Biomedical subjects

S Forderkunz

Publications and source records attributed to S Forderkunz.

4 recordsLinked to original sources

PubMed1998

Maximum workplace concentration values and carcinogenicity classification for mixtures.

In Germany, the Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) generally sets maximum workplace concentration values (i.e., a proposed occupational exposure level [OEL]) for single substances, not for mixtures. For mixtures containing substances with a genotoxic and carcinogenic potential, the commission considered it scientifically inappropriate to establish a safe threshold. This approach is currently under discussion. Carcinogenic mixtures are categorized according to either the carcinogenicity of the mixture or the classification of the carcinogenic substances included. In regulating exposure to mixtures, an approach similar to that used by the American Conference of Governmental Hygienists is proposed: For components with the same target organ and mode of action or interfering metabolism, synergistic effects must be expected and the respective OELs must be lowered. However, if there is proof that the components act independently, the OELs of the individual compounds are not considered to be modified. In the view of the commission, calculating OELs for solvent mixtures according to their liquid phase composition is not justified, and the setting of scientifically based OELs for complex mixtures is not possible.

Carcinogens↗

PubMed1995

Determination of Cu-containing metallothionein: comparison of Ag saturation assay, thiomolybdate assay, and enzyme-linked immunosorbent assay.

Three methods for the quantification of Cu-containing metallothionein (MT) (Ag saturation assay, thiomolybdate assay, and enzyme-linked immunosorbent assay (ELISA)) were compared for their ability to recover in vitro prepared standard Cu-MT both in absence and presence of rat liver cytosol. Uniform molar calibration of the assays was achieved using the nitrogen content of the standard Cu-MT measured by the Kjeldahl procedure. With all three methods Cu-MT reliably could be quantified. The Ag saturation assay and the thiomolybdate assay, dependent on the amount of Cu-MT and the presence of hepatic cytosol, showed a tendency to over- or underestimate the theoretical expectation. The ELISA generally performed best and moreover was three orders of magnitude more sensitive than the other two assays. With all three methods corresponding MT levels were found in the Cu-rich liver of a Long-Evans Cinnamon rat.

Animals↗

PubMed1991

Influence of selective phosphodiesterase inhibitors on human neutrophil functions and levels of cAMP and Cai.

Chromatographic analysis of 3',5'-cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the cytosol of human neutrophils shows the predominant presence of PDE IV (cAMP specific) and PDE V (cGMP specific). PDE IV is characterized by (1) cAMP selectivity, (2) a KM for cAMP of 1.2 microM and (3) a typical rank order of IC50-values for PDE inhibitors: 0.13, 0.17, 47 and 9.5 microM for PDE IV selective rolipram, PDE III/IV selective zardaverine, PDE III selective motapizone and unselective 3-isobutyl-1-methylxanthine (IBMX), respectively. Functions of polymorphonuclear leukocytes (PMN) such as N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated superoxide release and fMLP/thimerosal elicited leukotriene (LT) biosynthesis are inhibited by these PDE inhibitors with the same rank order and even lower IC50-values. Measurements of changes in cytosolic Cai in Fura-2 loaded PMN demonstrate a transient Cai increase after stimulation with 0.1 microM fMLP and an additional sustained elevation of Cai levels in the presence of thimerosal. PDE inhibitors suppress this sustained phase of Cai release with the same rank order of IC50-values as LT biosynthesis. The correlation between fMLP/thimerosal-induced LT biosynthesis and Cai levels reveal a Cai threshold of 150 nM for arachidonic acid metabolism. cAMP levels in PMN were elevated by PDE inhibitors alone by less than 2-fold. In the presence of fMLP however, cAMP was increased up to 10-fold and the efficacy of PDE inhibitors to increase cAMP paralleled their potency to inhibit PDE IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonate 5-Lipoxygenase↗

PubMedDate not supplied

Examples of MAK values and carcinogenicity classification for mixtures.

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) generally sets MAK values for single pure substances. MAK values for mixtures are only established after specific toxicological evaluation of the particular mixture. In practice, there are a few cases in which a common MAK value for the sum of all components was set, such as for mixtures of isomers (e.g. xylenes) or mixtures of related compounds (e.g. Kathon), in which the components of the mixture show comparable toxicological effects. For mixtures of isomers with different toxicological potentials, different MAK values for the single isomers are usually established. The only exception is for the isomer mixture of alpha- and beta-hexachlorocyclohexane, for which a mathematically calculated MAK value was proposed. A safe threshold cannot be established for mixtures containing substances with a genotoxic and carcinogenic potential. These mixtures are categorized either according to the proven carcinogenicity of the mixture, such as alpha-chlorinated toluenes, or according to the carcinogenic substances included, as for pyrolysis products such as coal tars.

Animals↗