Carcinogenic Effects of Formaldehyde Occupational Exposure

Carcinogenic Effects of Formaldehyde Occupational Exposure: History

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Subjects: Health Care Sciences & Services

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Formaldehyde is a chemical compound present in many working activities and indoor workplaces. Occupational exposure occurs primarily by inhaling airborne formaldehyde, but it can also be absorbed through the skin or ingested. Formaldehyde, classified as a carcinogen in 2004, as of today is widely used in many work activities. The evidence of correlation between formaldehyde occupational exposure and the occurrence of cancer is limited. Recent evidence suggest that its carcinogenicity should be re-evaluated, especially in view of current exposure limits.

formaldehyde
carcinogenicity
occupational exposure
cancer risk

1. Introduction

Formaldehyde (FA) is a chemical compound naturally occurring in the atmosphere, in some foods, and in the organisms of mammals as a product of oxidative metabolism and, thus, is considered a ubiquitous pollutant. In addition to these sources, FA can be released in the environment through combustion processes or by degradation of some hydrocarbons such as methane. Besides, due to its chemical–physical characteristics, FA is widely applied in many productive processes, such as the construction materials industry, the chemical industry (resins, paintings, etc.), the wood-processing and furniture industry, the food industry, biomedical laboratories, gross anatomy rooms, handicrafts, etc. [1]. Consequently, many types of occupational activities determine FA exposure. Driscoll et al. [2] conducted a study based on data obtained from the Australian Workplace Exposures Study about the prevalence and patterns of exposure to 38 known or suspected carcinogens, including FA, among the Australian working population. As a result, 2.5% of the workers were likely to have been exposed to FA. The main working activities that exposed them to this chemical were the processing of chipboards or plywood panels for carpentry, building maintenance, and sanding before painting. The other workers most exposed were firefighters [3,4,5], healthcare workers [6], and beauticians. FA has also been detected in restaurants [7,8] when grilling dishes and adding sauces, in copy shops [9,10], in gardening [11], in the agri-food sector [12,13], in veterinary clinics, in embalming laboratories, in industrial launderings, etc. Besides, FA is frequently found in building environments, posing at potential risk of exposure to all indoor workers [14,15,16,17,18,19].

Exposure occurs primarily by inhaling airborne FA, but it can also be absorbed through the skin or ingested. The International Agency for Research on Cancer (IARC) in 2004 concluded that there was sufficient evidence of the carcinogenicity of FA for humans to reclassify FA from Group 2A (probably carcinogenic to humans) to Group 1 (carcinogenic to humans) [20]. In the subsequent monograph n. 100 of 2012, in summary, the IARC confirmed that there was sufficient epidemiological evidence that FA causes tumors of the nasopharynx, insufficient evidence of a causal relationship with leukemia, and limited epidemiological evidence for nasal sinus cancer [21]. EU Regulation 2015/491 also imposed the reclassification of FA from suspected carcinogen to carcinogen for humans in category 1B (i.e., it can cause cancer) on the basis of sufficient evidence both in humans [22,23] and in experimental animals [24,25]. However, all the scientific evidence that led to these classifications date back to before 2005. Besides, most of the studies on the relationship between FA and cancer were in vitro experiments demonstrated the effects on culture cells. Researchers have found many cellular damages, like DNA and RNA alterations [26,27], the onset of DNA–protein crosslinks, changes in p53 protein expression [28], and histone modifications [29]. On the other hand, epidemiological studies have not been able to confirm this association. In addition, several previous reviews investigated the relationship between occupational FA exposure and the onset of specific cancers, often obtaining conflicting conclusions [30,31,32,33,34].

2. Carcinogenic Effects of Formaldehyde Occupational Exposure

Most of the studies dealt with occupational settings, characterized by a deliberate use of FA as a component of the production cycle. Those were mainly represented by chemical industries dedicated to the production of plastics, fiberglass, paints, etc.; it is reasonable to imagine that in such contexts the levels of exposure to FA were particularly high. Three studies were carried out in textile-/garment-producing plants, where FA is used to give resistance to the folds of clothing fabrics and for the processing of leathers. Another sector where this substance is widely used is that of woodworking and furniture making. In fact, FA, together with resins, gives strength and resistance to chipboard panels. FA is also widely used in the medical field: in the operating room it was used to disinfect instruments because of its high antibacterial power, and even today, it is used to avoid the deterioration of human tissues that must undergo histopathological analyses. Despite that, very few studies concerned the health sector, or the agri-food industry, where FA is used as a preservative. That is quite surprising, considering that there is much research about the occupational exposure to FA in pathological anatomy settings and sector rooms [61,62,63] that stress the needing for adequate preventive measures for workers [64].

Although the genotoxicity and immunotoxicity of FA is well known and has been demonstrated by several studies regarding its influence on DNA and pro-oxidative effects on cells [28,65,66,67,68,69,70,71,72], the evidence from human studies and diagnosed cancers is much less consistent [73]. Most of the studies focus on upper-airway neoplasms (ICD-10 codes: C10–C14 and C30–C33). In fact, the main way of entry of this substance into the body is by inhalation. Five studies explored the relationship between FA occupational exposure and the onset of lung cancer (ICD-10 code: C34). Their findings contrasted with each other: some did not provide evidence of a carcinogenic effect on the lungs [42,51,52], whereas others found a correlation [44,49]. These last studies, however, were performed on a very small sample and present several limitations (e.g., self-reported data on exposure levels). A recent meta-analysis [31] concluded no significant increase in the risk of lung cancer, even considering only groups of highly exposed workers. The small study sample of the study by Checkoway et al. about lung cancer was also checked for thyroid cancer, with some relationships found but with the same, considerable, limitations [46]. In 2012, the IARC affirmed that there was strong but insufficient evidence of a causal relationship with leukemia. Two studies included regarded the relationship between FA exposure and lympho-hematopoietic cancers (ICD-10 codes: C81–C96), but no association was observed for all leukemias [56], except for a small and weak association with non-Hodgkin lymphoma [48] and myeloid leukemia [50]. This is consistent with the results of other previous studies [30,33]. Five of the included publications evaluated the effects of FA occupational exposure on the onset of any kind of cancer. These were large cohort studies, carried out in Europe and the USA in industrial contexts, and almost all concluded no positive association with FA exposure and the mortality from any cancer, and very limited evidence with NPC and leukemia [43,53,54,55,56]. The most recent research included, published in 2018, was a multicenter study about FA and meningioma. Meningiomas are tumors that develop from the meninges, tissues that surround the outside of the brain and account for about 30% of brain tumors. Although benign, they are dangerous because dysphagia, dysarthria, ocular motility disorders, and facial numbness can occur. Intracranial hypertension, focal seizures, lack of strength, and balance and gait disturbances may also sometimes occur. The study concluded that FA did not provoke excess risks of meningioma [58].

This entry is adapted from the peer-reviewed paper 10.3390/cancers14010165

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