Nickel is absorbed mainly through the lungs and gastrointestinal tract. Once in the body it enters the bloodstream, where it binds to albumin, L-histidine, and _2-macroglobulin. Nickel tends to accumulate in the lungs, thyroid, kidney, heart, and liver. Absorbed nickel is excreted in the urine, wherease unabsorbed nickel is excreted in the faeces. Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L41, L96)
Nickel is known to substitute for other essential elements in certain enzmes, such as calcineurin. It is genotoxic, and some nickel compounds have been shown to promote cell proliferation. Nickel has a high affinity for chromatin proteins, particularly histones and protamines. The complexing of nickel ions with heterochromatin results in a number of alterations including condensation, DNA hypermethylation, gene silencing, and inhibition of histone acetylation, which have been shown to disturb gene expression. Nickel has also been shown to alter several transcription factors, including hypoxia-inducible transcription factor, activating transcription factor, and NF-KB transcription factor. There is also evidence that nickel ions inhibit DNA repair, either by directly inhibiting DNA repair enzymes or competing with zinc ions for binding to zinc-finger DNA binding proteins, resulting in structural changes in DNA that prevent repair enzymes from binding. Nickel ions can also complex with a number of cellular ligands including amino acids, peptides, and proteins resulting in the generation of oxygen radicals, which induce base damage, DNA strand breaks, and DNA protein crosslinks. Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin.. (L41, A40, L97)
Evaluation: There is sufficient evidence in humans for the carcinogenicity of nickel sulfate, and of the combinations of nickel sulfides and oxides encountered in the nickel refining industry. There is inadequate evidence in humans for the carcinogenicity of metallic nickel and nickel alloys. There is sufficient evidence in experimental animals for the carcinogenicity of metallic nickel, nickel monoxides, nickel hydroxides and crystalline nickel sulfides. There is limited evidence in experimental animals for the carcinogenicity of nickel alloys, nickelocene, nickel carbonyl, nickel salts, nickel arsenides, nickel antimonide, nickel selenides and nickel telluride. There is inadequate evidence in experimental animals for the carcinogenicity of nickel trioxide, amorphous nickel sulfide and nickel titanate. The Working Group made the overall evaluation on nickel compounds as a group on the basis of the combined results of epidemiological studies, carcinogenicity studies in experimental animals, and several types of other relevant data, supported by the underlying concept that nickel compounds can generate nickel ions at critical sites in their target cells. Overall evaluation: Nickel compounds are carcinogenic to humans (Group 1). Metallic nickel is possibly carcinogenic to humans (Group 2B). /Nickel compounds/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A1; 已确认的人类致癌物。/镍，不溶于水的无机化合物NOS（未特别指定），以Ni表示/
A1; Confirmed human carcinogen. /Nickel, insoluble inorganic compounds NOS (not otherwise specified), as Ni/
The most common harmful health effect of nickel in humans is an allergic reaction. This usually manifests as a skin rash, although some people experience asthma attacks. Long term inhahation of nickel causes chronic bronchitis and reduced lung function, as well as damage to the naval cavity. Ingestion of excess nickel results in damage to the stomach, blood, liver, kidneys, and immune system, as well as having adverse effects on reproduction and development. Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L41, L96, L97)
