Nasal mucosa inworkers exposed toformaldehyde: a pilot study

Annals of Oncology, 2007

Background: Occupational exposure to formaldehyde has been associated with excess risk of nasopharyngeal and selected other cancers. Patients and methods: We reviewed and pooled the results of cohort studies published through February 2007. Results: There were 5651 deaths from all cancers observed in six cohorts of industry workers and six of professionals, with a pooled relative risk (RR) of 0.95 for industry workers and of 0.87 for professionals. Nine deaths from nasopharyngeal cancer in three cohorts of industry workers yielded a pooled RR of 1.33, which declined to 0.49 after excluding six cases from one US plant. The pooled RR for lung cancer was 1.06 in industry workers and 0.63 in professionals. Corresponding values were 1.09 and 0.96 for oral and pharyngeal, 0.92 and 1.56 for brain, 0.85 and 1.31 for all lymphatic and hematopoietic cancers, and 0.90 and 1.39 for leukemia. Conclusions: Comprehensive review of cancer in industry workers and professionals exposed to formaldehyde shows no appreciable excess risk for oral and pharyngeal, sinonasal or lung cancers. A non-significantly increased RR for nasopharyngeal cancer among industry workers is attributable to a cluster of deaths in a single plant. For brain cancer and lymphohematopoietic neoplasms there were modestly elevated risks in professionals, but not industry workers.

Archives of Toxicology, 2010

Formaldehyde is a ubiquitous indoor air pollutant that is classified as ''Carcinogenic to humans (Group 1)'' (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39-325, 2006). For nasal cancer in rats, the exposure-response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (''worst-case'') considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure-response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87-91, 2000), 0.08 ppm (0.1 mg m -3 ) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings.

Cancers, 2021

Background: Formaldehyde, classified as a carcinogen in 2004, as of today is widely used in many work activities. From its classification, further studies were performed to evaluate its carcinogenicity. The aim of the systematic review is to update the evidence on occupational exposure to formaldehyde and cancer onset. Methods: The review, in accordance with the PRISMA statement, includes articles in English reporting original results of studies conducted on workers exposed to formaldehyde, considering all types of cancer, published from 1 January 2000 to 30 July 2021 and selected from the Pubmed and Scopus databases. The studies’ quality was assessed by the Newcastle–Ottawa Scale. Results: A total of 21 articles were included, conducted in different European, American, and Asian countries. The most investigated occupational areas are those characterized by a deliberate use of formaldehyde. Some studies evaluated all types of cancer, whereas others focused on specific sites such as ...

International Journal of Cancer, 1989

A case-control study was undertaken in Montreal to investigate the possible associations between occupational exposures and cancers of the following sites: oesophagus, stomach, colo-rectum, liver, pancreas, lung, prostate, bladder, kidney, melanoma and lymphoid tissue. In total, 3,726 cancer patients and 533 population controls were interviewed to obtain detailed lifetime job histories and information on potential confounders. Each job history was translated into a history of occupational exposures. Because of current concerns about formaldehyde carcinogenicity, we carried out a special analysis of the association between exposure to formaldehyde and each type of cancer covered by this study. Separate statistical analyses were carried out for each type of cancer using population controls as well as a control series drawn from among the other cancer sites in the study. Although nearly a quarter of all subjects had undergone occupational exposure to formaldehyde, the levels of exposure were in general quite low. There was no persuasive evidence of an increased risk of any type of cancer among men exposed to these levels of formaldehyde. However, the possibility of a small increase in risk could not be ruled out.

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2013

Environmental Health Perspectives, 1986

This article reviews the available data on the carcinogenicity of formaldehyde from experimental and epidemiologic studies and makes recommendations for further research. Two definitive chronic inhalation bioassays on rodents have demonstrated that formaldehyde produces nasal cancer in rats and mice at 14 ppm and in rats at 6 ppm, which is within the domain of present permissible human exposure (8-hr timeweighted average of 3 ppm, a 5 ppm ceiling, and a 10 ppm short-term exposure limit). Biochemical and physiologic studies in rats have shown that inhaled formaldehyde can depress respiration, inhibit mucociliary clearance, stimulate cell proliferation, and crosslink DNA and protein in the nasal mucosa. No deaths from nasal cancer have been reported in epidemiologic studies of cohorts exposed to formaldehyde, but three case-control studies suggest the possibility of increased risk. Although excesses of lung cancer deaths have been observed in some studies at industrial plants with formaldehyde exposure, uncertainties in interpretation limit the evaluation of these findings. Excess cancers of the brain and of lymphatic and hematopoietic tissues have been reported in certain studies of industrial groups and in most studies of formaldehyde-exposed professionals, but whether these excesses are related to formaldehyde exposure is not known. Several properties of formaldehyde pose unique problems for future research: the mechanisms responsible for its nonlinear response; its probable mechanism of carcinogenic action as a cross-linking agent; its formation in tissues as a normal metabolite; its possible action as a promoter and/or a cocarcinogen; and the importance of glutathione as a host defense at low exposure.

Occupational and Environmental Medicine, 2000

Objectives-To investigate whether occupational exposures to formaldehyde and wood dust increase the risk of nasopharyngeal cancer (NPC). Methods-A multicentred, population based case-control study was carried out at five cancer registries in the United States participating in the National Cancer Institute's SEER program. Cases (n=196) with a newly diagnosed NPC between 1987 and 1993, and controls (n=244) selected over the same period from the general population through random digit dialing participated in structured telephone interviews which inquired about suspected risk factors for the disease, including a lifetime history of occupational and chemical exposure. Histological type of cancer was abstracted from clinical records of the registries. Potential exposure to formaldehyde and wood dust was assessed on a job by job basis by experienced industrial hygienists who were blinded as to case or control status. Results-For formaldehyde, after adjusting for cigarette use, race, and other risk factors, a trend of increasing risk of squamous and unspecified epithelial carcinomas was found for increasing duration (p=0.014) and cumulative exposure (p=0.033) but not for maximum exposure concentration. The odds ratio (OR) for people cumulatively exposed to >1.10 ppm-years was 3.0 (95% confidence interval (95% CI) 1.3 to 6.6) compared with those considered unexposed. In analyses limited to jobs considered definitely exposed, these trends became stronger. The associations were most evident among cigarette smokers. By contrast, there was no association between potential exposure to formaldehyde and undiVerentiated and non-keratinising carcinomas. There was little evidence that exposure to wood dust increased risk of NPC, as modest crude associations essentially disappeared after control for potential exposure to formaldehyde. Conclusions-These results support the hypothesis that occupational exposure to formaldehyde, but not wood dust, increases risk of NPC. This association seems to be specific to squamous cell carcinomas. Established cohorts of workers exposed to formaldehyde and wood dust should continue to be monitored for NPC and other respiratory cancers. Future studies of NPC should take into account histological type in assessing risk from environmental and host factors.

Toxicologic Pathology, 2012

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 abil...

Toxicology Letters, 2010

Background: According to the Report on Carcinogens, formaldehyde ranks 25 th in the overall U.S. chemical production, with more than 5 million tons produced each year. Given its economic importance and widespread use, many people are exposed to formaldehyde environmentally and/or occupationally. Presently, the International Agency for Research on Cancer classifies formaldehyde as carcinogenic to humans (Group 1), based on sufficient evidence in humans and in experimental animals. Manyfold in vitro studies clearly indicated that formaldehyde can induce genotoxic effects in proliferating cultured mammalian cells. Furthermore, some in vivo studies have found changes in epithelial cells and in peripheral blood lymphocytes related to formaldehyde exposure.

Journal of Toxicology and Environmental Health, Part A, 2013