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Identification and toxicological evaluation of musk fragrances and thiophenes in extracts of river sediment samples
S198
Abstracts / Toxicology Letters 189S (2009) S57–S273
points, however, the effects on the bone microarchitecture have not yet been studied. We analysed the effect of repeated 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) exposure on bone microarchitecture in wild-type (WT) and AhR-knockout (AhRKO) mice. Tibia from AhRKO and WT female mice exposed to TCDD at a total dose of 200 g/kg bw for ten weeks, and their corresponding controls, were analysed by peripheral quantitative computed tomography (pQCT), microtomography (CT) and three-point-bending test. TCDD-exposure considerably increased the mineral density and volume of trabecular bone in WT mice. This increase was due to a higher number of trabeculae and lower trabecular separation, while the thickness of the trabeculae was unaffected. Furthermore, the trabeculae were more isotropically oriented, more interconnected and more plate-like in shape, compared to more rod-like trabeculae in the unexposed WT mice. In biomechanical testing maximal and yield bending breaking force and deformation as well as maximal energy absorption were decreased in TCDD-exposed WT mice. No effects of TCDD-exposure were observed on the AhRKO mice, indicating that lack of a functional AhR prevents the TCDD-induced effects on bone. A slightly lower trabeculae thickness and lower mechanical strength of Tibia could be ascribed to lack of the AhRgene. These findings provide further support for the distinct role of AhR in bone biology and TCDD-induced bone toxicity. 夽 Selected for Oral Presentation. doi:10.1016/j.toxlet.2009.06.598
E30 The noxological value of the environment in high schools Natalya Savicheva FMBA, Patology, Moscow, Russian Federation Purpose: Comparative research of pupils’ health level and factors of environment in the eight high schools of Zelenograd (Moscow district). Method: All schools were divide into two groups: one—the schools characterized by the worst environment indicators and the high level of morbidity (I); other—control group (II) included the schools characterized by satisfactory environment indicators and small level of pupils’ morbidity. We carry out of air pollution: chemical (carbon oxide (IV), ammonia, ethanol, methanol, acetone, phenol, formaldehyde, metiletilchetone, ozone, respirable dust); bacteriological (bacterium cells colonies and mycelial fungus), microclimatic parameters (relative air humidity, temperature, rate of air movement), the content of positive and negative ions, ventilation rate and the radon content in school buildings. Besides, the artificial illumination was measured. There were defined load and pupil’s nourishment at schools. We applied air summary indicator K for estimation of air chemical pollution level. Result: K of the I was 5.57 of maximum permissible concentration (MPC) against 3.26 of MPC of II before lessons, and it increased to 10.80 and 6.49 MPC after complete day’s studies. The ammonia, formaldehyde, carbon oxide (IV), acetone prevail in structure of air chemical pollution schoolrooms of I and II. Conclusion: The cumulative complex load (CCL) all concerned factors of the school environment in I was twice as many vs. II (9.33 and 4.80, correspondently) before lessons. After lessons the CCL doubled in both groups. doi:10.1016/j.toxlet.2009.06.599
E31 Assessment of the lung deposition of particulates originating from diesel engines Kati Oravisjärvi 1,∗ , Mari Pietikäinen 1 , Arja Rautio 2 , Arto Voutilainen 3 , Mauri Haataja 4 , Juhani Ruuskanen 5 , Riitta L. Keiski 1 1
University of Oulu, Department of Process and Environmental Engineering, Oulu, Finland, 2 University of Oulu, Thule Institute, Centre for Arctic Medicine, Oulu, Finland, 3 University of Kuopio, Department of Physics, Kuopio, Finland, 4 University of Oulu, Department of Mechanical Engineering, Oulu, Finland, 5 University of Kuopio, Department of Environmental Sciences, Kuopio, Finland The lung deposition of particulates originating from a city diesel bus was studied in silico. Estimates for the deposited particulates in five different regions of the respiratory system (ET1: the anterior nasal region, ET2: the main extrathoracic region, BB: the bronchial region, bb: the bronchiolar region, AI: the alveolar interstitial region) were computed using a lung deposition model, which is based on the ICRP 66 lung deposition model published by the International Commission on Radiological Protection. Exposure assessment was made for an adult male and female and 10- and 5-year-old children, who were performing light exercise (e.g. walking on a road near the bus) or sitting in a car behind a moving bus. Diesel particulate emissions and number size distributions were measured in the Technical Research Centre of Finland. The measured particulates were in the size range of 7 nm to 10 m and most of the particulates were smaller than 200 nm in their aerodynamic diameter. Part of the inhaled particulates comes out from the respiratory system by exhalation and clearance effects and only approximately half or less of the inhaled particulates stay in the respiratory system. The particulate deposition depends also on the way of breathing: nose or mouth breathing and the intensity of breathing. Compared to sitting the deposition of diesel particulates in human’s respiratory system increased more than threefold during light exercise. The majority of deposited diesel particulates penetrate deep into the unciliated and gas-exchange regions of human lungs. doi:10.1016/j.toxlet.2009.06.600
E32 Identification and toxicological evaluation of musk fragrances 夽 and thiophenes in extracts of river sediment samples Lenka Vykopalova 1,∗ , Katerina Pencikova 1 , Miroslav Ciganek 1 , Jiri Neca 1 , Jan Vondracek 2 , Werner Brack 3 , Urte Luebcke-Von Varel 3 , G. Streck 3 , Miroslav Machala 1 1
Veterinary Research Institute, Toxicology, Brno, Czech Republic, Academy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic, 3 Helmholtz-Zentrum für Umweltforschung, Leipzig, Germany 2
Reproductive dysfunction can result from exposure to environmental contaminants binding to aryl hydrocarbon receptor (AhR) or estrogenic receptors (ERs). We used effect-directed analysis (EDA) for identification of toxic organic compounds in river sediments, which interact with AhR and/or ER. EDA was based on multi-step fractionation of extracts of environmental samples, chemical identification (LC–MS/MS and GC/MS) and determination of AhR- and ER-mediated activities in DR-CALUX® and ER-CALUX® assays, respectively. Next evaluated individual
Abstracts / Toxicology Letters 189S (2009) S57–S273
in vitro toxic potencies of compounds found in the bioactive chromatographic fractions of river sediment samples, using the ER-CALUX® and DR-CALUX® assays. Apart from known ligands of AhR or ER, such as polycyclic aromatic hydrocarbons, estrone or estradiol, we identified a number of other polycyclic aromatic hydrocarbons and polar aromatic compounds with potential endocrine activities. Based on these results, we selected eight thiophenes (dibenzothiophene, benzo[b]naphtho[1,2-d]thiophene, benzo[b]naphtho[2,1-d]thiophene, benzo[b]naphtho[2,3d]thiophene, 2-(2 -naphthyl)benzo[b]thiophene (2-2 -NBT), 2-1 -NBT, 3-1 -NBT and 32 -NBT) and seven musk compounds (trade names: celestolide, galaxolide, phantolide, ambrettolide, velvione, habanolide, OTNE) for further analysis. All thiophenes, with exception of dibenzothiophene and 3-1 -NBT were efficient AhR agonists, with 2-2 -NBT being the most potent compound. Celestolide and OTNE were weak ER agonists. In contrast, ambrettolide, velvione and habanolide showed antagonistic activities towards hER␣. Phantolide elicited mixed-type dose-dependent estrogenic/antiestrogenic effects. These results suggested that thiophenes might contribute to overall AhR activity, while several musk compounds may interfere with ER functions. Acknowledgements: Supported by the FP6 Modelkey project (511237-GOCE) and the Czech Science Foundation, grant no. 525/081590. 夽 Selected for Oral Presentation. doi:10.1016/j.toxlet.2009.06.601
E33 Reverse osmosis in groundwater treatment for drinking water in southern Iran Zabihollah Yousefi 1,∗ , Ramazan Motalebi 2 1
Mazandaran University of Medical Sciences, Environmental Health, Sari, Islamic Republic of Iran, 2 Abfa, Environmental Engineering, Jask, Islamic Republic of Iran
This evaluation concentrated on physic-chemical efficiency of RO water desalination in Jask City in a Southern province of Iran. In this study, primary data on water supply and network collected. Multiple quality parameters of the water resource of the city (EC, Conductivity, Cl− , Na+ . . .) were higher than the Iranian drinking water standards. Most of water quality parameters analysis (Turbidity, Ph, EC, Conductivity, Cl− , Na+ , Alkalinity, Ca, Na, K, No3 , No2 , Fe, Mg, Mn, NH4 , Po4 , HCo3 − , So4 2− ,. . .) performed as Standard. The membranes of RO water desalination system was poly-Amid (CSM type). The efficiency of RO water desalination system was 94.16, 84.12, 92.00, and 96.17% respectively for Turbidity, Na+ , Mg2+ , So4 2− . P-value for entire analyzed parameters was less than 0.0005 that imply significant difference between influent and effluent water of the RO system. So the effluent water is agreement with national standard of drinking water. Also water exited from the RO system for TDS, Ca2+ and Mg2+ was less than minimum limit of the guideline. The RO technology modified the quality of the water parameters. Keywords: Reverse osmosis; Desalination groundwater; Southern Iran doi:10.1016/j.toxlet.2009.06.602
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E34 Quantitative characterization of changes in bone geometry, density and biomechanical properties in two rat strains with different Ah-receptor structure following long-term exposure 夽 to 2,3,7,8-tetrachlorodibenzo-p-dioxin Helen Håkansson 1,∗ , Maria Herlin 1 , Natalia Stern 1 , Fereshteh Kalantari 1 , Salomon Sand 2 , Sune Larsson 3 , Jouni T. Tuomisto 4 , Jouko Tuomisto 4 , Juha Tuukkanen 5 , Timo Jämsä 6,7 , P. Monica Lind 1 , Matti Viluksela 4 1
Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden, 2 National Food Administration, Uppsala, Sweden, 3 Uppsala University Hospital, Department of Orthopaedic Surgery, Uppsala, Sweden, 4 National Institute for Health and Welfare, Department of Environmental Health, Kuopio, Finland, 5 University of Oulu, Department of Anatomy and Cell Biology, Oulu, Finland, 6 University of Oulu, Department of Medical Technology, Oulu, Finland, 7 Oulu University Hospital, Department of Diagnostic Radiology, Oulu, Finland In recent years a number of industrial chemicals and environmental pollutants have been shown to interfere with bone development and remodeling. The present study used benchmark dose methodology to quantify any strain differences in sensitivity to bone insult by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) between the LongEvans (L-E) and Han/Wistar (H/W) rat strains, which differ in their AhR structure and dioxin sensitivity, and thereby further clarify the role of AhR in dioxin-induced bone abnormalities. Femur, tibia and vertebra from TCDD-exposed L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose–response modeling was performed to establish benchmark doses for the analyzed bone parameters, and differences between the two rat strains were estimated for parameters affected by TCDD-exposure in both strains. Benchmark dose analysis demonstrated significant strain differences in response to TCDD treatment, with the L-E rat being the most sensitive strain. Effects on bone parameters were observed in the same dose-range as other low-dose toxicological endpoints, which have been identified as critical for the health risk assessment of dioxins. The demonstrated quantitative differences in sensitivity between the L-E and H/W rat strains provide further support for a distinct role of AhR in dioxin-induced bone abnormalities. In addition, the present study provides novel information about dioxin-induced bone alterations at various skeletal sites, and suggests that bone quality and function are relevant and sensitive endpoints in toxicological studies. 夽 Selected for Oral Presentation. doi:10.1016/j.toxlet.2009.06.603
Abstracts / Toxicology Letters 189S (2009) S57–S273
points, however, the effects on the bone microarchitecture have not yet been studied. We analysed the effect of repeated 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) exposure on bone microarchitecture in wild-type (WT) and AhR-knockout (AhRKO) mice. Tibia from AhRKO and WT female mice exposed to TCDD at a total dose of 200 g/kg bw for ten weeks, and their corresponding controls, were analysed by peripheral quantitative computed tomography (pQCT), microtomography (CT) and three-point-bending test. TCDD-exposure considerably increased the mineral density and volume of trabecular bone in WT mice. This increase was due to a higher number of trabeculae and lower trabecular separation, while the thickness of the trabeculae was unaffected. Furthermore, the trabeculae were more isotropically oriented, more interconnected and more plate-like in shape, compared to more rod-like trabeculae in the unexposed WT mice. In biomechanical testing maximal and yield bending breaking force and deformation as well as maximal energy absorption were decreased in TCDD-exposed WT mice. No effects of TCDD-exposure were observed on the AhRKO mice, indicating that lack of a functional AhR prevents the TCDD-induced effects on bone. A slightly lower trabeculae thickness and lower mechanical strength of Tibia could be ascribed to lack of the AhRgene. These findings provide further support for the distinct role of AhR in bone biology and TCDD-induced bone toxicity. 夽 Selected for Oral Presentation. doi:10.1016/j.toxlet.2009.06.598
E30 The noxological value of the environment in high schools Natalya Savicheva FMBA, Patology, Moscow, Russian Federation Purpose: Comparative research of pupils’ health level and factors of environment in the eight high schools of Zelenograd (Moscow district). Method: All schools were divide into two groups: one—the schools characterized by the worst environment indicators and the high level of morbidity (I); other—control group (II) included the schools characterized by satisfactory environment indicators and small level of pupils’ morbidity. We carry out of air pollution: chemical (carbon oxide (IV), ammonia, ethanol, methanol, acetone, phenol, formaldehyde, metiletilchetone, ozone, respirable dust); bacteriological (bacterium cells colonies and mycelial fungus), microclimatic parameters (relative air humidity, temperature, rate of air movement), the content of positive and negative ions, ventilation rate and the radon content in school buildings. Besides, the artificial illumination was measured. There were defined load and pupil’s nourishment at schools. We applied air summary indicator K for estimation of air chemical pollution level. Result: K of the I was 5.57 of maximum permissible concentration (MPC) against 3.26 of MPC of II before lessons, and it increased to 10.80 and 6.49 MPC after complete day’s studies. The ammonia, formaldehyde, carbon oxide (IV), acetone prevail in structure of air chemical pollution schoolrooms of I and II. Conclusion: The cumulative complex load (CCL) all concerned factors of the school environment in I was twice as many vs. II (9.33 and 4.80, correspondently) before lessons. After lessons the CCL doubled in both groups. doi:10.1016/j.toxlet.2009.06.599
E31 Assessment of the lung deposition of particulates originating from diesel engines Kati Oravisjärvi 1,∗ , Mari Pietikäinen 1 , Arja Rautio 2 , Arto Voutilainen 3 , Mauri Haataja 4 , Juhani Ruuskanen 5 , Riitta L. Keiski 1 1
University of Oulu, Department of Process and Environmental Engineering, Oulu, Finland, 2 University of Oulu, Thule Institute, Centre for Arctic Medicine, Oulu, Finland, 3 University of Kuopio, Department of Physics, Kuopio, Finland, 4 University of Oulu, Department of Mechanical Engineering, Oulu, Finland, 5 University of Kuopio, Department of Environmental Sciences, Kuopio, Finland The lung deposition of particulates originating from a city diesel bus was studied in silico. Estimates for the deposited particulates in five different regions of the respiratory system (ET1: the anterior nasal region, ET2: the main extrathoracic region, BB: the bronchial region, bb: the bronchiolar region, AI: the alveolar interstitial region) were computed using a lung deposition model, which is based on the ICRP 66 lung deposition model published by the International Commission on Radiological Protection. Exposure assessment was made for an adult male and female and 10- and 5-year-old children, who were performing light exercise (e.g. walking on a road near the bus) or sitting in a car behind a moving bus. Diesel particulate emissions and number size distributions were measured in the Technical Research Centre of Finland. The measured particulates were in the size range of 7 nm to 10 m and most of the particulates were smaller than 200 nm in their aerodynamic diameter. Part of the inhaled particulates comes out from the respiratory system by exhalation and clearance effects and only approximately half or less of the inhaled particulates stay in the respiratory system. The particulate deposition depends also on the way of breathing: nose or mouth breathing and the intensity of breathing. Compared to sitting the deposition of diesel particulates in human’s respiratory system increased more than threefold during light exercise. The majority of deposited diesel particulates penetrate deep into the unciliated and gas-exchange regions of human lungs. doi:10.1016/j.toxlet.2009.06.600
E32 Identification and toxicological evaluation of musk fragrances 夽 and thiophenes in extracts of river sediment samples Lenka Vykopalova 1,∗ , Katerina Pencikova 1 , Miroslav Ciganek 1 , Jiri Neca 1 , Jan Vondracek 2 , Werner Brack 3 , Urte Luebcke-Von Varel 3 , G. Streck 3 , Miroslav Machala 1 1
Veterinary Research Institute, Toxicology, Brno, Czech Republic, Academy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic, 3 Helmholtz-Zentrum für Umweltforschung, Leipzig, Germany 2
Reproductive dysfunction can result from exposure to environmental contaminants binding to aryl hydrocarbon receptor (AhR) or estrogenic receptors (ERs). We used effect-directed analysis (EDA) for identification of toxic organic compounds in river sediments, which interact with AhR and/or ER. EDA was based on multi-step fractionation of extracts of environmental samples, chemical identification (LC–MS/MS and GC/MS) and determination of AhR- and ER-mediated activities in DR-CALUX® and ER-CALUX® assays, respectively. Next evaluated individual
Abstracts / Toxicology Letters 189S (2009) S57–S273
in vitro toxic potencies of compounds found in the bioactive chromatographic fractions of river sediment samples, using the ER-CALUX® and DR-CALUX® assays. Apart from known ligands of AhR or ER, such as polycyclic aromatic hydrocarbons, estrone or estradiol, we identified a number of other polycyclic aromatic hydrocarbons and polar aromatic compounds with potential endocrine activities. Based on these results, we selected eight thiophenes (dibenzothiophene, benzo[b]naphtho[1,2-d]thiophene, benzo[b]naphtho[2,1-d]thiophene, benzo[b]naphtho[2,3d]thiophene, 2-(2 -naphthyl)benzo[b]thiophene (2-2 -NBT), 2-1 -NBT, 3-1 -NBT and 32 -NBT) and seven musk compounds (trade names: celestolide, galaxolide, phantolide, ambrettolide, velvione, habanolide, OTNE) for further analysis. All thiophenes, with exception of dibenzothiophene and 3-1 -NBT were efficient AhR agonists, with 2-2 -NBT being the most potent compound. Celestolide and OTNE were weak ER agonists. In contrast, ambrettolide, velvione and habanolide showed antagonistic activities towards hER␣. Phantolide elicited mixed-type dose-dependent estrogenic/antiestrogenic effects. These results suggested that thiophenes might contribute to overall AhR activity, while several musk compounds may interfere with ER functions. Acknowledgements: Supported by the FP6 Modelkey project (511237-GOCE) and the Czech Science Foundation, grant no. 525/081590. 夽 Selected for Oral Presentation. doi:10.1016/j.toxlet.2009.06.601
E33 Reverse osmosis in groundwater treatment for drinking water in southern Iran Zabihollah Yousefi 1,∗ , Ramazan Motalebi 2 1
Mazandaran University of Medical Sciences, Environmental Health, Sari, Islamic Republic of Iran, 2 Abfa, Environmental Engineering, Jask, Islamic Republic of Iran
This evaluation concentrated on physic-chemical efficiency of RO water desalination in Jask City in a Southern province of Iran. In this study, primary data on water supply and network collected. Multiple quality parameters of the water resource of the city (EC, Conductivity, Cl− , Na+ . . .) were higher than the Iranian drinking water standards. Most of water quality parameters analysis (Turbidity, Ph, EC, Conductivity, Cl− , Na+ , Alkalinity, Ca, Na, K, No3 , No2 , Fe, Mg, Mn, NH4 , Po4 , HCo3 − , So4 2− ,. . .) performed as Standard. The membranes of RO water desalination system was poly-Amid (CSM type). The efficiency of RO water desalination system was 94.16, 84.12, 92.00, and 96.17% respectively for Turbidity, Na+ , Mg2+ , So4 2− . P-value for entire analyzed parameters was less than 0.0005 that imply significant difference between influent and effluent water of the RO system. So the effluent water is agreement with national standard of drinking water. Also water exited from the RO system for TDS, Ca2+ and Mg2+ was less than minimum limit of the guideline. The RO technology modified the quality of the water parameters. Keywords: Reverse osmosis; Desalination groundwater; Southern Iran doi:10.1016/j.toxlet.2009.06.602
S199
E34 Quantitative characterization of changes in bone geometry, density and biomechanical properties in two rat strains with different Ah-receptor structure following long-term exposure 夽 to 2,3,7,8-tetrachlorodibenzo-p-dioxin Helen Håkansson 1,∗ , Maria Herlin 1 , Natalia Stern 1 , Fereshteh Kalantari 1 , Salomon Sand 2 , Sune Larsson 3 , Jouni T. Tuomisto 4 , Jouko Tuomisto 4 , Juha Tuukkanen 5 , Timo Jämsä 6,7 , P. Monica Lind 1 , Matti Viluksela 4 1
Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden, 2 National Food Administration, Uppsala, Sweden, 3 Uppsala University Hospital, Department of Orthopaedic Surgery, Uppsala, Sweden, 4 National Institute for Health and Welfare, Department of Environmental Health, Kuopio, Finland, 5 University of Oulu, Department of Anatomy and Cell Biology, Oulu, Finland, 6 University of Oulu, Department of Medical Technology, Oulu, Finland, 7 Oulu University Hospital, Department of Diagnostic Radiology, Oulu, Finland In recent years a number of industrial chemicals and environmental pollutants have been shown to interfere with bone development and remodeling. The present study used benchmark dose methodology to quantify any strain differences in sensitivity to bone insult by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) between the LongEvans (L-E) and Han/Wistar (H/W) rat strains, which differ in their AhR structure and dioxin sensitivity, and thereby further clarify the role of AhR in dioxin-induced bone abnormalities. Femur, tibia and vertebra from TCDD-exposed L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose–response modeling was performed to establish benchmark doses for the analyzed bone parameters, and differences between the two rat strains were estimated for parameters affected by TCDD-exposure in both strains. Benchmark dose analysis demonstrated significant strain differences in response to TCDD treatment, with the L-E rat being the most sensitive strain. Effects on bone parameters were observed in the same dose-range as other low-dose toxicological endpoints, which have been identified as critical for the health risk assessment of dioxins. The demonstrated quantitative differences in sensitivity between the L-E and H/W rat strains provide further support for a distinct role of AhR in dioxin-induced bone abnormalities. In addition, the present study provides novel information about dioxin-induced bone alterations at various skeletal sites, and suggests that bone quality and function are relevant and sensitive endpoints in toxicological studies. 夽 Selected for Oral Presentation. doi:10.1016/j.toxlet.2009.06.603