Managing Formaldehyde indoor pollution in anatomy pathology departments

Abstract

BACKGROUND: Nearly eleven years have passed since the International Agency for Research on Cancer classified Formaldehyde (FA) as a known human carcinogen (group 1), yet the safety of anatomy pathology workers who are currently exposed to FA is still a matter of concern.

OBJECTIVE: The purpose of this study was to evaluate the literature to discover which topics have been focused on and what the latest developments are in managing FA indoor pollution in anatomy pathology departments. which topics have been focused on and what the latest developments in managing FA indoor pollution in anatomy pathology departments.

METHODS: For the purpose of this review, we searched for publications in PubMed and Web of Science using selected keywords. The articles were reviewed and categorized into one or more of the following three categories based on subject matter: exposure levels exposure controls and alternatives.

RESULTS: Our search resulted in a total of 31 publications that matched our inclusion criteria. The topics discussed, in order of frequency (from highest to lowest), were: “exposure controls”, “exposure levels” and “alternatives”. The most frequently suggested intervention was to improve local exhaust ventilation systems to minimize FA levels in gross anatomy laboratories.

CONCLUSIONS: We found a lack of evidence-based improvement interventions that aimed to control exposure to FA. According to this finding, and pending a valid chemical substitute for FA, we suggest the need for more in-depth studies targeting measures to minimize exposures to FA in pathology departments.

Keywords

Cancer occupational exposure risk assessment risk management

1 Introduction

Occupational exposure to Formaldehyde (FA) has led to a range of health outcomes reported in anatomy pathology workers due to its strong toxicity [1, 2]. There are several health effects that have been observed in humans resulting from exposure to FA (both short and long-term), including nausea, headache, irritation of the eyes, nose and upper and lower respiratory airways, nerve toxicity, ocularirritation, contact dermatitis [3, 4]; congenital de-fects, nasopharyngeal cancer and myeloid leukemia [1 , 5–8].

Nearly 11 years have passed since the International Agency for Research on Cancer (IARC) classified FA as a known human carcinogen (group 1) on the basis of induction of nasopharyngeal cancer [9]. Yet the safety of anatomy pathology workers who are currently exposed to FA still remains a current concern for a number of reasons. First, the evidence of chromosomal aberrations and DNA damage related to FA exposure is steadily increasing [10 –15]; second, in 2012, the IARC provided sufficient evidence linking FA to leukemia and nasopharyngeal cancer [16]; third, to date, regardless of its toxic effects, FA remains a popular tissue fixative due to its effectiveness, low cost and consistent results. To date, FA solutions are currently used as a fixative and tissue preservative [12 , 18]. The American Conference of Government Industrial Hygienists (ACGIH) has established a ceiling limit for occupational exposure (Threshold Limit Value) of 300 ppb (0,370 mg/m³) [19], but during the dissection of cadavers, FA vapors are emitted, exposing the workers to elevated levels of FA. Some studies showed that concentrations of FA and personal exposure levels in gross anatomy laboratories frequently exceeded the above-mentioned limit [7 , 21]. Excessive FA vapors in the working area can be caused by a work environment that facilitates the spillage of formalin; poor condition of cadavers, which causes embalming fluid to leak; poor ventilation in the dissection rooms; lack of strict and appropriate guidelines for handling embalmed cadavers and prosected specimens; and ignorance of the consequences of formalin exposure [1]. In anatomy pathology laboratories, examinations of the anatomic samples from autopsies or biopsies are performed in different steps that expose the workers to FA vapors; particularly in the “sampling” step where workers handle the anatomic piece from the container filled with formalin and, before slicing, rinse it under running water for 10–15 minutes. This step might imply the workers’ exposure to FA vapors due to their proximity to the formalin [20].

In the past, Bono et al. [14] demonstrated that working in the reduction rooms and being exposed to air-FA concentrations higher than 66μg/m³ were associated with increased levels of malondialdehyde-deoxyguanosine adducts (M1-dG), a biomarker of oxidative stress and lipid peroxidation.

Recently Costa et al. [18] studied the effects of exposure to FA in the human peripheral blood lymphocytes of 84 anatomy pathology laboratory workers who were occupationally exposed to FA and tested for chromosomal aberrations (CAs) and DNA damage (comet assay). Data obtained in this study showed a potential health risk for anatomy pathology laboratory workers exposed to FA (0.38 ppm). Based on these findings, the authors emphasized the need to develop safety programs in order to protect anatomy workers from FA exposure.

The purpose of this study was to evaluate the literature and discover which topics have been focused on and what the latest developments are in managing FA indoor pollution in anatomy pathology departments since the IARC classified FA as “carcinogenic in humans” (group 1).

2 Methods

2.1 Search strategy

We sought articles from two common literature databases: PubMed and Web of Science. Selected keywords were used to identify articles for the purposes of this non-structured review of literature. The keywords were: Formaldehyde, Anatomy Pathology Worker, Occupational Exposure, Safety Measures and Risk Management. The keywords were systematically combined together in order to conduct the literature search. For example, “Anatomy Pathology Worker,” AND “Formaldehyde” AND “Occupational Exposure” was one combination. There were a total of 18 combinations of keywords and all combinations were applied to each of the two databases. We aimed to identify original research articles (i.e. non-reviews) using the above-mentioned keywords with the following exclusion criteria: (1) not written in English; (2) not published after June 2004 (the year 2004 was chosen, as this was the release date of the original IARC Monographs on the Evaluation of Carcinogenic Risks to Humans that classified FA as “carcinogenic in humans” (group 1); (3) non-human studies; and (4) not full reports (i.e. letters to the editor).

2.2 Data extraction

The screening of articles was carried out in two phases. In the first phase, articles were screened on the basis of title and abstract. The abstracts of all the selected titles were sorted for a more detailed information. Two independent reviewers (G.D. and M.C.) read the abstracts and categorized them as relevant, not relevant and possibly relevant. In the second phase, the full-text articles were assessed for eligibility. Two reviewers (G.D. and M.C.) independently applied inclusion and exclusion criteria to potentially eligible papers and both reviewers then independently extracted data from the original articles. Any disagreements were independently checked by the second reviewer (M.M.) and consensus reached.

2.3 Categorization of selected articles

Every full-text article that met the inclusion criteria was reviewed and categorized into one or more of the following three categories based on its subject matter: exposure levels (e.g. personal exposure level, indoor concentration), exposure controls (e.g.methods to reduce exposure levels) and alternatives (e.g. substitute for FA).

3 Results

Our search of the two literature databases resulted in a total of 41 publications that matched our inclusion criteria. Ten of these were removed because they were deemed irrelevant (i.e. non research conference proceedings or not concerning anatomy workers). Therefore, 31 papers remained in the study (Fig. 1). These 31 papers were then categorized according to their subject matter. The topics, discussed in order of frequency from highest to lowest, were: “exposure controls”, “exposure levels” and “alternatives”. Eighteen papers focused on “exposure controls”; 14 papers on “exposure levels”; and 8 papers on “alternatives”. Ten papers discussed both “exposure levels” and “controls”; and one paper targeted all three topics (Table 1). The papers focused on the topic “exposure controls” studied the improvement of local exhaust ventilation systems [1 , 31], analyzed the FA indoor concentration before and after the implementation of such systems. The articles targeted on “alternatives” compared FA substitute fixatives to FA with regard to macroscopy, morphologic evaluation, and immunohistochemical analysis of fixed specimens.

Fig.1

Flow chart.

Table 1

Summary of literature review findings with a tally of the articles based on topics addressed

Author and year	Exposure levels	Exposure controls	Alternatives
Ahmed HO 2011 [22]	×	×
Shiraishi N et al. 2006 [5]	×	×
Azari MR 2012 [7]	×	×
Bono R et al. 2010 [14]	×
Lakchayapakorn K et al. 2010 [23]	×	×
Mirabelli, MC et al. 2011 [24]		×
Ohmichi K et al. 2006 [25]	×	×
Ochs S et al. 2012 [21]	×
Vimercati L et al. 2010 [20]	×
Vohra MS et al. 2011 [26]	×
Klein RC et al. 2014 [27]	×	×
Kurose T et al. 2004 [28]	×	×
Ohmichi K et al. 2007 [17]	×	×
Raja DS et al. 2012 [1]		×
Takahashi M et al. 2010 [29]		×
Whitehead MC et al. 2008 [30]	×	×	×
Dixit D et al. 2008 [31]		×
Khouri NA 2012 [32]	×	×
Zanini C et al. 2012 [33]			×
Ozkan N et al. 2012 [34]			×
Hammer N et al. 2011 [35]			×
Masir N et al. 2012 [36]			×
Wang YN et al. 2010 [37]			×
Dapson RW 2007 [38]			×
Zarbo RJ et al. 2015 [39]		×
Bussolati G et al. 2008 [40]		×
Di Novi C et al. 2010 [41]		×
Kristensen T et al. 2011 [42]		×
Moelans CB et al. 2011 [43]			×

4 Discussion

The findings of our study suggest that in the last 11 years, the main topic of the identified papers focused on “exposure controls”, with the aim of exploring methods to reduce exposure to FA. The most frequently suggested interventions were to improve local exhaust ventilation systems to minimize FA levels in gross anatomy laboratories [1 , 31], and appropriate use of effective PPE (e.g. aprons, lab coats, gloves, protective eyewear and face masks, and respirators). Three authors [7 , 29] who evaluated the effectiveness of interventions targeted on ventilation systems demonstrated the consequent reduction of FA air pollution in gross anatomy laboratories below the ceiling standard of 0.3 ppm established by the American Conference of Governmental Industrial Hygienists. Five authors [1 , 22–24] emphasized the effectiveness of specific guidelines for workers’ use of PPE and ventilation in order to protect them from chronic and acute exposures. Ohmichi et al. [17] demonstrated the effectiveness of Photocatalyst Technology to mitigate air pollution in gross anatomy laboratories, because photocatalyst decomposes volatile organic compounds (VOCs) into carbon dioxide and water; in this pilot study, FA indoor levels were successfully decreased by using a dissection table equipped with a photocatalyst device that reduced FA concentrations by about 80%. Di Novi et al. [41], Bussolati et al. [40] and recently Zarbo [39] highlighted the effectiveness of vacuum sealing technologies to minimize FA use by anatomy pathology laboratories. The authors described vacuum sealing systems as promising technologies for preserving fresh human specimens that can promote a safer environment by markedly reducing formalin use in operating room theaters [40–41].

The topic concerning the “exposure level” to FA aimed to assess personnel exposure [7, 14], indoor concentration [17 , 32], and both personal exposure and indoor concentration [20 , 30] in pathology departments. Omichi et al. [25] and Azari et al. [7] evidenced that in gross anatomy laboratories, the personal exposure levels are frequently 2–3-fold higher than the mean indoor FA level. Based on this finding, they suggested that the risk assessment should be based on personal exposure levels. This observation is confirmed by all the checked papers that evaluated both personal exposure and indoor concentration, and showed that in anatomy laboratories, the average personal exposures to FA were higher than the average indoor concentrations. This finding confirmed that working in close proximity to cadavers in the gross anatomy laboratory is the major risk factor that should be evaluated when assessing personal exposure to FA. This is not well evidenced by indoor concentration evaluations [25]. The most frequent issue highlighted by the studies that focused on “exposure levels” was the finding that exposure to FA in autopsy practice exceeds the recommended ceiling standard of 0.3 ppm established by the American Conference of Governmental Industrial Hygienists. In fact, eight papers concerning this topic showed values higher than the above-mentioned set limit [7 , 29] and showed the need for preventive actions that aim to minimize exposure to FA. Five papers showed personal exposures to FA and indoor concentrations lower than the ACGIH TLV ceiling level [17 , 32], and the consequential preventive interventions that aimed to control the exposure.

Regarding alternatives to FA, a large number of fixatives have been suggested as chemical substitutes for FA in histology, cytology and autopsy practice [33 –38]. The suggested alternatives checked by this review are alcohol-based fixatives, glyoxal-based fixatives, zinc-based fixatives and honey [33–38 , 43]. However, further studies are required to demonstrate that these potential substitutes can effectively maintain the morphological characteristics of formaldehyde-fixed tissue and fix cadavers, We think that a special effort is required to expand the search for an alternative fixative to FA that is easy to use and that combines satisfactory tissue preservation and safe disposal. In conclusion, our review of the literature indicates that since 2004, the most frequent topic concerning the management of FA indoor pollution in pathology departments was “exposure controls” with the aim of implementing interventions that can effectively minimize exposure levels to FA. We found a lack of evidence-based improvement interventions. In fact, fewer than 50 percent (3/18) of the papers concerning the topic “exposure controls” evaluated the effectiveness of the suggested interventions by monitoring exposure to FA before and after these interventions.

5 Conclusion

According to the findings of this review, and pending a valid chemical substitute for FA [43, 44], we suggest the need for more in-depth studies targeting measures to minimize exposure to FA and to protect the workers’ health [45, 46] in pathology departments. Future studies should consider the pre-post FA evaluation of comparison groups that involves local exhaust ventilation systems. Moreover, the findings of this review highlighted that FA levels should be measured periodically, both in the autopsy room and in the pathology anatomy laboratory, assessing personal exposure and the mean air concentration of FA. Personal protective equipment (e.g. aprons, lab coats, gloves, protective eyewear and face masks, and respirators) should be available and used to control the exposures. The use of PPE is not considered a priority safety measure but, rather at last resort if FA substitution or elimination is not being used. Industrial hygiene studies focusing on FA exposure assessment, that is required for pre-post evaluations, is also crucial to analyze the effectiveness of interventions aimed at minimizing the exposureto FA.

There were several limitations in this review. Firstly, because of the use of these three inclusion criteria we could have missed potentially relevant papers in the first step of data selection. Secondly, we conducted a non-structured literature review, without quantitative data, which might influence the precision of the findings.

Conflict of interest

The authors declare they have no financial or personal relationship with people or organizations that could inappropriately influence the work.

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