Determination of urinary acylcarnitines by ESI-MS coupled with solid-phase microextraction (SPME).

The determination of selected short-, medium- and long-chain acylcarnitines by electrospray ionization mass spectrometry (ESI-MS) is discussed. The differences in fragmentation behaviour and ionization efficiency are described in dependence on collision induced dissociation (CID) conditions and mixture composition. A new method combination, solid-phase microextraction (SPME)-ESI-MS, is introduced to characterize acylcarnitines in body fluids. This method utilizes SPME for pre-concentration of acylcarnitines from complex biological samples and ESI-MS for a selective and sensitive detection. The method is presented by standard experiments determining of acylcarnitines in aqueous solutions and urine samples from patients with secondary carnitine deficiency syndromes or related disorders.

Toxicological investigations in the semiconductor industry: III: Studies on prenatal toxicity caused by waste products from aluminum plasma etching processes.

The prenatal toxic effects of contaminated vacuum pump oil (Sample A) and solid waste products (Samples B and C) originating from aluminum plasma etching processes in semiconductor manufacturing were investigated. Three strains of pregnant mice with different degrees of sensitivity during organogenesis (days 6-15 of gestation) were treated daily with 1000 mglkg b.w. (Sample A), 500 or 750 mg/kg b.w. (Sample B), and 250, 500, or 750 mg/kg b.w. (Sample C). On day 18 of pregnancy, the animals were killed and examined for gross changes, number and weight of live fetuses, as well as the number of postimplantation losses and malformations. Analytical data showed that the investigated wastes contained various halogenated hydrocarbons and inorganic compounds. Sample A revealed no signs of prenatal toxic action. In contrast, administration of Samples B and C caused strong prenatal toxic effects. The number of live fetuses declined in a dose--related manner, and evidence of intrauterine growth retardation was noted in fetuses that survived to day 18. The number of fetuses with malformations (only cleft palates) rose significantly in accordance with the doses and sensitivity of the strains (> 95 % of the fetuses of the most sensitive strain after 750 mg/kg; 85% after 500 mg/kg).

Genotoxicity assessment of waste products of aluminum plasma etching with the SOS chromotest.

We evaluated 36 characteristic waste products from the plasma etching of aluminum for genotoxicity with the SOS chromotest. The majority of the samples showed genotoxic activity in tester strain Escherichia coli PQ37 without metabolic activation using S9 mix. In the presence of S9, a deactivation of the samples was regularly observed. Comparable studies with the Salmonella/microsome (Ames) test using tester strains Salmonella typhimurium TA98 and TA100 indicated actual mutagenicity of waste products. Gas chromatograms of the organic constituents of all waste products were performed in parallel with the genotoxicity assays. In contrast to the similarity of the peak patterns of all chromatograms, the biological effects of individual waste samples showed large differences. Information on chemical composition and the SOS chromotest results of a representative sample recovered over a period of 2 years is given. For this sample, the influences of sample preparation and cytotoxic matrix effects on the test parameters are also shown.

Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process.

In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased.

Gas chromatographic-mass spectrometric investigation of four commercial pristane (2.6.10.14-tetramethylpentadecane) preparations used for plasmacytoma induction in BALB/c mice.

The most widely studied model of plasmacytomagenesis is the induction of plasmacytomas by intraperitoneal injections of pure alkanes such as pristane (2.6.10.14-tetramethylpentadecane). The presence of small amounts of genotoxic contaminants, that could contribute to the complex oncogenic process, in commercial pristane preparations has not been completely ruled out. Therefore, we conducted a chemical analysis of different pristane preparations applying a combined GC/MS technique, but were not capable of identifying any obvious or putative genotoxic/cancerogenic contaminants.

Genotoxicity assessment of the plasmacytomagenic agent pristane (2.6.10.14-tetramethylpentadecane) and four related alkanes by the SOS chromotest.

The most extensively studied model of plasmacytomagenesis is the induction of plasmacytomas in BALB/c mice by i.p. injections of mineral oil or, chemically more defined, by several branched alkanes such as pristane (2.6.10.14-tetramethylpentadecane), phytane (2.6.10.14-tetramethylhexadecane), and 7-n-hexyloctadecane. The available evidence suggests that the primary biologic action of these plasmacytomagenic agents is to induce the formation of a chronic granulomatous tissue, the histological matrix of plasmacytoma development. However, certain genotoxic effects caused by the presence of these substances can not be ruled out a priori. Pristane, 2-methyldodecane, and 1.3-di-tert-butyl-5-methyl-cyclohexane as well as perhydroanthracene and hexahydrodibenzsuberane were proofed as potential genotoxic agents by the SOS chromotest, a quantitative bacterial colorimetric assay for genotoxins. The substances tested did not express any sign of genotoxicity, but exerted toxic effects to the E. coli tester strain.

Pyrolysis products of PCBs.

Model compound studies which were previously done for impurities and environmental residues of chlorophenols and for wastes of chlorination processes were extended to the impurities and pyrolysis products of polychlorinated biphenyls (PCBs). Model compounds were commercial products or synthesized and their structures proven by spectroscopic methods. These models were used as analytical reference substances in GC/ECD and GC/MS studies of the pyrolyzed PCB samples. In addition to previously known neutral components like polychlorinated dibenzofurans (PCDFs), chlorophenolic substances, especially polychlorophenols (PCPs) and polychlorinated biphenylols (PCB-OHs) were observed as major pyrolysis products of PCBs. Capacitor fires are suggested to produce in many cases chlorophenols which are major toxic hazards to people.