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- Exposição ocupacional a formaldeído: avaliação da exposição e efeitos genotóxicosPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, Mário; Prista, João; Gomes, Manuel Carmo; Brito, MiguelO formaldeído (FA) foi classificado, em 2004, pela International Agency for Cancer Research como agente cancerígeno. Este agente químico ocupa a 25ª posição em toda a produção química dos Estados Unidos da América, com mais de 5 milhões de toneladas produzidas por ano. Devido à sua importância económica e uso diversificado, muitos indivíduos estão expostos profissionalmente a FA. Com o estudo desenvolvido pretendeu‑se avaliar a exposição a FA em dois contextos ocupacionais distintos – na produção de FA e resinas e em laboratórios de anatomia patológica (AP) e relacionar com eventuais efeitos para a saúde, comparando a frequência de micronúcleos (MN) em linfócitos do sangue periférico e em células esfoliadas da mucosa bucal dos trabalhadores expostos a FA com indivíduos não expostos (controlos). Como amostra foram estudados 80 trabalhadores ocupacionalmente expostos a FA: 30 trabalhadores da fábrica de produção de FA e resinas e 50 trabalhadores de 10 laboratórios de AP. Foi constituído um grupo controlo de 85 indivíduos com atividades profissionais que não envolviam a exposição a formaldeído ou qualquer outro agente químico com propriedades genotóxicas. Aplicaram‑se duas metodologias distintas de avaliação ambiental do FA com o objetivo de conhecer a exposição profissional. Compararam‑se os resultados obtidos com os valores limite para a exposição média ponderada (TLV‑TWA=0,75 ppm) e para a concentração máxima (VLE‑CM=0,3 ppm). A totalidade dos laboratórios apresentou resultados superiores ao valor de referência existente para a concentração máxima. Nenhum dos resultados obtidos para a exposição média ponderada foi superior ao valor de referência. O exame macroscópico obteve os valores das concentrações máximas mais elevadas em 90% dos laboratórios. Os valores de MN foram mais elevados nos indivíduos expostos a FA comparativamente com os controlos. No caso dos MN nos linfócitos, a média foi de 3,96 nos expostos e de 0,81 nos não expostos. Os MN nas células esfoliadas da boca apresentaram uma média de 0,96 nos expostos e de 0,16 nos controlos. Os resultados obtidos nesta acção de biomonitorização podem revelar‑se particularmente úteis para as organizações responsáveis em definir os níveis aceitáveis para a exposição humana a FA. ABSTRACT: Since 2004, formaldehyde (FA) has been classified by the International Agency for Cancer Research as a carcinogen. The FA ranks 25th in the overall United States chemical production, with more than 5 million tons produced each year. Due to its economic importance and varied use, many individuals are exposed to FA at their occupational settings. This study aimed to assess the exposure to FA in two occupational settings – FA production factory and pathology anatomy (PA) laboratories – and relate it to possible health effects by comparing frequency of micronuclei (MN) in peripheral blood lymphocytes and exfoliated cells from the oral mucosa of workers exposed to FA with individuals not exposed to this agent (controls). This study was performed in 80 workers occupationally exposed to FA: 30 workers of the FA factory and 50 workers in 10 PA laboratories. The control group comprised 85 subjects without exposure. We have applied two different methodologies for environmental monitoring of FA. The results were compared with the reference to the exposure weighted average (TLV‑TWA = 0.75 ppm) and ceiling concentration (VLE‑MC = 0.3 ppm). All laboratories had results higher than the reference value to CM (1.41 ppm). None of the results obtained for the TWA exposure (0.16 ppm) were higher than the reference value. Macroscopic examination obtained the highest values of CM in 90% of laboratories. MN values were higher in individuals exposed to FA as compared to controls. As for MN in lymphocytes, the average was 3.96 in exposed compared with 0.81 in the unexposed. The MN in exfoliated cells of the buccal mucosa had an average of 0.96 in exposed, compared with 0.16 in controls. The results of this biomonitoring can be particularly useful to organizations responsible for defining acceptable levels for human exposure to FA.
- Exposição profissional a formaldeído em laboratórios de anatomia patológica: que realidade em Portugal?Publication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Prista, João; Gomes, Manuel C.; Brito, MiguelO formaldeído é um gás incolor, solúvel na água e que reage rapidamente com o local de contacto. É utilizado nos laboratórios de Anatomia Patológica (AP) como fixador de células e tecidos - importante local de exposição ocupacional ao formaldeído, nomeadamente por médicos patologistas, técnicos de AP e auxiliares de acção médica. Objectivos do estudo: conhecer a exposição a formaldeído nos laboratórios hospitalares de Anatomia Patológica em Portugal; comparar a frequência de MN em linfócitos do sangue periférico e em células esfoliadas da mucosa bucal dos trabalhadores expostos a formaldeído nos laboratórios de AP – patologistas, técnicos de AP e auxiliares com controlos.
- Effects of the interaction of tobacco smoke and alcohol consumption on buccal micronucleus in workers exposed occupationally to formaldehydePublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Prista, João; Gomes, Manuel C.; Brito, MiguelOccupational exposure to formaldehyde (FA) has been shown to induce nasopharyngeal cancer and has been classified as carcinogenic to humans (group 1) on the basis of sufficient evidence in humans. Tobacco smoke has been associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Alcohol is a recognized agent that influence cells in a genotoxic form, been citied as a strong agent with potential in the development of carcinogenic lesions. Epidemiological evidence points to a strong synergistic effect between cigarette smoking and alcohol consumption in the induction of cancers in the oral cavity. Approximately 90% of human cancers originate from epithelial cells. Therefore, it could be argued that oral epithelial cells represent a preferred target site for early genotoxic events induced by carcinogenic agents entering the body via inhalation and ingestion. The MN assay in buccal cells was also used to study cancerous and precancerous lesions and to monitor the effects of a number of chemopreventive agents.
- Occupational exposure to formaldehyde in anatomy and pathology laboratories: differences between exposure groups?Publication . Viegas, Susana; Ladeira, Carina; Nunes, Carla; Malta-Vacas, Joana; Gomes, Mário; Brito, Miguel; Mendonça, Paula; Prista, JoãoFormaldehyde, also known as formalin, formal and methyl aldehydes, is a colorless, flammable, strong-smelling gas. It has an important application in embalming tissues and that result in exposures for workers in the pathology anatomy laboratories and mortuaries. To perform exposure assessment is necessary define exposure groups and in this occupational setting the technicians and pathologists are the most important groups. In the case of formaldehyde, it seems that health effects are more related with peak exposures than with exposure duration.
- Risk assessment in occupational exposure to formaldehyde: differences between anatomy and pathology laboratories and formaldehyde-resins productionPublication . Viegas, Susana; Ladeira, Carina; Nunes, Carla; Malta-Vacas, Joana; Gomes, Mário; Mendonça, Paula; Prista, João; Brito, MiguelFormaldehyde (CH2O), the most simple and reactive of all aldehydes, is colorless, and readily polymerizing gas at normal temperature. The most extensive use is in production of resins and 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. A study was carried out in Portugal, in a formaldehyde production resins factory and in 10 pathology and anatomy laboratories. It was applied a risk assessment methodology based on Queensland University proposal that permitted to perform risk assessment for each activity developed in a work station. This methodology was applied in 83 different activities developed in the laboratories and in 18 activities of the factory. Also, Micronucleus Test was performed in lymphocytes from 30 factory workers and 50 laboratories workers.
- Genotoxicity biomarkers in occupational exposure to formaldehyde: the case of histopathology laboratoriesPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Prista, João; Gomes, Manuel C.; Brito, MiguelFormaldehyde, classified by the IARC as carcinogenic in humans and experimental animals, is a chemical agent that is widely used in histopathology laboratories. The exposure to this substance is epidemiologically linked to cancer and to nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it provides information on several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomere fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA. The aim of this study is to compare the frequency of genotoxicity biomarkers, provided by the CBMN assay in peripheral lymphocytes and the MN test in buccal cells, between individuals occupationally exposed and non-exposed to formaldehyde and other environmental factors, namely tobacco and alcohol consumption. The sample comprised two groups: 56 individuals occupationally exposed to formaldehyde (cases) and 85 unexposed individuals (controls), from whom both peripheral blood and exfoliated epithelial cells of the oral mucosa were collected in order to measure the genetic endpoints proposed in this study. The mean level of TWA8h was 0.16±0.11ppm (
- Formaldehyde's genotoxicity effects in pathology anatomy technologists and medical pathologistsPublication . Ladeira, Carina; Viegas, Susana; Prista, J.; Gomes, Manuel C.; Brito, MiguelFormaldehyde (FA) had been considered to be carcinogenic by the International Agency for Research on Cancer (group1), on the basis of sufficient evidence both in humans and in experimental animals, making it a subject of major environmental concern, especially in the occupational context. Manifold in vitro studies clearly indicated that FA is genotoxic, inducing various genotoxic effects in proliferating cultured mammalian cells. Cytokinesis-blocked micronucleus (CBMN) assay is used extensively in molecular epidemiology, and the chromosomal alterations most reported and studied by the CBMN are: micronucleus (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUDs). The pathology anatomy laboratories are work places that manipulate routinely FA and pathology anatomy technologists and pathologists contact daily with this chemical compound particularly in the macroscopic exam and grossing procedures. The aim of this study was to identify genotoxicity biomarkers in the set workers groups, such as micronucleus (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUD) in peripheral blood lymphocytes.
- Genotoxic effects of exposure to formaldehyde in two different occupational settingsPublication . Viegas, Susana; Ladeira, Carina; Gomes, Mário; Nunes, Carla; Brito, Miguel; Prista, JoãoFormaldehyde (CH2O), the most simple and reactive aldehyde, is a colorless, reactive and readily polymerizing gas at room temperature (National Toxicology Program [NTP]. It has a pungent suffocating odor that is recognized by most human subjects at concentrations below 1 ppm. Aleksandr Butlerov synthesized the chemical in 1859, but it was August Wilhelm von Hofmann who identified it as the product formed from passing methanol and air over a heated platinum spiral in 1867. This method is still the basis for the industrial production of formaldehyde today, in which methanol is oxidized using a metal catalyst. By the early 20th century, with the explosion of knowledge in chemistry and physics, coupled with demands for more innovative synthetic products, the scene was set for the birth of a new material–plastics. 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. Formaldehyde annual production rises up to 21 million tons worldwide and it has increased in China with 7.5 million tons produced in 2007. Given its economic importance and widespread use, many people are exposed to formaldehyde environmentally and/or occupationally. Commercially, formaldehyde is manufactured as an aqueous solution called formalin, usually containing 37% by weight of dissolved formaldehyde. This chemical is present in all regions of the atmosphere arising from the oxidation of biogenic and anthropogenic hydrocarbons. Formaldehyde concentration levels range typically from 2 to 45 ppbV (parts per billion in a given volume) in urban settings that are mainly governed by primary emissions and secondary formation.
- Polimorfismos genéticos no gene XRCC3 e dano no DNA em trabalhadores expostos ocupacionalmente a formaldeídoPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, Manuel C.; Brito, MiguelA exposição a formaldeído (FA), classificado como cancerígeno pela International Agency for Cancer Research (IARC), está epidemiologicamente associada a cancro e a alterações nucleares detectáveis pelo ensaio dos micronúcleos por bloqueio da citocinese (CBMN). Este método permite determinar vários marcadores de genotoxicidade, nomeadamente micronúcleos – biomarcadores de quebra ou perda de cromossomas; pontes nucleoplásmicas – biomarcador de re-arranjo cromossómico, pouca reparação e fusão de telómeros e, protusões nucleares – biomarcador de DNA amplificado. O gene X-ray repair cross-complementing group 3 (XRCC3) está envolvido na reparação de ligações cruzadas na recombinação de homólogos e quebras na cadeia dupla de DNA. Foi reportado pelo menos um polimorfismo no gene, o Thr241Met que tem sido associado a um aumento do dnao no DNA em vários estudos.
- Micronuclei in peripheral blood lymphocytes in formaldehyde occupationally exposed workersPublication . Ladeira, Carina; Viegas, Susana; Prista, João; Malta-Vacas, Joana; Gomes, Mário; Mendonça, Paula; Brito, MiguelFormaldehyde (CH2O) the most simple and reactive of all aldehydes, is a colorless, reactive and readily polymerizing gas at normal temperature. It has a pungent, suffocating odour that is recognized by most human subjects at concentrations below 1 ppm. According to the Report on Carcinogens, formaldehyde (FA) ranks 25th in the overall U.S. chemical production with more than 11 billion pounds (5 million tons) produced each year. Is an important industrial compound that is used in the manufacture of synthetic resins and chemical compounds such as lubricants and adhesives. It has also applications as a disinfectant, preservative and is used in cosmetics. Estimates of the number of persons who are occupationally exposed to FA indicate that, at least at low levels, may occur in a wide variety of industries. The occupational settings with most extensive use of formaldehyde is in the production of resins and in anatomy and pathology laboratories. Several studies reported a carcinogenic effect in humans after inhalation of FA, in particular an increased risk for nasopharyngeal cancer. Nowadays, the International Agency for Research on Cancer (IARC) classifies FA as carcinogenic to humans (group 1), on the basis of sufficient evidence in humans and sufficient evidence in experimental animals. Manifold in vitro studies clearly indicated that FA is genotoxic. FA induced various genotoxic effects in proliferatin cultured mammalian cells. A variety of evidence suggests that the primary DNA alterations after FA exposure are DNA-protein crosslinks (DPX). Incomplete repair of DPX can lead to the formation of mutations.