA. The F-HSA conjugates migrate differently electrophoretically than HSA with an increased negative charge of F-HSA as compared with HSA. The F-HSA was used in an ELISA. The results demonstrated that in certain sera, IgG, IgM, IgA and IgE antibodies against F-HSA could be measured. In the highest titered sera, it was shown that the IgG antibody was not directed against F alone or F-lysine but against an antigenic grouping of F-HSA. No correlation of either IgG or IgE antibodies with immune complex or allergic reactions was found in this series of dialysis patients. Some sera from dialysis patients had antibody activity against HSA. Sera from 2 physicians with rhinitis after F exposure had no antibody activity against F-HSA or HSA. Two nurses with a history of F-induced asthma had no IgG antibodies but did have IgE antibodies against F-HSA and HSA. This spectrum of immunologic responses is analogous to responses in dogs immunized with F or F dog albumin. We have not been able to identify anti HSA antibodies in patients reactive to other hapten-HSA compounds and it is suggested that anti HSA antibodies in F-exposed humans may relate to the F exposure.

Antibody Specificity↗
PubMed1989

[Comparison of residues of glutaraldehyde and formaldehyde in urologic instruments after sterilization in aseptic conditions or in a formaldehyde gas sterilizer].

The aldehyde residues of thermolabile urological instruments, after the formaldehyde sterilization or sterilization in aseptic preparation from a 2% glutaraldehyde solution will be examined and compared. The results are discussed together with experimental toxicologic work from the literature. It is concluded that after sterilization in the 2% glutaraldehyde solution, the glutaraldehyde residues on the experimental materials are safe.

Aldehydes↗