毒理性
证据权重特征：根据当前指南（1986年），六价铬被归类为A组——已知的人类通过吸入途径的致癌物。通过口服途径的致癌性无法确定，被归类为D组。在拟议的指南（1996年）下，六价铬将被定性为通过吸入途径的已知人类致癌物，基于以下原因。已知六价铬通过吸入途径在人类中具有致癌性。对接触铬的工人的职业流行病学研究结果在研究者之间和研究人群中是一致的。已经建立了铬暴露与肺癌的剂量-反应关系。接触铬的工人既暴露于三价铬也暴露于六价铬化合物。然而，只有六价铬在动物研究中被发现的具有致癌性，因此得出结论，只有六价铬应该被归类为人类致癌物。动物数据与六价铬的人类致癌性数据一致。六价铬化合物在动物生物分析中具有致癌性，产生以下肿瘤类型：大鼠和小鼠的肌内注射部位肿瘤，各种六价铬化合物在大鼠的胸膜内植入部位肿瘤，各种六价铬化合物在大鼠的支气管内植入部位肿瘤，以及大鼠的皮下注射部位肉瘤。体外数据提示六价铬致癌性的潜在作用模式。六价铬的致癌性可能是由细胞内还原为三价形式后形成的致突变氧化DNA损伤的结果。六价铬容易通过细胞膜并迅速在细胞内还原，生成反应性的三价和四价铬中间体和活性氧种。在六价铬还原过程中形成了许多潜在的致突变DNA损伤。六价铬在细菌分析、酵母和V79细胞中具有致突变性，六价铬化合物减少了体外DNA合成的准确性，并因DNA损伤产生非计划性DNA合成。铬酸盐已被证明能转化原代细胞和细胞系。
人类致癌性数据：职业暴露于铬化合物已在铬酸盐生产、镀铬和铬颜料、铁铬生产、金矿开采、皮革鞣制和铬合金生产行业中得到研究。铬酸盐行业的工人暴露于三价和六价铬化合物。对日本、英国、西德和美国的铬酸盐生产厂进行的流行病学研究揭示了职业暴露于铬与肺癌之间的相关性，但没有确定导致癌症的具体铬形态……对铬颜料工人的研究一致表明，职业铬暴露（主要是六价铬）与肺癌有关。对镀铬行业进行的几项研究已经证明了癌症与暴露于铬化合物之间的正相关关系。
动物致癌性数据：动物数据与六价铬的人类流行病学研究结果一致……/六价铬/
WEIGHT OF EVIDENCE CHARACTERIZATION: Under the current guidelines (1986), Cr(VI) is classified as Group A - known human carcinogen by the inhalation route of exposure. Carcinogenicity by the oral route of exposure cannot be determined and is classified as Group D. Under the proposed guidelines (1996), Cr(VI) would be characterized as a known human carcinogen by the inhalation route of exposure on the following basis. Hexavalent chromium is known to be carcinogenic in humans by the inhalation route of exposure. Results of occupational epidemiological studies of chromium-exposed workers are consistent across investigators and study populations. Dose-response relationships have been established for chromium exposure and lung cancer. Chromium-exposed workers are exposed to both Cr(III) and Cr(VI) compounds. Because only Cr(VI) has been found to be carcinogenic in animal studies, however, it was concluded that only Cr(VI) should be classified as a human carcinogen. Animal data are consistent with the human carcinogenicity data on hexavalent chromium. Hexavalent chromium compounds are carcinogenic in animal bioassays, producing the following tumor types: intramuscular injection site tumors in rats and mice, intrapleural implant site tumors for various Cr(VI) compounds in rats, intrabronchial implantation site tumors for various Cr(VI) compounds in rats and subcutaneous injection site sarcomas in rats. In vitro data are suggestive of a potential mode of action for hexavalent chromium carcinogenesis. Hexavalent chromium carcinogenesis may result from the formation of mutagenic oxidatitive DNA lesions following intracellular reduction to the trivalent form. Cr(VI) readily passes through cell membranes and is rapidly reduced intracellularly to generate reactive Cr(V) and Cr(IV) intermediates and reactive oxygen species. A number of potentially mutagenic DNA lesions are formed during the reduction of Cr(VI). Hexavalent chromium is mutagenic in bacterial assays, yeasts and V79 cells, and Cr(VI) compounds decrease the fidelity of DNA synthesis in vitro and produce unscheduled DNA synthesis as a consequence of DNA damage. Chromate has been shown to transform both primary cells and cell lines. HUMAN CARCINOGENICITY DATA: Occupational exposure to chromium compounds has been studied in the chromate production, chromeplating and chrome pigment, ferrochromium production, gold mining, leather tanning and chrome alloy production industries. Workers in the chromate industry are exposed to both trivalent and hexavalent compounds of chromium. Epidemiological studies of chromate production plants in Japan, Great Britain, West Germany, and the United States have revealed a correlation between occupational exposure to chromium and lung cancer, but the specific form of chromium responsible for the induction of cancer was not identified ... Studies of chrome pigment workers have consistently demonstrated an association between occupational chromium exposure (primarily Cr(VI)) and lung cancer. Several studies of the chromeplating industry have demonstrated a positive relationship between cancer and exposure to chromium compounds. ANIMAL CARCINOGENICITY DATA: Animal data are consistent with the findings of human epidemiological studies of hexavalent chromium ... /Chromium (VI)/
来源:Hazardous Substances Data Bank (HSDB)
