After iv injection into rats, tetraethyl lead (TEL) is converted into triethyl lead, which is considered to be responsible for toxic effects seen. ... After iv injections of 25 mg/kg bw of TEL into rabbits, main metabolite was triethyl lead ...
Dealkylation of tetraethyl lead occurs in microsomes and requires oxygen and NADPH, and has been observed in homogenates of liver, kidney, and brain of rat and rabbit.
Biological degradation of tetraethyllead to the triethyllead cation by rat liver microsomes from untreated, phenobarbital pretreated and methylcholanthrene pretreated rats was studied; nicotinamide-adenine dinucleotide phosphate and oxygen are essential.
Nicotinamide-adenine dinucleotide phosphate and oxygen dependent microsomal metabolism of tetraethyl-substituted derivatives of lead gave rise to ethylene as a major product and ethane as minor product in rats. Reactions were catalyzed by liver microsomal cytochrome P450 dependent monooxygenase. Since formation of ethane and ethylene was differentially inhibited by anaerobiosis, results suggested that a large portion of the ethane produced was derived by a reductive mechanism.
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)
There is limited evidence in humans for the carcinogenicity of inorganic lead cmpd. There is inadequate evidence in humans for the carcinogenicity of organic lead cmpd. There is sufficient evidence in exptl animals for the carcinogenicity of inorganic lead cmpd ... There is inadequate evidence in exptl animals for the carcinogenicity of organic lead cmpd. There is inadequate evidence in exptl animals for the carcinogenicity of tetraethyl lead ... Inorganic lead cmpd are probably carcinogenic to humans (Group 2A). Organic lead cmpd are not classifiable as to their carcinogenicity to humans (Group 3). The working group noted that organic lead cmpd are metabolized, at least in part, to ionic lead both in humans and animals. To the extent that ionic lead, generated from organic lead, is present in the body, it will be expected to exert the toxicities associated with inorganic lead.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4：不能分类为人类致癌物。/如铅/
A4: Not classifiable as a human carcinogen. /As Pb/
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)
Organic lead cmpd, such as tetraethyl lead and tetramethyl lead, behave as gases in the respiratory tract, and are absorbed to a greater extent than are inorganic lead particles. Organic lead cmpd are also absorbed through the skin of both humans and exptl animals. Tetraethyl lead and tetramethyl lead are oxidatively dealkylated in the body. Any inorganic lead produced endogenously is distributed in the same pattern as admin inorganic lead, but the parent cmpd and the intermediate dealkylated products are distributed quite differently and in accordance with their lipophilicity. In humans exposed to tetraethyl lead, concn of the parent cmpd and its metabolites, including inorganic lead, are highest in the liver and kidneys followed by the brain and heart ... The highest concn of total lead in rats after exposure to alkyl leads are found in the kidney and liver, followed by the brain. In humans, tetraethyl lead was found to be excreted in the urine as diethyl lead and inorganic lead. In rats and rabbits, dialkyl lead is the major metabolite found in urine. Tetraalkyl leads would also be excreted in the feces as inorganic lead, the end product of metabolism. In humans, exhalation of tetraethyl lead and tetramethyl lead from the lung is a major route of excretion, accounting for 40% (tetramethyl lead) and 20% (tetraethyl lead) of the inhaled dose at 48 hr after inhalation..
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
七名意外四烷基铅中毒的受害者在中毒后5-19天死亡。在脾脏、肝脏和肾脏组织中检测到最高的铅浓度。
Seven victims of accidental tetraalkyllead poisoning died 5-19 days after poisoning. The highest lead concentration was detected in spleen, liver and kidney tissue.
Tissue distribution studies of lead in rats and dogs exposed to lethal inhalation doses of tetraethyl lead (TEL) or tetramethyl lead (TML) and in men fatally poisoned by TEL revealed lead (Pb) levels of 0.7-13.0 mg/100 g tissue in lung, brain, liver and kidney in three species. Human Pb levels in brain, liver and kidney resembled those seen in corresponding rat and dog tissues.
In cases of accidental poisoning with tetraethyl lead (TEL), liver, kidney, pancreas, brain and heart accumulate triethyllead, and total tissue lead (Pb) concentration correlate with triethyllead concentrations in corresponding tissues.
279,106. Daudt, H. W. Oct. 15, 1926, [Convention date]. Lead tetraethyl is prepared by the action of magnesium ethyl chloride upon lead salts. In an example, ethyl chloride is added to magnesium turnings in the presence of ether containing a small proportion of methyl iodide and a crystal of iodine. The resulting solution of magnesium ethyl chloride is then treated with a suspension of lead chloride in ether for some hours. The product is poured into water, the ether distilled off, and the lead tetraethyl obtained by steam distillation. The Specification as open to inspection under Sect. 91 (3) (a) comprises also the use of alkyl iodides other than methyl iodide. This subjectmatter does not appear in the Specification as accepted.
279,106. Daudt, H. W. 1926年10月15日，[会议日期]。四乙基铅是通过镁乙基氯与铅盐作用制备的。例如，将乙基氯加入镁粉中，在含有少量甲基碘和一小片碘的醚的存在下进行。然后，将得到的镁乙基氯溶液与乙醚中的氯化铅悬浮液处理数小时。将产物倒入水中，蒸馏去除醚，通过蒸汽蒸馏得到四乙基铅。根据第91条（3）（a）款公开检查的说明书还包括使用除甲基碘以外的烷基碘。这一主题在已接受的说明书中没有出现。
Oxidative carbonylation of hydroxyaromatic compounds
申请人：General Electric Company
公开号：US06462217B1
公开（公告）日：2002-10-08
Organolead compounds such as tetraethyllead are useful in catalyst compositions for the oxidative carbonylation of hydroxyaromatic compounds to diaryl carbonates. They are employed in combination with a Group 8, 9, or 10 metal such as palladium, or a compound thereof, and a bromide or chloride such as tetraethylammonium bromide.
(4i)) and the small J coupling constants between the element and the remote vinyl carbons in the case of 4h and 4i (J(CSn) = 26 Hz, J(CPb) = 16 Hz) give experimental evidence for the intramolecular interaction and the charge transfer between the positively charged element and the remote C=C double bond. The experimental results are supported by quantum mechanical calculations of structures, energies, and
14 族元素 Si --> Pb 的降冰片基阳离子已从取代的 3-环戊烯甲基前体通过将瞬时阳离子分子内加成到 3-环戊烯甲基取代基的 C=C 双键（pi-路线到降冰片基阳离子）合成。降冰片基阳离子 4a (E = Si, R = Me), 4e (E = Si, R = Et), 4f (E = Si, R = Bu), 4g (E = Ge, R = Bu), 4h (E = Sn, R = Bu) 和 4i (E = Pb, R = Et) 已通过其特征 NMR 化学位移 (4a,e,f, delta((29)Si) = 80-87, delta((( 13)C)(CH=) = 149.6-150.6; 4g, delta((13)C)(CH=) = 144.8; 4h, delta((119)Sn) = 334, delta((13)C)(CH =) = 141.5; 4i, delta((207)Pb)
Synthesis of a non-symmetric azodicarbonyl compound and its regioselective reaction with organometallic reagents
The non-symmetric azodicarbonyl compound 7 reacted with R-M/Lewis acid regioselectively at the nitrogen atom attached to the amide group giving 9, whereas it reacted with R-M at the nitrogen atom attached to the ester group producing 8 in high yield.
