Normal lead burden

Reiders (R2) has found that the urinary lead excretion following intravenous administration of CaNa-.-EDTA is increased significantly more in persons with excessive lead burden than in unexposed individuals, and he has suggested this as a definite diagnostic test. Intoxicated patients or those with increased lead absorption excrete at least 1 mg of lead in the first 24 hours following treatment, while normal individuals excrete a maximum of 700 /xg. CaNaaEDTA is frequently used in the treatment of lead intoxication (E4). 

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. 

In animal studies, decreased zinc status also contributes to lead and cadmium toxicity. In studies with rats, Cerklewski and Forbes (1976) demonstrated that an increase of zinc in the diet decreased the tissue lead levels and reduced other indicators of lead toxicity. Cerklewski (1979) also demonstrated that high levels of zinc fed to pregnant rats resulted in significantly lower levels of lead in the blood and liver of the rat pups. Using Japanese quail, Jacobs et al. (1977) reported that supplemental zinc markedly decreased concentrations of cadmium in the liver, kidney and small intestine, while Fox et al. (1979) showed that marginally adequate levels of dietary zinc markedly increased retention of cadmium in the duodenum, jejunum, ileum and liver as compared with zinc-supplemented birds. The association between increased lead burdens and lower serum zinc levels in children was reported by Markowitz and Rosen (1981). However, the mean levels of serum zinc in the children with elevated blood lead levels were not considered to be outside the lower limits of normal for plasma cited by Hambidge (1977). 

Purification A variety of creative and innovative open-access LC/MS formats were developed to address throughput needs within the industrial laboratory. As the preparation of large libraries for lead discovery became routine, the burden placed on analytical techniques focused mainly on throughput and quality (Kyranos and Hogan, 1998 Van Hijfte et al., 1999). Biological assay requirements, however, normally required pure compounds. Thus, the focus shifted toward the use of automated high-throughput purification methods applied to libraries of discrete compounds (Weller, 1998-99). 

The half-life of lead in humans is estimated to be about six years for the whole body burden and from 15 to 20 years for the skeleton. Thus, an excretion from the skeleton is very slow. Lead, like mercury, is a cumulative poison. The skeletal burdens of lead increase almost linearly with age. This suggests that the Pb steady state is not normally reached. Chelation of with ethylendiaminetetraacetic acid (ADTA) has been found beneficial in reducing Pb body burden for clinically affected patients. 

Ideal chemotherapeutics should target only tumor cells and should decrease tumor burden by inducing cytostatic or cytotoxic effects. Their lack of specificity, however, allows most chemotherapeutic drugs to have an adverse effect on normal cells and organs, leading to various side effects, including nephrotoxicity, hematotoxicity, cardiotoxicity, neurotoxicity, and impairment of other functions [87-89]. 

The bioaccumulation of a substance into an organism is not an adverse effect hazard in itself. Bioconcentration and bioaccumulation may lead to an increase in body burden which may cause toxic effects due to direct and/or indirect exposure. Bioaccumulative substances characterized by high persistence and toxicity, negligible metabolism and a log ATow between 5 and 8 may represent a concern when widely dispersed in the environment. The potential of a substance to bioaccumulate is primarily related to its lipophilicity. A surrogate measure of this quality is the n-octanol - water partition coefficient (/fow), which is correlated with bioconcentration potential. Therefore, /fow values are normally used as predictors in quantitative structure - activity relationships (QSARs) for bioconcentration factors (BCFs) of organic non-polar substances. 

Lead is ubiquitous in everyday life - it is in the atmosphere, the soil, and present in varying concentrations in food and drink. When Devergie and Hervy (1838) first suggested that lead was present in the body normally, they initiated a controversy that was not finally resolved until the advent of methods sensitive enough to detect traces of lead with reasonable reliability. Today the presence of the human body burden of lead is unquestioned. 

The zinc protoporphyrin test, unlike the blood lead determination, measures an adverse metabolic effect of lead and as such is a better indicator of lead toxicity than the level of blood lead itself. The level of ZPP reflects lead absorption over the preceding 3 to 4 months, and therefore is a better indicator of lead body burden. The ZPP requires more time than the blood lead to read significantly elevated levels the return to normal after discontinuing lead exposure is also slower. Furthermore, the ZPP test is simpler, faster, and less expensive to perform and no contamination is possible. Many investigators believe it is the most reliable means of monitoring chronic lead absorption. 

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