Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from various occupational, environmental, medicinal, and dietary sources. PAH metabolites in human urine can be used as biomarkers of internal dose to assess recent exposure to PAHs. PAH metabolites that have been detected in human urine include 1-hydroxypyrene (1-OHP), 1-hydroxypyrene-O-glucuronide (1-OHP-gluc), 3-hydroxybenzo[a]pyrene, 7,8,9,10-tetrahydroxy-7,8,9, 10-tetrahydrobenzo[a]pyrene, and a number of other hydroxylated PAHs. The most widely used of these is 1-OHP-gluc, the major form of 1-OHP in human urine, by virtue of its relatively high concentration and prevalence in urine and its ease of measurement. This metabolite of pyrene can be measured as 1-OHP after deconjugation of the glucuronide with beta-glucuronidase or directly as 1-OHP-gluc without deconjugation. Elevated levels of 1-OHP or 1-OHP-gluc have been demonstrated in smokers (versus nonsmokers), in patients receiving coal tar treatment (versus pretreatment), after workshifts in road pavers (versus before shifts or versus controls), after shifts in coke oven workers (versus before shift), and in subjects ingesting charbroiled meat (versus preingestion). More importantly, this metabolite is found (at low levels) in most human urine, even in persons without apparent occupational or smoking exposure. Although measurement of these metabolites is useful in assessing recent exposure to PAHs, their value as predictive markers of biological effect or health outcomes has not been rigorously tested and at present can only be inferred by association.

Objectives-Previous research suggests that binding of lead by 3-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA). Methods-57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALADl-2) from among all current workers in the two plants (n = 290). Subjects with ALADl-1 (n = 38) were frequency matched with subjects with ALADl-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead. Results-Blood lead concentrations ranged from 11 to 53 ug/dl, with a mean (SD) of 25 4 (10.2) ug/dl. After 5 mglkg DMSA orally, the workers excreted a mean (SD) 85 4 (45.0),ug lead during a four hour urine collection (range 16*5-184-1 jug). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALADl-2 excreted, on average, 24 Mg less lead during the four hour urine collection than did subjects with ALADl-l (P = 0.05). ALAD genotype seemed to modify the relation between plasma 3-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALADl-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALADl-1 (P value for interaction = 0.01). Conclusions-DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALADl-l. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long term retention and deposition of lead. (Occup Environ Med 1997;54:241-246)

The first intermediate substrate in the heme synthetic pathway, 5‐aminolevulinic acid (ALA), is neurotoxic in animal models and may be responsible for some of the adverse neurologic outcomes in lead poisoning and porphyria in adult humans. ALA is a substrate for the enzyme aminolevulinic acid dehydratase (ALAD; EC 4.2.1.24), which is encoded by the ALAD gene containing 2 co‐dominant alleles, 1 and 2. We measured plasma ALA (ALAP) and urinary ALA (ALAU) in 65 Korean lead workers, of whom 44 were homozygous for ALAD1 (ALAD1‐1 genotype) and 21 were heterozygous for ALAD (ALAD1‐2 genotype). ALAP in subjects with the ALAD1‐1 genotype was significantly higher than in those with the ALAD1‐2 genotype (Wilcoxon rank sum test, P = 0.01). No difference between ALAD genotypes was found for age, zinc protoporphyrin (ZPP), blood lead levels (PbB), ALAU, or ALAU adjusted for creatinine. ALAP was significantly correlated with ZPP (Spearman's r = 0.38, P = 0.002) and with PbB (r = 0.34, P = 0.006), and marginally with employment duration (r = 0.22, P = 0.08). ALAP remained significantly elevated (P = 0.032) in ALAD1‐1 subjects after adjustment for PbB and age by multiple linear regression. These results suggest that ALAD1‐1 subjects respond differently and may be more susceptible than ALAD1‐2 subjects to the ALA‐mediated neurotoxic effects of lead. Am. J. Ind. Med. 32:15‐20, 1997. © 1997 Wiley‐Liss, Inc.

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from various occupational, environmental, medicinal, and dietary sources. PAH metabolites in human urine can be used as biomarkers of internal dose to assess recent exposure to PAHs. PAH metabolites that have been detected in human urine include 1-hydroxypyrene (1-OHP), 1-hydroxypyrene-O-glucuronide (1 -OHP-gluc), 3-hydroxybenzo[alpyrene, 7,8,9,1 0-tetrahydroxy-7,8 927-932 (1996)

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