Stearns D M, Wise J P, Patierno S R, Wetterhahn K E
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755-3564, USA.
FASEB J. 1995 Dec;9(15):1643-8.
Chromium(III) complexes currently being sold as dietary supplements were tested for their ability to cause chromosomal aberrations in Chinese hamster ovary cells. Complexes were tested in soluble and particulate forms. Chromium picolinate was found to produce chromosome damage 3-fold to 18-fold above control levels for soluble doses of 0.050, 0.10, 0.50, and 1.0 mM after 24 h treatment. Particulate chromium picolinate doses of 8.0 micrograms/cm2 (corresponding to a 0.10 mM solublized dose) and 40 micrograms/cm2 (0.50 mM) produced aberrations 4-fold and 16-fold above control levels, respectively. Toxicity was measured as a decrease in plating efficiency relative to controls. The above treatments produced > or = 86% survival for all doses except 1.0 mM chromium picolinate, which produced 69 +/- 10% survival. Chromium nicotinate, nicotinic acid, and chromium(III) chloride hexahydrate did not produce chromosome damage at equivalent nontoxic doses. Damage was inferred to be caused by the picolinate ligand because picolinic acid in the absence of chromium was clastogenic. Data are evaluated in terms of their relevance to human exposure based on pharmacokinetic modeling of tissue accumulation and are discussed in terms of literature reporting toxic effects of picolinic acid.
对目前作为膳食补充剂销售的铬(III)配合物进行了测试,以检测其在中国仓鼠卵巢细胞中引起染色体畸变的能力。对配合物的可溶形式和颗粒形式都进行了测试。在24小时处理后,发现对于0.050、0.10、0.50和1.0 mM的可溶剂量,吡啶甲酸铬会产生比对照水平高3倍至18倍的染色体损伤。8.0微克/平方厘米(相当于0.10 mM溶解剂量)和40微克/平方厘米(0.50 mM)的颗粒状吡啶甲酸铬剂量分别产生比对照水平高4倍和16倍的畸变。毒性通过相对于对照的铺板效率降低来衡量。除1.0 mM吡啶甲酸铬产生69±10%的存活率外,上述处理对所有剂量均产生≥86%的存活率。烟酸铬、烟酸和六水合氯化铬(III)在等效无毒剂量下未产生染色体损伤。推断损伤是由吡啶甲酸配体引起的,因为在没有铬的情况下,吡啶甲酸具有致断裂作用。根据组织积累的药代动力学模型对数据与人体暴露的相关性进行了评估,并根据报道吡啶甲酸毒性作用的文献进行了讨论。