Soft tissues, lead distribution

Among the soft tissues, lead is distributed to the bone marrow, liver and kidney (Barry 1975, Skerfving etal. 1993). Lead does, to some extent, pass the blood-brain barrier into the nervous system and, according to animal experiments, such passage is most likely higher in infants than in adults (Mahaffey 1983). Distribution in the central nervous system (CNS) is uneven, with higher levels in the hippocampus and amygdala. Lead concentrations in the cerebrospinal fluid are very low, and seem to correlate positively with plasma lead concentrations rather than with B-Pb. 

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. 

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). 

The total body burden of lead is a function of the balance between the amount being taken in (all routes combined), the amount distributed throughout the tissues, and the amount being excreted. Most of the body burden of lead is sequestered in the bones and teeth over 70% in children and over 90% in adults. The remainder of the body burden is distributed between soft tissue and the blood. Lead is stored in the bone for the greatest length of time. The estimated half-lives of lead range from 10 to 30 years in bone, are 40 days in soft tissues, and range from 28 to 36 days in blood (in adults). Children tend to retain approximately five times more absorbed lead than adults. 

Children absorb lead from the diet with greater efficiency than adults (WHO, 2000). After absorption and distribution in blood, where most lead is found in erythrocytes, it is initially distributed to soft tissues throughout the body. Subsequently, lead is deposited in the bone, where it eventual accumulates. The half-life of lead in blood and other soft tissues is 28-36 days. Lead that is deposited in physiologically inactive cortical bones may persist for decades without substantially influencing the concentrations of lead in blood and other tissues. On the other hand, lead that is accumulated early in life may be released later when bone resorption is increased, e.g., as result of calcium deficiency or osteoporosis. Lead that is deposited in physiologically active trabecular bones is in equilibrium with blood. The accumulation of high concentrations of lead in blood when exposure is reduced may be due to the ability of bones to store and release lead. 

Colon tissue was selected as a model for the comparative analysis of soft tissue by FT-IR and Raman imaging at low and high lateral resolution, because it contains aU four major tissue types such as muscle, connective tissue, epithelium and also nerve cells. The vibrational spectroscopic fingerprints of normal tissues and their distribution in control samples were determined. The compilation of such data is important before a method can be applied to pathological colon tissue such as colorectal adenocarcinoma, which is the third most common form of cancer and the second leading cause of death among cancer patients in the Western world. Colorectal adenocarcinomas originate from epithelial cells and are able to infiltrate the subjacent layers of colon and rectum. 

Once absorbed from the intestines, lead enters the blood stream and is rapidly distributed throughout the body, to the erythrocytes, bones, and soft tissue (10). In adults, 90-95% of the total lead body burden is found in bone (5, 435, 436), resulting in a mean level of 14 pg Pb/g of skeletal bone ash (14 ppm) in middle-aged adults in the United States today (27, 437) (Table XVI). In children, the percent of total body lead that resides in bone is closer to 70-80% (436). By contrast, lead concentrations in soft tissues are typically 0.5 ppm (438) and lead concentrations in brain are usually <0.2 ppm, with the highest levels being found in the hippocampus and frontal cortex (10). The average concentration of lead in whole blood for people in the United States in 1999 was 1.6 pg/dL (16 ppb) (18) 94—99% of blood lead is found in the erythrocytes and only 1-6% is in the plasma (10, 27). (Methods for the analysis of lead content in blood are discussed in Section Vl.E.)... 

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... 

From the blood plasma absorbed lead is distributed to the soft tissues, teeth, and the skeleton. The distribution of lead in soft tissues is subject to both between-tissue and within-tissue variation [6]. Indicative values of lead in liver, kidney, and brain are 0.29-0.77, 0.17-0,47, and 0.02-0.07 i.mol/g ash, respectively [6]. Lead is accumulated in the nervous system, where the lead... 

Once absorbed, lead is deposited in mineral tissue such as bones and teeth, in some soft tissues such as the liver, kidneys and brain, and some is retained in the blood stream. The distribution of total body lead to the bones is about 70 per cent, increasing to 90 per cent with age. 

Lead that enters the bloodstream of humans and experimental animals after absorption is first distributed to plasma/serum, followed by movement to erythrocyte and soft tissue binding sites with subsequent re-equilibration to longer-term binding sites in soft and mineralizing tissues. Lead entry into and removal from plasma/semm is rapid. Chamberlain et al. (1978) reported that injected radiolabeled Pb in adult volunteers entered and was removed from plasma/serum in less than 1 hour. Table 8.7 summarizes data for Pb distribution and clearance in human blood. 

SubceUular distribution of Pb in human soft tissues appears to mainly involve the mitochondria and nuclei, two organelles known to either be affected toxicologically by lead or be involved in Pb sequestration and toxicokinetics. Intranuclear inclusion bodies, for example, have long been known to form as a transitory protective mechanism for averting or delaying lead toxicity. Lead in relatively large amounts is sequestered in nuclear inclusions and the biochemical and structural characteristics of these bodies have been described (Carroll et al., 1970 Moore et al., 1973). Cramer et al. (1974) showed the formation of intranuclear inclusions as an early response to Pb in kidney proximal tubule cells in new lead workers. 

Analysis of tissues of monkeys and rodents [369] sacrificed some days after administering Pb(C2H5)4 showed lead widely distributed in soft tissue with an excess In the liver but not in the brain. Following injection, enhanced lead concentrations were also found in bone [369]. No significant reduction in cholinesterase activity on addition of Pb(C2H5)4 to various enzyme sources is observed in vitro. Transient cholinesterase inhibition found in in vivo experiments with rhesus monkeys is considered to be biologically insignificant [368]. 

A single dose of lead to rats initially produces high concentrations of lead in soft tissues, with a rapid reduction of this concentration as the result of transfer to the bone and excretion. The characteristics of the distribution of lead in animals has been found to be independent of the dose, over a wide range. As in humans... 

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