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. (L136)
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. (T4, A20, A22, L136)
A3; Confirmed animal carcinogen with unknown relevance to humans. /Lead, elemental, and inorganic compounds, as Pb/ American Conference of Governmental Industrial Hygienists TLVs and BEIs.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
铅、铅化合物：合理预期为人类致癌物
Lead, lead compounds: Reasonably anticipated to be a human carcinogen
Organic lead compounds are not classifiable as to their carcinogenicity to humans (Group 3). To the extent that organic lead compounds are metabolized in part to ionic lead, they are expected to exert the toxicities associated with inorganic lead (Group 2A, probably carcinogenic to humans). (L135)
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. (L21)
Adult male dogs were given daily doses of 34.1 mg and 68.2 mg basic lead carbonate (white lead) for 60 days. Ratio of urinary lead excretion to total lead admin was very small; 0.24% and 0.09% respectively. 98.7% and 98.9% respectively of total lead admin was fecally excreted. Urinary and fecal excretions totalled 98.4 and 97.9% respectively. The highest concn was found in teeth and bones, followed by bone marrow, hair, and trachea.
