Bone, lead distribution

Witimers LE Jr, Aufdcrheide AC, Wallgren J, et al. 1998. Lead in bone IV. Distribution of lead in the human skeleton. Arch Environ Health 43 381-391. 

Williams CT, Potts PJ (1988) Element distribution maps in fossil bones. Archaeometry 30 237-247 Wittmers LE, Aufderheide AC, Wallgren J, Rapp G, Alich A (1988) Lead in Bone IV Distribution of lead in the human skeleton. Arch Environ Health 43 381-391 Wood BJ, Blundy ID (1997) A predictive model for rare earth element partitioning between clinopyroxene and anhydrous silicate melt. Contrib Mineral Petrol 129 166-181 Wright J, Seymour R S, Shaw HF (1984) REE and Nd isotopes in conodont apatite variations with geologic age and depositional enviromnent. In Conodont Biofacies and Provincialism. Clark DL (ed) Geol Soc Am Spec Paper, p 325-340... 

Because of its wide distribution in the body, biologic measures of lead dose in a nmnber of tissues—including blood, plasma, umbiUcal cord blood, hair, fingernails and toenails, breast ntilk, urine, semen, soft tissue, and bone— are available (see review by Hu et al. 2007). The excretion of lead in urine can be enhanced by CaNa2EDTA or DMSA, and chelatable lead has been used to estimate lead dose (Schiitz et al. 1987 Tell et al. 1992 Lee et al. 1995, 2000 Schwartz et al. 2001). Because CaNa2EDTA can partially chelate bone lead... 

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. 

Changing the distribution of a drug can lead to toxic effects not described before. It is possible that after liposomal delivery high concentrations of drugs (e.g., cytotoxic drugs) inside macrophages affect these cells detrimentally (Poste and Kirsch, 1983). This results in toxic effects in liver, spleen, and bone marrow which were not previously associated with the use of these drugs. 

Your body does not change lead into any other form. Once it is taken in and distributed to your organs, the lead that is not stored in your bones leaves your body in your urine or your feces. About 99% of the amount of lead taken into the body of an adult will leave in the waste within a couple of weeks, but only about 32% of the lead taken into the body of a child will leave in the waste. Under conditions of continued exposure, not all the lead that enters the body will be eliminated, and this may result in accumulation of lead in body tissues, notably bone. For more information on how lead can enter and leave your body, please refer to Chapter 2. 

Numerous observations of non-linear relationships between PbB concentration and lead intake in humans provide further support for the existence of a saturable absorption mechanism or some other capacity limited process in the distribution of lead in humans (Pocock et al. 1983 Sherlock et al. 1984, 1986). However, in immature swine that received oral doses of lead in soil, lead dose-blood lead relationships were non-linear whereas, dose-tissue lead relationships for bone, kidney and liver were linear. The same pattern (nonlinearity for PbB and linearity for tissues) was observed in swine administered lead acetate intravenously (Casteel et al. 1997). These results suggest that the non-linearity in the lead dose-PbB relationship may derive from an effect of lead dose on some aspect of the biokinetics of lead other than absorption. Evidence from mechanistic studies for capacity-limited processes at the level of the intestinal epithelium is compelling, which would suggest that the intake-uptake relationship for lead is likely to be non-linear these studies are discussed in greater detail in Section 2.4.1. 

It does not contain a probabilistic modeling component that simulates variability therefore, it is not used to predict PbB probability distributions in exposed populations. Accordingly, the current version will not predict the probability that children exposed to lead in environmental media will have PbB concentrations exceeding a health-based level of concern (e.g., 10 pg/dL). Efforts are currently underway to explore applications of stochastic modeling methodologies to investigate variability in both exposure and biokinetic variables that will yield estimates of distributions of lead concentrations in blood, bone, and other tissues. 

Lead is initially distributed throughout the body and then redistributed to soft tissues and bone. In human adults and children, approximately 94% and 73% of the total body burden of lead is found in bones, respectively. Lead may be stored in bone for long periods of time, but may be mobilized, thus achieving a steady state of intercompartmental distribution (see Section 2.3.2). 

Aufderheide AC, Wittmers LE Jr. 1992. Selected aspects of the spatial distribution of lead in bone. Neurotoxicol. 13 809-820. 

---