Lead nitrate is a nitrate of lead produced synthetically by dissolving metallic lead or lead(II) oxide in nitric acid. It is an oxidizing agent and is used to make other lead compounds. It is also used as a heat stabiliser in nylon and polyesters, as a coating for photothermographic paper, and in rodenticides. Lead is a heavy metal and stable element with the symbol Pb and the atomic number 82, existing in metallic, organic, and inorganic forms. It is mainly found in nature as the mineral galena (PbS), cerussite (PbCO3) or anglesite (PbSO4), usually in ore with zinc, silver, or copper. Nitrite is a toxic compound known to cause methemoglobinemia. (10, 5, 9)
belongs to the class of inorganic compounds known as post-transition metal nitrates. These are inorganic compounds in which the largest oxoanion is nitrate, and in which the heaviest atom not in an oxoanion is a post-transition metal.
Lead mimics other biologically important metals, such as zinc, calcium, and iron, competing as cofactors for many of their respective enzymatic reactions. For example, lead has been shown to competitively inhibit calcium's binding of calmodulin, interferring with neurotransmitter release. It exhibits similar competitive inhibition at the NMDA receptor and protein kinase C, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Lead also affects the nervous system by impairing regulation of dopamine synthesis and blocking evoked release of acetylcholine. However, it's main mechanism of action occurs by inhibiting delta-aminolevulinic acid dehydratase, an enzyme vital in the biosynthesis of heme, which is a necesssary cofactor of hemoglobin. 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. (4, 11, 12, 2, 3, 8)
Metabolism
Lead is absorbed following inhalation, oral, and dermal exposure. It is then distributed mainly to the bones and red blood cells. In the blood lead may be found bound to serum albumin or the metal-binding protein metallothionein. Organic lead is metabolized by cytochrome P-450 enzymes, whereas inorganic lead forms complexes with delta-aminolevulinic acid dehydratase. Lead is excreted mainly in 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. (10, 8)
Ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans (Group 2A). (7)
Uses/Sources
Lead nitrate is used as a heat stabiliser in nylon and polyesters, as a coating for photothermographic paper, in rodenticides, and in gold cyanidation. (9)
Lead is a neurotoxin and has been known to cause brain damage and reduced cognitive capacity, especially in children. Lead exposure can result in nephropathy, as well as blood disorders such as high blood pressure and anemia. Lead also exhibits reproductive toxicity and can results in miscarriages and reduced sperm production. Nitrate and nitrite poisoning causes methemoglobinemia. Nitrites may cause pregnancy complications and developmental effects. They may also be carcinogenic. (10, 5)
Symptoms
Symptions of chronic lead poisoning include reduced cognitive abilities, nausea, abdominal pain, irritability, insomnia, metal taste in the mouth, excess lethargy or hyperactivity, chest pain, headache and, in extreme cases, seizures, comas, and death. There are also associated gastrointestinal problems, such as constipation, diarrhea, vomiting, poor appetite, weight loss, which are common in acute poisoning. Nitrate and nitrite poisoning causes methemoglobinemia. Symptoms include cyanosis, cardiac dysrhythmias and circulatory failure, and progressive central nervous system (CNS) effects. CNS effects can range from mild dizziness and lethargy to coma and convulsions. (10, 1, 5)
Treatment
Lead poisoning is usually treated with chelation therapy using DMSA, EDTA, or dimercaprol. 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. (11, 5)
