Occupational exposure to formaldehyde and risk of lung cancer: A systematic review and meta-analysis.

BACKGROUND: Formaldehyde exposure is associated with nasopharyngeal cancer and leukemia. Previously-described links between formaldehyde exposure and lung cancer have been weak and inconsistent. We performed a systematic review and meta-analysis to evaluate quantitatively the association between formaldehyde exposure and lung cancer. METHODS: We searched for articles on occupational formaldehyde exposure and lung cancer in PubMed, EMBASE, Web of Science, and CINAHL databases. In total, 32 articles were selected and 31 studies were included in a meta-analysis. Subgroup analyses and quality assessments were also performed. RESULTS: The risk of lung cancer among workers exposed to formaldehyde was not significantly increased, with an overall pooled risk estimate of 1.04 (95% confidence interval [CI], 0.97-1.12). The pooled risk estimate of lung cancer was increased when higher exposure studies were considered (1.19; 95% CI, 0.96-1.46). More statistically robust results were obtained when high quality (1.13; 95% CI, 1.08-1.19) and recent (1.13; 95% CI, 1.07-1.19) studies were used in deriving pooled risk estimates. CONCLUSIONS: No significant increase in the risk of lung cancer was evident in the overall pooled risk estimate; even in higher formaldehyde exposure groups. Our findings do not provide strong evidence in favor of formaldehyde as a risk factor for lung cancer. However, since risk estimates were significantly increased for high-quality and recent studies, the possibility that exposure to formaldehyde can increase the risk of lung cancer might still be considered.

Occupational exposure to formaldehyde and risk of non hodgkin lymphoma: a meta-analysis.

BACKGROUND: Formaldehyde, a widely used chemical, is considered a human carcinogen. We report the results of a meta-analyses of studies on the relationship between occupational exposure to formaldehyde and risk of non-Hodgkin lymphoma (NHL). METHODS: We performed a systematic review and meta-analysis according to international guidelines and we identified 12 reports of occupational populations exposed to formaldehyde. We evaluated inter-study heterogeneity and we applied a random effects model. We conducted a cumulative meta-analysis and a meta-analysis according to estimated average exposure of each study population. RESULTS: The meta-analysis resulted in a summary relative risk (RR) for NHL of 0.93 (95% confidence interval 0.83-1.04). The cumulative meta-analysis suggests that higher RRs were detected in studies published before 1986, while studies available after 1986 did not show an association. No differences were found between different levels of occupational exposure. Conclusions Notwithstanding some limitations, the results of this meta-analysis do not support the hypothesis of an association between occupational exposure to formaldehyde and risk of NHL.

Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment.

Formaldehyde is a widely used high production chemical that is also released as a byproduct of combustion, off-gassing of various building products, and as a fixative for pathologists and embalmers. What is not often realized is that formaldehyde is also produced as a normal physiologic chemical in all living cells. In 1980, chronic inhalation of high concentrations of formaldehyde was shown to be carcinogenic, inducing a high incidence of nasal squamous cell carcinomas in rats. Some epidemiologic studies have also found increased numbers of nasopharyngeal carcinoma and leukemia in humans exposed to formaldehyde that resulted in formaldehyde being considered a Known Human Carcinogen. This article reviews the data for rodent and human carcinogenicity, early Mode of Action studies, more recent molecular studies of both endogenous and exogenous DNA adducts, and epigenetic studies. It goes on to demonstrate the power of these research studies to provide critical data to improve our ability to develop science-based cancer risk assessments, instead of default approaches. The complexity of constant physiologic exposure to a known carcinogen requires that new ways of thinking be incorporated into determinations of cancer risk assessment for formaldehyde, other endogenous carcinogens, and the role of background endogenous DNA damage and mutagenesis.

Homicidal acute formalin poisoning in an infant from a rural sericulture family presenting with multisystem failure.

Acute poisoning of formalin is rare because of its strong irritating effect and alarming odor. Although few cases of acute poisoning in adults have been reported in literature, to our knowledge, this is the first case report of formalin poisoning in an infant presenting with multisystem failure. Despite proper supportive treatment in the absence of antidote, the infant died within 13 hours after deliberate poisoning.

Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions.

Forty-one volunteers (male non-smokers) were exposed to formaldehyde (FA) vapours for 4 h/day over a period of five working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 p.p.m. At concentrations of 0.3 and 0.4 p.p.m., four peaks of 0.6 or 0.8 p.p.m. for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (∼80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange test and the cytokinesis-block micronucleus test were performed with blood samples. The micronucleus test was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the glutathione (GSH)-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time reverse transcription-polymerase chain reaction with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA did also not cause alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.

Exposure to formaldehyde and its potential human health hazards.

A widely used chemical, formaldehyde is normally present in both indoor and outdoor air. The rapid growth of formaldehyde-related industries in the past two decades reflects the result of its increased use in building materials and other commercial sectors. Consequently, formaldehyde is encountered almost every day from large segments of society due to its various sources. Many governments and agencies around the world have thus issued a series of standards to regulate its exposure in homes, office buildings, workshops, public places, and food. In light of the deleterious properties of formaldehyde, this article provides an overview of its market, regulation standards, and human health effects.

[Isocyanates and formaldehyde--low molecular weight xenobiotics]. / Izocyjaniany i formaldehyd--maloczasteczkowe ksenobiotyki.

Isocyanates and formaldehyde are a low molecular weight environmental xenobiotics. Acute poisonings are relatively rare, chronic exposure not enough recognized. A source, mechanism of toxicity and ability of those low molecular weight compounds to stimulation of different types of immune response are presented in the study.

Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde.

DNA and chromosome damages in peripheral blood lymphocytes were evaluated in 151 workers occupationally exposed to formaldehyde (FA) and 112 non-FA exposed controls. The effects of polymorphisms in three glutathione-S-transferase (GSTs) genes on the DNA and chromosome damages were assessed as well. Alkaline comet assay and cytokinesis-block micronucleus (CBMN) assay were used to determine DNA and chromosome damages, respectively. The genotypes of GSTP1 (Ile105Val), GSTT1, and GSTM1 were assayed. The mean 8-h time-weighted average (TWA) concentrations of FA in two plywood factories were 0.83ppm (range: 0.08-6.30ppm). FA-exposed workers had higher olive tail moment (TM) and CBMN frequency compared with controls (Olive TM, 3.54, 95%CI=3.19-3.93 vs. 0.93, 95%CI=0.78-1.10, P<0.01; CBMN frequency, 5.51+/-3.37 vs. 2.67+/-1.32, P<0.01). Olive TM and the CBMN frequency also had a dose-dependent relation with the personal FA exposure. Significant association between FA exposure history and olive TM and CBMN frequency were also identified. The level of olive TM was slightly higher in FA-exposed workers with GSTM1 null genotype than those with non-null genotype (3.86, 95%CI=3.31-4.50 vs. 3.27, 95%CI=2.83-3.78, P=0.07) with adjustment of covariates. We also found that FA-exposed workers carrying GSTP1 Val allele had a slightly higher CBMN frequency compared with workers carrying only the wild-type allele (6.32+/-3.78 vs. 5.01+/-2.98, P=0.05). Our results suggest that the FA exposure in this occupational population increased DNA and chromosome damages and polymorphisms in GSTs genes may modulate the genotoxic effects of FA exposure.

Formalin: nephrotoxic teratogen?

Formaldehyde is an extensively used chemical; its ill effects have been of concern. Its nephrotoxic effects in laboratory animals and carcinogenic effects on humans are well established. We report of a pregnant woman with a normal ongoing pregnancy with a morphologically normal fetus. She was exposed to high doses of formaldehyde through inhalational route in the second trimester. Six weeks later she was found to have severe oligohydramnios with dysplastic fetal kidneys and fetal ascites. The various known causes for this problem reported in the literature are discussed. Based on the discussion the author has drawn a conclusion that the fate of the fetus reported can be attributed to transplacental nephrotoxic effect of formaldehyde. Previously two cases of malformations have been reported but this appears to be the first case of transplacental nephrotoxicty of formaldehyde.

[Advancement of methanol poisoning mechanism research].

The methanol poisoning by oral intake or skin contact occurs occasionally, which may have serious consequences including blindness and/or death. Methanol and its metabolites, formaldehyde and formic acid, are associated with metabolic acidosis, visual dysfunction and neurological symptoms. At present, the mechanism of methanol poisoning primarily focuses on the cell hypoxia, the alteration of structure and biological activity induced by free radical and lactic acid. Meanwhile, methanol poisoning causes changes in the balance between the production of free radicals and antioxidant capacity and in the proteases-protease inhibitors system, which lead to a series of disturbances.

The impact of co-morbidities on a 6-year survival after methanol mass poisoning outbreak: possible role of metabolic formaldehyde.

Context: The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden of co-morbidities, complications, and methanol-induced brain lesions on hospital, follow-up, and total mortality.Methods: All patients hospitalized with methanol poisoning during a mass poisoning outbreak were followed in a prospective cohort study until death or final follow-up after 6 years. The age-adjusted Charlson co-morbidity index (ACCI) score was calculated for each patient. A multivariate Cox regression model was used to calculate the adjusted hazards ratio (HR) for death. The survival was modeled using the Kaplan-Meier method.Results: Of 108 patients (mean age with SD 50.9 ± 2.6 years), 24 (54.4 ± 5.9 years) died during hospitalization (mean survival with SD 8 ± 4 days) and 84 (49.9 ± 3.0 years; p = .159) were discharged, including 27 with methanol-induced brain lesions. Of the discharged patients, 15 (56.3 ± 6.8 years) died during the follow-up (mean survival 37 ± 11 months) and 69 (48.5 ± 3.3 years; p = .044) survived. The hospital mortality was 22%, the follow-up mortality was 18%; the total mortality was 36%. Cardiac/respiratory arrest, acute respiratory failure, multiorgan failure syndrome, and arterial hypotension increased the HR for hospital and total (but not follow-up) mortality after adjustment for age, sex, and arterial pH (all p < .05). All patients who died in the hospital had at least one complication. A higher ACCI score was associated with greater total mortality (HR 1.22; 1.00-1.48 95% CI; p = .046). Of those who died, 35 (90%) had a moderate-to-high ACCI. The Kaplan-Meier curve demonstrated that patients with a high ACCI had greater follow-up mortality compared to ones with low (p = .027) or moderate (p = .020) scores. For the patients who died during follow-up, cancers of different localizations were responsible for 7/15 (47%) of the deaths.Conclusions: The character and number of complications affected hospital but not follow-up mortality, while the burden of co-morbidities affected follow-up mortality. Methanol-induced brain lesions did not affect follow-up mortality. Relatively high cancer mortality rate may be associated with acute exposure to metabolic formaldehyde produced by methanol oxidation.

[Work-related disease]. / Ziek door blootstelling aan toxische stoffen op het werk.

Work-related health complaints occur frequently. Occupational health departments and primary and secondary care physicians are confronted with these patients. Awareness of work-related disease is crucial. Three case histories with work-related diseases are described. The first concerned a 39-year-old woman who showed acute neurotoxicity due to inhalation of formaldehyde and methanol after opening a coffin with an embalmed corpse. Within weeks the symptoms diminished and complete recovery occurred within nine months. The second was a 61-year-old carpenter who experienced acute and chronic pulmonary and neurotoxic effects after exposure to organic solvents during ground and carpenter's work on a terrain of a former gas plant. He developed severe chronic toxic encephalopathy. The last patient was a 61-year-old man who developed acute and chronic manganese toxicity leading to inability to work while employed at a brick factory where manganese was used to colour the bricks. The acute effects subsided, but chronic neuropsychological symptoms remained.

[The effects of a novel local ventilation system to reduce the health hazard to students during gross anatomy courses].

Formaldehyde or formalin is indispensable not only as a preservative but also as a disinfectant of cadavers for gross anatomy. It has recently attracted a great deal of attention as a health hazard for students and lecturers. To reduce the concentration of formaldehyde gas (FAG), we improved a novel local ventilation system of the push-pull type. This is the first report dealing with the effects of this ventilation system on the health of students before (over 1 ppm) and after (0.1 ppm) the installation. The percentages of students with lacrymal symptoms or airway irritation were reduced to a third of what they were before the installation. In particular, the number of those with continuously strong symptoms was reduced to a sixth of the pre-installation levels. This local ventilation system draws in fresh air from outside, and directs it to the breathing zone of the students, effectively reducing their symptoms.

[Accidental intravenous injection of formaldehyde]. / Omylkowe dozylne podanie roztworu formaliny.

BACKGROUND: Formaldehyde can be found in operating theatres where it is used for preservation of biopsied tissues. Several misuse accidents have been described previously.We present a case where formaldehyde was mistakenly injected intravenously. CASE REPORT: A 33-year-old man, scheduled for excision of a knee meniscus under spinal anaesthesia, was to receive an intravenous antibiotic at the end of surgery. The attending anaesthesiologist received a vial of cephazolin, marked with the patient name from a scrub nurse and injected its contents intravenously. Immediately after injection, the patient complained about strong pain at the site of injection and started to cough.The vial was checked again and a piece of meniscus preserved with 4% formaldehyde was found inside. It was intended to be offered to the patient on departure. The possible amount offormaldehyde injected was 400 mg (a lethal dose has been described as 12 g). The patient, despite the lack of cardiorespiratory failure, was intubated, ventilated and dialysed for six hours, and then extubated without further consequences. His biochemical markers remained in the normal range. Based on the case as described, the possible medico-legal consequences of poor organisation and preventive measures are discussed.

A case of attempted suicide from the ingestion of formalin.

The ingestion of formalin causes disorders in the oral cavity, the gastrointestinal tract, liver, kidney, lung, heart, and central nervous system in the early phase of reaction. The stomach suffers the most severe damage in such cases because the formalin is in contact with the gastric mucosa longer than in the other parts of the gastrointestinal tract. Gastric ulcers and mild hemorrhaging are frequently seen. There are no reported cases of gastric perforations in Japan (n= 15), and there are only two reported cases in other countries since 1950 (n = 11). The ingestion of formalin could lead to peritonitis without perforation because of gastric wall inflammation. Cicatrical stricture of the stomach tends to be a major problem in the late phase of formalin ingestion. Similar to our case, seven of twelve reported cases of cicatrical deformity survived without operation. Therefore, a gastrectomy for the cicatrical deformity might not be always indicated if the patients are able to feed themselves sufficiently or if parenteral nutrition can be provided.

The Effects of Formaldehyde on Cytochrome P450 Isoform Activity in Rats.

Formaldehyde (FA) is an occupational and indoor pollutant. Long-term exposure to FA can irritate the respiratory mucosa, with potential carcinogenic effects on the airways. The effects of acute FA poisoning on the activities of CYP450 isoforms CYP1A2, CYP2C11, CYP2E1, and CYP3A2 were assessed by determining changes in the pharmacokinetic parameters of the probe drugs phenacetin, tolbutamide, chlorzoxazone, and testosterone, respectively. Rats were randomly divided into three groups: control, low FA dose (exposure to 110 ppm for 2 h for 3 days), and high FA dose (exposure to 220 ppm for 2 h for 3 days). A mixture of the four probe drugs was injected into rats and blood samples were taken at a series of time points. Plasma concentrations of the probe drugs were measured by HPLC. The pharmacokinetic parameters t1/2, AUC(0-t), and Cmax of tolbutamide, chlorzoxazone, and testosterone increased significantly in the high dose versus control group (P < 0.05), whereas the CL of chlorzoxazone and testosterone decreased significantly (P < 0.05). However, t1/2, AUC(0-t), and Cmax of phenacetin decreased significantly (P < 0.05), whereas the CL of phenacetin increased significantly (P < 0.05) compared to controls. Thus, acute FA poisoning suppressed the activities of CYP2C11, CYP2E1, and CYP3A2 and induced the activity of CYP1A2 in rats. And the change of CYP450 activity caused by acute FA poisoning may be associated with FA potential carcinogenic effects on the airways.

N-Methylenvaline in a group of subjects occupationally exposed to formaldehyde.

Aim of this pilot study was to correlate the human exposure to formaldehyde (F) with N-methylenvaline, a molecular adduct formed by addiction of F to the N-terminal valine in hemoglobin. A group of 21 subjects employed in a plywood factory and a laminate factory, and occupationally exposed to F, together with a group of 30 controls, were recruited as volunteers to test this biomarker. Each subject received a questionnaire and a passive personal F sampler. Exposure to F vapors and occurrence of N-methylenvaline in blood were measured. Integrated F concentrations always proved lower than threshold limit value as a ceiling (TLV-TWA) (0.37 mg/m(3), 0.3 ppm). N-Methylenvaline distribution in blood, as measured by GC/MS upon derivatization, showed direct positive relationship to F exposure, with r=0.465. Prevalence of the molecular adduct expressed in nmol/g of globin was significantly higher in the exposed group (p<0.04) than in the control group. However, the N-methylenvaline marker was unable to provide significant distinction between the subjects exposed to F through tobacco smoke habit and the non smokers. Despite this interference, in this pilot study the usefulness of N-methylenvaline as a biomarker for testing occupational exposure to F was demonstrated.