National Institute of Health, Environmental Health Department, Rua Alexandre Herculano, 321, 4000-055, Porto, Portugal; EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal.
National Institute of Health, Environmental Health Department, Rua Alexandre Herculano, 321, 4000-055, Porto, Portugal; EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, nº 135, 4050-600, Porto, Portugal.
Environ Res. 2019 Dec;179(Pt A):108740. doi: 10.1016/j.envres.2019.108740. Epub 2019 Sep 14.
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.
甲醛（FA）是一种高产量的生产化学物质，在全球范围内制造，许多人在环境和职业环境中都接触到 FA。FA 最近被重新归类为人类致癌物。几项流行病学研究表明，接触 FA 的工人癌症发病风险增加。尽管在各种实验系统中证实了 FA 的遗传毒性，但来自人体研究的数据存在冲突。本研究的目的是通过多阶段方法评估 FA 的职业暴露，将暴露与不同的生物标志物（剂量和效应）和个体易感性联系起来。在轮班工作期间进行空气监测以估计 FA 的暴露水平。对来自医院解剖病理学实验室的 85 名接触 FA 的工人和 87 名对照进行了淋巴细胞（微核、MN；姐妹染色单体交换、SCE）和 T 细胞受体（TCR）突变试验的细胞遗传学改变测试。还评估了脱落口腔细胞（第一接触组织）中的 MN 频率。选择不同淋巴细胞亚群的百分比作为免疫毒性生物标志物。尿中甲酸的含量作为内剂量的潜在生物标志物进行了研究。确定了外源性代谢酶和 DNA 修复酶多态性基因对研究终点的影响。FA 暴露的平均水平为 0.38±0.03ppm。与对照组相比，FA 暴露工人的淋巴细胞和口腔细胞中的 MN（微核）和 SCE（姐妹染色单体交换）显著增加。MN 频率与 FA 暴露水平和持续时间呈正相关。组间发现 T 细胞毒性淋巴细胞、NK 细胞和 B 淋巴细胞的百分比有显着变化。CYP2E1、GSTP1 和 FANCA 基因的多态性与 FA 暴露个体遗传损伤增加有关。获得的信息可能为健康和安全护理计划以及负责制定 FA 职业暴露可接受水平的政府机构提供新的重要数据。
