Bones, lead accumulation

The absorption, distribution, and accumulation of lead in the human body may be represented by a three-part model (6). The first part consists of red blood cells, which move the lead to the other two parts, soft tissue and bone. The blood cells and soft tissue, represented by the liver and kidney, constitute the mobile part of the lead body burden, which can fluctuate depending on the length of exposure to the pollutant. Lead accumulation over a long period of time occurs in the bones, which store up to 95% of the total body burden. However, the lead in soft tissue represents a potentially greater toxicological hazard and is the more important component of the lead body burden. Lead measured in the urine has been found to be a good index of the amount of mobile lead in the body. The majority of lead is eliminated from the body in the urine and feces, with smaller amounts removed by sweat, hair, and nails. 

The O Flaherty Model simulates the age-dependence of lead kinetics on such factors as absorption efficiency, excretion efficiency, uptake into bone and loss from bone, and partitioning between plasma and red blood cells. The model does not incorporate age, dose rate, or time dependence of lead accumulation in every organ (e g., kidney) because the complex patterns of lead accumulation in certain tissues are not known (O Flaherty 1991a) (see Section 2.4.1). However, the basic model structure allows for additional modules to be incorporated, depending on its intended use in risk assessment. For example, additional modules that are currently being developed are a pregnancy model and a model of net bone loss in older women and men. 

Fimreite, N. 1984. Effects of lead shot ingestion in willow grouse. Bull. Environ. Contam. Toxicol. 33 121-126. Finley, M.T. and M.P. Dieter. 1978. Influence of laying on lead accumulation in bone of mallard ducks. Jour. Toxicol. Environ. Health 4 123-129. 

It turns out that most of these compounds have similar characteristics that contribute to their toxicity to both humans and other species of plants and animals. First, the compounds are environmentally persistent. Many of the early pesticides, and certainly the metals, do not break down in the environment or do so only very slowly. If persistent chemicals are released continually to the environment, the levels tend to rise ever higher. This means they are available to cause harm to other organisms, often not even the target of the pesticide. Second, the early pesticides were broad acting and toxic to many species, not just the target species. These poisons often killed beneficial insects or plants. Third, many of these compounds would bioaccumulate or concentrate in species as they moved up the food chain. The chlorinated pesticides accumulate in the fat of animals. Animals that consumed other animals accumulated more and more of these pesticides. Most species could not metabolize or break down the compounds. Lead accumulates in bone and methyl mercury in muscle. And finally, because of their persistence in the environment and accumulation in various species, the persistent toxicants spread around the world even to places that never used them. Animals at the top of the food chain, such as polar bears and beluga whales, routinely have fat PCB levels greater that 6 ppm. 

Did the plentiful use of lead cause severe outbreaks of lead poisoning in the Romans Archaeological chemists looking into this issue have examined skeletons dating from Roman times. Lead accumulates in the bones as the body absorbs this heavy element. The University of Minnesota researcher Arthur C. Aufderheide and his colleagues tested Roman... 

Chronic exposures to lead by inhalation or the oral route cause adverse effects that include damage to the peripheral and central nervous system, anemia, and chronic kidney damage. Lead accumulates in the soft tissues and bones, with the highest accumulation in the liver and kidneys, and elimination is slow. Lead has shown developmental and reproductive toxicity in both male and female... 

The Roman aristocracy had greater access to lead vessels and cosmetics containing lead compounds. It is believed that their life expectancy may have been as low as 25 years because of lead poisoning. In the body, lead accumulates in bones and the central nervous system. The production of hemoglobin is inhibited by lead because it binds to the enzymes that catalyze the reaction. High levels of lead cause anemia, kidney disfunction, and brain damage to occur, and the accumulation of lead interferes with proper development of the brain in children. Because of their toxicity, lead and its compounds are used much less today as paints or glazes than they were in earlier times. 

It should be noted that in the majority of the above mentioned studies, metal-induced renal injury was considered as if exposure occurred to only one metal at a time. In reality it is clear that environmental and occupational exposure may involve several metals at the same time and in varying concentrations [34]. It has been shown that with combined exposure various metals may interact with each other and that one metal may alter the potential toxicity of another in either a beneficial or deleterious way. As an example, whilst arsenic has been shown to worsen cadmium-induced nephrotoxicity, data from experimental studies have shown that selenium may protect against the renal effects induced by cadmium [52]. Other studies have shown that the iron status may alter the toxic effects of aluminium at the level of the bone and the parathyroid gland [53,54], whilst in a recent increased lead accumulation was associated with disturbances in the concentration of a number of essential trace elements [55]. 

It is axiomatic that the toxicity of the ligand selected for the treatment and any side effects, such as co-liberating essential metals during therapy, ought, collectively, to add up to less than the residual toxicity of the element that has been deposited in the body. However, factors other than simple toxicity or unpleasant side effects need to be considered. For example, about 90% of the lead accumulated in the human body is sequestered in non-toxic form in bone. Incautious chelation therapy with an agent like EDTA, or administration of large amounts of... 

Cautionary reports regarding the postmortem accumulation of lead into bones have not always been headed. Correlations between soil and bone lead content from a depositional environment, and failures to remove diagenetic lead from buried bone have been reported (Waldron 1982, Patterson et al. 1987). Lead does not only accumulate in bone diagenetically, but can also be lost through migration out of bone (Jaworowski et al. 1985). The possibility of both uptake and loss of any element, without knowledge of uptake or leaching profiles within a bone, makes dietary or environmental interpretations suspect. 

An intermediate Pb toxicokinetic scenario reflecting exposures captured in the short term and in bone compartment accumulations would be exposures of older children with significant histories of earlier lead exposures. One case in which the main contributor of Pb to PbB is accumulated bone Pb would be bone Pb resorption to blood in retired Pb workers. 

Lead accumulates in the metaphyses of growing bone, causirtg metaphyseal sde-rosis and reducing the rate of linear grov. ... 

The lateral resolution of 0.5 allows experiments at the subcellular level. Initial work has concentrated on the localization of elements In specific sites of the tissue. Typical examples involve the assessment of aluminium levels in the bones of chronic haemodialysis patients, the study of lead accumulation in kidneys and calcifications in intraperitoneal soft tissue as a result of chronic lead intoxication, and the detection of several heavy metals in the amalgam tattoos of the oral mucose membrane and human gingiva in direct contact with dental alloys. The relatively low lateral resolution, the lack of automated mapping and the almost impossible quantization strongly hinder the use of LMMS, especially in view of analytical electron microscopy (AEM) with X-ray analysis and the emerging possibilities of nuclear microscopy. 

Lead accumulates in the trabecular and cortical bone as a function of both age and exposure. It represents the major repository of lead in the human body, accounting for at least 95% of total body burden. While the overall biokinetics of lead in bone suggest a compartment with a long biological half-life, of the order of a decade or so, some fraction of this amount can be remobilized via various bone resorption processes as noted earlier in this report. 

Another important storage depot for toxic compounds is the skeleton. In particular, cadmium and lead bind and accumulate in the bone tissue from which they are released very slowly. The half-life of elimination of cadmium is several years, the half-life of lead is several months. 

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