Formaldehyde

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Contents 1 Summary 2 Studies and Reports 3 Related topics 4 Additional Resources

Summary

TBD.

Studies and Reports

• Cole P et al. Formaldehyde and lymphohematopoietic cancers: A review of two recent studies, Regulatory Toxicology and Pharmacology 58:2;161-166, November 2010.
  • Summary. "This paper reviews and evaluates two recent epidemiologic studies of formaldehyde exposure and lymphohematopoietic cancers. One is an update of mortality in a retrospective cohort study of industrial workers and the other is a proportional mortality and case-control study among embalmers. Both studies included subjects with considerable exposure to formaldehyde and both are focused on the myeloid leukemias... There is no statistically significant absolute excess mortality from any lymphohematopoietic cancer in either study. The study of industrial workers showed only a weak and transitory relationship between peak exposure to formaldehyde and the myeloid leukemias. Limited exposure–response relationships for the myeloid leukemias in the case-control study of embalmers apparently have not been analyzed for statistical significance. These limited exposure–response relationships do not provide clear evidence of a causal relationship between formaldehyde and the myeloid leukemias."
• Pyatt D, Is inhalation exposure to formaldehyde a biologically plausible cause of lymphohematopoietic malignancies?, Regulatory Toxicology and Pharmacology 51:1;119-133, June 2008.
  • Summary. "The United States Environmental Protection Agency (EPA) recently proposed a hypothetical mode of action (MOA) to explain how inhaled formaldehyde (FA) might induce leukemia, lymphoma and a variety of other lymphohematopoietic (LHP) malignancies in occupationally exposed workers. The central hypothesis requires that B lymphocytes or hematopoietic progenitor cells (HPC) present at the “portal of entry (POE)” undergo sustained mutagenic change as a result of direct FA exposure. These modified cells would then migrate back to the bone marrow or primary lymphatic tissue and subsequently develop into specific LHP disease states. Chemical interaction at the POE is an absolute requirement for the hypothesized MOA as there is no convincing evidence that inhaled FA causes distant site (e.g., bone marrow) toxicity. The purpose of this review is to critically evaluate this proposed MOA within the context of the existing data concerning the toxicokinetic and biological properties of FA, the current understanding of the induction of chemically-induced leukemias and lymphomas, as well as within EPA’s specific guidelines for evaluating the MOA of chemically-induced cancers. Specifically, we examine the scientific support for the hypothesis that FA exposure may induce carcinogenic transformation of localized lymphocytes or peripheral hematopoietic progenitor cells (HPC) in the absence of discernable systemic hematopoietic toxicity (i.e., peripheral transformation). While little or no empirical evidence exists upon which to fully evaluate the proposed hypothesis, available data does not support the proposed concept of “peripheral transformation” at the chemical entry site. Numerous animal bioassays evaluating chronic inhalation of FA clearly do not support this hypothesis since no properly conducted study as ever shown an increase in any LHP malignancy. Moreover, the notion that FA can cause any LHP malignancy is not supported with either epidemiologic data or current understanding of differing etiologies and risk factors for the various hematopoietic and lymphoproliferative malignancies. It is therefore concluded that existing science does not support the proposed MOA as a logical explanation for proposing that FA is a realistic etiological factor for any LHP malignancy."
• Lang I et al., Formaldehyde and chemosensory irritation in humans: A controlled human exposure study, Regulatory Toxicology and Pharmacology 50:1;23-36, February 2008.
  • Conclusion. "The results of the present study indicated eye irritation as the most sensitive parameter. Minimal objective eye irritation was observed at a level of 0.5 ppm with peaks of 1 ppm. The subjective complaints of ocular and nasal irritation noted at lower levels were not paralleled by objective measurements of eye and nasal irritation and were strongly influenced by personality factors and smell. It was concluded that the no-observed-effect level for subjective and objective eye irritation due to formaldehyde exposure was 0.5 ppm in case of a constant exposure level and 0.3 ppm with peaks of 0.6 ppm in case of short-term peak exposures."
• Bocetti C et al., Formaldehyde and cancer risk: a quantitative review of cohort studies through 2006, Ann Oncol. 2008 Jan;19(1):29-43. Epub 2007 Sep 25.
  • 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."
• Marsh G et al., Work in the metal industry and nasopharyngeal cancer mortality among formaldehyde-exposed workers, Regulatory Toxicology and Pharmacology 48:4;308-319, August 2007.
  • Conclusion. "The results of our nested case–control study suggest that the large nasopharyngeal cancer mortality excess in the Wallingford cohort may not be due to formaldehyde exposure, but rather reflects the influence of external employment in the ferrous and non-ferrous metal industries of the local area that entailed possible exposures to several suspected risk factors for upper respiratory system cancer (e.g., sulfuric acid mists, mineral acid, metal dusts and heat). Our findings may also help to explain why the associations with formaldehyde and nasopharyngeal cancer reported in the 1994 update of the 10-plant NCI formaldehyde cohort study were unique to the Wallingford plant (Plant 1 in NCI study)."
• Cole P and Axten C, Formaldehyde and leukemia: an improbable causal relationship, Regul Toxicol Pharmacol. 2004 Oct;40(2):107-12.
  • Abstract. "Formaldehyde has been the subject of numerous toxicological and epidemiological investigations for almost 25 years. Though most toxicology studies have focused on the effects of the chemical on the nasal tract and respiratory system, epidemiology investigations have been more extensive evaluating the association between formaldehyde and cancers not only of the nasal cavities, nasopharynx, and lung, but also of the brain, prostate, pancreas, and hematopoietic system. Recently, three studies have been published which report on the possible association between exposure to formaldehyde and an increased incidence of leukemia, specifically myeloid leukemia. The article summarizes the results of these three studies, evaluates the evidence for causality based on recognized epidemiologic criteria, and provides an assessment that the association between formaldehyde and the increased incidence of leukemia reported in these studies is not plausible."
• Mclaughlin J, Formaldehyde and cancer: a critical review, Int Arch Occup Environ Health. 1994;66(5):295-301.
  • Abstract. "Formaldehyde is a naturally occurring chemical found in every human cell. It has been in widespread use for over a century as a disinfectant and preservative agent, and more recently in a number of industrial products. Animal studies indicate that formaldehyde is a rat carcinogen at high levels (> or = 10 ppm) of exposure. Results for lower levels of exposure show less clear-cut carcinogenic effects, and some species, such as mice and hamsters, appear much less sensitive to any carcinogenic potential of formaldehyde. Epidemiologic studies of the effects of formaldehyde exposure among humans provide inconsistent results. In general, these nonexperimental studies suffer from a number of biases and flaws. The epidemiologic studies fall into three categories: formaldehyde industry workers, case-control studies, and studies of professionals who use formaldehyde. Studies of industry workers with known exposure to formaldehyde report little evidence of an excess cancer risk. Nasopharyngeal cancer, the one cancer considered most strongly linked to formaldehyde among humans, appears after close examination to be likely a result of multiple subgroup analyses and misclassification. The case-control studies usually lack any direct measure of formaldehyde exposure and rely instead on hypothetical exposure based on occupational exposure matrices. Most of these studies, after adjustment for confounding factors, fail to find a significant association with putative formaldehyde exposure. The studies that do report a significant association suffer from methodologic problems limiting their interpretation."
• Chang C and Gershwin M, Perspectives on formaldehyde toxicity: Separating fact from fantasy, Regulatory Toxicology and Pharmacology 16:2;150-160, October 1992.
  • Summary. "Formaldehyde (IUPAC name, methanal) is one of the simplest, most ubiquitous molecules in our environment and troposphere. Exposure to large amounts of formaldehyde can produce a variety of respiratory and dermatologic problems in humans, in both the home and the workplace. However, in spite of anecdotal reports on formaldehyde-induced illness over the past 20 years there is a paucity of data regarding its potential as either an allergen or an antigen in humans. In addition, many of our current impressions about formaldehyde are based on studies of dubious scientific validity. In this review, we discuss the biological and chemical properties of formaldehyde and its presence in materials which we come in contact with, and finally attempt to put in perspective our current understanding of the detrimental effects of formaldehyde on our health, or lack thereof. There is no evidence at present that formaldehyde causes immunological diseases. Finally, and unfortunately, many of the studies have drawn invalid conclusions and are based on poorly controlled anecdotal observations."
• Broder I et al., Formaldehyde exposure and health status in households, Environ Health Perspect. 1991 Nov;95:101-4.
  • Abstract. "This report describes a case study concerned with acute and subacute health effects of formaldehyde in the indoor air, which is based on a large group of control houses and houses retroinsulated 4 to 5 years earlier with urea formaldehyde foam insulation (UFFI). Both groups underwent an environmental and health assessment on two occasions separated by an interval of 12 months, during which about one-half of the UFFI group performed remedial work on their houses. The results show that in the first survey of the study population, before remedial work, there was a moderate excess of many adverse health status indicators among the UFFI subset relative to the controls. This was associated with the presence of direct exposure-response relationships between formaldehyde levels in the UFFI houses and the prevalence of a number of symptoms. No comparable relationships were seen among the controls. At the second survey, performed following the removal of the UFFI, there was an appreciable reduction in the excess of most adverse health status indicators among the UFFI subjects. This improvement in health status among the UFFI removal subset was not associated with any significant diminution of formaldehyde exposures, although the previously observed exposure-response relationships had vanished. These observations imply that the findings obtained in the preremedial stage of the study cannot be explained by formaldehyde exposure alone."
• Uma G et al., Prospective study of respiratory effects of formaldehyde among healthy and asthmatic medical students, Am J Ind Med. 1989;15(1):91-101.
  • Abstract. "We conducted a prospective evaluation of pulmonary function and respiratory symptoms among 103 medical students exposed to formaldehyde over a 7-month period to determine the incidence of bronchoconstriction and respiratory symptoms in response to exposure. Time-weighted average formaldehyde exposures were generally less than 1 part per million (ppm) and peak exposures were less than 5 ppm. Acute symptoms of eye and upper respiratory irritation were significantly associated with exposure. There was no pattern of bronchoconstriction in response to exposure after either 2 weeks or 7 months. Twelve subjects had a history of asthma; they were no more likely to have symptoms of respiratory irritation or changes in pulmonary function than those without such a history. These findings are consistent with previous case reports that indicate exposure to formaldehyde vapor at levels that are commonly encountered in occupational and residential settings do not commonly cause significant bronchoconstriction, even among subjects with preexisting asthma."

Related topics

• Skin painting studies

Additional Resources

• Caswell E, The Precautionary Principle: A Cautionary Tale, GCDSpa Blog, August 2, 2010.
• Butterworth T, Babies, Bathtime, and Cancer?, STATS.org, March 13, 2009.