Aside from acute occupational exposure, an important part of the population may be chronically exposed to the trace amounts of organophosphorothionate pesticides (OPTs) via residues in nutrients and drinking water. P-glycoprotein (P-gp) is a transmembrane protein responsible for the efflux of numerous drugs. OPTs were shown to inhibit P-gp function in vitro and increase its expression in vivo. Digoxin is a probe drug for the investigation of P-gp. To evaluate the effect of repeated low-dose OPT exposure on P-gp, commercial formulations of diluted OPT or tap water were administered to female Wistar rats for 8 consecutive days. On the ninth day each group was further divided into two groups and digoxin was administered either intraduodenally (ID) or intravenously (IV). Blood sampling and bile and urine collection were taken during 6 h at various intervals. The peak concentration in serum (C(max)) of digoxin was found to be decreased and the mean absorption time (MAT) was significantly increased in the digoxin OPT group. The mean residence time was significantly elevated in the digoxin(ID) OPT group. The biliary excretion% digoxin was significantly increased in the digoxin OPT group, while the renal excretion% digoxin rose only in the digoxin(ID) OPT group. No significant differences in time to reach C(max) (t(max)), area under the plasma concentration-time curve (AUC)(0-360), area under the moment curve (AUMC)(0-360), and bioavailability (F) were detected. In our study, repeated low-dose OPT exposure reduced the absorption and increased the excretion% digoxin, which may be related to enhanced P-gp expression. However, alterations of digoxin pharmacokinetic parameters did not change the systemic availability of digoxin.

Parathion undergoes enzymatic oxidation by hepatic cytochrome P-450 (CYP450) enzymes to the active metabolite paraoxon. Consequently, alterations in CYP450-dependent oxidation may affect the pharmacokinetics and pharmacodynamics of drugs that are metabolized in the liver. The CYP3A family is known to be responsible for the majority of cyclosporine metabolism. The aim of the present study was to assess the disposition kinetics of cyclosporine during subchronic parathion exposure. Male Wistar rats were administered either water or two different doses of parathion (1/100 LD50, 1/25 LD50; LD50 = 14 mg/kg) by gavage for 6 wk. Subsequently, rats in each experimental group received a single oral dose of cyclosporine (10 mg/kg), and serial blood samples were drawn from the carotid artery over a period of 48 h. Pharmacokinetic analysis showed that parathion increased the blood cyclosporine concentration twofold as evidenced by AUC (area under the curve), half life (t 1/2) and peak plasma concentration (Cmax). This may be due to inhibition of cyclosporine metabolism, an interaction that may be of clinical relevance in immunosuppression therapy.

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This study was undertaken to investigate the extent of environmental tobacco smoke (ETS) exposure in coffeehouses, as these are commonly frequented public places in Turkey. From 86 coffeehouses in the 3 districts, 59 coffeehouse workers and 35 hospital staff members (as a control group) were evaluated. Participants answered a questionnaire about demographics, working characteristics, smoking behavior, and ETS exposure during their daily life lives. The amount of nicotine in hair was determined by using gas chromatography/mass spectrometry (GC/MS). The mean hair nicotine level of the nonsmoker and smoker coffeehouse workers were 23.2 +/- 12.3 microg/g and 62.5 +/- 49.8 microg/g, respectively. Among the hospital staff, mean hair nicotine levels were 4.5 +/- 6 microg/g in nonsmokers and 30.6 +/- 14 microg/g in smokers. Working in coffeehouses has a marked effect on hair nicotine levels and potential adverse health effects.

Introduction: Methyl bromide is a toxic substance that has hazardous effects on human health with acute and chronic exposure. Our previous study showed that methyl bromide applicators frequently use large amounts of methyl bromide haphazardly in greenhouses in the prefectures of Narlidere and Balcova in the Aegean city of Izmir. This study aims to evaluate the health conditions of these workers. Materials and Methods: Our previous study showed that there are 38 methyl bromide applicators in our study area. After the informed consent of methyl bromide applicators was obtained, a questionnaire was used for a survey of demography and symptoms. Each subject was examined before and after application of the compound. Blood and urine samples were collected and stored. Blood samples were analysed for methyl bromide and bromide ion, kidney and liver function tests and lipid profile. Results: The age range of subjects was 19 to 53 years (mean age: 41 ± 8.57). This study showed that methyl bromide applicators use large amounts of methyl bromide disregarding legal regulations and that some of them had non- specific complaints. Subjects had been working as methyl bromide applicators for approximately 9.7 ± 4.15 years. A total of 69.7% of methyl bromide applicators reported that they did not use protective equipment while 33.3% of them had a history of acute methyl bromide intoxication. A statistically significant relationship was found between the usage of protective equipment and the level of blood bromide ion in the blood (P <0.05). Conclusion: Usage of methyl bromide, training, screening and follow-up of applicators must be rigorously controlled in accordance with national legal arrangements and international protocols. Greater efforts are required in the implementation of controls to achieve the targets set by the legal regulations and to ensure continual improvement in the limitation of the risks of this environmental hazard. Key words: Applicator’s health, Chronic exposure, Forensic medicine, Greenhouse workers