Biomarkers of lead exposure.

Biomarkers of exposure, effect, and susceptibility are reviewed in relation to lead exposure. Of the biomarkers of lead exposure, blood lead (Pb-B), mainly red cell lead, is a representative of soft tissue lead, and most widely used as measures of body burden and absorbed (internal) doses of lead. Urine lead (Pb-U) as well as plasma lead (Pb-P) increases exponentially with increasing Pb-B under a steady-state situation and is a reflection of recent exposure.

Mobilized plasma lead as an index of lead body burden and its relation to the heme-related indices.

Plasma lead (Pb-P) from workers were distributed in two main fractions: a protein bound fraction and low molecular weight fractions. Lead mobilized into plasma by CaEDTA was mainly observed in the low molecular weight fraction corresponding to lead disodium ethylenediamine tetraacetic acid (PbEDTA). The peak levels of Pb-P was attained around 1.

Simple and rapid method for determining nicotinamide adenine dinucleotide synthetase activity by high-performance liquid chromatography.

A method is described for the determination of nicotinamide adenine dinucleotide synthetase (NADS) activity in human blood. Using high-performance liquid chromatography (HPLC), the formed NAD is separated from the substrates and the other blood components in less than 13 min. The activity of NADS determined by HPLC is closely correlated with that determined by the conventional spectrophotometric method, which requires two steps of enzyme reaction.

[Studies on the evaluation of exposure to industrial chemicals].

Among the biological exposure indices of lead, lead in plasma was the most direct indicator of current exposure. Lead mobilized into plasma as well as in urine could be used as an indicator of the internal dose of lead. The ratio of non-treated to restored activity of delta-aminolevulinic acid dehydratase (ALA-D) was a more specific index than ALA-D activity itself at low levels of lead exposure, excluding the familial or genetic variation in the activity.

delta-Aminolevulinic acid in plasma or whole blood as a sensitive indicator of lead effects, and its relation to the other heme-related parameters.

To evaluate the subclinical effect of lead exposure, we determined delta-aminolevulinic acid (ALA) levels in plasma (ALA-P), blood (ALA-B), and urine (ALA-U) and the activity of delta-aminolevulinic acid dehydratase (ALAD) in lead workers. Almost all of the ALA molecules in blood were present in plasma and not in blood cells, irrespective of the blood lead concentration (Pb-B). ALA-P or ALA-B levels increased slowly at Pb-B levels below 40 micrograms/dl (slow phase) and rapidly at levels above 40 micrograms/dl (rapid phase).

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

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.

Biological monitoring of workers exposed to N,N-dimethylformamide by determination of the urinary metabolites, N-methylformamide and N-acetyl-S-(N-methylcarbamoyl) cysteine.

Biological monitoring of workers exposed to N,N-dimethylformamide (DMF) was carried out by determination of the urinary metabolites, N-methylformamide (MF, mainly from N-hydroxymethylformamide) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC), which were derived from two different routes of metabolism of the solvent. The urinary levels of MF increased rapidly at the start of the work shift, and decreased almost to zero within 24 h after the beginning of the last exposure. The highest level was found between the end of the afternoon shift and bedtime.

Analysis of toxic gas produced by heating tar epoxy resin paint to assess work atmosphere.

Two male workers were acutely intoxicated with gas produced by heating tar epoxy resin paint, and developed peripheral neuropathy. To assess the work atmosphere, we analyzed the degradation products by GC-MS. The major toxic products emitted by heating tar epoxy resin were hydrogen cyanide, phenol, and benzene, as well as naphthalene.

Gaschromatographic determination of butoxyacetic acid after hydrolysis of conjugated metabolites in urine from workers exposed to 2-butoxyethanol.

For the gaschromatographic determination of total butoxyacetic acid (BAA), i.e., free plus conjugated BAA in urine, we studied the acid hydrolysis condition to cleave the conjugate.

Determination of urinary alkoxyacetic acids by a rapid and simple method for biological monitoring of workers exposed to glycol ethers and their acetates.

In control subjects and workers exposed to glycol ethers and their acetates, we determined the urinary metabolites (three alkoxyacetic acids) by a simple and rapid method. Levels of urinary metabolites were significantly higher in the solvent workers than in the nonexposed subjects. The exposure levels measured by personal monitoring of breathing zone air were far below the threshold limit value.

[Effect of hydrolysis conditions on the determination of urinary 2,5-hexanedione in workers exposed or not exposed to N-hexane].

In order to determine the optimal conditions of acid hydrolysis for urinary 2,5-hexanedione (HD) measurement, the effects of urine pH or volume of HCl added to urine and hydrolysis period were studied using gas chromatography-mass spectrometry (GC-MS). When 0.3 ml of concentrated HCl was added to 3 ml of urine, complete hydrolysis to liberate HD was attained 2 h after the start of heating at 100 degrees C for urine from non-exposed subjects.

[Determination of protoporphyrins in blood using HPLC. Standardization of protoporphyrins and interlaboratory comparison of analyses].

1) In order to compare the results of determination of protoporphyrin IX (PP) and zinc protoporphyrin IX (ZP) using HPLC, the preparation procedures for standard solutions of PP and ZP were studied at four laboratories. According to the methods mutually agreeable to the four laboratories, the absorption values using UV-Vis spectrometer from the 4 laboratories were found to be identical. 2) The total of 28 whole blood samples obtained from the same workers whose Pb-B levels ranged from 2.

Accumulation of erythrocyte nucleotides and their pattern in lead workers.

Nucleotides in erythrocytes of lead-exposed subjects were analyzed by high-performance liquid chromatography (HPLC). Most of the pyrimidine levels correlated well with blood lead concentrations (Pb-B) and pyrimidine 5'-nucleotidase (P5N) activity. Highly significant correlations were found between Pb-B and uridine 5'-diphosphate-glucose (UDPG), cytidine 5'-triphosphate (CTP), or CDP-choline (CDPC).

[Method for simultaneous determination of six metabolites of toluene, xylene and ethylbenzene, and its application to exposure monitoring of workers in a printing factory with gravure machines].

For the biological monitoring of exposure to solvent composed of toluene, xylene, and ethylbenzene used in a printing factory with gravure machines, we developed a HPLC method for the simultaneous determination of urinary metabolites of this solvent, i.e. hippuric acid, o-, m-, and p-methylhippuric acid, mandelic acid and phenylglyoxylic acid.

Determination of erythrocyte porphyrins by reversed-phase high-performance liquid chromatography using capsule-type silica gels coated with silicone polymer.

A simple, rapid and reliable method is described for determining erythrocyte porphyrins using a new type of reversed-phase silica whose surface is coated with silicone polymer. After a single-step extraction of blood with N,N-dimethylformamide, zinc protoporphyrin IX and protoporphyrin IX were separately quantified in a single run in 5 min. The column life was so long that no alteration in elution profile or retention time was apparent after 1500 injections of samples.

Determination of pyrimidine 5'-nucleotidase (P5N) activity in whole blood as an index of lead exposure.

A simple method for determining pyrimidine 5'-nucleotidase (P5N) activity in whole blood has been developed, inhibiting the plasma activity for UMP-hydrolysis by concanavalin (Con A). Con A specifically inhibits the activity of plasma 5'-nucleotidase (5N) but does not affect erythrocyte P5N activity. The anticoagulant EDTA partially inhibits 5N activity but slightly activates P5N.