Intervention study on the influence of reduction of occupational exposure to styrene on sister chromatid exchanges in lymphocytes.

An intervention study was performed on 28 workers exposed by inhalation to styrene in the reinforced plastics industry and 20 controls not occupationally exposed to the compound. The workers involved were 14 laminators exposed to a time-weighted average of approximately 40 ppm styrene and 14 formers exposed to an average of about 10 ppm styrene. Ambient air monitoring data and the concentration of mandelic acid in the urine were used for the assessment of exposure. From each subject, peripheral blood lymphocytes were analysed for sister chromatid exchanges (SCEs). In the laminators, the mean SCE frequency was significantly higher than in the controls in both the group of smokers (9.59 +/- 0.77 SCEs/cell vs 7.23 +/- 1.00 SCEs/cell) and the group of non-smokers (10.25 +/- 1.08 SCEs/cell vs 5.98 +/- 0.60 SCEs/cell). The mean SCE frequency of the formers (7.42 +/- 128 SCEs/cell in smokers) did not differ statistically from the controls (7.23 +/- 1.00 SCEs/cell in smokers). No evaluation was made for non-smoking formers since all but one worker in this group were smokers. In order to comply with a lowering of the occupational exposure limit (MAK value) for occupational exposure to styrene in the Federal Republic of Germany from 100 ppm to 20 ppm, considerable technical and hygienic improvements were made at the work site of the laminators. This intervention led to a reduction of average exposure of these workers by inhalation from 40 ppm to approximately 20 ppm. One year after these improvements were made, a second investigation was performed. In all but one of the laminators, the concentration of mandelic acid in urine had dropped considerably. The SCE frequency in blood lymphocytes of the laminators had likewise dropped significantly to 7.74 +/- 0.59 SCEs/cell in the non-smokers. In the smokers, it was also lower than on the first occasion (9.02 +/- 1.19), yet statistical evaluation was not possible due to insufficient numbers. Overall, the results of the intervention study show that the lowering of the occupational exposure limit for styrene to 20 ppm in Germany was justified and that a reduction of occupational exposure to the chemical has led to a prevention of adverse cytogenetic effects.

[Effect of 2-hydroxyestradiol-17beta on NADPH-dependent electron transfer in rat liver microsomes in vitro (author's transl)]. / Wirkung von 5-Hydroxyöstradiol-17beta auf den NADPH-abhängigen Elektronentransport

If rat liver microsomes are incubated with NADPH and 2-hydroxyestradiol-17beta in vitro, the following is observed: 1. Inhibition of lipid peroxidation, 2.inhibition of cytochrome P-450 reduction, and 3.inhibition of cytochrome b5 reduction. Beyond this the catechole inhibits lipid peroxidation of liposomes in vitro. These phenomena can be explained by interaction of different states of oxidation of the estrogen with the NADPH-cytochrome reductase and with 0-2 radicals, which leads to terminal "uncoupling" of microsomal electron transport.

Reliability of non-invasively acquired human genomic DNA as a substrate for real-time PCR-assisted analysis of genetic polymorphisms.

Molecular epidemiological studies require high numbers of participants. The combination of an non-invasive access to human DNA with a rapid genotyping analysis, e.g. by use of LightCycler assisted real-time polymerase chain reaction (PCR), can be helpful in conducting such trials. The aim of our study was to define, for the first time, the use of LightCycler technology in analysis of non-invasively derived DNA. DNA extracted from blood, mouthwash and buccal cytobrush samples from 100 volunteers was analyzed for the genotypes of cytochrome P450 CYP1B1, and glutathione S-transferases GSTT1, GSTM1 and GSTP1. The median amounts of DNA isolated from blood, mouthwash and buccal cytobrush samples were 95, 11 and 8 microg, respectively. While genotyping for CYP1B1 codon 432 polymorphism and GSTP1 codon 105 polymorphism resulted in a complete correspondence for all three modes of sampling, the identification of individuals with null-genotype for GSTT1 or GSTM1 failed in some cases due to atypical courses of the corresponding melting curves, leading to high false-positive rates in the group of non-invasively derived samples. Thus, the results presented here call for caution in using LightCycler assisted real-time PCR in non-invasively collected samples, at least when appropriate control strategies are not implemented.

Children as a sensitive subgroup and their role in regulatory toxicology: DGPT workshop report.

There is increasing discussion that children might be considered as a specific subgroup in public health regulations which could be more sensitive than the average "adult" human being. Differences between children and adults, with regard to susceptibility towards toxicants, may result from a combination of toxicokinetic, toxicodynamic and exposure factors. Kinetic factors are of importance mainly in the early postnatal period, largely as the result of immature elimination systems, i.e. metabolising enzymes and/or renal function. Specific vulnerability may prevail during several time periods, related to the development and maturation of organs (for example, brain, bone, endocrine system). For some substances, it has been shown that children at a specific age are less sensitive than adults. Specific exposures of toddlers to environmental chemicals may be high due to their moving behaviour and hand-to-mouth activities. Existing scenarios and models for exposure of children should be improved, in particular with respect to different ages. The outcome of model calculations must be verified by human biomonitoring analysis. At present, there is ongoing discussion of toxicological test models suitable to delineate human postnatal development. Experience with infant-orientated test systems is scarce (for example in developmental neurotoxicity). In general, tools for predicting toxicological sensitivity of children must be further improved. Regulators should also be aware that reduction of lifestyle-related toxic exposures such as smoking and drug abuse in children and adolescents is now an increasing public health problem in many countries.