QUANTITATIVE-EVALUATION OF HEME BIOSYNTHETIC-PATHWAY PARAMETERS AS BIOMARKERS OF LOW-LEVEL LEAD-EXPOSURE IN RATS

Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, ery throcyte zinc protoporphyrin (ZPP)/heme ratio, and urinary coproporphy rin (UC) concentration have been employed as biological indicators of moderate- to high-level lead exposure, corresponding to blood levels i n excess of 50 mu g/dl, in human subjects. The comparative efficacy of these measures as indicators of lead exposure consistent with sustain ed lower blood lead levels has not been systematically evaluated. In t he present studies, we examined the relative sensitivity and magnitude of response of these three bioindicators in rats during chronic expos ure to 0, 100, or 1000 ppm lead as lead acetate in drinking water for up to 10 wk, followed by a 10-wk postexposure period, with weekly asse ssments, or during subchronic exposure to 0 or 1000 ppm lead as lead a cetate in drinking water for 6 d, with daily assessments. Analysis of variance (ANOVA) was used to determine if the lead-treated rats differ ed from controls and to distinguish between dose groups with respect t o the three biochemical indices of lead exposure. The data were normal ized by conversion to Z scores in order to compare indicators with reg ard to magnitude of change in response to lead treatment The order oi sensitivity of each indicator was determined by considering the magnit ude of the correlation coefficient (r) between the indicator and the b lood lead concentration in each study. The indicators in order of decr easing sensitivity to lead in the chronic study were UC > ZPP/heme > A LAD. The indicators in order of decreasing magnitude of change in resp onse to change in blood lead level were also UC > ZPP/heme > ALAD. Non e of the heme pathway parameters was judged a satisfactory substitute for direct blood lead measurement as an indicator of low-level lead ex posure. However, urinary coproporphyrin appears most useful in this re spect owing to highest sensitivity and magnitude of change relative to blood lead content and relatively low variation of mean coproporphyri n levels.