Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Nikolai-Fuchs-Str. 1, D-30625 Hannover, Germany.
Mutat Res. 2010 Mar 29;697(1-2):38-46. doi: 10.1016/j.mrgentox.2010.02.002. Epub 2010 Feb 10.
Sulfur dioxide (SO2) is a non-flammable, non-explosive, colorless gas. It is a ubiquitous environmental pollutant and an important chemical intermediate in several industrial processes. The toxicological properties of SO2, including its genotoxic potential, have been studied extensively. The majority of the available in vitro data indicate a lack of genotoxicity of SO2, while for sulfite salts some positive results have been reported. However, recent in vivo studies, using Kunming albino mice, have pointed to in vivo clastogenicity of SO2. To re-evaluate these positive findings, a bone-marrow micronucleus test according to OECD Guideline No. 474 was performed. NMRI mice (m/f) were exposed by inhalation via whole-body exposure to 0 (clean air), 2.7, 8, 27, or 80mg/m3 (0, 1, 3, 10, or 30ppm) SO2 for 4h/day on 7 consecutive days. Animals were sacrificed 24h after start of the last exposure, and blood samples (for complementing hematology) and bone marrow smears (for analysis of micronuclei) were prepared. Under the conditions used, exposure to SO2 caused no acute toxicity, mortality, or reduction in body weight. Compared with the clean-air controls, hematological parameters such as hematocrit, hemoglobin, erythrocyte/platelet/total leukocyte counts, differential white blood cell counts, and indicators of blood formation (reticulocyte counts, ratio of polychromatic to normochromatic erythrocytes in the bone marrow) remained unchanged by SO2 treatment. Unlike the previously reported studies on micronucleus formation, SO2 did not induce micronuclei in polychromatic erythrocytes of the bone marrow, whereas the positive control cyclophosphamide (60mg/kg body weight) was quite effective in this respect. Interestingly, SO2 treatment significantly enhanced malondialdehyde levels in erythrocyte lysates (TBARS method), indicating SO2-mediated oxidative stress, but also demonstrating systemic availability of the inhaled SO2. In conclusion, the present study could not reproduce the genotoxicity findings of the previously reported studies. SO2 is thus considered non-genotoxic in polychromatic erythrocytes in the bone marrow of NMRI mice under the conditions and in the concentrations used.
二氧化硫（SO2）是一种不可燃、不易爆、无色的气体。它是一种普遍存在的环境污染物，也是几种工业过程中的重要化学中间体。SO2 的毒理学特性，包括其遗传毒性潜力，已经得到了广泛的研究。大多数现有的体外数据表明 SO2 没有遗传毒性，而对于亚硫酸盐盐，一些阳性结果已经报道。然而，最近使用昆明白化小鼠的体内研究指出 SO2 具有体内致裂变性。为了重新评估这些阳性发现，根据 OECD 指南 474 进行了骨髓微核试验。NMRI 小鼠（雌雄）通过全身暴露于 0（清洁空气）、2.7、8、27 或 80mg/m3（0、1、3、10 或 30ppm）SO2 中进行 4 小时/天，连续 7 天。在最后一次暴露开始后 24 小时，处死动物，并制备血液样本（用于补充血液学）和骨髓涂片（用于分析微核）。在使用的条件下，SO2 暴露没有引起急性毒性、死亡率或体重减轻。与清洁空气对照相比，SO2 处理并未改变血液学参数，如血细胞比容、血红蛋白、红细胞/血小板/总白细胞计数、白细胞分类计数以及血液形成指标（网织红细胞计数、骨髓中多色性与正常红细胞的比例）。与以前关于微核形成的研究不同，SO2 没有在骨髓的多色性红细胞中诱导微核，而阳性对照环磷酰胺（60mg/kg 体重）在这方面非常有效。有趣的是，SO2 处理显著增加了红细胞裂解物中的丙二醛水平（TBARS 法），表明 SO2 介导的氧化应激，但也证明了吸入的 SO2 在体内的可用性。总之，本研究无法重现以前报道的研究中的遗传毒性发现。因此，在使用的条件和浓度下，SO2 被认为在 NMRI 小鼠的骨髓多色性红细胞中没有遗传毒性。
