Hematopoietic toxicity, levels

The main targets of lead toxicity are the hematopoietic system and the nervous system. Several of the enzymes involved in the synthesis of heme are sensitive to inhibition by lead, the two most susceptible enzymes being ALAD and heme synthetase (HS). Although clinical anemia occurs only after moderate exposure to lead, biochemical effects can be observed at lower levels. For this reason inhibition of ALAD or appearance in the urine of ALA can be used as an indication of lead exposure. 

The results of inhalation studies conducted in experimental animals have been fairly consistent across species. It has been suggested that benzene fetotoxicity in animals is a function of maternal toxicity because the joint occurrence of a decrease in fetal weight and an increase in skeletal variants usually occurs when there is a decrease in maternal weight (Tatrai et al. 1980b). However, the mechanism underlying developmental toxicity has not been fully elucidated, and there are few data on the effect of benzene on maternal food consumption and on blood levels of benzene and its metabolites in the dams and their fetuses. There are apparently none of the usual fetotoxic findings after exposure in utero to low concentrations of benzene ( 10 ppm) (Coate et al. 1984 Kuna and Kapp 1981). As stated above, there is evidence for persistent hematopoietic anomalies in animals exposed in utero to benzene at 20 ppm (Keller and Snyder 1988). They may also exist at lower concentrations, but adequate testing has not been performed. 

Elucidation of some of the mechanisms of lead toxicity on the cellular and biochemical level has led to the development of several relatively sensitive biomarkers of lead exposure and toxicity, including measurements of the effects of lead on enzymes of the hematopoietic system. Lead-induced alterations in blood zinc protoporphyrin (ZPP) and erythrocyte 6-aminolevu-linic acid dehydratase (ALAD) activity have been established as relatively specific biomarkers of lead toxicity to the heme biosynthetic pathway (NRC 1993 USEPA 1986). Increases in blood ZPP occur as a result of inhibition of ferrochelatase (FC) by lead. Inhibition of ALAD by lead, which begins at a blood lead level of about 5 tg/dL (Chisolm et al. 1985 USEPA 1986), is considered to be one of the most sensitive biomarkers currently available. 

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