alt=Two chemical diagrams of tetra-ethyl<unk> , or (CH3CH2)4Pb. On the left one, carbon and hydrogen are labeled, on the right they are shown as lines only. Exposure occurs through inhalation, ingestion or occasionally skin contact.<unk>  may be taken in through direct contact with mouth, nose, and eyes (mucous membranes), and through breaks in the skin. Tetraethyllead, which was a gasoline additive and is still used in aviation gasoline, passes through the skin; however inorganic<unk>  found in paint, food, and most<unk> -containing consumer products is only minimally absorbed through the skin. The main sources of absorption of inorganic<unk>  are from ingestion and inhalation. In adults, about 35–40% of inhaled<unk>  dust is deposited in the lungs, and about 95% of that goes into the bloodstream. Of ingested inorganic<unk> , about 15% is absorbed, but this percentage is higher in children, pregnant women, and people with deficiencies of calcium, zinc, or iron. Infants may absorb about 50% of ingested<unk> , but little is known about absorption rates in children. The main body tissues that store<unk>  are the blood, soft tissues, and bone; the half-life of<unk>  in these tissues is measured in weeks for blood, months for soft tissues, and years for bone.<unk>  in the bones, teeth, hair, and nails is bound tightly and not available to other tissues, and is generally thought not to be harmful. In adults, 94% of absorbed<unk>  is deposited in the bones and teeth, but children only store 70% in this manner, a fact which may partially account for the more serious health effects on children. The half-life of<unk>  in bone has been estimated as years to decades, and bone can introduce<unk>  into the bloodstream long after the initial exposure is gone. The half-life of<unk>  in the blood in men is about 40 days, but it may be longer in children and pregnant women, whose bones are undergoing remodeling, which allows the<unk>  to be continuously re-introduced into the bloodstream. Also, if<unk>  exposure takes place over years, clearance is much slower, partly due to the re-release of<unk>  from bone. Many other tissues store<unk> , but those with the highest concentrations (other than blood, bone, and teeth) are the brain, spleen, kidneys, liver, and lungs.<unk>  is removed from the body very slowly, mainly through urine. Smaller amounts of<unk>  are also eliminated through the feces, and very small amounts in hair, nails, and sweat.<unk>  has no known physiologically relevant role in the body, and its harmful effects are myriad.<unk>  and other heavy metals create reactive radicals which damage cell structures including DNA and cell membranes.<unk>  also interferes with DNA transcription, enzymes that help in the synthesis of vitamin D, and enzymes that maintain the integrity of the cell membrane. Anemia may result when the cell membranes of red blood cells become more fragile as the result of damage to their membranes.<unk>  interferes with metabolism of bones and teeth and alters the permeability of blood vessels and collagen synthesis.<unk>  may also be harmful to the developing immune system, causing production of excessive inflammatory proteins; this mechanism may mean that<unk>  exposure is a risk factor for asthma in children.<unk>  exposure has also been associated with a decrease in activity of immune cells such as polymorphonuclear leukocytes.<unk>  also interferes with the normal metabolism of calcium in cells and causes it to build up within them. Enzymes ALAD enzyme with<unk>  bound () The primary cause of<unk> 's toxicity is its interference with a variety of enzymes because it binds to sulfhydryl groups found on many enzymes. Part of<unk> 's toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act.<unk>  is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme's ability to catalyze its normal reaction or reactions. Among the essential metals with which<unk>  interacts are calcium, iron, and zinc. The<unk>  ion has a lone pair in its electronic structure, which can result in a distortion in the coordination of ligands, and in 2007 was hypothesized to be important in<unk> 's effects on enzymes (see ). One of the main causes for the pathology of<unk>  is that it interferes with the activity of an essential enzyme called delta-aminolevulinic acid dehydratase, or ALAD (see image of the enzyme structure), which is important in the biosynthesis of heme, the cofactor found in hemoglobin.<unk>  also inhibits the enzyme ferrochelatase, another enzyme involved in the formation of heme. Ferrochelatase catalyzes the joining of protoporphyrin and Fe2+ to form heme.<unk> 's interference with heme synthesis results in production of zinc protoporphyrin and the development of anemia. Another effect of<unk> 's interference with heme synthesis is the buildup of heme precursors, such as aminolevulinic acid, which may be directly or indirectly harmful to neurons. Elevation of aminolevulinic acid results in<unk>  having symptoms similar to acute porphyria. Neurons<unk>  exposure damages cells in the hippocampus, a part of the brain involved in memory. Hippocampi of<unk> -exposed rats (bottom) show structural damage such as irregular nuclei (IN) and denaturation of myelin (DMS) compared to controls (top).|alt=Two black-and-white photos; one shows dark, fairly regular rings on a lighter background, and the other shows irregular, smaller, and not as dark clusters. The brain is the organ most sensitive to<unk>  exposure.<unk>  is able to pass through the endothelial cells at the blood brain barrier because it can substitute for calcium ions and be uptaken by calcium-ATPase pumps.<unk>  interferes with the normal development of a child's brain and nervous system; therefore children are at greater risk of<unk>  neurotoxicity than adults are. In a child's developing brain,<unk>  interferes with synapse formation in the cerebral cortex, neurochemical development (including that of neurotransmitters), and organization of ion channels. It causes loss of neurons' myelin sheaths, reduces numbers of neurons, interferes with neurotransmission, and decreases neuronal growth.<unk> -ions (Pb), like magnesium-ions (Mg), block NMDA receptors. Therefore, an increase in Pb concentration will effectively inhibit ongoing long-term potentiation (LTP), and<unk>  to an abnormal increase in long-term depression (LTD) on neurons in the affected parts of the nervous system. These abnormalities<unk>  to the indirect downregulation of NMDA-receptors, effectively initiating a positive feedback-loop for LTD. The targeting of NMDA receptors is thought to be one of the main causes for<unk> 's toxicity to neurons.
Lead poisoning
Anxiety disorder
Mercury poisoning
Iron-deficiency anemia
Zinc toxicity
Malabsorption
Iron poisoning
Polyneuropathy