Bis(nitrato-O)dioxouranium

Intermediate Inhalation: 0.0004 mg/m3 (Soluble uranium salts) (L134) Chronic Inhalation: 0.0003 mg/m3 (Soluble uranium salts) (L134) Intermediate Oral: 0.002 mg/kg/day (Soluble uranium salts) (L134) Intermediate Inhalation: 0.008 mg/m3 (Insoluble uranium compounds) (L134)

Methemoglobinemia can be treated with supplemental oxygen and methylene blue 1% solution administered intravenously slowly over five minutes followed by IV flush with normal saline. Methylene blue restores the iron in hemoglobin to its normal (reduced) oxygen-carrying state. (L1613)

Uranium primarily damages the kidney, but may also damage the lungs, central nervous system, and immune system. Uranium's radioactivity is believed to damage the DNA, resulting in carcinogenic effects and reproductive and developmental damage. Nitrate and nitrite poisoning causes methemoglobinemia. Nitrites may cause pregnancy complications and developmental effects. They may also be carcinogenic. (L1137, L248, L249)

Uranium is combined with either bicarbonate or a plasma protein in the blood but once in the kidney, it is released and forms complexes with phosphate ligands and proteins in the tubular wall, causing damage. Uranium may also inhibit both sodium transport-dependent and independent ATP utilization and mitochondrial oxidative phosphorylation in the renal proximal tubule. Uranium causes respiratory diseases by damaging alveolar epithelium type II cells in the lungs. Uranium induces c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) activation, which in turn induces tumor necrosis factor alpha (TNF-alpha) secretion and generates and inflammatory response in the lungs. Studies have shown that the more soluble the uranium salt, the more toxic it is. Ionizing radiation produced by uranium damages the DNA, resulting in gene mutations and chromosomal aberrations. This can both both initiate and promote carcinogenesis, and interfere with reproduction and development. Nitrate's toxicity is a result of it's conversion to nitrite once in the body. Nitrite causes the autocatalytic oxidation of oxyhemoglobin to hydrogen peroxide and methemoglobin. This elevation of methemoglobin levels is a condition known as methemoglobinemia, and is characterized by tissue hypoxia, as methemoglobin cannot bind oxygen. (A2450, L1613, L249, A160)

Uranium is absorbed in low amounts via oral, inhalation, and dermal routes. Uranium in body fluids generally exists as the uranyl ion (UO2)2+ complexed with anions, such as citrate and bicarbonate, or plasma proteins. Uranium preferentially distributes to bone, liver, and kidney. The large majority of uranium that enters the body is not absorbed and is eliminated from the body via the urine and faeces. Intake of some amount of nitrates and nitrites is a normal part of the nitrogen cycle in humans. In vivo conversion of nitrates to nitrites can occur in the gastrointestional tract under the right conditions, significantly enhancing nitrates' toxic potency. The major metabolic pathway for nitrate is conversion to nitrite, and then to ammonia. Nitrites, nitrates, and their metabolites are excreted in the urine. (L1137, L248)