Soft tissues lead burden

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). 

Lead Inorganic lead oxides and salts Gastrointestinal, respiratory Soft tissues redistributed to skeleton (> 90% of adult body burden) CNS deficits peripheral neuropathy anemia nephropathy hypertension reproductive toxicity Inhibits enzymes interferes with essential cations alters membrane structure Renal (major) feces and breast milk (minor)... 

A striking aspect of lead in the body is its very rapid transport to bone and storage there. Lead tends to undergo bioaccumulation in bone throughout life, and about 90% of the body burden of lead is in bone after long-term exposure. The half-life of lead in human bones is estimated to be around 20 years. Some workers exposed to lead in an industrial setting have as much as 500 mg of lead in their bones. Of the soft tissues, the liver and kidney tend to have somewhat elevated lead levels. 

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. 

Kinetic studies in man show that the lead body burden consists essentially of three compartments (1) a rapid exchange pool in blood and soft tissues (2) an intermediate exchange pool in muscles, skin and bone marrow (3) a slow exchange pool in dense bones and teeth (biological half-life about 20 years). The amount of lead stored in the latter compartment increases throughout life (Steenhout, 1982 Steenhout and Pourtois, 1981). 

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.)... 

C. Urinary lead excretion increases and decreases more rapidly than blood lead. Normal urinary lead excretion is less than 50 mcg/day. Several empiric protocols that measure 6- or 24-hour urinary lead excretion after calcium EDTA challenge have been developed to identify persons with elevated body lead burdens. However, since chelatable lead predominantly reflects lead in soft tissues, which in most cases already correlates satisfactorily with blood lead, chelation challenges are seldom indicated in clinical practice. 

Diet provides the major pathway for lead exposure, and amounts in bone are indicative of estimated lead exposure and metabolism. Amounts of whole body lead and feeding habits of roadside rodents were correlated body burdens were highest in insectivores such as shrews intermediate in herbivores, and lowest in granivores. Food chain biomagnification of lead, although uncommon in terrestrial communities, may be important for carnivorous marine mammals, such as the California sea lion accumulations were highest in hard tissues, such as bone and teeth, and lowest in soft tissues, such as fat and muscle. A similar pattern was observed in the harbor seal. 

The blood lead level is a good index of current or recent lead absorption when there is no anemia present and when the worker has not taken any chelating agents. However, blood lead levels along with urinary lead levels do not necessarily indicate the total body burden of lead and are not adequate measures of past exposure. One reason for this is that lead has a high affinity for bone and up to 90 percent of the body s total lead is deposited there. A very important component of the total lead body burden is lead in soft tissue (liver, kidney, and brain). This fraction of the lead body burden, the biologically active lead, is not entirely reflected by blood lead levels since it is a function of the dynamics of lead absorption, distribu-... 

Most chemicals have longer residence times in the body than carbon monoxide. The term used to denote the length of time that 50 percent of the body burden of a substance is excreted is the biological half-life. The biological half-life of a compound can vary from one tissue to another. Thus, the biological half-life of lead in bone is between ten to twenty years, but in blood and soft tissues it is in the 30-day range. 

The earliest models of lead toxicokinetics are typified by that of Rabinowitz et al. (1976, 1977), using stable lead isotope in human volunteers, and which indicate that there are at least three kinetically distinct body compartments for lead disposition in vivo. These compartments consist of a central blood compartment, a second lead depository in peripheral soft tissues, and, finally, the large bone compartment for lead. Lead in blood is the most kinetically labile, whereas lead in soft tissues has a somewhat larger biological half-life. The bone compartment retains lead for the longest time. Blood and soft tissues contain relatively small burdens of lead, ca. 1.9 and 0.6 mg respectively, while the vast majority of the body burden of lead is sequestered in a kinetically slow compartment of bone, with levels that can exceed 200 mg of the toxicant. 

Blood lead reflects, biokinetically, both relatively recent lead exposure and the toxicologically active fraction of lead body burden in various soft tissues, at least under steady-state conditions or near steady state. 

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