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Formaldehyde exposure at various workplaces.

The results of formaldehyde determinations in the air at various workplaces in the period 1980-1988 are presented. The airborne concentrations varied between less than 0.01 and 10.9 mg m-3 (mean 0.7 mg m-3). For ambient air monitoring, active sampling and capillary gas chromatography are reliable and sensitive methods. Formic acid excretion in urine is an unspecific and insensitive biological indicator for monitoring low-dose formaldehyde exposure.

Air Pollutants, Occupational↗

A study of the effects of glutaraldehyde and formaldehyde on the mechanical behaviour of bovine pericardium.

The inherent variability in the mechanical behavior of bovine pericardium causes difficulties in establishing the effects of treatment procedures used in the manufacture of bioprosthetic cardiac valves. A new experimental technique has been developed in which the specimen acts as its own control, obviating the need to perform large numbers of experiments to obtain statistically significant results. The procedure used is described in detail as is the equipment employed. The technique was used to assess the effect of glutaraldehyde and formaldehyde on the stress/strain response of bovine pericardium. The results show that the fixing process in glutaraldehyde is virtually complete within two hours and causes significant changes in the mechanical behaviour of the tissue. The tissue becomes progressively stiffer as the treatment period is extended, which is especially pronounced at low levels of stress. Formaldehyde storage subsequent to fixing in glutaraldehyde was found to have no effect on the stress/strain response of the bovine pericardium.

Aldehydes↗

Formaldehyde-induced mutagenesis: a novel mechanism for its action.

A novel and unique mechanism for formaldehyde-induced mutagenesis is described which is mediated by the formation of an N6-substituted adenine ribonucleoside analogue, N6-hydroxymethyl adenosine, after an in vitro reaction of formaldehyde with adenosine. This type of ribonucleoside analogue (the deoxyribose derivative is ineffective) exhibits a powerful and remarkable germ-cell-stage-specific mutagenic effect in male Drosophila larvae, apparently by interfering with DNA repair. Circumstantial evidence is presented which indicates that the analogue most probably acts by its utilisation in the synthesis of diadenosine tetraphosphate (Ap4A) to form an antimetabolite(s) of Ap4A which subsequently interferes with Ap4A-mediated intracellular events, amongst which an effect on DNA repair would appear to be its mutagenic mechanism of action.

Adenine Nucleotides↗

Relationship between DNA damage and survival in formaldehyde-treated mouse cells.

Mouse cells exposed to formaldehyde (FA) were examined for colony-forming ability and DNA synthesis as well as the induction of DNA damage. Cell survival was unaffected until the FA concentration exceeded 150 microM after which there was an exponential decay in survival. Formaldehyde-treated cells studied by the DNA-alkaline-elution technique exhibited a low frequency of single-strand breaks but extensive DNA-protein crosslinking. These crosslinks were repaired following removal of the drug. The DNA damage was accompanied by inhibition of DNA synthesis.

Animals↗

Micronucleated cells in nasal mucosa of formaldehyde-exposed workers.

The frequency of micronuclei (MN) and cytology of respiratory nasal mucosa cells were evaluated in 15 non-smokers exposed to formaldehyde in a plywood factory. Each subject was paired with a control matched for age and sex. Mean levels of exposure to formaldehyde ranged from about 0.1 mg/m3 in the sawmill and shearing-press departments to 0.39 mg/m3 in the warehouse area. There was a contemporary exposure to low levels of wood dust (inspirable mass ranged from 0.23 mg/m3 in the warehouse to 0.73 mg/m3 during sawing operations). Nasal respiratory cell samples were collected by an otorhinolaryngologist near the inner turbinate using a brush for endocervical cytology. After staining (Feulgen plus Fast Green and Papanicolaou's method for MN analysis and cytology, respectively), about 6000 cells were screened for micronuclei and scored in parallel for cytology according to a histopathological scale. A higher frequency of micronucleated cells was observed in the exposed group than in the controls (0.90 +/- 0.47 vs. 0.25 +/- 0.22, Mann-Whitney U test: p less than 0.01). Cytological examination indicated chronic phlogosis in the nasal respiratory mucosa of plywood factory workers, with a high frequency of squamous metaplasia cells (mean score 2.3 +/- 0.5 vs. 1.6 +/- 0.5 in the control group, Mann-Whitney U test: p less than 0.01).

Adult↗

Monoclonal antibodies detecting components of the bovine immune system in formaldehyde-fixed paraffin-embedded tissue specimens.

Although the use of monoclonal antibodies in the diagnosis of fixed human material is a daily routine, the lack of suitable reagents recognizing epitopes resistant to formaldehyde fixation is an obvious limit to extending this approach to veterinary research and practice. To find reagents that retain their binding capacity to the recognized epitopes in formaldehyde-fixed samples, bovine lymphoid tissue sections were immunostained using various antigen retrieval procedures with monoclonal antibodies raised against ruminant leukocyte cell surface molecules. As a results, a set of antibodies could be established that allowed the identification of different immune cell types including all or a distinct subpopulation of B and T lymphocytes, monocytes, macrophages, granulocytes, red blood cells, and vascular endothelial cells.

Animals↗

Genetic effects in the mouse of formaldehyde in combination with adenosine and hydrogen peroxide.

Male mice of the Q strain were injected (i.p.) with a synthetic methylene dinucleotide (Ado-CH2-Ado) and with a mixture of formaldehyde and hydrogen peroxide. Neither injection induced any chromosome lesions in spermatogonia. In the dominant lethal mutation test, the mixture of formaldehyde and hydrogen peroxide had an effect throughout spermatogenesis, but only the rate of pre-implantation losses was increased. Injection of Ado-CH2-Ado increased both pre-and post-implantation deaths at the 1st week but only the frequency of pre-implantation losses at the 6th week.

Adenosine↗

Toxic and mutagenic effects of formaldehyde in Salmonella typhimurium.

Toxic and mutagenic activities of formaldehyde were studied in Salmonella typhimurium strain TM677, using forward mutation to 8-azaguanine (8-AG) resistance both in the absence and in the presence of Aroclor-induced rat-liver postmitochondrial supernatant (PMS). The results showed that formaldehyde was toxic and mutagenic to the bacteria in both systems, but toxicity and mutagenicity were reduced in the presence of PMS. The minimum concentration required to induce toxicity and mutagenicity was 0.17 mM in the absence of PMS and 0.33 mM in the presence of PMS.

Animals↗

Chromosome aberrations and sister-chromatid exchange frequencies in pathology staff occupationally exposed to formaldehyde.

Past studies have shown that formaldehyde is mutagenic in microbial tests and Drosophila and causes chromosomal aberrations in cultured mammalian cells. Chromosomal analysis of bone marrow cells and spermatocytes from exposed laboratory animals has failed to show any genotoxic effect. Information on individuals occupationally exposed is limited and there is no evidence to date that formaldehyde can induce chromosome damage at occupational levels of exposure. This study examines the chromosome aberration and sister-chromatid exchange frequencies in lymphocytes from a group of 6 pathology workers and 5 unexposed controls. No detectable differences could be found between the groups in either chromosomal aberration induction or sister-chromatid exchange frequencies.

Cells, Cultured↗

Sister-chromatid exchanges in lymphocytes of anatomy students exposed to formaldehyde-embalming solution.

Sister-chromatid exchanges measured in the peripheral lymphocytes of 8 non-smoking persons after exposure to formaldehyde-embalming solution during a 10-week anatomy class showed a small (P = 0.02) average increase when compared with samples obtained from the same individuals immediately before exposure began. Breathing-zone air samples collected during dissection procedures showed a mean concentration of 1.2 ppm (1.5 mg/m3) formaldehyde.

Adult↗

Toxin inactivation and antigen stabilization: two different uses of formaldehyde.

Since the 1920s, when Ramon discovered the detoxifying properties of formaldehyde, this compound has been used to inactivate toxins, whole bacterial cells and viruses. With the development of vaccines that are detoxified by genetic manipulation, formaldehyde has a new role as a stabilizer of such genetically detoxified antigens.

Animals↗

Rinsing time and disinfectant release of reused dialyzers: comparison of formaldehyde, hypochlorite, warexin, and renalin.

The influence of disinfecting agent (DA) type on the rinsing time of reused dialyzers and DA rebound release after rinsing is unknown. We compared 10 groups of five dialyzers each: cellulose acetate capillaries and AN69 plates disinfected with formaldehyde (F), polysulfone and cuprophane capillaries disinfected with 3.5% Renalin (R; Renal Systems, Minneapolis, MN), polysulfone capillaries and AN69 plates disinfected with 0.5% R, and AN69 capillaries and plates disinfected with Hypochlorite (H; Solvay, Brussels, Belgium) or Warexin (W; Guardian Chemical, Division of United Guardian Inc, Hauppage, NY), respectively. Formaldehyde, R, H, and W were detected by standard tests. The rinsing time required to reach undetectable levels of DA is shortest for H and W, intermediate for R 0.5% and 3.5%, and longest for F (F v R, H, and W; R v H and W; and H v W: P < 0.001). The rebound release 30 minutes after completion of rinsing is the highest for F (average 6 ppm), intermediate for R 0.5% and 3.5% (mean 1.4 ppm, P < 0.002 compared with F and mean 2.95 ppm, P < 0.05 compared with F, respectively), and low (< or = 1 ppm) for W and H (P < 0.001 compared with F and P < 0.01 compared with R 3.5% and 0.5%). We conclude that the dialyzer rinsing time needed to obtain undetectable levels of DA depends on the DA type. In addition, we demonstrate that like F, R is released from reused dialyzers after "adequate rinsing." The potential clinical consequences of this phenomenon require further investigation.

Acetic Acid↗

An analysis of potential carcinogenic risk from formaldehyde.

Formaldehyde was recently shown to be carcinogenic in the nasal cavities of rats and mice following chronic inhalation at vapor concentrations which were cytotoxic. The epidemiological, physiological, and toxicological data on formaldehyde are evaluated as they pertain to the analysis of carcinogenic risk. It is concluded that humans are likely to be less susceptible than test rodents to potential carcinogenic effects and that the risk at low-level exposure would not be linearly related to that observed at the higher levels which were found to be carcinogenic in animals. Risk assessment procedures and risk management decisions should incorporate all of the relevant biological information, such as that discussed, rather than rely solely on a mathematical approach which is likely to yield inaccurate and misleading conclusions.

Aerosols↗

The effects of maternally inhaled formaldehyde on embryonal and foetal development in rats.

Sprague-Dawley rats were exposed to 0, 5, 10, 20 or 40 ppm formaldehyde for 6 hr/day from day 6 to 20 of gestation. On day 21 of gestation the rats were killed for evaluation of maternal reproductive and foetal parameters. No effect on embryonic or foetal lethality, nor significant alterations in the external, visceral or skeletal appearance of the foetuses were noted in any of the exposed groups. Significant concentration-related reduction of foetal body weight occurred at 20 and 40 ppm, and at 40 ppm foetal body weights were 20% less than those of the controls. Maternal toxicity, indicated by significant reduction in body weight and absolute weight gain, was observed at 40 ppm. The results of this study show that formaldehyde is slightly foetotoxic at 20 ppm. Neither embryolethal nor teratogenic effects were observed following inhalation exposure at levels up to 40 ppm.

Animals↗

Toxicity of formaldehyde vapor in B6C3F1 mice exposed for 13 weeks.

Groups of 10 male and 10 female B6C3F1 mice were exposed to 0, 2, 4, 10, 20, or 40 ppm of formaldehyde vapor 6 h/day, 5 days/week for 13 weeks. Clinical abnormalities (dyspnea, listlessness, and hunched posture), significant mortality, and body weight loss were observed in the 40 ppm groups. Pathologic changes were observed in the nose, larynx, trachea, and bronchi of treated males and females and in the uterus and ovaries of treated females. Squamous metaplasia and inflammation were present in the nasal tissues of male and female mice in the 10, 20, and 40 ppm groups and in the larynx of males and females in the 20 and 40 ppm groups. The trachea had squamous metaplasia and hyperplasia of the epithelium in addition to submucosal fibrosis and inflammation in the 20 and 40 ppm groups. In some mice, epithelial-lined, irregular connective tissue bands spanned the tracheal lumen. Metaplasia of the bronchial epithelium was confined to the 40 ppm exposure groups. These effects on the respiratory system were more prevalent in male than in female mice. Hypoplasia of the uterus and ovaries, probably secondary to body weight loss, was confined to the 40 ppm exposure group. In conclusion, 13-week inhalation exposures of B6C3F1 mice to 10, 20, and 40 ppm of formaldehyde vapor induced histologic lesions in the upper respiratory system and concentrations of 40 ppm were lethal to those mice.

Animals↗

Chronic toxicity study on formaldehyde administered orally to rats.

Groups of 20 male and 20 female Wistar rats were given formaldehyde solution in their drinking water at concentrations of 0.50, 0.10, 0.02 and 0% for 24 months. Significant decreases in body weight and food and water intake were observed in the 0.50% group of both sexes and all rats in this group died by 24 months. Various non-neoplastic lesions were observed in rats, mostly in the 0.50% group. In this group, erosions and/or ulcers were evident in both the forestomach and glandular stomach. In the forestomach, squamous cell hyperplasia with or without hyperkeratosis and downward growth of basal cells were observed. Glandular hyperplasia of the fundic mucosa was noted along the limiting ridge. A few of such changes of the upper GI tract were seen in the 0.10% group. No toxicological abnormalities were found in 0.02% group of both sexes. There were no significant differences in the incidences of any tumors among groups of both sexes. Based on these findings, the no observable effect level of formaldehyde was 0.02% in the drinking water (10 mg/kg body wt./day).

Administration, Oral↗

Endrin-induced urinary excretion of formaldehyde, acetaldehyde, malondialdehyde and acetone in rats.

Previous studies have shown that endrin induces an oxidative stress in rats as demonstrated by an increase in hepatic lipid peroxidation, a decrease in glutathione content and a decrease in the activity in selenium-dependent glutathione peroxidase. We have therefore examined the effects of orally administering 1.5, 3.0, 4.5 and 6.0 mg endrin/kg on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. The simultaneous determination of these four lipid metabolites may be a useful biomarker for assessing exposure to xenobiotics which induce an oxidative stress and enhanced lipid peroxidation. Urine samples were collected up to 72 h post-treatment. The identities of the lipid metabolites were confirmed by gas chromatography-mass spectroscopy, while the 2,4-dinitrophenylhydrazine derivatives of these metabolic products were quantitated by high pressure liquid chromatography. Maximum increases in the excretion of the four lipid metabolites occurred at approx. 24 h post-treatment at all doses with no significant increases in excretion occurring thereafter. The maximum increases in excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approx. 160%, 93%, 121% and 162%, respectively, relative to control values. Seventy-two hours after endrin administration, the liver weight/body weight and spleen weight/body weight ratios significantly increased while the thymus weight/body weight ratio markedly decreased. The results demonstrate that endrin induces dose- and time-dependent alterations in lipid metabolism with the enhanced excretion of specific metabolic products in the urine.

Acetaldehyde↗

Does formaldehyde cause nasopharyngeal cancer in man?

Formaldehyde is a widely used industrial chemical, which also has uses in consumer products, and hence large numbers of people are exposed to it. It is also an endogenous metabolite with measurable levels in body fluids and tissues. The reports of its carcinogenicity to rats have raised concern about its potential to cause a carcinogenic response in exposed populations. This letter reviews the information on the carcinogenicity of formaldehyde, particularly to the upper respiratory tract, in animals and man.

Adenoma↗