H. Savolainen

Analysis of oak tannins by liquid chromatography-electrospray ionisation mass spectrometry

Extractable tannins were analysed by liquid chromatography-electrospray ionisation mass spectrometry in two oak species, North American white oak (Quercus alba) and European red oak (Quercus robur). They mainly included various glucose gallic and ellagic acid esters. The structures were partially determined, and they included grandinin/roburin E, castalagin/vescalagin, gallic acid, valoneic acid bilactone, monogalloyl glucose, digalloyl glucose, trigalloyl glucose, ellagic acid rhamnose, quercitrin and ellagic acid.

Biological monitoring of occupational exposure to toluene diisocyanate

SummaryThe study validated the use of urinary toluene diamine (TDA) in postshift samples as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine workers exposed in TDI-based polyurethane foam production were studied. Their exposure levels varied in 8-h time-averaged samples from 9.5 to 94 μg/m3. The urinary TDA concentrations varied from 6.5 to 31.7μg/g creatinine and they were linearly related to the atmospheric TDI levels. Approximately 20% of TDI is metabolized to diamines but their specificity is remarkable to the extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the percutaneous absorption may be had.

Urinary atrazine metabolites as indicators for rat and human exposure to atrazine

Rats were given atrazine (2-chloro-4-ethylamino-6-(isopropylamino)-s-triazine) in drinking water for 1 or 3 weeks at 0.1 (0.45 mM), 0.2 (0.9 mM) or 0.5 g/l (2.3 mM) concentrations of the commercial agent. They excreted at both time points as the principal metabolite 2-chloro-4-ethylamino-6-amino-s-trazine in a dose-dependent fashion. The same urine test was applied on 6 railway men engaged in the weeding operation of railway lines with known atrazine exposure measured with hygienic techniques in their breathing zone. The spectrum of their atrazine metabolites was comprised of fully N-dealkylated atrazine and 2-chloro-4-ethylamino-6-amino-s-triazine. The sum of the two urinary metabolites reflected quantitatively the exposure.

Cadmium-associated renal disease.

Cadmium is widely used in industry, causing exposure of workers and environmental pollution because of its persistence in the biosystems. Its very long half-life in the human organism causes its accumulation over the lifetime in liver and kidneys. Cadmium ions have a high affinity for tissue thiols, induce the synthesis of a carrier cysteine-rich polypeptide called metallothionein, and impair proteoglycan metabolism. Significant renal effects include tubular nephropathy manifested by proteinuria, amino aciduria, glucosuria, phosphaturia, and calcium wastage. Chronic sequels include decrease in the glomerular filtration rate and increased risk of kidney stone disease. Biological monitoring of cadmium absorption includes determination of urinary cadmium and of low molecular weight marker proteins, such as beta2-microglobulin or retinol binding protein, the tubular reabsorption of which is impaired before a frank proteinuria.

Urinary hexane diamine as an indicator of occupational exposure to hexamethylene diisocyanate

The occupational exposure of 19 men to hexamethylene diisocyanate (HDI) vapour was monitored during one 8-h shift. It ranged from 0.30 to 97.7 μg/m3. This was compared with the urinary output of hexane diamine (HDA) liberated by acid hydrolysis from its conjugates in post-shift samples. The excretion varied from 1.36 to 27.7 μg/g creatinine, and there was a linear association of HDI air concentration with urinary HDA excretion. The validity of the urinary analysis was confirmed by simultaneous blind analysis in another laboratory. The results had an excellent linear concordance. Thus, it seems that while the gas chromatographic-mass spectrometric detection method requires sophisticated apparatus, the results are very useful to occupational health practices. A biological exposure index limit of 19 μg HDA/g creatinine in a post-shift urine specimen is proposed as an occupational limit level of HDI monomer (time-weighted average=75 μg/m3). Most importantly, biological monitoring of HDA is sensitive enough to be used at and below the current allowable exposure limit levels.

Bicarbonate-catalyzed hydrolysis of hexamethylene diisocyanate to 1,6-diaminohexane

The hydrolysis of hexamethylene diisocyanate (HDI) in water was tested in a dynamic and stationary system. Without catalysts, the reaction was very slow (less than 1% in 10 min at 30 degrees C) while the addition of simple carboxylic-acid-containing neutral buffers markedly catalyses the formation of 1,6-diaminohexane as the known hydrolysis product. The catalytic efficiency of formic acid, oxalic acid, acetic acid, lactic acid, citric acid and carbonic acid increased in this order while phosphate, glycine and glutamate were inactive even at very high concentrations. A 20 mM bicarbonate buffer was the optimal catalyst, but below this concentration the rate of HDI hydrolysis was drastically reduced. It is suggested that the hydrolysis of inhaled HDI in the lungs may be catalysed by bicarbonate in the blood, giving rise to amines found as urinary metabolites following occupational exposure.

Effects of single and repeated exposures to thermo-oxidative degradation products of poly(acrylonitrile-butadiene-styrene) (ABS) on rat lung, liver, kidney, and brain.

Male Wistar rats were exposed to thermo-oxidative degradation products of heated poly(acrylonitrile-butadiene-styrene) (ABS). The exposures were conducted once, three times or ten times (5 nights/week, 6 h/night) in the nighttime. The degradation products included styrene, various nitriles, aldehydes, acids, and a significant aerosol fraction. The oxygen concentration in the exposure chamber was constantly above 20%. The shortest exposures caused a significant reduction of the 0-deethylation activity in lung and kidney but not in liver, as well as a decrease in tissue reduced glutathione concentration in liver and kidney but not in lung. These effects well-nigh disappeared during the two-week exposure. In these rats the cerebral glutathione was below the control range. Superoxide dismutase activity increased in liver and brain during the three-day exposure. In liver the activity reached the control value after the two-week exposure but the cerebral activity was significantly lower than in controls. The complex mixture of noxious compounds in the ABS fumes does not readily allow identification of causative agents. Nitrile-dependent histotoxic, peroxidative and reactive metabolite mediated mechanisms may be involved.

Kinetics and renal effects of formic acid in occupationally exposed farmers.

Twelve male farmers (38 ± 14 years of age, mean ± SD) were exposed to 7.3 ± 2.2 mg formic acid/m3 for 8 h in the silage making (mean ± SD,N=12). Each gave urine samples immediately, 15 h and 30 h after the end of the exposure. The excretion of formate was linearly related to the exposure 15 and 30 h after the exposure. Exposure increased renal ammoniagenesis and urinary calcium at 30 h post-exposure. Both biochemical effects may be explained by the interaction of formic acid with the oxidative metabolism of renal tubular cells, as formic acid is a known inhibitor of the cytochrome oxidase. In view of these renal effects, the current hygienic limits may not entirely protect exposed individuals.

2-Ethylhexanoic acid inhibits urea synthesis and stimulates carnitine acetyltransferase activity in rat liver mitochondria

Adult male 3-month-old Wistar rats were given 0, 100 mg/l, 1, 5 or 10 g/l 2-ethylhexanoic acid in their drinking water for 20 days. Their daily consumption of contaminated water was measured and compared with the free acid found in their 24-h urine samples. The excretion was dose and time dependent. At the termination of the experiment, liver mitochondrial carnitine acetyltransferase activity was induced dose dependently and the citrulline synthesis in the urea cycle inhibited. Our results compare very well with the toxicity of a structural congener of the 2-ethylhexanoic acid, i.e. valproate, an antiepileptic drug.

Determination of gallic acid in wood dust as an indicator of oak content

A high-performance liquid chromatography (HPLC) method was developed for the detection of extracted gallic acid in wood dust. Gallic acid is a polyphenol present in carcinogenic oak wood dust, but not in beech, ash, pine or spruce dusts, as confirmed by HPLC analyses. The method involved the extraction of gallic acid from the oak dust, followed by liquid chromatographic analysis. The correlation coefficient for the share of oak dust vs. the gallic acid concentration of wood dust was 0.995. The method was tested with oak wood dust samples collected on polycarbonate membrane filters during an 8 h workshift in a floor board factory, where the dust content of the air samples was determined gravimetrically. The oak dust and the gallic acid concentrations varied from 0.2 to 13.8 mg m-3 and from 0.03 to 3.8 micrograms m-3, respectively. These parameters were linearly correlated with a correlation coefficient of 0.95. The airborne gallic acid determination is a useful technique to confirm occupational exposure to oak wood dust, a recognized human carcinogen.