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Journal Details
Format
Journal
eISSN
1848-6312
ISSN
0004-1254
First Published
26 Mar 2007
Publication timeframe
4 times per year
Languages
English

Search

Volume 61 (2010): Issue 1 (March 2010)

Journal Details
Format
Journal
eISSN
1848-6312
ISSN
0004-1254
First Published
26 Mar 2007
Publication timeframe
4 times per year
Languages
English

Search

14 Articles
Open Access

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Published Online: 25 Mar 2010
Page range: 1 - 9

Abstract

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Irinotecan is a topoisomerase I interactive agent, widely used in the treatment of metastatic colorectal cancer. The genotoxic effects of the maximum single dose (18 μg mL-1), recommended monotherapy dose (9 μg mL-1), and recommended combined therapy dose (4.5 μg mL-1) of irinotecan were studied on V79 cells using the comet assay, chromosome aberration assay, and micronucleus test. The cells were treated with irinotecan for 2 h or 24 h. The statistical significance of the results was determined using the one-way ANOVA test and a nonparametric Mann Whitney U test. The comet assay did not show dose-dependent or time-dependent effects. The chromosome aberration analysis showed large DNA rearrangements, i.e., chromosome exchanges. Although the exposed cultures showed a significant increase in micronucleated cells in respect to control, no dose-dependent relation was established among the treated cultures. Time-dependent effect was also not observed.

Keywords

  • alkaline comet assay
  • antineoplastic drug
  • cell cultures
  • DNA and cytogenetic damage
  • topoisomerase
Open Access

Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat Liver

Published Online: 25 Mar 2010
Page range: 11 - 18

Abstract

Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat Liver

We studied the antioxidative role of melatonin against benzene toxicity in rat liver. The inhibition of mitochondrial and microsomal lipid peroxidation differed between 24-hour (single-dose), 15-day, and 30-day treatments. Inhibition of mitochondrial lipid peroxidation was the highest after the single dose of melatonin, whereas highest microsomal inhibition was recorded after 30 days of melatonin treatment. No significant difference was recorded between 15-day and 30-day treatments. Cytochrome P 4502E1 (CYP 4502E1) activity declined after the single-dose and 15-day melatonin treatment in the benzene-treated group, but it rose again, though not significantly after 30 days of treatment. Liver histopathology generally supported these findings. Phenol concentration in the urine samples declined in melatonin and benzene-treated rats. Our results show that melatonin affects CYP 4502E1, which is responsible for benzene metabolism. Inhibition of its metabolism correlated with lower lipid peroxidation. In conclusion, melatonin was found to be protective against lipid peroxidation induced by benzene.

Keywords

  • CYP2E1
  • GSH
  • histopathology
  • mitochondria
  • microsomes
  • phenol
  • urine
Open Access

Brain Toxicokinetics of Prometryne in Mice

Published Online: 25 Mar 2010
Page range: 19 - 27

Abstract

Brain Toxicokinetics of Prometryne in Mice

Prometryne is a methylthio-s-triazine herbicide. Significant trace amounts are found in the environment, mainly in water, soil, and food plants. The aim of this study was to establish brain and blood prometryne levels after single oral dose (1 g kg-1) in adult male and female mice. Prometryne was measured using the GC/MS assay at 1, 2, 4, 8, and 24 h after prometryne administration. Peak brain and blood prometryne values were observed 1 h after administration and they decreased in a time-dependent manner. Male mice had consistently higher brain and blood prometryne levels than female mice. The observed prometryne kinetics was similar to that reported for the structurally related herbicide atrazine.

Keywords

  • blood
  • herbicide
  • nervous system
  • toxicity
  • triazine
Open Access

Cage Exposure of European Sea Bass (Dicentrarchus Labrax) for in Situ Assessment of Pollution-Related Genotoxicity

Published Online: 25 Mar 2010
Page range: 29 - 36

Abstract

Cage Exposure of European Sea Bass (<italic>Dicentrarchus Labrax</italic>) for <italic>in Situ</italic> Assessment of Pollution-Related Genotoxicity

Genotoxic effects are often the earliest signs of pollution-related environmental disturbance. In this study, we used the comet assay and micronucleus test to assess DNA damage in the erythrocytes of the European sea bass (Dicentrarchus labrax) exposed to environmental pollution in situ. Fish were collected from a fish farm in the Trogir Bay and their cages placed at an unpolluted reference site Šolta (Nečujam Bay) and a polluted site Vranjic (Kaštela Bay) for four weeks. A group of fish which remained at the fish farm Trogir Bay were used as the second control group. Fish exposed at the Vranjic site showed a significantly higher erythrocyte DNA damage, measured by the comet assay, than either control group. Micronucleus induction showed a similar gradient of DNA damage, but did not reach statistical significance. Our results show that cage exposure of a marine fish D. labrax can be useful in environmental biomonitoring and confirm the comet assay as a suitable tool for detecting pollution-related genotoxicity.

Keywords

  • Adriatic Sea
  • comet assay
  • fish
  • ecogenotoxicology
  • marine biomonitoring
  • micronucleus test
Open Access

Dustfall Measurements in Primorsko-Goranska County, 1975-2008

Published Online: 25 Mar 2010
Page range: 37 - 43

Abstract

Dustfall Measurements in Primorsko-Goranska County, 1975-2008

Dustfall measurements in Primorsko-goranska county started in 1975 in the Bakar Bay (Site 2 - Bakar and Site 3 - Kraljevica). The measurements were extended to the city of Rijeka (Site 1 - Rijeka) in 1982, to the nearby islands (Site 4 - Krk and Site 5 - Cres) in 1986, and inland to Gorski Kotar (Site 6 - Delnice and Site 7 - Lividraga) in 1995. This article brings the results of dustfall measurements from 1975 to 2008. Dustfall was low in the city, the nearby islands, and Gorski Kotar. Recommended and limit values were occasionally exceeded in the Bakar Bay due to emissions from the coke plant and harbour at Site 2 (1979-1997) and from the shipyard at Site 3. Lead content in the dustfall was below the national limits, save for two occasions at Site 2. Deposition of sulphur and nitrogen at the inland sites were below the respective critical load values.

Keywords

  • lead
  • nitrogen deposition
  • sulphates
  • sulphur deposition
Open Access

Mesothelioma Risk Associated with Asbestos Production in Slovenia

Published Online: 25 Mar 2010
Page range: 45 - 52

Abstract

Mesothelioma Risk Associated with Asbestos Production in Slovenia

The aim of this study was to assess malignant mesothelioma morbidity due to exposure to asbestos in a population living in districts Nova Gorica and Tolmin (49,850 people) near the asbestos manufacturing village Anhovo (Slovenia) and to compare it with the entire Slovene population (1,949,750 people). Crude rates per 100,000 people were calculated from the total number of mesotheliomas, and risk assessment in the studied vs. total population was based on 23 years worth of data. Time series data on mesothelioma cases were also processed as a forecast of new cases by 2010.

The crude incidence of mesothelioma per 100,000 individuals for all of Slovenia was 21.4, while for the Nova Gorica district including the village Anhovo it is 170.2 and for the Tolmin district 60.9. The probability of a mesothelioma case in the studied population was 8.5 times the probability of the same diagnosis in the whole of Slovenia. Over 23 years, 28% of all mesothelioma cases in Slovenia were diagnosed in the studied population, which makes only 2.5% of the total Slovene population.

The outbreak of asbestosis and mesothelioma epidemics in the studied population is associated with manufacture of asbestos products in the local factory from 1922 to 1996.

Keywords

  • asbestosis
  • lung malignancies
  • mesothelioma
  • Salonit Anhovo
Open Access

Toxicological Methods for Tracing Drug Abuse: Chromatographic, Spectroscopic and Biological Characterisation of Ecstasy Derivatives

Published Online: 25 Mar 2010
Page range: 53 - 59

Abstract

Toxicological Methods for Tracing Drug Abuse: Chromatographic, Spectroscopic and Biological Characterisation of Ecstasy Derivatives

Analysis often reveals variability in the composition of ecstasy pills from pure 3,4-methylenedioxymethamphetamine (MDMA) to mixtures of MDMA derivatives, amphetamine, and other unidentified substances. For a comprehensive toxicological analysis one needs to know all steps to MDMA synthesis which may originate impurities. The aim of this study was to synthesise and determine the chemical-physical and in vitro biological properties of a series of MDMA derivatives.

3,4-methylendioxyphenyl-2-nitropropene (MDNP) was obtained by condensation of piperonal with an excess of nitroethane in the presence of ammonium acetate. MDNP was then reduced to methylenedioxyamphetamine (MDA) by LiAlH3. All compounds were analysed using HPLC and spectroscopic technique [Raman, nuclear magnetic resonance (NMR), or infrared (IR)] at all the steps of synthesis. In addition, we assessed the biological potentials of these compounds by measuring in vitro their (i) blood cell/whole blood partition coefficient, (ii) binding to plasmatic proteins (Fbp), and (iii) membrane adsorption. Chemical structure was determined with antibody fluorescence polarisation immunoassay (FPIA). This study showed the presence of solid impurities, particularly of a neurotoxic compound of Al3+ in the final products. FPIA identified the aminoethane group close to the substituted benzene ring, but did not detect the two major precursors of MDMA: MDNP and piperonal. Raman spectroscopy is an attractive alternative technique to characterise ecstasy pills and it can identify stereoisomeric forms such as cis-MDNP and trans-MDNP, which exhibit signals at 1650 cm-1 and 1300 cm-1, respectively.

Keywords

  • IR
  • MDA
  • MDMA
  • MDNP
  • NMR
  • Raman
  • toxicology
Open Access

Qualitative GC-MS Assessment of TCP and Tamorf Elimination in Rats

Published Online: 25 Mar 2010
Page range: 61 - 67

Abstract

Qualitative GC-MS Assessment of TCP and Tamorf Elimination in Rats

Nerve agents are highly toxic organophosphorus (OP) compounds. They inhibit acetylcholinesterase (AChE), an enzyme that hydrolyses acetycholine (ACh) in the nervous system. Pathophysiological changes caused by OP poisonings are primarily the consequence of surplus ACh on cholinergic receptors and in the central nervous system. Standard treatment of OP poisoning includes combined administration of carbamates, atropine, oximes and anticonvulsants. In order to improve therapy, new compounds have been synthesised and tested. Tenocyclidine (TCP) and its adamantane derivative 1-[2-(2-thienyl)-2-adamantyl] morpholine (TAMORF) have shown interesting properties against soman poisoning. In this study, we developed a qualitative GC-MS method to measure elimination of TCP and TAMORF through rat urine in order to learn more about the mechanisms through which TCP protects an organism from OP poisoning and to determine the duration of this protective effect. GC-MS showed that six hours after treatment with TCP, rat urine contained only its metabolite 1-thienylcyclohexene, while urine of rats treated with TAMORF contained both TAMORF and its metabolites.

Keywords

  • antidote
  • metabolite
  • qualitative method
  • urine
  • tenocyclidine
Open Access

Identification of Counterfeit Medicines for Erectile Dysfunction from an Illegal Supply Chain

Published Online: 25 Mar 2010
Page range: 69 - 75

Abstract

Identification of Counterfeit Medicines for Erectile Dysfunction from an Illegal Supply Chain

The appearance of counterfeit medicines in supply chains is a global public health problem that may seriously affect patients. Counterfeit drugs do not meet quality standards and do not declare their real composition and/or source for the purposes of fraud. They may be generic or innovative, they may contain genuine constituents in a fake packaging, or wrong ingredients, or inactive ingredients, or an incorrect quantity of the active substance. In Croatia, no cases of counterfeit medicines have been detected so far, but the Agency for Medicinal Products and Medical Devices has received 34 samples of medicines and other products for testing from Zagreb City Police. The samples included medicines for erectile dysfunction: sildenafil, tadalafil, and vardenafil. Twenty-three samples of tablets without marketing authorisation in Croatia were tested with high-performance liquid chromatography (HPLC) for the declared sildenafil and tadalafil content. Samples labelled 1 (batch T/33), 3 (batch T/33), 5 (batch 4), 6 (batch M0016J), 10 (batch T-070235), 12 (batch T-070544), 15 (batch 314833201), 16 (batch 832718474), and 17 (batch 504830028) containing sildenafil and samples labelled 20 (batch 070356), 21 (batch 05668), and 22 (batch T 378 5) containing tadalafil did not contain the active substance within the acceptable 95 % to 105 % margin of deviation from the declared content. While most samples cannot be described as fake with a reasonable amount of certainty, there is still a suspicion of counterfeit. A correct conclusion can be drawn only with the assistance of the manufacturers and by conducting additional laboratory tests.

Keywords

  • HPLC
  • pharmaceutical crime
  • quality control
  • sildenafil
  • tadalafil
  • vardenafil
Open Access

Dose Rate Effect of Pulsed Electron Beam on Micronucleus Frequency in Human Peripheral Blood Lymphocytes

Published Online: 25 Mar 2010
Page range: 77 - 83

Abstract

Dose Rate Effect of Pulsed Electron Beam on Micronucleus Frequency in Human Peripheral Blood Lymphocytes

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7±0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Keywords

  • dosimetry
  • microtron
  • 8 MeV electrons
  • pulse repetition rate
Open Access

Allergotoxicology: Research of Pollutant Influence on the Development of Allergic Reactions

Published Online: 25 Mar 2010
Page range: 85 - 94

Abstract

Keywords

  • air polluants
  • allergens
  • asthma
  • bioaerosols
  • IgE antibody
  • LLNA
  • particulate matter
  • pollen allergy
  • protein-hapten conjugates
Open Access

Surfactants in the Environment

Published Online: 25 Mar 2010
Page range: 95 - 110

Abstract

Surfactants in the Environment

Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.

Keywords

  • biodegradation
  • detergents
  • surface-active agents
  • toxicity
  • wastewater
Open Access

Thallium Toxicity in Humans

Published Online: 25 Mar 2010
Page range: 111 - 119

Abstract

Thallium Toxicity in Humans

Thallium is a naturally occurring trace element, widely distributed in the earth's crust, but at very low concentrations. It does not have a known biological use and does not appear to be an essential element for life. It has been considered one of the most toxic heavy metals.

Occasionally, there are reports on thallium poisoning as results of suicide or murder attempt or accident. The main threat to humans is through occupational exposure, environmental contamination, and accumulation in food, mainly in vegetables grown on contaminated soil. Increasing use in emerging new technologies and demanding high-tech industry constantly raise concern about exposure risk to all living organisms. Thallium is considered a cumulative poison that can cause adverse health effects and degenerative changes in many organs. The effects are the most severe in the nervous system. The exact mechanism of thallium toxicity still remains unknown, although impaired glutathione metabolism, oxidative stress, and disruption of potassium-regulated homeostasis may play a role. The lack of data about mutagenic, carcinogenic, or teratogenic effects of thallium compounds in humans calls for further research.

Keywords

  • alopecia
  • environmental contamination
  • heavy metals
  • neuropathy
  • peripheral
  • poisoning
Open Access

Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers

Published Online: 25 Mar 2010
Page range: 121 - 146

Abstract

Keywords

  • chromosome aberrations
  • comet assay
  • DNA
  • micronuclei
  • sister chromatid exchanges
14 Articles
Open Access

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Published Online: 25 Mar 2010
Page range: 1 - 9

Abstract

Assessment of Cyto/Genotoxicity of Irinotecan in V79 Cells Using the Comet, Micronucleus, and Chromosome Aberration Assay

Irinotecan is a topoisomerase I interactive agent, widely used in the treatment of metastatic colorectal cancer. The genotoxic effects of the maximum single dose (18 μg mL-1), recommended monotherapy dose (9 μg mL-1), and recommended combined therapy dose (4.5 μg mL-1) of irinotecan were studied on V79 cells using the comet assay, chromosome aberration assay, and micronucleus test. The cells were treated with irinotecan for 2 h or 24 h. The statistical significance of the results was determined using the one-way ANOVA test and a nonparametric Mann Whitney U test. The comet assay did not show dose-dependent or time-dependent effects. The chromosome aberration analysis showed large DNA rearrangements, i.e., chromosome exchanges. Although the exposed cultures showed a significant increase in micronucleated cells in respect to control, no dose-dependent relation was established among the treated cultures. Time-dependent effect was also not observed.

Keywords

  • alkaline comet assay
  • antineoplastic drug
  • cell cultures
  • DNA and cytogenetic damage
  • topoisomerase
Open Access

Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat Liver

Published Online: 25 Mar 2010
Page range: 11 - 18

Abstract

Melatonin Inhibits Benzene-Induced Lipid Peroxidation in Rat Liver

We studied the antioxidative role of melatonin against benzene toxicity in rat liver. The inhibition of mitochondrial and microsomal lipid peroxidation differed between 24-hour (single-dose), 15-day, and 30-day treatments. Inhibition of mitochondrial lipid peroxidation was the highest after the single dose of melatonin, whereas highest microsomal inhibition was recorded after 30 days of melatonin treatment. No significant difference was recorded between 15-day and 30-day treatments. Cytochrome P 4502E1 (CYP 4502E1) activity declined after the single-dose and 15-day melatonin treatment in the benzene-treated group, but it rose again, though not significantly after 30 days of treatment. Liver histopathology generally supported these findings. Phenol concentration in the urine samples declined in melatonin and benzene-treated rats. Our results show that melatonin affects CYP 4502E1, which is responsible for benzene metabolism. Inhibition of its metabolism correlated with lower lipid peroxidation. In conclusion, melatonin was found to be protective against lipid peroxidation induced by benzene.

Keywords

  • CYP2E1
  • GSH
  • histopathology
  • mitochondria
  • microsomes
  • phenol
  • urine
Open Access

Brain Toxicokinetics of Prometryne in Mice

Published Online: 25 Mar 2010
Page range: 19 - 27

Abstract

Brain Toxicokinetics of Prometryne in Mice

Prometryne is a methylthio-s-triazine herbicide. Significant trace amounts are found in the environment, mainly in water, soil, and food plants. The aim of this study was to establish brain and blood prometryne levels after single oral dose (1 g kg-1) in adult male and female mice. Prometryne was measured using the GC/MS assay at 1, 2, 4, 8, and 24 h after prometryne administration. Peak brain and blood prometryne values were observed 1 h after administration and they decreased in a time-dependent manner. Male mice had consistently higher brain and blood prometryne levels than female mice. The observed prometryne kinetics was similar to that reported for the structurally related herbicide atrazine.

Keywords

  • blood
  • herbicide
  • nervous system
  • toxicity
  • triazine
Open Access

Cage Exposure of European Sea Bass (Dicentrarchus Labrax) for in Situ Assessment of Pollution-Related Genotoxicity

Published Online: 25 Mar 2010
Page range: 29 - 36

Abstract

Cage Exposure of European Sea Bass (<italic>Dicentrarchus Labrax</italic>) for <italic>in Situ</italic> Assessment of Pollution-Related Genotoxicity

Genotoxic effects are often the earliest signs of pollution-related environmental disturbance. In this study, we used the comet assay and micronucleus test to assess DNA damage in the erythrocytes of the European sea bass (Dicentrarchus labrax) exposed to environmental pollution in situ. Fish were collected from a fish farm in the Trogir Bay and their cages placed at an unpolluted reference site Šolta (Nečujam Bay) and a polluted site Vranjic (Kaštela Bay) for four weeks. A group of fish which remained at the fish farm Trogir Bay were used as the second control group. Fish exposed at the Vranjic site showed a significantly higher erythrocyte DNA damage, measured by the comet assay, than either control group. Micronucleus induction showed a similar gradient of DNA damage, but did not reach statistical significance. Our results show that cage exposure of a marine fish D. labrax can be useful in environmental biomonitoring and confirm the comet assay as a suitable tool for detecting pollution-related genotoxicity.

Keywords

  • Adriatic Sea
  • comet assay
  • fish
  • ecogenotoxicology
  • marine biomonitoring
  • micronucleus test
Open Access

Dustfall Measurements in Primorsko-Goranska County, 1975-2008

Published Online: 25 Mar 2010
Page range: 37 - 43

Abstract

Dustfall Measurements in Primorsko-Goranska County, 1975-2008

Dustfall measurements in Primorsko-goranska county started in 1975 in the Bakar Bay (Site 2 - Bakar and Site 3 - Kraljevica). The measurements were extended to the city of Rijeka (Site 1 - Rijeka) in 1982, to the nearby islands (Site 4 - Krk and Site 5 - Cres) in 1986, and inland to Gorski Kotar (Site 6 - Delnice and Site 7 - Lividraga) in 1995. This article brings the results of dustfall measurements from 1975 to 2008. Dustfall was low in the city, the nearby islands, and Gorski Kotar. Recommended and limit values were occasionally exceeded in the Bakar Bay due to emissions from the coke plant and harbour at Site 2 (1979-1997) and from the shipyard at Site 3. Lead content in the dustfall was below the national limits, save for two occasions at Site 2. Deposition of sulphur and nitrogen at the inland sites were below the respective critical load values.

Keywords

  • lead
  • nitrogen deposition
  • sulphates
  • sulphur deposition
Open Access

Mesothelioma Risk Associated with Asbestos Production in Slovenia

Published Online: 25 Mar 2010
Page range: 45 - 52

Abstract

Mesothelioma Risk Associated with Asbestos Production in Slovenia

The aim of this study was to assess malignant mesothelioma morbidity due to exposure to asbestos in a population living in districts Nova Gorica and Tolmin (49,850 people) near the asbestos manufacturing village Anhovo (Slovenia) and to compare it with the entire Slovene population (1,949,750 people). Crude rates per 100,000 people were calculated from the total number of mesotheliomas, and risk assessment in the studied vs. total population was based on 23 years worth of data. Time series data on mesothelioma cases were also processed as a forecast of new cases by 2010.

The crude incidence of mesothelioma per 100,000 individuals for all of Slovenia was 21.4, while for the Nova Gorica district including the village Anhovo it is 170.2 and for the Tolmin district 60.9. The probability of a mesothelioma case in the studied population was 8.5 times the probability of the same diagnosis in the whole of Slovenia. Over 23 years, 28% of all mesothelioma cases in Slovenia were diagnosed in the studied population, which makes only 2.5% of the total Slovene population.

The outbreak of asbestosis and mesothelioma epidemics in the studied population is associated with manufacture of asbestos products in the local factory from 1922 to 1996.

Keywords

  • asbestosis
  • lung malignancies
  • mesothelioma
  • Salonit Anhovo
Open Access

Toxicological Methods for Tracing Drug Abuse: Chromatographic, Spectroscopic and Biological Characterisation of Ecstasy Derivatives

Published Online: 25 Mar 2010
Page range: 53 - 59

Abstract

Toxicological Methods for Tracing Drug Abuse: Chromatographic, Spectroscopic and Biological Characterisation of Ecstasy Derivatives

Analysis often reveals variability in the composition of ecstasy pills from pure 3,4-methylenedioxymethamphetamine (MDMA) to mixtures of MDMA derivatives, amphetamine, and other unidentified substances. For a comprehensive toxicological analysis one needs to know all steps to MDMA synthesis which may originate impurities. The aim of this study was to synthesise and determine the chemical-physical and in vitro biological properties of a series of MDMA derivatives.

3,4-methylendioxyphenyl-2-nitropropene (MDNP) was obtained by condensation of piperonal with an excess of nitroethane in the presence of ammonium acetate. MDNP was then reduced to methylenedioxyamphetamine (MDA) by LiAlH3. All compounds were analysed using HPLC and spectroscopic technique [Raman, nuclear magnetic resonance (NMR), or infrared (IR)] at all the steps of synthesis. In addition, we assessed the biological potentials of these compounds by measuring in vitro their (i) blood cell/whole blood partition coefficient, (ii) binding to plasmatic proteins (Fbp), and (iii) membrane adsorption. Chemical structure was determined with antibody fluorescence polarisation immunoassay (FPIA). This study showed the presence of solid impurities, particularly of a neurotoxic compound of Al3+ in the final products. FPIA identified the aminoethane group close to the substituted benzene ring, but did not detect the two major precursors of MDMA: MDNP and piperonal. Raman spectroscopy is an attractive alternative technique to characterise ecstasy pills and it can identify stereoisomeric forms such as cis-MDNP and trans-MDNP, which exhibit signals at 1650 cm-1 and 1300 cm-1, respectively.

Keywords

  • IR
  • MDA
  • MDMA
  • MDNP
  • NMR
  • Raman
  • toxicology
Open Access

Qualitative GC-MS Assessment of TCP and Tamorf Elimination in Rats

Published Online: 25 Mar 2010
Page range: 61 - 67

Abstract

Qualitative GC-MS Assessment of TCP and Tamorf Elimination in Rats

Nerve agents are highly toxic organophosphorus (OP) compounds. They inhibit acetylcholinesterase (AChE), an enzyme that hydrolyses acetycholine (ACh) in the nervous system. Pathophysiological changes caused by OP poisonings are primarily the consequence of surplus ACh on cholinergic receptors and in the central nervous system. Standard treatment of OP poisoning includes combined administration of carbamates, atropine, oximes and anticonvulsants. In order to improve therapy, new compounds have been synthesised and tested. Tenocyclidine (TCP) and its adamantane derivative 1-[2-(2-thienyl)-2-adamantyl] morpholine (TAMORF) have shown interesting properties against soman poisoning. In this study, we developed a qualitative GC-MS method to measure elimination of TCP and TAMORF through rat urine in order to learn more about the mechanisms through which TCP protects an organism from OP poisoning and to determine the duration of this protective effect. GC-MS showed that six hours after treatment with TCP, rat urine contained only its metabolite 1-thienylcyclohexene, while urine of rats treated with TAMORF contained both TAMORF and its metabolites.

Keywords

  • antidote
  • metabolite
  • qualitative method
  • urine
  • tenocyclidine
Open Access

Identification of Counterfeit Medicines for Erectile Dysfunction from an Illegal Supply Chain

Published Online: 25 Mar 2010
Page range: 69 - 75

Abstract

Identification of Counterfeit Medicines for Erectile Dysfunction from an Illegal Supply Chain

The appearance of counterfeit medicines in supply chains is a global public health problem that may seriously affect patients. Counterfeit drugs do not meet quality standards and do not declare their real composition and/or source for the purposes of fraud. They may be generic or innovative, they may contain genuine constituents in a fake packaging, or wrong ingredients, or inactive ingredients, or an incorrect quantity of the active substance. In Croatia, no cases of counterfeit medicines have been detected so far, but the Agency for Medicinal Products and Medical Devices has received 34 samples of medicines and other products for testing from Zagreb City Police. The samples included medicines for erectile dysfunction: sildenafil, tadalafil, and vardenafil. Twenty-three samples of tablets without marketing authorisation in Croatia were tested with high-performance liquid chromatography (HPLC) for the declared sildenafil and tadalafil content. Samples labelled 1 (batch T/33), 3 (batch T/33), 5 (batch 4), 6 (batch M0016J), 10 (batch T-070235), 12 (batch T-070544), 15 (batch 314833201), 16 (batch 832718474), and 17 (batch 504830028) containing sildenafil and samples labelled 20 (batch 070356), 21 (batch 05668), and 22 (batch T 378 5) containing tadalafil did not contain the active substance within the acceptable 95 % to 105 % margin of deviation from the declared content. While most samples cannot be described as fake with a reasonable amount of certainty, there is still a suspicion of counterfeit. A correct conclusion can be drawn only with the assistance of the manufacturers and by conducting additional laboratory tests.

Keywords

  • HPLC
  • pharmaceutical crime
  • quality control
  • sildenafil
  • tadalafil
  • vardenafil
Open Access

Dose Rate Effect of Pulsed Electron Beam on Micronucleus Frequency in Human Peripheral Blood Lymphocytes

Published Online: 25 Mar 2010
Page range: 77 - 83

Abstract

Dose Rate Effect of Pulsed Electron Beam on Micronucleus Frequency in Human Peripheral Blood Lymphocytes

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7±0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Keywords

  • dosimetry
  • microtron
  • 8 MeV electrons
  • pulse repetition rate
Open Access

Allergotoxicology: Research of Pollutant Influence on the Development of Allergic Reactions

Published Online: 25 Mar 2010
Page range: 85 - 94

Abstract

Keywords

  • air polluants
  • allergens
  • asthma
  • bioaerosols
  • IgE antibody
  • LLNA
  • particulate matter
  • pollen allergy
  • protein-hapten conjugates
Open Access

Surfactants in the Environment

Published Online: 25 Mar 2010
Page range: 95 - 110

Abstract

Surfactants in the Environment

Surfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.

Keywords

  • biodegradation
  • detergents
  • surface-active agents
  • toxicity
  • wastewater
Open Access

Thallium Toxicity in Humans

Published Online: 25 Mar 2010
Page range: 111 - 119

Abstract

Thallium Toxicity in Humans

Thallium is a naturally occurring trace element, widely distributed in the earth's crust, but at very low concentrations. It does not have a known biological use and does not appear to be an essential element for life. It has been considered one of the most toxic heavy metals.

Occasionally, there are reports on thallium poisoning as results of suicide or murder attempt or accident. The main threat to humans is through occupational exposure, environmental contamination, and accumulation in food, mainly in vegetables grown on contaminated soil. Increasing use in emerging new technologies and demanding high-tech industry constantly raise concern about exposure risk to all living organisms. Thallium is considered a cumulative poison that can cause adverse health effects and degenerative changes in many organs. The effects are the most severe in the nervous system. The exact mechanism of thallium toxicity still remains unknown, although impaired glutathione metabolism, oxidative stress, and disruption of potassium-regulated homeostasis may play a role. The lack of data about mutagenic, carcinogenic, or teratogenic effects of thallium compounds in humans calls for further research.

Keywords

  • alopecia
  • environmental contamination
  • heavy metals
  • neuropathy
  • peripheral
  • poisoning
Open Access

Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers

Published Online: 25 Mar 2010
Page range: 121 - 146

Abstract

Keywords

  • chromosome aberrations
  • comet assay
  • DNA
  • micronuclei
  • sister chromatid exchanges

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