Reviews on biochemical markers of lead exposure with special emphasis on heme and nucleotide metabolisms

Abstract

Biochemical marker in heme and nucleotide metabolisms were reviewed and evaluated in terms of biological monitoring of lead exposure. Analytical methods, reference values, threshold values, dose-effect relationships, validity, applicable range of Pb-B levels, and confounding factors were studied for the biochemical parameters: delta-aminolevulinic acid dehydratase activity (ALA-D), delta-aminolevulinic acid in plasma (ALA-P), delta-aminolevulinic acid in urine (ALA-U), coproporphyrin in urine (CP-U), erythrocyte protoporphyrin (EP) or zinc protoporphyrin (ZP), pyrimidine 5'-nucleotidase (P5N), and pyrimidine nucleotides in blood (PN). The threshold value of Pb-B for ALA-D by CEC method or restoration method was 5 micrograms/dl. The high validity (> 1.8) was found at a wide range of Pb-B levels between 5 and 50 micrograms/dl, while that of ALA-D activity by CEC method was between 20 and 50 micrograms/dl. The threshold value of Pb-B for ALA-P was also as low as 5 micrograms/dl, and that for ALA-U (corrected for creatinine) was between 15 and 30 micrograms/dl or 20 and 40 micrograms/dl in HPLC or colormetric method, respectively. ALA-P showed a high validity (> 1.8) at Pb-B levels of 30 and 60 micrograms/dl, whereas ALA-U did at Pb-B of 60 micrograms/dl alone. EP (ZP) and CP-U were significantly increased in the Pb-B levels higher than 20 to 30 micrograms/dl and 40 micrograms/dl, respectively. The threshold level of Pb-B for P5N activity was less than 10 micrograms/dl, and showed a linear reduction in activity with a rise in Pb-B values between 10 and 60 micrograms/dl. The validity of P5N (1.86 at a cut off of < 10 mumol/h/g Hb) was the highest among biochemical parameters examined at Pb-B values over 40 micrograms/dl. PN was increased in the Pb-B levels higher than 60 micrograms/dl. Individual variation of ALA-U, CP-U, and ZP were relatively larger than those of PN. ALA-P seemed to be one of the most desirable biomarkers for lead exposure, because of simplicity, sensitivity and specificity of analytical method, and of wide range of applicable Pb-B, from normal to intoxication levels. PN might be of diagnostic value for lead intoxication. Lead effect or intoxication could be assessed more exactly by the combination of some specific biomarkers mentioned above.