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Immune parameters were examined in 224 sera of non-exposed controls and in 304 sera of pesticide applicators in the agricultural environment. In comparison to the control group pesticide applicators showed significant increased odds ratios for neopterin and soluble tumor necrosis factor receptor (sTNF RII) and a decreased odds ratio for immunoglobulin M. Obtained results indicate an enhanced macrophage activation and an impaired humoral defense. These alterations have been found to correlate with exposure duration in the group of pesticide applicators in agriculture. For subjects who worked in indoor pest control an inverse correlation for sTNF RII with exposure duration was obtained indicating impairment of cell mediated immune function. It can be concluded that exposure to pesticides in the agricultural environment may contribute to modulation of the immune system. Since immune modulating agents can potentially lead to adverse health consequences the involvement of immune biomarkers in pesticide-related health studies seems to be of considerable value for risk assessment studies.

The aim of this study was to find a suitable biomarker for pyrethroid adverse effects. It was shown that there is a correlation between the half-life time (t(1/2)) of pyrethroids in plasma and the clinical findings. We hypothized that this finding indicates an interindividual different amount of total esterase activity or even a polymorphism. By in vitro experiments it was demonstrated that pyrethroids are cleaved by carboxylesterases. After it turned out that carboxylesterase activity in human plasma is too low for detection, a method for specific determination of carboxylesterase activity in human isolated lymphocytes was developed. As a substrate for carboxylesterase activity, cyfluthrin was added to the lymphocyte suspension. As a proof for cyfluthrin degradation by carboxylesterases the produced hydrocyanic acid was determined by GC/MS. First hints for interindividual differences in carboxylesterase activity in lymphocytes were found.

Chrysanthemate insecticides like (S)-bioallethrin, natural pyrethins, and related pyrethroids are subjected to extensive hydrolytic and oxidative degeneration by the mammalian metabolism, leading to a complex series of metabolites partially conjugated and finally eliminated in the urine. The major oxidation products of chrysanthemic acid, cis-(E)- and trans-(E)-chrysanthemumdicarboxcylic acid (cis-(E) and trans-(E)-CDCA), were synthesized and their structures were established by nuclear magnetic resonance spectrometry (H1-NMR) and mass spectrometry (MS). Diastereoselective separation was by high performance liquid chromatography (HPLC) and capillary gas chromatography (GC). An analytical method for extraction and identification of CDCA from human urine was developed. Quantitation was by gas chromatography and electron-impact mass spectrometry (GC/MS). The limit of detection was 20 microg/l for cis-(E)-CDCA and 10 microg/l for trans-(E)-CDCA. To test the applicability of the presented method, urine samples of humans exposed to (S)-bioallethrin were investigated. Urinary peak excretion of trans-(E)-CDCA occurred within 24 h after exposure.

Five pyrethroids (fenvalerate, deltamethrin, cypermethrin, permethrin, cyfluthrin) differing in their chemical purity were investigated on their cytotoxic effects, especially on their ability to induce mitotic cell division disturbances using Chinese hamster lung cells of line V79. The colony forming ability (CFA) resulted in distinct differences of the cytotoxic effect of the tested pyrethroids, whereby permethrin was found to be most toxic. With the exception of fenvalerate all tested pyrethroids gave rise to inhibition of cell cycle progression as shown by G2/M-arrest of synchronized V79 cells by flow cytometry as well as by the increase of the mitotic index as evaluated by light microscopy. The mitotic arresting activity could be attributed to the occurrence of abnormal mitotic figures such as initial and full C-metaphases. The results however indicate, that pyrethroids per se do not contribute to the cytotoxic effects but that other factors such as chemical impurities, source as well as manufacturing process and isomer composition may be responsible for the observed cytotoxic effects.

Due to their low mammalian toxicity but high insectical activity, pyrethroids are increasingly used for pest control. The objective of the present study was the development of a biological monitoring program to determine exposure to pyrethroids. A diastereoselective detection of the major pyrethroid metabolites cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid, 3-phenoxybenzoic acid and fluorophenoxybenzoic acid by capillary gas chromatography in combination with mass selective detection was applied. The limits of determination ranged between 0.5 and 1 microgram/l urine, depending on the metabolite concerned. It was demonstrated that pyrethroid metabolites were detectable in urine for a period of elimination up to 3.5 days after exposure to cyfluthrin. Fluorophenoxybenzoic acid was shown to be a suitable biomarker for exposure to cyfluthrin. The presented method was adequate for monitoring pyrethroids in occupationally exposed subjects.

The present study aimed to investigate immune parameters in sera of adult persons chronically exposed to different degrees of ambient air pollution. As related to air pollution derived from coal mining industry and coke plants, a significantly increased prevalence of cases with abnormally high serum levels of the immunoglobulins IgA and IgM as well as the complement component C3c was found as compared with a less polluted control area, indicating a higher stimulation of acute reactants in combination with a polyclonal immune response. These findings may be attributed to elevated concentrations of airborne particulates, suggesting that permanent exposure to increased levels of airborne particulates leads to chronic irritation of the airways in association with activation of the immune system, which may give rise to an enhanced risk for chronic airway diseases.

The reliability of human scalp hair as an indicator of mercury vapour exposure is contentious. In this study mercury concentrations in hair were compared with those in blood and urine of 20 dental students during their first "occupational" exposure to mercury vapour. Samples were collected before, at the end of the technical course of operating dentistry which lasted 6 weeks, and 3 months later. Mercury was measured by cold vapour atomic absorption spectrometry. In all biological media studied, mercury levels significantly (P < 0.05) reflected exposure to mercury vapour. After the time period without exposure mercury content decreased. Hair mercury levels were correlated to those in erythrocytes at sampling times 1 and 3 (r = 0.686 and r = 0.492) and to the frequency of fish consumption at sampling time 1. It is concluded that hair may be used as an indicator of internal uptake of mercury provided that it was not externally exposed to mercury vapour. In cases of occupational exposure to mercury vapour, hair is an useful tool for monitoring external exposure.