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Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde
Abstract
Sister chromatid exchange (SCE) was measured in peripheral lymphocytes of 90 workers from 14 hospital pathology departments in Israel who were occupationally exposed to formaldehyde (FA) and of 52 unexposed workers from the administrative section of the same hospitals. The mean exposure period to FA was 15.4 years (range 1-39). The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the exposed compared with that of the unexposed group (P<0.01). Adjustment was made for age, sex, smoking habits, education workers and origin. Evaluation of the influence of years of exposure on the frequency of SCEs showed that the two variables of SCEs were higher among those who were exposed to FA for 15 or more than among those with less than 15 years of exposure. Concerning levels of exposure, both variables of SCEs were the same in the low and in the high levels of exposure sub-groups. However, among the smokers, both variables of SCEs were higher in the high exposure sub-group than in the low exposure sub-group. Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in pathology staff indicates a potential cytogenetic hazard due to FA exposure. We conclude that our data indicate that FA is mutagenic to humans.
... Nevertheless, the FA genotoxic potential in occupationally exposed individuals is conflicting. At this concern, in some biomonitoring studies, cytogenetic effects, such as increased sister chromatide exchanges (SCE), chromosomal aberrations (CAs), and micronucleated cells (MNc), were described (Burgaz et al. 2001;Shaham et al. 2002;Ye et al. 2005;Jakab et al. 2010), while in other reports, these evidences were lacking (Thomson et al. 1984;Pala et al. 2008). Thus, in the present study, we evaluated the frequency of CAs in peripheral blood lymphocytes from workers in pathology wards who have been exposed to low daily concentration levels of FA (mean ± SE, 72.70 ± 12.81 lg/m 3 ). ...
... The genotoxic properties of FA were confirmed in a variety of experimental models, ranging from bacteria to rodents in vivo. In humans, the cytogenetic assays provided conflicting results with both positive and negative outcomes, depending on the type of cell system or biomarker utilized (Thomson et al. 1984;Burgaz et al. 2001;Shaham et al. 2002;Ye et al. 2005;Pala et al. 2008;Jakab et al. 2010). In general, the genotoxic effects of FA exposure on first contact tissues such as the nose and the respiratory tract have been increasingly convincing. ...
... On the other hand, Bauchinger and Schmid (1985) observed a significant increase in structural CAs (but not in SCE frequency) in lymphocytes from workers exposed to FA. More recently, Shaham et al. (2002Shaham et al. ( , 2003 observed, in peripheral lymphocytes of a pathology staff, a significant increase in SCE frequency, DNA-protein crosslinks, and p53 protein expression, while Costa et al. (2008) observed significantly higher levels of MN and SCE in pathologists exposed to very high level of air FA. Finally, Jakab et al. (2010) showed an increased level of CAs and apoptosis in FA-exposed female lymphocytes from four pathology departments. ...
... Several studies demonstrated that both DNA damage and chromosome changes were induced by FA in cell culture experiments, and in vivo in humans and experimental animals at the sites of FA exposure (Liu et al. 2009;IARC 2006). Increased number of chromosomal aberrations (CA) (Jakab et al. 2010), elevated micronucleus (MN) frequency Orsiére et al. 2006;Costa et al. 2008) and enhanced sister chromatid exchange (SCE) frequency (Shaham et al. 2002;Costa et al. 2008) were reported in peripheral blood lymphocytes from individuals occupationally exposed to FA. However, these results are more variable, with increases in damage being reported in some studies but not in others (Ying et al. 1999;Heck and Casanova 2004;Schmid and Speit 2007). ...
... Occupational exposure involves not only individuals employed in the direct manufacture of FA and products containing this chemical, but also those subjects using these products, namely, in pathology and anatomy laboratories where FA is commonly used as a fixative and tissue preservative. Indoor air analyses showed that the levels of airborne FA in pathology and anatomy laboratories exceeded the recommended exposure criteria levels (Paustenbach et al. 1997;Shaham et al. 2002;Akbar-Khanzadeh and Pulido 2003). In these settings, absorption of FA occurs mainly through inhalation. ...
... Several studies on environmental monitoring of pathology/anatomy laboratories (Akbar-Khanzadeh and Pulido 2003; Dufresne et al. 2002;Shaham et al. 1997) also found levels of FA near or higher than recommended limit values. Shaham et al. (2002) reported for 14 pathology departments mean levels of FA exposure of 0.4-2.24 ppm. ...
Formaldehyde (FA) is a world high-production chemical with industrial and medical purposes. Given its economic importance and widespread use, many people are exposed to FA both environmentally and/or occupationally. Increased incidences of nasopharyngeal cancer were found in populations occupationally exposed to FA. Based on sufficient epidemiological and experimental evidence, IARC has reclassified FA as a human carcinogen. FA's genotoxicity is confirmed in a variety of experimental systems ranging from bacteria to humans. The highest level of human exposure occurs in occupational settings. Several studies point to pathology/anatomy laboratories as one of the occupational settings where the workers are frequently exposed to levels of FA near or superior to recommended limit values. The aim of the present study was to assess the potential health effects of long-term occupational exposure to FA. A group of pathology/anatomy workers were evaluated for micronucleus test and comet assay. Air sampling was performed in worker's breathing zone for representative working periods and 8 h-time weighted average (TWA) was assessed. Both micronucleus frequency and comet assay were significantly higher in the exposed subjects when compared with controls. TWA mean value for FA exposed workers was 0.43 ± 0.06 ppm. Data obtained confirm an association between genetic damage and occupational exposure to FA. Such results along with the recent implications of human carcinogenicity, point out for the need of close monitoring of FA occupational exposure.
This work is supported by Fundação para a Ciência e a Tecnologia (FCT) under the grants SFRH/BD/46929/2008 and PTDC/SAU-ESA/102367/2008.
... Nevertheless, the FA genotoxic potential in occupationally exposed individuals is conflicting. At this concern, in some biomonitoring studies, cytogenetic effects, such as increased sister chromatide exchanges (SCE), chromosomal aberrations (CAs), and micronucleated cells (MNc), were described (Burgaz et al. 2001;Shaham et al. 2002;Ye et al. 2005;Jakab et al. 2010), while in other reports, these evidences were lacking (Thomson et al. 1984;Pala et al. 2008). Thus, in the present study, we evaluated the frequency of CAs in peripheral blood lymphocytes from workers in pathology wards who have been exposed to low daily concentration levels of FA (mean ± SE, 72.70 ± 12.81 lg/m 3 ). ...
... The genotoxic properties of FA were confirmed in a variety of experimental models, ranging from bacteria to rodents in vivo. In humans, the cytogenetic assays provided conflicting results with both positive and negative outcomes, depending on the type of cell system or biomarker utilized (Thomson et al. 1984;Burgaz et al. 2001;Shaham et al. 2002;Ye et al. 2005;Pala et al. 2008;Jakab et al. 2010). In general, the genotoxic effects of FA exposure on first contact tissues such as the nose and the respiratory tract have been increasingly convincing. ...
... On the other hand, Bauchinger and Schmid (1985) observed a significant increase in structural CAs (but not in SCE frequency) in lymphocytes from workers exposed to FA. More recently, Shaham et al. (2002Shaham et al. ( , 2003 observed, in peripheral lymphocytes of a pathology staff, a significant increase in SCE frequency, DNA-protein crosslinks, and p53 protein expression, while Costa et al. (2008) observed significantly higher levels of MN and SCE in pathologists exposed to very high level of air FA. Finally, Jakab et al. (2010) showed an increased level of CAs and apoptosis in FA-exposed female lymphocytes from four pathology departments. ...
The formaldehyde (FA) genotoxic potential in occupationally exposed individuals is conflicting. A relevant indoor-air FA pollution was found in hospitals and scientific institutions where FA is used as a bactericide and tissue preservative. In the present study, we evaluated the frequency of chromosomal aberrations (CAs) in peripheral blood lymphocytes from workers in pathology wards who have been exposed to FA, compared with a group of unexposed subjects. The subjects were also analyzed for the GSTM1 and GSTT1 metabolic gene polymorphisms. The exposed subjects showed a significant increase in the frequency of CA per cell and in the percentage of cells with aberrations compared to control subjects. The different GST genotypes did not affect the level of cytogenetic damage since CA frequencies were not statistically different between the GST "null" genotypes and the GST "positives". The generalized linear models showed that the number of CAs and cells with CAs increased with age, but, independent of age, it was significantly higher in the experimental rather than in the control group. Cubic-spline regression confirmed the linear relationship between CAs and age, but it provided evidence for a non-linear relationship between CAs and the number of years of FA exposure. Similar results were observed when the model included the number of cells with CAs as dependent variables. Our results demonstrate that air FA induces CAs even consequently to low levels of daily exposure, indicating an increased risk of genetic damage for workers exposed to this air pollutant.
... Workers directly involved in the production or use of FA and FA-based compounds, are exposed to higher concentration of this pollutant than the general population (Motta et al. 2021;Kang et al. 2021). Due to its ability in preserving cell and tissue morphology, formalin, an aqueous solution containing dissolved FA, is widely used in pathology wards (Shaham et al. 2002;Motta et al. 2021). Pathologists are exposed to FA in several steps of their workflow. ...
... Several studies to date assessed increased SCEs frequency as a consequence of FA exposure, both in vitro and in exposed worker's PBL (Shaham et al. 2002;Speit et al. 2007;Costa et al. 2008Costa et al. , 2019Bernardini et al. 2020). ...
Formaldehyde (FA) is a ubiquitous toxic chemical employed worldwide due to its disinfectant and preservative properties. Despite being classified as a human carcinogen, FA is still employed as formalin in pathology wards as standard fixative. We evaluated its relationship with the formation of sister-chromatid exchanges (SCEs) in cultured peripheral blood lymphocytes on 57 pathologists and 48 controls and the risk/protective role played by several genetic polymorphisms. All subjects were assessed for SCEs and genotyped for the most common cancer-associated gene polymorphisms: CYP1A1 exon 7 (A > G), CYP1A1 *2A (T > C), CYP2C19 *2 (G > A), GSTT1 (presence/absence), GSTM1 (presence/absence), GSTP1 (A > G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα − 308 G > A), IL10 − 1082 (G > A), and IL6 − 174 (G > C). Air-FA concentration was assessed through passive personal samplers. Pathologists, exposed to 55.2 μg/m ³ of air-FA, showed a significantly higher SCEs frequency than controls, exposed, respectively, to 18.4 μg/m ³ . Air-FA was directly correlated with SCEs frequency and inversely with the replication index (RI). Regression models showed FA exposure as a significant predictor in developing SCEs, while did not highlight any role of the selected polymorphisms. Our study confirms the role of low air-FA levels as genotoxicity inductor, highlighting the importance to define exposure limits that could be safer for exposed workers.
... The International Agency for Research on Cancer (IARC) (Kwon;et al., 2018)has classified 2 Formaldehyde (FA) as a Group 1 carcinogen based on sufficient data for nasopharyngeal cancer and 3 leukemia.(Arts; Rennen;de Heer, 2006;Kriebel;et al., 2001;Lu;et al., 2010;Shaham;Gurvich;Kaufman, 4 2002;Swenberg;et al., 2011;Ye;et al., 2005). It is generally accepted that exposure to FA can have a variety 5 of toxic effect (Andersen;et al., 2019;Hu;et al., 2019;Santana;et al., 2019). ...
... The International Agency for Research on Cancer (IARC) (Kwon;et al., 2018)has classified 2 Formaldehyde (FA) as a Group 1 carcinogen based on sufficient data for nasopharyngeal cancer and 3 leukemia.(Arts; Rennen;de Heer, 2006;Kriebel;et al., 2001;Lu;et al., 2010;Shaham;Gurvich;Kaufman, 4 2002;Swenberg;et al., 2011;Ye;et al., 2005). It is generally accepted that exposure to FA can have a variety 5 of toxic effect (Andersen;et al., 2019;Hu;et al., 2019;Santana;et al., 2019). ...
In order to study the e of formaldehyde exposure on learning and memory ability of mice. We used Kun Ming (KM) mice to demonstrate the neurotoxic effects of FA, and Balb/c mice to explore the neurobiological mechanism. The Morris water maze (MWM) test showed that the exposure of gaseous formaldehyde could cause spatial learning and memory impairment in mice. H & E staining showed that in the 3.0 mg/m³ formaldehyde exposed group, the arrangement of pyramidal cells in CA1 area of mouse hippocampus was loose and disordered, the cell morphology was swollen and deformed, and the apical dendrites were shortened or even disappeared. Biochemical indicators revealed high doses of FA exposure could cause oxidative damage in brain. Compared with the control group, there were significant differences in the levels of ROS, MDA, GSH and 8-OHDG in the 3.0 mg/m3 group (P < 0.01), also the monoamine neurotransmitters content and the content of TNF-α, IL-1β and Caspase-3 (P < 0.01). Furthermore, the concentrations of cAMP, cGMP, NO and the activity of NOS in the cerebral cortex, hippocampus and brain stem after high doses of FA exposure were significantly different from those in the control group, indicating that FA exposure could interfere with the transduction of NO/cGMP signaling pathway. The results showed that FA could induce cognitive deficits and this extended investigation found that the toxicity of FA to the mouse nervous system is related to the NO/cGMP and cAMP signaling pathways.
... However, this approach is changing and biological monitoring is recommended for hazardous chemicals as the method of choice for monitoring exposure and health risk assessment (15). There are several attempts for biological monitoring of FA such as: exploring DNAprotein cross-links in workers exposed to FA (16) and sister chromatid exchange rate in the personnel with exposure to FA in the range of 0.04 to 6.9 ppm (17). In clinical monitoring of cancer patients and cigarette smokers, FA was measured in their exhaled breath (12,18). ...
... Therefore, considering the task of validation processes of the NIOSH method No. 2016 locally in this study and statistically significant positive correlation between FA concentrations in breathing zone and FA concentrations in exhaled breath of healthy exposed subjects, measurement of FA in the exhaled breath as biomarker of exposure in healthy and nonsmokers workers seemed feasible in this study. Generally, established biomarkers of exposure of FA through measuring DNA adducts and sister chromatid exchange rate in blood samples, are more complex than measuring FA through exhaled breath samples (16,17). The method presented in this study does not require invasive sampling and elaborate analysis. ...
... In pathology anatomy labs, FA is a wellknown compound traditionally used as a fixative and tissue preservative. Indoor air analyses consistently show that the levels of airborne FA in pathology anatomy labs exceeded recommended exposure criteria (Shaham et al., 2002; Akbar-Khanzadeh and Pulido, 2003). In these settings, absorption of FA occurs mainly through inhalation. ...
... The results showed that SCE frequency was significantly higher in samples taken at the end of the course compared to samples obtained from the same individuals immediately before FA exposure began. Shaham et al. (1997 Shaham et al. ( , 2002) examined a group of 90 pathology workers. Based on different FA exposure levels, the exposed group was divided into a low-exposure group (0.04 to 0.7 ppm) and a high-exposure group (0.72 to 5.6 ppm). ...
Formaldehyde (FA) is a widely used industrial chemical for which exposure is associated with nasopharyngeal and sinonasal cancer. Based on sufficient evidence of carcinogenicity from human investigations, supporting studies on mechanisms underlying carcinogenesis, and experimental evidence in animals, FA status was recently revised and reclassified as a human carcinogen. The highest level of exposure to FA occurs in occupational settings. Although several studies reported FA ability to induce genotoxic responses in exposed workers, not all findings were conclusive. In addition, published studies on the immunological effects of FA indicate that this compound may be able to modulate immune responses, although data in exposed subjects are still preliminary. In this study a group of pathology anatomy workers exposed to FA was evaluated for cytogenetic and immunological parameters. A control group with similar sociodemographic characteristics and without known occupational exposure to FA was also included. Genotoxicity was evaluated by means of micronucleus (MN) test, sister chromatid exchanges (SCE), and T-cell receptor (TCR) mutation assay. Percentages of different lymphocyte subpopulations were selected as immunotoxic biomarkers. The mean level of FA environmental exposure was 0.36 ± 0.03 ppm. MN and SCE frequencies were significantly increased in the exposed group. A significant decrease of the percentage of B cells in the exposed group was also found. Data obtained in this study indicate that genotoxic and immunotoxic increased risk due to FA occupational exposure cannot be excluded. Implementation of effective control measures along with hazard prevention campaigns may be crucial to decrease the risk.
... Contradictory results were obtained in vivo in cytogenetic analysis of peripheral blood lymphocytes of exposed workers. The genotoxic effects of FA have been studied and cytogenetic effects, such as increased chromosomal aberrations, sister chromatid exchanges, and micronucleated cells, have been described [31][32][33][34][35][36][37][38][39]. ...
... Shaham et al. [36] described a significant increase of SCE frequency in peripheral lymphocytes in pathology staff (90 exposed workers and 52 unexposed workers; level of exposure ranging from 0.4 ppm (0.5 mg/m 3 ) (range 0.04-0.7 ppm (0.05-0.6 mg/m 3 )-low) to 2.24 ppm (2.7 mg/m 3 ) (range 0.72-5.6 ppm (0.89-6.9 mg/m 3 )-high)). ...
The aim of this study was to verify the presence of a relationship between formaldehyde exposure in the work environment with biological markers of exposure and of effect.
Exposure to formaldehyde (FA) of 36 workers in different laboratories of a Cancer Research Institute and biomarkers of exposure, such as formaldehyde human serum albumin conjugate (FA-HSA) and biomarkers of effect, such as chromosome aberration (CA), micronuclei (MN) and sister chromatid exchanges (SCEs) were measured in peripheral blood lymphocytes of the same workers.
Individual FA levels of exposure ranged from 4.9 microg/m(3) to 268.7 microg/m(3). Subjects with high FA exposure showed a significant increase of the biomarker of exposure FA-HSA, but biomarkers of effect did not show any significant differences.
A significant relationship was observed between occupational exposure to FA and a biological marker of exposure (FA-HSA). The markers of effect used (CA, MN and SCE) failed to indicate the presence of genetic damage.
... The International Agency for Research on Cancer (IARC) has classified formaldehyde as a Group 1 human carcinogen, primarily associated with nasopharyngeal carcinoma but also potentially associated with lung cancer and leukemia (8). The carcinogenicity of formaldehyde is primarily attributed to its ability to fragment DNA and cross-link DNA and protein structures (9)(10)(11)(12). Moreover, formaldehyde, as a potent oxidant that can generate reactive oxygen radicals resulting in cellular and tissue damage (13)(14)(15). ...
Background
The prevalence of lung cancer, a major type of malignant tumor, has been increasing over the years greatly impacting the health of Chinese residents. This study investigates the epidemiological characteristics of lung cancer among healthcare workers in the Hunan Province, as well as the occupational risk factors.
Methods
The data analyzed in this study was collected from the largest tumor hospital in the province: the Hunan Provincial Tumor Hospital affiliated with Central South University, School of Medicine. The data collected encompasses input collected between the years of 2004 to 2013 of the population of healthcare workers who were hospitalized for lung cancer treatments. Information was obtained through statistical analysis and telephonic interviews.
Results
The prevalence of lung cancer among healthcare workers was much higher than that of the general population, as revealed by the difference between number of healthcare worker cases per 1,000 cases and number of healthcare workers per 1,000 population in the decade from 2004 to 2013. Analysis of the data further demonstrates that lung cancer prevalence among healthcare workers increases exponentially with age. Although smoking has been shown to increase the incidence of lung cancer to some extent, it is most likely not the main cause of lung cancer. In addition, it appears that the highest rates of lung cancer incidence occurs in mainly in primary general practitioners, medical radiologists, and nurses. The lack of awareness of personal safety measures may place healthcare workers at a greater risk of lung cancer.
... Formaldehyde (FA) (CAS RN 50-00-0), which is also known as formalin, methanal, formal, and methylene oxide, is a colorless, toxic, pungent, and irritating gas, highly volatile and flammable at room temperature (Leso et al., 2020;Shaham et al., 2002). With the chemical formula of H-CHO, FA occurs naturally in the atmosphere, some foods, and also in the mammal and human organisms as a product of oxidative metabolism (Yalcin et al., 2015;Yang et al., 2017). ...
Formaldehyde is one of the most widely used substances in a variety of industries, although it was classified as a human carcinogen by the International Agency for Research on Cancer (IARC). The present systematic review was conducted to retrieve studies related to occupational exposure to formaldehyde until November 2, 2022. Aims of the study were to identify workplaces exposed to formaldehyde, to investigate the formaldehyde concentrations in various occupations and to evaluate carcinogenic and non-carcinogenic risks caused by respiratory exposure to this chemical among workers. A systematic search was done in Scopus, PubMed and Web of Science databases to find the studies done in this field. In this review, studies that did not meet the criteria specified by Population, Exposure, Comparator, and Outcomes (PECO) approach were excluded. In addition, the inclusion of studies dealing with the biological monitoring of FA in the body and review studies, conference articles, books, and letters to the editors were avoided. The quality of the selected studies was also evaluated using the Joanna Briggs Institute (JBI) checklist for analytic-cross-sectional studies. Finally, 828 studies were found, and after the investigations, 35 articles were included in this study. The results revealed that the highest formaldehyde concentrations were observed in waterpipe cafes (1,620,000 μg/m3) and anatomy and pathology laboratories (4237.5 μg/m3). Carcinogenic and non-carcinogenic risk indicated the potential health effects for employees due to respiratory exposure as acceptable levels of CR = 1.00 × 10-4 and HQ = 1, respectively were reported to be exceeded in more than 71% and 28.57% of the investigated studies. Therefore, according to the confirmation of formaldehyde's adverse health effects, it is necessary to adopt targeted strategies to reduce or eliminate exposure to this compound from the occupational usage.
... Formaldehyde (HCHO), also known as formalin, methanal, formal, and methylene oxide, is an organic carbonyl compound that is colorless, is flammable, and has an irritatingly pungent gas/vapor odor in the aliphatic series (Shaham et al., 2002;Santovito et al., 2011). It has high solubility in water and high reactivity (Orsiere et al., 2006;Salthammer et al., 2010). ...
... Кроме того, хромосомные нарушения у работников патанатомических лабораторий были обнаружены в нескольких контролируемых исследованиях, которые не были включены в обзор по причине малой выборки, отсутствия мониторинга воздуха в рабочей зоне или несбалансированной контрольной группы. Так, авторы исследования [45] описали значительное увеличение частоты СХО в периферических лимфоцитах у патологов (90 экспонированных работников и 52 контрольных субъекта; уровень воздействия 0,5-2,7 мг/м 3 (0,4-2,24 ppm)). В другой работе исследователи [46] продемонстрировали значимое увеличение уровня хромосомных аберраций в лимфоцитах периферической крови (36 экспонированных, 16 контрольных субъектов; уровень воздействия 0,073 мг/м 3 (0,06 ppm)). ...
Introduction. A systematic review and analysis of literature on genotoxic examinations of individuals occupationally exposed to formaldehyde vapors (FAV) when working in pathomorphological laboratories of medical institutions has been performed. Formaldehyde is classified by the WHO International Agency for Research on Cancer as a class I carcinogen. Many studies have been published concerning testification of the genotoxic damage of pathomorphological laboratory personnel working with formaldehyde, identification using various biomonitoring cytogenetic methods, in particular, the micronucleus test in peripheral blood lymphocytes and buccal epithelial cells, a chromosomal aberrations test, and the DNA comet assay.Material and methods. Literature was searched until December 2019 using the MedLine / PubMed database of scientific literature (https://www.ncbi.nlm.nih.gov/PubMed). Key search terms included formaldehyde laboratory micronuclei, formaldehyde laboratory chromosomal aberration, or formaldehyde laboratory DNA comet. Full-text articles published in English in journals with assigned DOIs were considered.Results. All studies reported the presence of FAV in the workplace, while in only half of the cases the level of formaldehyde was not higher than the maximum permissible values. The average exposure to formaldehyde over an 8-hour working day was 0.79 ± 0.43 mg/m3. All studies reported the presence of an increased level of the studied cytogenetic biomarkers compared to controls. A total analysis of the data showed more than a 2.5-fold excess in the level of micronuclei in the peripheral blood lymphocytes of laboratory workers compared with the control groups (8.15 ± 2.57 ‰ vs. 3.56 ± 1.15 ‰; p < 0.05), and more than a 5-fold excess in case of the level of micronuclei in buccal epithelial cells (0.83 ± 0.09 ‰ vs. 0.16 ± 0.01 ‰; p < 0.05).Conclusion. Thus, pathomorphological laboratory personnel exposed to FAV is at potential risk to life and health from the long-term impact of genotoxic eff
... Formaldehyde (HCHO), also known as formalin, methanal, formal, and methylene oxide, is an organic carbonyl compound that is colorless, is flammable, and has an irritatingly pungent gas/vapor odor in the aliphatic series (Shaham et al., 2002;Santovito et al., 2011). It has high solubility in water and high reactivity (Orsiere et al., 2006;Salthammer et al., 2010). ...
Background and objective:
Exposure to formaldehyde has adverse effects on health both acutely and over the long term (e.g., carcinogenicity). The substance is widely used in pathology and histology departments. This study focused on cancer risk of formaldehyde in pathology department of five hospitals in Rasht.
Materials and methods:
Sampling and determination of formaldehyde in pathology department were carried out based on the NIOSH method of 3500. The working condition and working environment were investigated and a semi quantitative risk assessment were used to health risk assessment of formaldehyde and The individual lifetime cancer probability, which is defined as the increase in the probability of developing cancer during continuous exposure to an air pollutant were used to assess health risks with formaldehyde.
Results:
The results showed that the exposure level of all subjects were higher than the Occupational Exposure Limit for 8 hours exposure time of formaldehyde. However, in the five occupational groups, the highest weekly exposure index was observed for the Lab Technicians (0.664 ppm) at Hospital no. 5, which could have been due to more daily working hours at this sampling site and a lack of adequate ventilation. The formaldehyde concentration was in the 0.0192 to 0.326 ppm ranges for five hospital pathology departments. The cancer risk ranged from 9.52×10-5 to 1.53×10-3, and it was greater than the WHO acceptable cancer risk level.
Conclusions:
The results of the risk assessments can be used for managing the chemical exposure of allocated resources for defining control actions. This process plays an important role in reducing the level of exposure to formaldehyde in pathology departments.
.
... 59 Levels of short-term exposure to formaldehyde were also high in embalmers 60 and pathologists. 61 ...
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.
... Our results on SCE frequency ( Figure 1 and Table 1) agree with data from other studies which reported a 441 higher frequency of this cytogenetic biomarker in FA exposed workers compared to referents, including a 442 previous study published by us and carried in a smaller group of anatomy-pathology workers (Costa et al., 443 2008). Shaham et al. (1997Shaham et al. ( , 2002 reported similar findings in two studies involving pathology workers 444 exposed to FA; both groups of workers showed significantly higher SCE frequencies compared to controls. 445 ...
Formaldehyde (FA) is a high-volume production chemical manufactured worldwide to which many people are exposed to both environmentally and occupationally. FA was recently reclassified as a human carcinogen. Several epidemiological studies have revealed an increased risk of cancer development among workers exposed to FA. Although FA genotoxicity was confirmed in a variety of experimental systems, data from human studies are conflicting. The aim of the present study was to evaluate the occupational exposure to FA in a multistage approach relating the exposure with different biomarkers (dose and effect) and individual susceptibility. Air monitoring was performed to estimate the level of exposure to FA during shift work. Eighty-five workers from hospital anatomy-pathology laboratories exposed to FA and 87 controls were tested for cytogenetic alterations in lymphocytes (micronucleus, MN; sister-chromatid exchange, SCE) and T-cell receptor (TCR) mutation assay. The frequency of MN in exfoliated buccal cells, a first contact tissue was also assessed. Percentages of different lymphocyte subpopulations were selected as immunotoxicity biomarkers. The level of formic acid in urine was investigated as a potential biomarker of internal dose. The effects of polymorphic genes of xenobiotic metabolising enzymes and DNA repair enzymes on the endpoints studied were determined. The mean level of FA exposure was 0.38 ± 0.03 ppm. MN (in lymphocytes and buccal cells) and SCE were significantly increased in FA-exposed workers compared to controls. MN frequency positively correlated with FA levels of exposure and duration. Significant alterations in the percentage of T cytotoxic lymphocytes, NK cells and B lymphocytes were found between groups. Polymorphisms in CYP2E1, GSTP1 and FANCA genes were associated with increased genetic damage in FA-exposed subjects. The obtained information may provide new important data to be used by health and safety care programs and by governmental agencies responsible for setting the acceptable levels for occupational exposure to FA.
... Additionally, men are more vulnerable to alcohol consumption (Huang et al. 2015). However, in agreement with other studies (Celik et al. 2007;Shaham et al. 2002;Pinto et al. 2000), there was no influence of alcoholic drinks on DNA damage. ...
Several negative health effects have been associated with environmental pollution. Coal mining activities are related to DNA damage. However, the impact of lifestyle as well as environmental exposure must be considered when evaluating the extent of DNA damage. The aim of this cross-sectional study was to analyze nutritional status, dietary patterns, and the prevalence of non-communicable diseases (CNCDs) among coal miners as well as to investigate the correlation of these variables with DNA damage. We used a questionnaire to assess demographics, health, and dietary habits. The nutritional status was measured in terms of BMI (body mass index) and DNA damage was assessed by the comet assay. The sample population was composed of 158 coal miners from the largest coal mining company in South of Brazil, and majority of them were classified as overweight (51.3%) or obese (28.5%). Hypertension was the most common CNCD (50.6%) and a majority of these workers consumed all groups of foods three or more times a week. There was a significant positive correlation between BMI and DNA damage (r = 0.1646, p = 0.04) and this association was stronger (r = 0.2556, p = 0.04) in coal miners with some CNCD. There was no significant correlation between dietary patterns and DNA damage in coal miners. These results suggest that the nutritional status and CNCD increase the extent of DNA damage in coal miners. Since this population is at high occupational risk, specific strategies should be designed to improve the health of these workers, aiming to achieve health equity.
... Formaldehyde in air was evaluated in the selected laboratories and the mean levels was 1.3 ug/m3 ±1.5which exceeds the local standard levels of 0.37 ug\m 3 and also the international standards of Occupational Safety and Health Administration (OSHA) which is 0.75 ppm. (13) The characterization of the population studied is summarized in Table 1. Controls and exposed workers did not differ significantly in age, gender distribution and in smoking habits.. (14) For routine screening of chemicals that are known or suspected to cause hepatocellular injury, the ALT is considered to be the aminotransferase most specific for the liver.. ...
Background: Increased levels of tumour markers: carcinoembryonic antigen (CEA),
squamous cell carcinoma antigen (SCC -Ag), Alpha feto protein (AFP), and neuron-specific enolase (NSE) may indicate the onset of the carcinogenic process. The aminotransferases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are the most commonly measured enzymes that detect hepatocellular injury. Formaldehyde has an important application as a disinfectant and preservative, reason why relevant workplace exposure may also occur in pathology and anatomy laboratories and in mortuaries. Urinary thioethers are excretion products resulting from a series of metabolic reactions which involve oxidation of lipophilic chemicals to water-soluble compounds
Objective: The aim of the present study was to evaluate of the hazardous effects of occupational exposure to formaledehyde among lab technicians through measuring liver enzymes, hepatic tumor marker (AFP, CEA) and levels of urinary thioether as indicator of exposure to Carcinogenic compounds.
Method: the study was conducted on thirty male workers employed in medical pathology and anatomy teaching laboratories. Thirty subjects were recruited as a control group matched for age, sex and socio-economic status. Results: the results revealed a high significant increase in the levels of urinary thioethers in exposed workers than those of control group and high significant elevation in the levels of tumors markers (CEA and AFP) in exposed workers in comparison with control group. Moreover, a significant increase in the levels of liver functions (AST and ALT) was observed in formaldehyde exposed workers.
Conclusion: Present data indicate that formaldehyde exposed workers exhibit an increase in tumor markers levels and additionally increase in the levels of urinary thioethers. Safety Preventive measures should be applied for reduction of the formaldehyde vapors in these laboratories.
... This may be explained by their presence at areas with formaldehyde levels higher than areas where workers are present since the study done byCosta et al., (2008)mentioned that Mn frequencies will increase with increasing levels of formaldehyde. Our results agreed with the results ofLadeira et al., (2011), Ye et al., (2005) and Shaham et al., (2002who compared the frequency of genotoxicity biomarkers between individuals occupationally exposed and non-exposed to formaldehyde and found that significant increases in DPC, SCE and Mn frequencies among exposed workers in comparison with the control but this disagreed with the results of Saad et al., (2006) who found no significant differences in SCE among exposed workers compared to their control.Tobacco smoke contains a high number of mutagenic and carcinogenic substances and is causally linked to an elevated incidence of several forms of cancers. Hence, smoking is an important variable to consider in biomonitoring studies and particularly in this study since FA is present in tobacco smoke. ...
... As can be seen in Table 3, many of the older studies (<2000) only comprised small study populations (apart from Shaham et al., 2002Shaham et al., , 2003 and positive as well as negative results were obtained. More recent investigations often report on larger groups and positive genotoxic findings predominate. ...
8-hour TWA: 0.3 ppm (0.369 mg/m3)
STEL: 0.6 ppm (0.738 mg/m3)
BLV: -
Additional categorisation: SCOEL carcinogen group C
(genotoxic carcinogen with a mode-of action based threshold)
Notation: Sensitisation (Dermal)
Recommendation Executive Summary
When reviewing the scientific data available for formaldehyde (FA), SCOEL recognised that FA is a very well investigated substance, for which a high number of reliable high-quality studies relevant for the occupational situation are available. This includes a variety of epidemiological studies on exposed workers, studies on human volunteers for sensory irritation and a broad database on experimental animal studies.
SCOEL has assessed all available information. FA has a potential to cause adverse health effects and is therefore a hazardous chemical agent. FA also is a genotoxic carcinogen, for which a mode-of-action based limit value can be derived. For FA the available information is adequate for deriving a health-based OEL (8-hour TWA and STEL).
Analytical measurement systems exist to determine the recommended levels of formaldehyde with an appropriate level of precision and accuracy.
Due to the high water solubility and the high reactivity of FA, it shows intrinsic hazardous properties predominantly with respect to local effects. In addition, directly induced systemic effects of inhalation at concentrations relevant for the workplace are considered unlikely. The following key effects were considered as being relevant for the protection of workers and in particular the OEL derivation:
(a) the potential of the substance to produce respiratory irritation and chemosensory effects, both in humans and animals, and
(b) the local carcinogenicity in studies with experimental animals exposed by inhalation.
Ad (a): Sensory irritation has been investigated in experimental animals, in exposed workers, and most importantly also under controlled exposures in volunteers.
Ad (b): Tumour induction of the upper respiratory tract has been studied in experimental animals including mechanistic investigations on events that will trigger carcinogenesis, like DNA-protein crosslinks (DPX), DNA-adducts and sustained cytotoxicity leading to cell proliferation. In addition, several high quality epidemiological studies are available on exposed workers. A review by RAC (ECHA 2012) concluded that these data would not provide sufficient evidence to classify FA as a human carcinogen but a classification as Cat. 1B carcinogen (H350 “May cause cancer”; based on CLP criteria) would be appropriate.
Mechanistic studies have provided strong evidence that tumour induction in the nasal mucosa of rats and mice is the result of chronic proliferative processes caused by the cytotoxic effects of the substance in combination with DNA alterations by endogenous and exogenous FA. The dose-response relationships for all parameters investigated, such as damage to the nasal epithelium, cell proliferation, tumour incidence, the formation of DPX and DNA-adducts, is very flat for low level exposures and becomes much steeper at higher concentrations. For these endpoints no-effect concentrations were demonstrated with the exception of the formation of DPX and DNA-adducts. However, at the lowest concentrations investigated so far (0.7 ppm), adducts caused by the endogenous, physiological FA by far exceeded the amounts caused by exogenous FA. The background incidence of nasal tumours in rodents and of nasopharyngeal tumours in humans is very low in spite of the appreciable amount of endogenous DNA adducts. One of the reasons may be the low physiological proliferation rate of the respiratory epithelium, and as long as this is not increased (which requires exposure to concentrations of more than 2 ppm), the probability of tumour formation also is low. At prolonged exposure at 2 ppm in rats, the half-life of the most sensitive biomarker of DNA-adducts, N2-hydroxymenthy-dG, was 7 days. At 2 days of exposure in monkeys, the biomarker was estimated to be by a factor of 5-11 lower for the exogenous adduct than that of the endogenous adduct in the nasal epithelium. Comparing short term exposures, the relationship of exogenous/endogenous DNA–adducts was by a factor of about 5-fold lower for monkeys than for rats, suggesting monkeys being a less sensitive species than rats. Taking into consideration the strong non-linearity of the dose response curve after a single exposure at lower exposure concentrations, the ratio between exogenous/endogenous adducts will at low exposures be dominated by the endogenous adducts, but the ration will increase disproportionately with increasing FA concentrations. Also in the low dose range, cell proliferation is not increased. It has therefore been considered that the genotoxicity of FA plays no or at most a minor role in a potential carcinogenic effect at this exposure-range.
Therefore SCOEL considers FA as a group C carcinogen (genotoxic carcinogens for which a limit value derived from mode-of-action based threshold is supported) (SCOEL, 2008).
Experimental studies support that the local carcinogenesis at the portal-of-entry is pivotal. In the sensitive rat species, the apparent LOAEC was 6 ppm, and the apparent NOAEC was 2 ppm for nasal cancer. Experimentally, the histopathological NOAEC for nasal effects of FA in rats and monkeys is 1 ppm and the NOAEC for regenerative cell replication 2 ppm. At these NOAECs, the FA-DNA adducts were less in monkeys than in rats as was the relationship of exogenous/endogenous DNA adducts, which is in line with the assumption that humans should be a less sensitive species. The new studies confirm that local FA-DNA adducts show a highly non-linear relationship with external FA exposures. At ≤ 2 ppm FA, the FA DNA-adducts induced by external exposures comprise a minor portion of the total FA-DNA adducts, which were driven mainly by internal (naturally generated) FA. This is supported by considerations on toxicokinetics, concluding that the intracellular FA concentration increases only slightly, and the intracellular glutathione concentration decreases only slightly in this range and that the homeostasis within the epithelial cells would not be affected. Therefore, the apparent NOAEC of 1 ppm can be considered a mode-of-action based NOAEC for carcinogenic effects at the portal-of-entry.
Ad (a): Preventing histopathological effects, like irritation, inflammation and regenerative cell replication caused by cytotoxic irritation, will also prevent nasal cancer as at such low exposure concentrations (< 1 ppm) the total intracellular FA concentration is dominated by the internal (natural) FA. This experimentally derived paradigm, namely the avoidance of cell proliferation in the upper respiratory tract being critical to prevent local carcinogenicity, also holds valid for humans. Ideally the lower sensitivity against cytotoxic irritation of humans as compared to rats should be taken into consideration. While cytotoxic irritation cannot be investigated in humans, mainly for ethical reasons, there is a broad database available for sensory irritation from volunteer studies under controlled exposure conditions. By derivation of limit values for sensory irritation of eye and upper respiratory tract in humans also the critical effects of irritation-induced local cell proliferation and subsequent possible carcinogenesis shall be covered (Brüning et al 2014).
In this respect, numerous studies, comprising in total more than 400 volunteers, have addressed human sensory irritation effects of FA. The Paustenbach et al (1997) review [and two similar reviews of Bender (2002) and Arts et al. (2006)], concluded that sensory irritation would seldom be observed at 0.5 ppm FA and extrapolated these results to suggest that a limit of 0.3 ppm would prevent sensory irritation in nearly all occupational exposed individuals. Two recent chamber studies (Lang et al. 2008; Mueller at al. 2013) found no pure sensory irritation, as measured by objective parameters, in the concentration range from 0.5 to 0.7 ppm at a constant exposure to FA during a 4-hour period. Both studies applied slightly different concentration regimes. Exposures with 4 superimposed peaks being most relevant for derivation of an OEL with STEL were 0.3 ppm + peaks of 0.6 ppm and 0.5 ppm + peaks of 1 ppm in the Lang study, and in that of Mueller 0.3 ppm + peaks of 0.6 ppm and 0.4 ppm + peaks of 0.8 ppm. Objective signs of irritation were only observed at 0.5 ppm + peaks of 1 ppm. Because 0.3 ppm + peaks of 0.6 ppm was a consistent NOAEC in both of these investigations this exposure regime is taken forward for derivation of the OEL, TWA with STEL. The recent study (Mueller et al. 2013) was conducted with hypo- and hyper-sensitive individuals, who showed no difference in sensory irritation sensitivity to FA, but the hypersensitive individuals reported significantly higher effects for olfactory induced symptoms as ”perception of impure air”.
Based on these experimental studies in human volunteers SCOEL derives an OEL of 0.3 ppm (8 h TWA) with a STEL of 0.6 ppm. As sensory irritation is a concentration rather than a cumulative dose-driven effect, a STEL value is appropriate. This OEL based on sensory irritation will also protect workers from undue annoyance and discomfort at the workplace.
Ad (b): The OEL of 0.3 ppm derived from human volunteer studies is supported by data in experimental animals. The histopathological NOAEC for nasal effects of FA in rats and monkeys is 1 ppm and for regenerative cell proliferation in rats is 2 ppm. Preventing these effects will also prevent nasal cancer. As a strong support, toxicokinetic studies suggest that at an exposure level of 1 ppm the local intracellular concentration of formaldehyde is dominated by the internal (naturally produced) FA. Backed by this finding, SCOEL considers an uncertainty factor of 3 to be sufficiently protective. This supports the proposed OEL (8h-TWA) of 0.3 ppm.
As a result of the predominantly local effects of FA, a “skin” notation is not required. FA is a well-known contact allergen to the skin (skin sensitizer). A notation sensitisation (Dermal) is therefore added. Against the background of a widespread use, respiratory sensitization has been reported only occasionally, and therefore the designation as respiratory sensitizer is not warranted.
A biological limit value (BLV) or biological guidance value (BGV) is not proposed.
For additional details, which were considered in the OEL derivation by SCOEL, see chapter 7.11.
... Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of formaldehyde are well documented in mammalian cells and in rodents, in vivo genotoxic effects and carcinogenic properties in humans remain to be documented. Several studies have reported the induction of DPC [32], sister chromatid exchange [33][34][35], chromosomal aberrations [36] and micronuclei (MN) using the cytokinesis-blocked micronucleus (CBMN) assay [35,[37][38][39][40][41][42] in individuals occupationally exposed to formaldehyde. ...
Aim of the study: To evaluate the genotoxic effect of occupational exposure to formaldehyde of pathology and anatomy laboratory workers. Methods: Exposure to formaldehyde was determined by the use of passive air monitoring badges clipped near the breathing zone of 59 workers for 15 minutes and 8 hours. Assessment of chromosomal damage was carried out by the use of cytokinesis-blocked micronucleus assay (CBMN) in peripheral lymphocytes of 59 exposed subjects in comparison with 37 gender -, age- and smoking habits- matched controls. The CBMN assay was combined with fluorescent in situ hybridization with a pancentromeric DNA probe in 18 exposed subjects and 18 controls randomized from the initial populations. Results and discussion: Mean concentrations of formaldehyde were 2.0 ppm (range 0.1 - 20.4 ppm) and 0.1 ppm (range 0.1 - 0.7 ppm) for sampling time of 15 minutes and 8 hours, respectively. Binucleated micronucleated cell rates were significantly higher in the exposed subjects than in controls (16.9‰ ± 9.3 versus 11.1 ‰ ± 6.0, P = 0.001). Centromeric micronucleus rates were higher in exposed subjects than in controls (17.3‰ ± 11.5 versus 10.3‰ ± 7.1) but the difference was not significant. Acentromeric micronuclei were similar in exposed subjects and controls. Conclusion: The enhanced chromosomal damage (particularly chromosome loss) in peripheral lymphocytes of pathologists/anatomists emphasizes the need to develop safety programs.
... Vários estudos realizados em animais e em populações humanas demonstraram que a frequência de SCE aumenta em células que tenham estado expostas a agentes mutagénicos e carcinogénicos (Yager et al., 1986;He et al., 1998;Shaham et al., 2002). (Fenech, 2000). ...
... Thus, there were very likely people who had been exposed to several risks, and therefore, they were considered as a separate group. Although it was not possible to measure chemical compound exposure at the workplace of these individuals, other studies reported that an increased count of SCE frequency was observed after occupational exposure to formaldehyde [41,42], benzene [43] and polycyclic aromatic hydrocarbons [44], as well as among interventional cardiology laboratory workers [45] and among nurses handling cytostatic drugs [46]. ...
Sister chromatid exchange (SCE) is a widely used sensitive cytogenetic biomarker of exposure to genotoxic and cancerogenic agents. Results of human monitoring studies and cytogenetic damage have revealed that biological effects of genotoxic exposures are influenced by confounding factors related to life-style. Vegetable and fruit consumption may play a role, but available results are not consistent. The purpose of the study was to investigate the effect of consumption of raw and cooked vegetables and fruits on SCE frequency.
A total of 62 participants included colorectal cancer (CRC) patients, hospital-based controls and healthy laboratory workers. SCE frequency was assessed in blood lymphocytes. Frequency of vegetable and fruit consumption was gathered by structured semi-quantitative food frequency questionnaire.
SCE frequency was lowest among hospital-based controls (4.4 ± 1.1), a bit higher in CRC patients (4.5 ± 1.0) and highest among laboratory workers (7.4 ± 1.2) (p < 0.05). Multivariable linear regression showed a significant inverse effect (b = -0.20) of raw vegetable consumption, but not so for intake of cooked vegetables and fruits.
The results of the study have shown the beneficial effect of consumption of raw vegetables on disrupted replication of DNA measured by SCE frequency, implying protection against genotoxic agents. Further effort is required to verify the role of cooked vegetables and fruits.
... Although several studies in humans have shown genotoxic effects such as chromosome aberrations or micronuclei in peripheral blood lymphocytes (He et al., 1998;Shaham et al., 1997Shaham et al., , 2002Yager et al., 1986;Ye et al., 2005); these are neither hematopoietic stem cells, nor are they physiological surrogates for hematopoietic stem cells. The cells in which these effects are demonstrated are mature T-lymphocytes that circulate in blood and infiltrate mucosa, submucosa, subcutaneous and subdermal tissues at all body surfaces. ...
Abstract A recent study (Zhang et al., 2010) has provided results attributed to aneuploidy in circulating stem cells that has been characterized as providing potential support for proposed mechanisms for formaldehyde to impact bone marrow. A critical review of the study, as well as a reanalysis of the underlying data, was performed and the results of this reanalysis suggested factors other than formaldehyde exposure may have contributed to the effects reported. In addition, although the authors stated in their paper that "all scorable metaphase spreads on each slide were analyzed, and a minimum of 150 cells per subject was scored," this protocol was not followed. In fact, the protocol to evaluate the presence of monosomy 7 or trisomy 8 was followed for three or less samples in exposed workers and six or less samples in non-exposed workers. In addition, the assays used (CFU-GM) do not actually measure the proposed events in primitive cells involved in the development of acute myeloid leukemia. Evaluation of these data indicates that the aneuploidy measured could not have arisen in vivo, but rather arose during in vitro culture. The results of our critical review and reanalysis of the data, in combination with recent toxicological and mechanistic studies, do not support a mechanism for a causal association between formaldehyde exposure and myeloid or lymphoid malignancies.
... Our results on SCE frequency ( Figure 1 and Table 1) agree with data from other studies which reported a 441 higher frequency of this cytogenetic biomarker in FA exposed workers compared to referents, including a 442 previous study published by us and carried in a smaller group of anatomy-pathology workers (Costa et al., 443 2008). Shaham et al. (1997Shaham et al. ( , 2002 reported similar findings in two studies involving pathology workers 444 exposed to FA; both groups of workers showed significantly higher SCE frequencies compared to controls. 445 ...
Given its economic importance and widespread use, formaldehyde (FA) is an important industrial compound to witch many people is exposed both environmentally and/or occupationally. Because of its sensitising properties, irritating effects and potential cancer hazard, FA is of great environmental health interest. The highest level of human exposure to this aldehyde occurs in occupational settings, namely in pathology and anatomy laboratories. In order to evaluate the potential health effects due to long-term occupational exposure to FA a group of pathology/anatomy workers was tested for a variety of biological endpoints: micronuclei (MN); sister chromatid exchange (SCE)- and comet assay (comet tail length, TL). In addition, the frequency of polymorphic genes of xenobiotic metabolising enzymes (GSTM1, GSTT1) and DNA repair enzymes (ERCC1, ERCC4, ERCC5-2, ERCC5-5) were also studied. A non-exposed group with same sociodemographic characteristics was also studied and data obtained from both groups were compared. Controls did not differ from exposed workers in gender, age and smoking habits. Air sampling was performed in worker's breathing zone for representative working periods, and time weighted average (TWA) level of exposure for each exposed subject assessed. The TWA mean value for FA exposed workers was 0.44 ± 0.08 ppm. Both MN and SCE frequencies were significantly higher in the exposed subjects when compared with controls. Comet assay data showed significantly increase of TL in FA-exposed workers with respect to the control group. Gender, age and smoking habits did not have a significant effect on the frequencies of studied biomarkers. A positive correlation was found between TWA values and MN frequency (r = 0.384, p = 0.001) and TL (r = 0. 333, p = 0.005). Results obtained confirm an association between genetic damage and occupational exposure to FA. Such results along with the recent implications of human carcinogenicity, point out for the need of close monitoring of FA occupational exposure.
... Research focused on anatomists, pathologists, and embalmers spanning over 30 years has found correlations with brain cancer and leukemia and was more recently expanded to include chromosomal damage. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] Although limited, there has been research on student exposure during professional training. [46][47][48][49][50] Yeager reported a significant change in sister-chromatid exchanges in lymphocytes in 8 non-smoking students over the duration of the 10-week anatomy class, with each medical student acting as their own control. ...
The purpose of this descriptive study was to investigate current and future instructional practices and the most important factors influencing those practices in anatomy laboratories within medical schools and physical therapy schools.
A survey instrument was developed using the Delphi method in 2008. In addition to refining the survey instrument, the participants in the Delphi study also provided their expert testimony on current and future teaching methods as well as influencing factors. The survey was then administered in 2009 to a random sampling of anatomy instructors in physical therapy (n = 60) and medical schools (n = 15).
Cadaver dissection is currently the most common instructional technique, but its use is predicted by our experts and our general survey respondents to decline by 2020 in both medical and physical therapy schools. In the future, more instructional time will be devoted to imaging, computerized teaching aids, living/surface anatomy instruction, and prosections. The most important factors influencing anatomy education for all groups were budget, instructional time, and the availability of qualified anatomy instructors. Factors predicted to have little influence on anatomy instruction include student learning styles and ethical considerations. Contrary to current concerns expressed by some, health and safety concerns were also judged to have little influence on anatomy instruction.
Evidence supports a trend of decreasing time on cadaver dissection and increasing time on technology-based instructional methods.
... coli) cells2345. In both cellular and human studies, formaldehyde exposure is associated with increased levels of chromosomal aberrations, sister chromatid exchange and micronuclei formation67891011. Increased ring and dicentric chromosomes were also observed in lymphocytes of workers exposed to formaldehyde [12]. ...
Formaldehyde is a reactive chemical that is commonly used in the production of industrial, laboratory, household, and cosmetic products. The causal association between formaldehyde exposure and increased incidence of cancer led the International Agency for Research on Cancer to classify formaldehyde as a carcinogen. Formaldehyde-induced DNA-protein crosslinks (DPCs) elicit responses involving nucleotide excision repair (NER) and homologous recombination (HR) repair pathways; however, little is known about the cellular and genetic changes that subsequently lead to formaldehyde-induced genotoxic and cytotoxic effects. Herein, investigations of genes that modulate the cytotoxic effects of formaldehyde exposure revealed that of five NER-deficient Chinese Hamster Ovary (CHO) cell lines tested, XPF- and ERCC1-deficient cells were most sensitive to formaldehyde treatment as compared to wild-type cells. Cell cycle analyses revealed that formaldehyde-treated XPF-deficient cells exhibited an immediate G2/M arrest that was associated with altered cell ploidy and apoptosis. Additionally, an elevated number of DNA double-strand breaks (DSBs), chromosomal breaks and radial formation were also observed in XPF-deficient cells following formaldehyde treatment. Formaldehyde-induced DSBs occurred in a replication-dependent, but an XPF-independent manner. However, delayed DSB repair was observed in the absence of XPF function. Collectively, our findings highlight the role of an XPF-dependent pathway in mitigating the sensitivity to formaldehyde-induced DNA damage as evidenced by the increased genomic instability and reduced cell viability in an XPF-deficient background. In addition, centrosome and microtubule abnormalities, as well as enlarged nuclei, caused by formaldehyde exposure are demonstrated in a repair-proficient cell line.
... e exposed to levels of airborne FA that exceed both the national guideline limit value and the ACGIH recommended exposure criteria. Several studies on environmental monitoring of pathology/anatomy laboratories ( Khanzadeh and Pulido 2003; Dufresne et al. 2002; Shaham et al. 1997) also found levels of FA near or higher than recommended limit values. Shaham et al. (2002) reported for 14 pathology departments mean levels of FA exposure of 0.4–2.24 ppm. Ohmichi et al. (2006) measured FA indoor concentrations and personal exposure levels in a gross anatomy lab during 3 sessions out of a total 20 sessions over 10 wk; the mean level of exposure to FA obtained was 0.44 ppm, while the average personal FA expos ...
Formaldehyde (FA) is a world high-production compound with numerous applications ranging from production of resins to medicines. Due to its sensitizing properties, irritating effects and potential cancer hazard FA is of great environmental health concern. Numerous studies in humans and experimental animals demonstrated that inhaled FA produced toxicity, genotoxicity, and cancer at distal sites. IARC, based on sufficient data, reclassified FA as a human carcinogen. The highest level of human exposure to this aldehyde occurs in occupational settings, namely, in pathology and anatomy laboratories, where FA is commonly used as a fixative and tissue preservative. Several studies consistently showed that the levels of airborne FA in anatomy laboratories exceeded recommended exposure criteria. In order to assess the genotoxic effects of chronic occupational exposure to FA, a group of pathology/anatomy workers was assessed using a micronucleus (MN) test and comet assay. The level of exposure to FA was also determined and the time-weighted average (TWA) of exposure was calculated for each subject. The TWA mean value for FA exposed workers was 0.43 ± 0.06 ppm, exceeding national and international recommended limit levels of 0.3 ppm. Both MN frequency and comet assay parameters were significantly higher in exposed subjects. Data obtained confirm a correlation between genetic damage and occupational exposure to FA. These data, along with recent implications of human carcinogenicity, point out the need for close monitoring of occupational exposure to FA. Implementation of security and hygiene measures as well as good practices campaigns may be crucial to decrease risk.
... In our results, there was no influence of alcohol consumption, age or time of service in the exposed individuals on Comet assay parameters tail length, % of tail DNA and damage index or the MN frequency (Celik et al., 2007;Shaham et al., 2002;Pinto et al., 2000). The results obtained with respect the alcohol consumption are in Table 2 Comet assay and Micronucleus test parameters in non-exposed control and Exposed group divided by work areas activities (mean ± standard deviation). ...
Coal mining is one of the most important causes of environmental pollution, as large quantities of coal dust particles are emitted. Colombia-South America has large natural coal reserves and "El Cerrejón" is the world's largest open-cast mine located in the northern department of Guajira. The aim of the present study was to evaluate genotoxic effects in a population exposed to coal residues from the open-cast mine "El Cerrejón". 100 exposed workers and 100 non-exposed control individuals were included in this study. The exposed group was divided according to different mining area activities: (i). Transport of extracted coal, (ii). Equipment field maintenance, (iii). Coal stripping and, (iv). Coal embarking. Blood samples were taken to investigate biomarkers of genotoxicity, specifically, primary DNA damage as damage index (DI), tail length and% of tail DNA using the Comet assay (alkaline version) and chromosome damage as micronucleus (MN) frequency in lymphocytes. Both biomarkers showed statistically significantly higher values in the exposed group compared to the non-exposed control group. No difference was observed between the exposed groups executing different mining activities. These results indicate that exposure to coal mining residues may result in an increased genotoxic exposure in coal mining workers. We did not find a correlation between age, alcohol consumption and service time with the biomarkers of genotoxicity. Our results are the first data of genotoxic effects induced by coal mining exposure in Colombia, and thus, contribute to the exploration of test batteries use for monitoring of exposed populations and may stimulate designing control, hygiene and prevention strategies for occupational health risk assessment in developing countries.
... Studies of humans exposed to formaldehyde have relatively frequently been reported as positive for genotoxic effects. [27][28][29][30][31][32][33][34][35][36] Not all studies have been positive [37][38][39] ; and the studies reported to be positive for genotoxicity have not been without controversy. 40 In contrast, most, but not all, studies of genotoxic endpoints in animals experimentally exposed to formaldehyde have been negative. ...
Epidemiological findings suggesting that formaldehyde exposure is associated with a higher risk of acute myelogenous leukemia (AML) and other hematological cancers have led to consideration of the potential mechanism of action by which inhalation of this rapidly reactive agent can cause bone marrow cancer. Two major mechanism-based arguments against formaldehyde as a leukemogen have been the difficulty in envisioning how inhaled formaldehyde might penetrate to the bone marrow; and the lack of similarity of non-cancer effects to other known human myeloleukemogens, particularly the absence of pancytopenia in humans or laboratory animals exposed to high levels. However, both of these arguments have been addressed by the recent finding of a pancytopenic effect and chromosomal abnormalities in heavily exposed Chinese workers which, if replicated, are indicative of a genotoxic effect of formaldehyde on hematopoietic stem cells that is in keeping with other known human leukemogens. Review of the body of evidence suggests an apparent discrepancy between studies in laboratory animals, which generally fail to show evidence of penetration of formaldehyde into the blood or evidence of blood or bone marrow genotoxicity, and studies of exposed humans in which there tends to be evidence of genotoxicity in circulating blood cells. One possible explanation for this discrepancy is species difference. Another possible explanation is that myeloid precursors within the nasal mucosa may be the site for leukemogenesis. However, chloromas, which are local collections of myeloid tumor cells, are rarely if ever found in the nose. Other proposed mechanisms for formaldehyde leukemogenesis are reviewed, and dose issues at the interface between the epidemiological and hematotoxicological findings are explored.
... The present results obtained in the laboratories, evidence a difference between the two exposure metrics (0.28 ppm for TWA 8 h and 2.52 ppm for ceiling level). These results are in good agreement with previous ones reported by Shaham et al. [30]. A difference of the same order of magnitude was described in 14 pathology laboratories (0.4 ppm for TWA and 2.24 ppm for ceiling level). ...
According to the Report on Carcinogens, formaldehyde ranks 25th 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.
A study was carried out in Portugal, using 80 workers occupationally exposed to formaldehyde vapours: 30 workers from formaldehyde and formaldehyde-based resins production factory and 50 from 10 pathology and anatomy laboratories. A control group of 85 non-exposed subjects was considered. Exposure assessment was performed by applying simultaneously two techniques of air monitoring: NIOSH Method 2541 and Photo Ionization Detection equipment with simultaneously video recording. Evaluation of genotoxic effects was performed by application of micronucleus test in exfoliated epithelial cells from buccal mucosa and peripheral blood lymphocytes.
Time-weighted average concentrations not exceeded the reference value (0.75 ppm) in the two occupational settings studied. Ceiling concentrations, on the other hand, were higher than reference value (0.3 ppm) in both. The frequency of micronucleus in peripheral blood lymphocytes and in epithelial cells was significantly higher in both exposed groups than in the control group (p<0.001). Moreover, the frequency of micronucleus in peripheral blood lymphocytes was significantly higher in the laboratories group than in the factory workers (p < 0.05). A moderate positive correlation was found between duration of occupational exposure to formaldehyde (years of exposure) and micronucleus frequency in peripheral blood lymphocytes (r=0.401; p<0.001) and in epithelial cells (r=0.209; p < 0.01).
The population studied is exposed to high peak concentrations of formaldehyde with a long-term exposure. These two aspects, cumulatively, can be the cause of the observed genotoxic endpoint effects. The association of these cytogenetic effects with formaldehyde exposure gives important information to risk assessment process and may also be used to assess health risks for exposed workers.
... Some endpoints were analyzed in vitro and in epidemiological studies, including the formation of micronucleus (MN) and sister chromatide exchange (SCE) in peripheral blood lymphocytes. To assess the DNA damage in chromosomes of populations occupationally exposed to FA, SCE were used as cytogenetic biomarker in pathology laboratory workers (14,15,16). FA can also induce the formation of DNA adducts. ...
Formaldehyde is an ubiquitous pollutant to which humans are exposed. Pathologists can experience high formaldehyde exposure levels. Formaldehyde-among other properties-induce oxidative stress and free radicals, which react with DNA and lipids, leading to oxidative damage and lipid peroxidation, respectively. We measured the levels of air-formaldehyde exposure in a group of Italian pathologists and controls. We analyzed the effect of formaldehyde exposure on leukocyte malondialdehyde-deoxyguanosine adducts (M(1)-dG), a biomarker of oxidative stress and lipid peroxidation. We studied the relationship between air-formaldehyde and M(1)-dG adducts. Air-formaldehyde levels were measured by personal air samplers. M(1)-dG adducts were analyzed by a (32)P-postlabeling assay. Reduction room pathologists were significantly exposed to air-formaldehyde with respect to controls and to the pathologists working in other laboratory areas (p < 0.001). A significant difference for M(1)-dG adducts between exposed pathologists and controls was found (p = 0.045). The effect becomes stronger when the evaluation of air-formaldehyde exposure was based on personal samplers (p = 0.018). Increased M(1)dG adduct levels were only found in individuals exposed to air-formaldehyde concentrations higher than 66 microg/m(3). When the exposed workers and controls were subgrouped according to smoking, M(1)-dG tended to increase in all of the subjects, but a significant association between M(1)-dG and air-formaldehyde was only found in nonsmokers (p = 0.009). Air-formaldehyde played a role positive but not significant (r = 0.355, p = 0.075, Pearson correlation) in the formation of M(1)-dG, only in nonsmokers. Working in the reduction rooms and exposure to air-formaldehyde concentrations higher than 66 microg/m(3) are associated with increased levels of M(1)-dG adducts.
... Table 2 continued Exposure Number of participants; exposed (E), controls (C) and smokers (S) Exposure in years, mean (range) or as indicated. Exposure in ppm.Mean (M) (range)Peak (P) (range) Statistically significant outcome of FA exposures FA manufacturing and processing n E: 15 C: 15 (matched: age and sex) (S: ?) 28 (23–35) After 1971) B 1 Before 1971 B 5 Numerically the frequency of aberrant metaphases was lowest in exposed workers a Costa et al. (2008) b Orsière et al. (2006) c Shaham et al. (2002) d Thomson et al. (1984) e Ying et al. (1999) f He et al. (1998). No details on exposure characterization g Vasudeva and Anand (1996). ...
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.
Aldehydes and acetals are both naturally occurring and the result of manufacturing processes, resulting in potential human exposures in occupational settings and from the ambient air and the use of consumer products. Aldehydes and acetals have been identified as genotoxicants, carcinogens, reproductive and developmental toxicants, and irritants. However, many also demonstrate limited toxicological effects at anticipated exposure levels in the general population. Here, 64 aldehydes and acetals are cataloged by sub‐class, chemical and physical properties, toxicological effects, and regulatory standards for occupational and general population cohorts. This summary of selected aldehydes and acetals represents the range of potential toxicological effects, which may cause difficulty in utilizing read‐across to predict the toxicity of aldehydes and acetals without toxicological data.
Despite the toxicity and health risk characteristics of formaldehyde (FA), it is currently used as a cytological fixative and the definition of safe exposure levels is still a matter of debate. Our aim was to investigate the alterations in both oxidative and inflammatory status in a hospital working population. The 68 workers recruited wore a personal air-FA passive sampler, provided a urine sample to measure 15-F2t-Isoprostane (15-F2t-IsoP) and malondialdehyde (MDA) and a blood specimen to measure tumour necrosis factor α (TNFα). Subjects were also genotyped for GSTT1 (Presence/Absence), GSTM1 (Presence/Absence), CYP1A1 exon 7 (A > G), and IL6 (−174, G > C). Workers were ex post split into formalin-employers (57.3 μg/m3) and non-employers (13.5 μg/m3). In the formalin-employers group we assessed significantly higher levels of 15-F2t-IsoP, MDA and TNFα (<0.001) in comparison to the non-employers group. The air-FA levels turned out to be positively correlated with 15-F2t-IsoP (p = 0.027) and MDA (p < 0.001). In the formalin-employers group the MDA level was significantly higher in GSTT1 Null (p = 0.038), GSTM1 Null (p = 0.031), and CYP1A1 exon 7 mutation carrier (p = 0.008) workers, compared to the wild type subjects. This study confirms the role of FA in biomolecular profiles alterations, highlighting how low occupational exposure can also result in measurable biological outcomes.
SARS-CoV-2 is a novel betacoronavirus that has caused the global health crisis known as COVID-19. The implications of mitochondrial dysfunction with COVID-19 are discussed as well as deregulated mitochondria and inter-organelle functions as a posited comorbidity enhancing detrimental outcomes. Many environmental chemicals (ECs) and endocrine-disrupting chemicals can do damage to mitochondria and cause mitochondrial dysfunction. During infection, SARS-CoV-2 via its binding target ACE2 and TMPRSS2 can disrupt mitochondrial function. Viral genomic RNA and structural proteins may also affect the normal function of the mitochondria-endoplasmic reticulum-Golgi apparatus. Drugs considered for treatment of COVID-19 should consider effects on organelles including mitochondria functions. Mitochondrial self-balance and clearance via mitophagy are important in SARS-CoV-2 infection, which indicate monitoring and protection of mitochondria against SARS-CoV-2 are important. Mitochondrial metabolomic analysis may provide new indicators of COVID-19 prognosis. A better understanding of the role of mitochondria during SARS-CoV-2 infection may help to improve intervention therapies and better protect mitochondrial disease patients from pathogens as well as people living with poor nutrition and elevated levels of socioeconomic stress and ECs.
Le formol, utilisé dilué au 1/10ème ou sous forme de fixateurs composés de formules variées, représente à l'heure actuelle l'agent fixant le plus employé en pathologie. C'est à partir de prélèvements fixés par des liquides à base de formaldéhyde qu'ont été établies les sémiologies macroscopiques et microscopiques d'une majorité de maladies et définis le plus grand nombre des paramètres pronostiques et prédictifs de la réponse thérapeutique. Le formol n'est, cependant, pas un fixateur idéal. Il présente notamment des risques pour la santé et a récemment été classé par le Centre International de Recherche sur le Cancer (CIRC) comme cancérogène pour l'homme. La réglementation impose sa substitution si la mesure est techniquement possible. Ceci a conduit de nombreux fabricants à commercialiser des substituts qui, tout en étant "inoffensifs", présenteraient les qualités attendues d'un fixateur polyvalent pour l'histologie. Il s'agit, le plus souvent, de fixateurs composés à base de glyoxal. Dans notre travail, les propriétés fixatrices de plusieurs solutions de glyoxal ont été comparées à celles correspondantes du formol. Sur la plupart des points étudiés (respect de la microanatomie et de l'antigénicité, conservation des acides nucïéiques, aptitude à conserver les pièces opératoires, biocidie, etc), les solutions de glyoxal se sont révélées très inférieures au formol. Elles ne peuvent donc être recommandées comme fixateur polyvalent.
This work described an analysis study of the risk of occupational exposure to formaldehyde in pathology labs of university. One hundred thirty-two air samples of the breathing zone were collected in the activity labs (macroscopic examination of surgical pieces or biopsy, tissue processing and chemical waste disposal), during five weeks. To quantify the formaldehyde present in the ambient of histology laboratory, NIOSH 2016 method was used, for this matrix, based on the formaldehyde derivatization reaction in tubes acidified with 2,4-DNPH was optimized. The geometric mean ambient concentrations of formaldehyde, among the activities under investigation, were between 0.7 and 3.7 ppm indicating high levels of the substance during the week. It was verified that 100 % of the students had exposures above the exposure limit, i.e., greater than a maximum concentration (MC) of 0.3 ppm (NP 1796: 2007).
Background: Formaldehyde is a reactive chemical that is commonly used in the production of industrial, laboratory, household, and cosmetic products. Formaldehyde (FA) is a potential carcinogen and mutagen. Objectives: This study was designed to evaluate the systemic genotoxicity of formaldehyde in experimental animals and in subjects exposed to FA. Material, Subjects and Methods: The animal study included twenty one rats that were divided into Group (1): Negative control rats,Group (2): Positive control rats: received daily intraperitoneal injected with distilled water,Group (3): Formaldehyde group, received single intraperitoneal injection of Formaldehyde (0.2 mg/kg/day) after 4 weeks of treatment, rats were sacrificed then submitted to cytogenetic examination by detection of their chromosomal pattern and mitotic index in bone marrow cells. The human study comprised two groups: 30 individuals occupationally exposed to formaldehyde in Zagazig University (cases) and 15 unexposed individuals (controls), from whom peripheral blood were collected and used for evaluation of the chromosomal aberrations (CAs) frequency and the comet assay for detection of DNA damage.Results: This study revealed increased frequency of structural chromosomal aberrations and decreased mitotic index of bone marrow cells of rats exposed to FA. Individuals exposed to FA also showed high frequency of chromosomal aberrations and increased levels of DNA damage in the Comet assay in terms of tail length and tail moment in peripheral blood lymphocytes compared to controls. Conclusion: Exposure to formaldehyde induced Chromosomal aberrations and DNA damage in peripheral blood lymphocytes of exposed subjects and bone marrow cells of albino rats.
Formaldehyde (FA) is a very reactive compound that forms DNA adducts and DNA-protein crosslinks, which are known to contribute to FA-induced mutations and carcinogenesis. Post-translational modifications to histones have recently attracted attention due to their link with cancer. In the present study, we examined histone modifications following a treatment with FA. FA significantly phosphorylated histone H3 at serine 10 (H3S10), and at serine 28 (H3S28), the time-course of which was similar to the phosphorylation of H2AX at serine 139 (γ-H2AX), a marker of DNA double strand breaks. The temporal deacetylation of H3 was observed due to the reaction of FA with the lysine residues of histones. The phosphorylation mechanism was then analyzed by focusing on H3S10. The nuclear distribution of the phosphorylation of H3S10 and γ-H2AX did not overlap, and the phosphorylation of H3S10 could not be suppressed with an inhibitor of ATM/ATR, suggesting that the phosphorylation of H3S10 was independent of the DNA damage response. ERK and JNK in the MAPK pathways were phosphorylated by the treatment with FA, in which the JNK pathway was the main target for phosphorylation. The phosphorylation of H3S10 increased at the promoter regions of c-fos and c-jun, indicating a relationship between FA-induced tumor promotion activity and phosphorylation of H3S10. These results suggested that FA both initiates and promotes cancer, as judged by an analysis of histone modifications.
Copyright © 2014 Elsevier B.V. All rights reserved.
Aim of the study
To evaluate the genotoxic effect of occupational exposure to formaldehyde of pathology and anatomy laboratory workers.
Methods
Exposure to formaldehyde was determined by the use of passive air monitoring badges clipped near the breathing zone of 59 workers for 15 minutes and 8 hours. Assessment of chromosomal damage was carried out by the use of cytokinesis-blocked micronucleus assay (CBMN) in peripheral lymphocytes of 59 exposed subjects in comparison with 37 gender -, age- and smoking habits- matched controls. The CBMN assay was combined with fluorescent in situ hybridization with a pancentromeric DNA probe in 18 exposed subjects and 18 controls randomized from the initial populations.
Results and discussion
Mean concentrations of formaldehyde were 2.0 ppm (range 0.1 - 20.4 ppm) and 0.1 ppm (range 0.1 - 0.7 ppm) for sampling time of 15 minutes and 8 hours, respectively. Binucleated micronucleated cell rates were significantly higher in the exposed subjects than in controls (16.9 ‰± 9.3 versus 11.1 ‰ ± 6.0, P = 0.001). Centromeric micronucleus rates were higher in exposed subjects than in controls (17.3 ‰ ±11.5 versus 10.3 ‰ ± 7.1) but the difference was not significant. Acentromeric micronuclei were similar in exposed subjects and controls.
Conclusion
The enhanced chromosomal damage (particularly chromosome loss) in peripheral lymphocytes of pathologists/anatomists emphasizes the need to develop safety programs.
Formaldehyde (FA), which is an important chemical with a wide commercial use, has been classified as carcinogenic to humans by International Research on Cancer (IARC). The genotoxic and carcinogenic potential of FA has been documented in mammalian cells and in rodents. A recent evaluation by the E.U. Scientific Committee for Occupational Exposure Limits (SCOEL) anticipated that an 8-h time-weighted average exposure to 0.2 ppm FA would not be irritating and not genotoxic in humans. In order to verify this prediction, a field study was performed that aimed at evaluating immune alterations and genetic damage in peripheral lymphocytes of workers in medium density fiberboard plants exposed to a level of FA equivalent to the OEL recommended by SCOEL (0.2 ppm). Subsets of peripheral lymphocytes, immunoglobulins (IgG, IgA, IgM), complement proteins, and tumor necrosis factor-alpha (TNF-α) levels were evaluated. DNA damage of the workers was assessed by the Comet assay. The absolute numbers and the percentages of T lymphocytes and of natural killer cells, and the levels of TNF-α were higher than the controls, whereas IgG and IgM levels were found to be lower in workers. Other examined immunological parameters were not different from those of the controls. There was no increased DNA damage in the workers compared to controls.
Background Single-Exposure Health Effects Effects of Multiple Exposures References
In the present study genotoxicological and immunotoxicological follow-up investigations were made on 811 donors including 94 unexposed controls and 717 nurses with various working conditions from different hospitals (The Hungarian Nurse Study). The nurses were exposed to different chemicals: cytostatic drugs, anesthetic, and sterilizing gases, such as ethylene oxide (ETO) and formaldehyde. The measured biomarkers were: clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations [CA], sister chromatid exchange [SCE]), and immune-toxicological monitoring (ratio of lymphocyte subpopulations, lymphocyte activation markers, and leukocyte oxidative burst). The highest rate of genotoxicologically affected donors (25.4%) was found in the group of cytostatic drug-exposed nurses. Comparing geno- and immunotoxicological effect markers, we found that among genotoxicologically affected donors the frequency of helper T cell (Th) lymphocytes, the ratio of activated T and B cells increased, whereas the oxidative burst of leukocytes decreased. In hospitals with lack of protective measures increased CA yields were observed compared to those with ISO 9001 quality control or equivalent measures. Anemia, serum glucose level, thyroid dysfunctions, benign, and malignant tumors were more frequent in the exposed groups than in controls. The hygienic standard of the working environment is the basic risk factor for the vulnerability of nurses. On the basis of these results, it is suggested, that the used cytogenetic and immunological biomarkers are appropriate to detect early susceptibility to diseases. The Hungarian Nurse Study proved that the use of safety measures could protect against occupational exposure at work sites handling cytostatic drugs, anesthetic, and sterilizing gases.
The descriptive epidemiology of primary central nervous system (CNS) tumors is based on population-based cancer registries that include tumors of the brain, cranial nerves, cerebral meninges, spinal cord, and spinal meninges. Malignant CNS tumors in adults account for 1.7% of new cancers and 2.1% of cancer deaths. In Europe, Australia/New Zealand, and North America there are 7.5-14 new cases per 100000 population per year in males, and 4-11 new cases in females. Incidence rates of benign and borderline CNS tumors are available from the Surveillance, Epidemiology, and End Results (SEER) Program for the time period 1975-2004: incidence was 8.1 new cases per 100000 population per year in males, and 12.1 in females. Incidence and mortality significantly increased in white males and females from 1975-1991; subsequently, the incidence remained steady, and mortality decreased significantly from 1992-2004. In population-based studies less than 5% of glioma risk is hereditary. Well-identified genetic syndromes that include primary brain tumors (PBTs) are most often autosomal dominant, and have variable penetrance. The most common syndrome is neurofibromatosis type 1. Ionizing radiation has a proven etiological role in experimental studies in monkeys and primates and, as a late complication of therapeutic X-irradiation, in humans. Extensive epidemiological research conducted during the past 20 years on occupational electromagnetic field exposure did not indicate strong or consistent associations with adult PBTs. The WHO/IARC has classified RF electromagnetic fields as possibly carcinogenic to humans (Group 2B) based on an increased risk for glioma associated with wireless phone use. Additional research needs to be conducted into the long-term use of mobile phones.
In this study, the harmful effects of formaldehyde (FA) on serum testosterone levels and epididymal sperm characteristics were investigated. In addition, possible protective effect of lavender oil was evaluated.
For this purpose, 21 adult male Wistar-Albino rats were used. The rats of group I was used as control group. The rats of group II were exposed FA (10 ppm/1 hour) for 35 days. The rats of group III inhaleted lavender oil (1 ml/1 hour) with FA.
While the testosterone levels, the epididymal sperm concentration and the progressive sperm motility were significantly decreased, the abnormal sperm rate was significantly increased in FA treated group when compared to control group. However, in group III, the epididymal sperm concentration and the progressive sperm motility were significantly increased, the abnormal sperm rate was significantly decreased in comparison with the FA treated group.
It can be expressed that serious damages occured via formaldehyde exposure in reproductive system and that the lavender oil had protective effects against these damages.
A novel method for the determination of trace formaldehyde in blood plasma has been established by using resonance fluorimetry technique. It was based on the fact that oxidation of pyronine Y by potassium bromate was catalyzed by formaldehyde in sulfuric acid. When the wavelength interval was at Δλ=0 nm, it was found that the decreased intensity (ΔF) of resonance fluorescence at 574.6 nm was proportional to the concentration of formaldehyde in the range of 1.27×10(-2) to 2.28 μg mL(-1). The limit of detection and the average recovery for formaldehyde were 3.80 ng mL(-1) and 101.6% (n=6), respectively. The present method had been applied to the determination of trace formaldehyde in blood plasma, and the obtained results were in good agreement with those obtained by the resonance light scattering method.
Extrapolating from extensive field measurements on foliar emissions in the U.S. approximate global inputs of isoprene and terpenes of 3.5 times 10 to the 14th power and 4.8 times 10 to the 14th power g(C)/yr, respectively, are obtained. The oxidation of these hydrocarbons could contribute in an important way to the atmospheric sources of CO (4.2-13.3 times 10 to the 14th power g/yr) and H2 (10-35 times 10 to the 12th power g/yr), and to organic species soluble in rainwater
The ability of 51 compounds, of known carcinogenic potential, to induce "unscheduled DNA synthesis" in HeLa cells has been tested in the presence or absence of a rat liver mixed-function oxidase preparation. Chemicals tested included those giving erroneous results in bacterial mutagenicity assays as well as representative compounds from various classes of chemical carcinogens including nitrosamines, polycyclic aromatic hydrocarbons, aromatic amines, and mycotoxins. Of the compounds assayed, all noncarcinogens failed to induce DNA repair; of 38 compounds of demonstrated carcinogenicity, 34 were active; safrole, N-propyl-N-nitrosourea, aflatoxin B2 and N-butyl-N-nitrosourea were, however, inactive. Six compounds for which carcinogenicity data are incomplete were active, namely, 4-nitro-o-phenylenediamine, 2-nitro-p-phenylenediamine, formaldehyde, 2,2'-dichlorobenzidine, 3,3',5,5'-tetrafluorobenzidine, and 3,3',5,5'-tetrachlorobenzidine. Three carcinogens that are weakly active or inactive in bacterial mutagenicity assays, i.e., urethan, N-dimethyl-p-aminoazobenzene, and diethylstilbestrol were active in our assay. The bacterial mutagens sodium azide and 9-aminoacridine were both inactive. The use of this assay in a tier scheme for the short-term testing of potential chemical carcinogens is discussed.
Groups of approximately 120 male and 120 female Fischer 344 rats and C57BL/6 X C3H F1 mice were exposed by inhalation to 0, 2.0, 5.6, and 14.3 ppm of formaldehyde gas 6 hr/day, 5 days/week, for 24 months. This exposure period was followed by up to 6 months of nonexposure. Interim sacrifices were conducted at 6, 12, 18, 24, 27, and 30 months. Significant formaldehyde-induced lesions were restricted to the nasal cavity and proximal trachea. The distribution and severity of these lesions were concentration dependent. Rhinitis, epithelial dysplasia, and squamous metaplasia occurred in all exposure groups of rats and in the intermediate and high exposure groups of mice. There was regression of rhinitis, dysplasia, and metaplasia at 27 months (3 months postexposure) in the 14.3- and 5.6-ppm groups of mice and in the 2.0- and 5.6-ppm groups of rats. Squamous cell carcinomas were observed in the nasal cavities of 103 rats (52 females and 51 males) and 2 male mice exposed to 14.3 ppm and in 2 rats (one male and one female) exposed to 5.6 ppm of formaldehyde gas. Formaldehyde inhalation was also weakly associated with an increase in the frequency of polypoid adenomas in the nasal cavity of male rats.
Groups of 120 male and 120 female rats were exposed by inhalation to 0, 2, 6, or 15 ppm formaldehyde vapor 6 hr/day, 5 days/week, for 18 months of a 24-month study. The present communication describes interim findings based on data available after 18 months of exposure. Squamous cell carcinomas occurred in the nasal cavities of 36 rats exposed to 15 ppm formaldehyde. The tumors ranged from small early carcinomas of the nasal turbinate to large invasive osteolytic neoplasms which extended into the subcutis of the premaxilla. Similar tumors were not detected in rats exposed for 18 months to 2 or 6 ppm or in mice exposed to 2, 6, or 15 ppm formaldehyde. Rhinitis, epithelial dysplasia, and squamous metaplasia occurred in rats from all exposure levels of formaldehyde; however, the severity and extent of the lesions were dose related. In contrast, papillary hyperplasia and squamous atypia occurred only in animals exposed to 15 ppm formaldehyde.
The effect of low-level exposure to formaldehyde on oral, nasal, and lymphoycte biological markers was studied prospectively in a group of 29 mortician students who were about to take a course in embalming. During the 85-day study period, the subjects performed an average of 6.9 embalmings and had average cumulative formaldehyde exposures of 14.8 ppm-h, with an average air concentration of 1.4 ppm during embalming. Since the average time spent embalming was 125 min, formaldehyde exposures calculated as an 8-h time-weighted average were 0.33 ppm on days when embalmings were done, which was less than the Occupational Safety and Health Administration permissible exposure limit of 0.75 ppm. Epithelial cells from the buccal area of the mouth showed a 12-fold increase in micronucleus frequency during the study period, from 0.046 +/- 0.17/1000 cells preexposure to 0.60 +/- 1.27/1000 cells at the end of the course (P < 0.05). Nasal epithelial micronuclei increased 22%, from 0.41 +/- 0.52/1000 cells to 0.50 +/- 0.67/1000 cells (P = 0.26). In blood cells, the frequency of micronucleated lymphocytes increased 28%, from 4.95 +/- 1.72/1000 cells to 6.36 +/- 2.03/1000 cells (P < 0.05), while sister chromatid exchanges decreased 7.5% (P < 0.05). A dose-response relationship was observed between cumulative exposure to formaldehyde and increases in buccal micronuclei in the 22 male subjects but not in the 7 female subjects. We conclude that low-level exposure to formaldehyde is associated with cytogenetic changes in epithelial cells of the mouth and in blood lymphocytes. These cytogenetic effects may be useful as markers of biologically effective dose.
Forty bone marrow aspirates from maintenance hemodialysis patients were prepared for chromosomal analyses. Among the 1,187 metaphases studied, only 58% were diploidies. Other abnormalities included: pseudodiploidies (5.8%), acentric fragments (3.6%), translocated chromosomes (1.9%) and one dicentric chromosome. The abnormalities found may be due to abnormal DNA synthesis in chronic renal failure or uremia, or infusion of formaldehyde which can denature DNA. This chemical was used to sterilize dialysis equipment. Incomplete rinsing can introduce this substance into the circulation.
Low concentrations of formaldehyde induce nuclear mutations when yeast cells are allowed to grow in the presence of this compound. The induction of reversions is a linear function of the concentration and depends upon the repair capacities of the treated cells. A strain defective in excision-repair (rad3-12) is more mutable by formaldehyde than the isogenic wild-type whereas a strain blocked in the mutagenic pathway (rad6-1) is not mutable after the same treatment. Allele specificities were found. In particular the lys1-1 mutation is not reversible by formaldehyde. Higher concentrations of formaldehyde induce efficiently the cytoplasmic "petite" mutation in non-growing conditions when a lethal effect is noticeable. The growth phase as well as the physiological state influence this mutagenic effect. The mutagenic effect of formaldehyde in yeast is discussed in relation with the repair processes involved.
Haploid and diploid cells of Saccharomyces cerevisiae have the same sensitivity to formaldehyde, exponentially growing cells being more sensitive than stationary phase cells for both degrees of ploidy. Strains defective (rad 1-3) or with a reduced capacity (p-, cytoplasmic respiratory deficient mutants) in excision repair of ultraviolet-induced pyrimidine dimers show a greater sensitivity to formaldehyde than the corresponding wild type. A mutant defective in radiation-induced gene conversion (rec5) shows the same sensitivity as the wild-type strain. It appears that the excision-repair system plays an important role, especially in stationary phase cells, in repairing a fraction of formaldehyde-induced lesions.
A historical cohort study evaluated the mortality experience of 26,561 workers employed in 10 formaldehyde-producing or -using facilities. Approximately 600,000 person-years of follow-up accrued as workers were followed to January 1, 1980. Estimates of historical exposure to formaldehyde by job were developed by project industrial hygienists using monitoring data available from participating plants, comments from long-term workers, and comprehensive monitoring data specifically collected for this study. Mortality from all causes combined was about as expected [standardized mortality ratio (SMR) = 96] based on mortality rates of the general U.S. population. Significantly fewer deaths occurred from infective and parasitic diseases (SMR = 51) and from accidents (SMR = 72) than expected. Cancer overall was not related to formaldehyde exposure. Workers exposed to formaldehyde had slight excesses for Hodgkin's disease and cancers of the lung and prostate gland, but these excesses were not consistently related to duration of or average, cumulative, or peak formaldehyde exposure levels. Recent animal studies found nasal cancer among rats exposed to formaldehyde, but no excess of this tumor occurred in this study. Mortality from brain cancer and leukemia among these industrial workers was not excessive in contrast to reported excesses among professional groups (e.g., anatomists, embalmers, and pathologists) with exposure to formaldehyde. Although there was a deficit for cancer of the buccal cavity and pharynx, mortality from certain subsites, i.e., the nasopharynx and oropharynx, was elevated. These subsites did not, however, show a consistently rising risk with level of exposure. These data provide little evidence that mortality from cancer is associated with formaldehyde exposure at levels experienced by workers in this study.
Sister-chromatid exchanges measured in the peripheral lymphocytes of 8 non-smoking persons after exposure to formaldehyde-embalming solution during a 10-week anatomy class showed a small (P = 0.02) average increase when compared with samples obtained from the same individuals immediately before exposure began. Breathing-zone air samples collected during dissection procedures showed a mean concentration of 1.2 ppm (1.5 mg/m3) formaldehyde.
Formaldehyde, a common environmental pollutant, inhibits repair of O6-methylguanine and potentiates the mutagenicity of an alkylating agent, N-methyl-N-nitrosourea, in normal human fibroblasts. Because formaldehyde alone also causes mutations in human cells, the compound may cause genotoxicity by a dual mechanism of directly damaging DNA and inhibiting repair of mutagenic and carcinogenic DNA lesions caused by other chemical and physical carcinogens.
In this paper concentration levels of various classes of organic chemicals in The Netherlands are reported for the base year 1980. From these levels the average intake of the Dutch population by inhalation was calculated to be approximately 1.5 g year-1. This gives reason for concern because many of the compounds either seem to exhibit carcinogenic properties or are suspected human carcinogens. Apart from (photo)chemical reactions, dry deposition seems to be an important way by which these chemicals are removed from the atmosphere. Although the deposition velocity of many organic chemicals is not well established or is completely unknown we have estimated the yearly deposition in The Netherlands to be approximately 89 000 t.
Chromosome analyses were carried out in lymphocytes from 20 male papermakers exposed to formaldehyde (FA) for 2-30 years. 20 male workers from the same factory but without FA exposure served as controls. In the exposed group a significantly increased incidence of dicentrics or dicentrics and ring chromosomes was observed for 11 workers currently employed as supervisors. In contrast to 9 operators their total mean exposure time to FA was about 2.5 times longer. No significantly higher SCE values were found for smoking or for non-smoking FA workers compared with the corresponding control subjects.
IF human lymphocytes1 or Chinese hamster2 cells are treated with the base analogue 5-bromodeoxyuridine (BrdU) in the latter part of the S period, Giemsa stained chromosomes exhibit a pattern of condensed and extended segments along their length. This phenomenon has been attributed to a delay in the spiralisation pattern of the late replicating regions along the chromosomes. Other experiments3 with Chinese hamster ovary (CHO) cells have shown that after two rounds of replication in the presence of BrdU or IdU, sister chromatids stain differentially with Giemsa, allowing the identification of the two chromatids, and the observation of sister chromatid exchanges (SCEs) without recourse to autoradiography. The chromatid with the bifilarly substituted DNA (BrdU substituted in both strands of DNA) is less condensed and stains more weakly with Giemsa than the unifilarly substituted sister chromatid. The yield of SCEs is approximately that observed by autoradiography.
Past studies have shown that formaldehyde is mutagenic in microbial tests and Drosophila and causes chromosomal aberrations in cultured mammalian cells. Chromosomal analysis of bone marrow cells and spermatocytes from exposed laboratory animals has failed to show any genotoxic effect. Information on individuals occupationally exposed is limited and there is no evidence to date that formaldehyde can induce chromosome damage at occupational levels of exposure. This study examines the chromosome aberration and sister-chromatid exchange frequencies in lymphocytes from a group of 6 pathology workers and 5 unexposed controls. No detectable differences could be found between the groups in either chromosomal aberration induction or sister-chromatid exchange frequencies.
Telephone interviews were completed in Western Massachusetts in April 1983 for 399 households (91.5 per cent) in a random sample of households with elementary school children. Woodstoves were used in 64.7 per cent of the homes, but such use was not associated with acute respiratory illness. However, formaldehyde exposure was significantly related, with a risk ratio of 2.4 (95 per cent confidence interval 1.7-3.4). New construction/remodeling and new upholstered furniture had additive effects. Neither woodstove use nor formaldehyde exposure were significantly associated with asthma, chronic bronchitis, or allergies.
Although official efforts to control air pollution have traditionally focused on outdoor air, it is now apparent that elevated
contaminant concentrations are common inside some private and public buildings. Concerns about potential public health problems
due to indoor air pollution are based on evidence that urban residents typically spend more than 90 percent of their time
indoors, concentrations of some contaminants are higher indoors than outdoors, and for some pollutants personal exposures
are not characterized adequately by outdoor measurements. Among the more important indoor contaminants associated with health
or irritation effects are passive tobacco smoke, radon decay products, carbon monoxide, nitrogen dioxide, formaldehyde, asbestos
fibers, microorganisms, and aeroallergens. Efforts to assess health risks associated with indoor air pollution are limited
by insufficient information about the number of people exposed, the pattern and severity of exposures, and the health consequences
of exposures. An overall strategy should be developed to investigate indoor exposures, health effects, control options, and
public policy alternatives.
The carcinogenic response to the combined and separate exposures to formaldehyde (HCHO) and hydrochloric acid (HCl) was investigated in male inbred SD rats. The rats were exposed to gaseous HCHO, 14 ppm, and HCl, 10 ppm, in two experiments. In one experiment the gases were premixed at high concentrations before being diluted in the exposure chamber air to maximize the formation of the carcinogen bis(chloromethyl)ether (BCME). In the second experiment exposure was repeated to HCl and HCHO premixed at high concentrations, and not premixed (to minimize BCME formation), as well as to HCHO alone and HCl alone. The second experiment is being reported on at an interim stage. HCHO alone induced squamous carcinomas of the nasal cavity as did the combined exposures to HCHO and HCl. No carcinogenic response was observed with HCl alone. HCHO accounted for most, if not all, of the carcinogenic activity of the mixture of HCHO-HCl.
A chromosomal analysis of spermatocytes at metaphase I failed to reveal any chromosomal lesions during spermatogenesis of mice treated with formaldehyde. Similarly, the dominant lethal test, except during the first and third weeks, showed no detectable effect.
The effects of formaldehyde were evaluated in the C3H/10T1/2 Cl 8 cell transformation system. Treatment of the cells with 0.1-2.5 micrograms/ml for formaldehyde alone did not result in significant rates of transformation. If formaldehyde treatment was followed by continuous treatment with 0.1 microgram/ml of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), transformed foci were produced. Methanol and formic acid lacked significant transforming activity under either treatment regimen. The results suggest that formaldehyde is an initiating agent for C3H/10T1/2 Cl 8 transformation. The fact that some compounds may act solely as initiators should be considered when this transformation system is used to study chemicals which may interact with cells by mechanisms similar to that of formaldehyde.
Cytokinesis-blocked micronucleus assay was applied as a biological dosimeter to detect abnormalities in human peripheral lymphocytes of thirteen students exposed to formaldehyde (FA) during a 12-week (10 h per week) anatomy class. Breathing-zone air samples collected during dissection procedures showed a mean concentration of 2.37 ppm (3.17 mg/m3). Ten students from the same school but without FA exposure served as controls. Chromosome aberrations (CA) and sister chromatid exchanges (SCE) were detected in both groups. The micronuclei (MN) rate (6.38 +/- 2.50 /1000) and CA rate (5.92 +/- 2.40%) in the FA-exposed group showed a significant increase (P < 0.01) when compared with those of the controls (3.15 +/- 1.46 /1000 and 3.40 +/- 1.57% respectively). A correlation between MN and CA in individuals was observed. SCE in the exposed group were also increased (P < 0.05), but not so greatly as MN or CA. The results indicated that FA might damage the chromosomes of human lymphocytes.
Formaldehyde is classified as a probable human carcinogen. DNA-protein crosslinks (DPCs) and sister chromatid exchanges (SCEs) may represent early lesions in the carcinogenic process. The authors examined the DPCs and SCEs in peripheral-blood lymphocytes of 12 and 13 workers exposed to formaldehyde and eight and 20 unexposed workers, respectively. The amounts of DPCs and SCEs in the exposed and the unexposed differed significantly after adjustment for smoking. There was a linear relationship between years of exposure and the amounts of DPC and SCE. The authors conclude that the data indicate a possible mechanism of carcinogenicity of formaldehyde, and that formaldehyde is mutagenic to humans. These results support the use of DPCs as a biomarker of occupational exposure to formaldehyde and to detect high-risk populations for secondary prevention.
Environmental Health Criteria 89. World Health Organization
- Formaldehyde Ipcs
IPCS, Formaldehyde, Environmental Health Criteria 89. World Health Organization, Geneva, 1989, pp. 11–176.
Studies of chromosomes aberrations in human lymphocytes under the influence of formaldehyde, I. Formaldehyde treatment of lymphocytes in vitro
- Miretskaya
L.M. Miretskaya, P.Y. Shvartsman, Studies of chromosomes aberrations in human lymphocytes under the influence of formaldehyde, I. Formaldehyde treatment of lymphocytes in vitro, Tsitologiia 24 (1982) 1056–1060.
Estimating human cancer risk from formaldehyde: critical issues Formaldehyde: Analytical Chemistry and Toxicology, Advances in Chemistry Series No
- R J Heck
- K T Levine
- J A Morgan
- Swenberg
Heck, R.J. Levine, K.T. Morgan, J.A. Swenberg, Estimating human cancer risk from formaldehyde: critical issues, in: V. Turoski (Ed.), Formaldehyde: Analytical Chemistry and Toxicology, Advances in Chemistry Series No. 210, American Chemical Society, Washington, DC, 1985, pp. 300–333.
Carbonyl compounds and the chemical mechanism of mutations
- Rapaport
Epidemiology of chronic occupational exposure to formaldehyde: report of the ad hoc panel on health aspects of formaldehyde