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The effect of glyphosate on the spontaneous motoric activity of rat isolated jejunum strips
S202
Abstracts / Toxicology Letters 221S (2013) S59–S256
freshwater/kg emitted) and effect factors (impact/kg to freshwater). The total sales in 2011 were 1707.5 t (0.7 kg/ha), herbicides and glyphosate were the most sold substance group and active ingredient, respectively. A recent emission model, PestLCI 2.0 was used to estimate the emissions assuming average Finnish field conditions. The impacts were assessed by the SETAC consensus LCIA model for ecotoxic impacts Usetox. The total ecotoxic pressure decreased over the time scale mainly because decreased sale amount of the main hazardous substance fluazinam. Overall single very hazardous substances had a strong increasing effect on the total impact. The main contributors to the total pressure were fungicides, and the most hazardous substances were fluazinam (used on potato), aclonifen (e.g. peas, carrot, onion), methiocarb (e.g. strawberry), pendimethalin (carrot, onion), prochloraz (cereals, oil seeds). In conclusion, the first priority in identifying the LCA end point environmental risks of single hazardous PPPs is to develop environmental management of plant protection and if needed build up restrictions which are properly directed to causes of impacts. In addition, the risk results are also recommended to be related to yield amount and quality for obtaining the benefits from using of PPPs. Finally, other LCA impact categories linked to crop production should also be evaluated for obtaining more realistic environmental effects of the studied area. http://dx.doi.org/10.1016/j.toxlet.2013.05.471
P17-15 The effect of glyphosate on the spontaneous motoric activity of rat isolated jejunum strips
P17-16 The role of microtubule on dithiocarbamate cytotoxicity Eugene Gonzalez-Lopez ∗ , Shu-Yuan Cheng John Jay College of Criminal Justice, NY, United States Dithiocarbamate compounds, such as maneb (MB), mancozeb (MZ) and diethyldithiocarbamate (DDC), are fungicides widely used in the United States. These compounds can potentiate the presence of the dopaminergic neurotoxin MPTP. However, the mechanisms for those effects are not so clear. Dopamine transporter (DAT) is essential for MPTP toxicity by transporting MPP+, the active metabolite of MPTP, into dopaminergic neurons. Preliminary results show that MB and MZ increase the interaction of DAT and alpha-synuclein followed by accumulating cell surface DAT expression which in turn enhances MPP+ cytotoxicity by increasing MPP+ uptake. The aim of this study is to elucidate the role of microtubules on dithiocarbamate cytotoxicity. Immunocytochemistry was performed on PC12 cells treated with DDC (75 M), MB (20 M), and MZ (20 M) for 4 h. The images showed that these dithiocarbamates disturbed the cytoskeleton network, with MZ having shown the most severe depolymerization. Cells pre-treated with microtubules stabilizer Taxol showed a significant alleviation in cell damage, proven by the cell viability MTT assay. These results indicate that these fungicides directly influence the microtubules; however, dithiocarbamates might also trigger other toxic mechanisms, resulting in cell death. http://dx.doi.org/10.1016/j.toxlet.2013.05.473
Marta Mendel ∗ , Magdalena Chlopecka, Natalia Dziekan, Wojciech Karlik Warsaw University of Life Sciences, Warsaw, Poland According to the results of preliminary studies, Roundup changes the motoric activity of isolated intestine strips. It is well known that the biological activity of glyphosate, the active substance of Roundup, is higher in lower pH. It may suggest that the character of reaction contributes to glyphosate’s mechanism of action. The aim of the study was to estimate the effect of glyphosate applied in incubation media of different pH value on the spontaneous motoric activity of rat isolated jejunum strips. The experiments were conducted under isotonic conditions. The application of glyphosate in every concentration was conducted twice in a non-cumulative manner. The obtained results revealed that glyphosate applied in the concentration range of 0.0027–1.7 g/L changes significantly, but not dose-dependently, the spontaneous motoric activity of jejunum strips. If applied in the lowest dose, glyphosate induces strong contractile response of jejunal smooth muscle during first treatment and only very weak contraction after repeated treatment. Glyphosate in the middle concentration (0.068 g/L) does not influence motoric activity of jejunum strips (applied for the first time) and next causes a contractile reaction (repeated administration). Eventually, glyphosate in the highest dose (1.7 g/L) induces the strongest miorelaxation of jejunal muscle after both applications. The administration of glyphosate dissolved in a medium of pH value 5.2 results in a permanent relaxation of jejunum strips, no contraction is observed. The force of the miorelaxation surpasses twice the size of the reaction evoked by glyphosate in a medium of pH value 7.4. http://dx.doi.org/10.1016/j.toxlet.2013.05.472
P17-17 Toxic effects of combined (tri)azole fungicides on prostate gland and testis in rats Flavia Schmidt 1 , Svenja Rieke 1 , Tanja Heise 1 , Mechthild Ladwig 1 , Wolfram Haider 2 , Karen Ildico Hirsch-Ernst 1 , Lars Niemann 1 , Rudolf Pfeil 1 , Philip Marx-Stoelting 1 Federal Institute for Risk Assessment, Berlin, Germany, 2 Institut für Tierpathologie, Berlin, Deutschland
1
The application of pesticides has changed over the last decades. In accordance with good agricultural practice, application of specific pesticide combinations at lower dose levels has become more common. Consequently consumers are exposed to “cocktails” of pesticides via the diet rather than to individual substances. Recent animal studies have shown that chemicals with the same mode/mechanism of action may act in a “dose additive” manner. Cumulative effects were observed even after exposure to doses close to their NOAEL. However, pesticide risk assessment is generally based on the evaluation of single substances but the authorities are currently developing regulatory approaches considering mixture effects. To deal with the huge amount of possible substance combinations, it is essential to define so-called cumulative assessment groups (CAGs) based on their toxicological profile. Triazoles share a common mode/mechanism of action and are consequently well suited to study potential mixture effects. To identify potential cumulative effects of triazoles, adult male rats were dosed for 28 days via diet. Ventral prostate and testis were examined as potential endocrine responsive target organs in regard to histopathological alterations and changes in gene expression by using quantitative real-time PCR and low density microarray. Based on preliminary results cyproconazole and epoxiconazole were selected to investigate mixture effects of these substances at three
Abstracts / Toxicology Letters 221S (2013) S59–S256
freshwater/kg emitted) and effect factors (impact/kg to freshwater). The total sales in 2011 were 1707.5 t (0.7 kg/ha), herbicides and glyphosate were the most sold substance group and active ingredient, respectively. A recent emission model, PestLCI 2.0 was used to estimate the emissions assuming average Finnish field conditions. The impacts were assessed by the SETAC consensus LCIA model for ecotoxic impacts Usetox. The total ecotoxic pressure decreased over the time scale mainly because decreased sale amount of the main hazardous substance fluazinam. Overall single very hazardous substances had a strong increasing effect on the total impact. The main contributors to the total pressure were fungicides, and the most hazardous substances were fluazinam (used on potato), aclonifen (e.g. peas, carrot, onion), methiocarb (e.g. strawberry), pendimethalin (carrot, onion), prochloraz (cereals, oil seeds). In conclusion, the first priority in identifying the LCA end point environmental risks of single hazardous PPPs is to develop environmental management of plant protection and if needed build up restrictions which are properly directed to causes of impacts. In addition, the risk results are also recommended to be related to yield amount and quality for obtaining the benefits from using of PPPs. Finally, other LCA impact categories linked to crop production should also be evaluated for obtaining more realistic environmental effects of the studied area. http://dx.doi.org/10.1016/j.toxlet.2013.05.471
P17-15 The effect of glyphosate on the spontaneous motoric activity of rat isolated jejunum strips
P17-16 The role of microtubule on dithiocarbamate cytotoxicity Eugene Gonzalez-Lopez ∗ , Shu-Yuan Cheng John Jay College of Criminal Justice, NY, United States Dithiocarbamate compounds, such as maneb (MB), mancozeb (MZ) and diethyldithiocarbamate (DDC), are fungicides widely used in the United States. These compounds can potentiate the presence of the dopaminergic neurotoxin MPTP. However, the mechanisms for those effects are not so clear. Dopamine transporter (DAT) is essential for MPTP toxicity by transporting MPP+, the active metabolite of MPTP, into dopaminergic neurons. Preliminary results show that MB and MZ increase the interaction of DAT and alpha-synuclein followed by accumulating cell surface DAT expression which in turn enhances MPP+ cytotoxicity by increasing MPP+ uptake. The aim of this study is to elucidate the role of microtubules on dithiocarbamate cytotoxicity. Immunocytochemistry was performed on PC12 cells treated with DDC (75 M), MB (20 M), and MZ (20 M) for 4 h. The images showed that these dithiocarbamates disturbed the cytoskeleton network, with MZ having shown the most severe depolymerization. Cells pre-treated with microtubules stabilizer Taxol showed a significant alleviation in cell damage, proven by the cell viability MTT assay. These results indicate that these fungicides directly influence the microtubules; however, dithiocarbamates might also trigger other toxic mechanisms, resulting in cell death. http://dx.doi.org/10.1016/j.toxlet.2013.05.473
Marta Mendel ∗ , Magdalena Chlopecka, Natalia Dziekan, Wojciech Karlik Warsaw University of Life Sciences, Warsaw, Poland According to the results of preliminary studies, Roundup changes the motoric activity of isolated intestine strips. It is well known that the biological activity of glyphosate, the active substance of Roundup, is higher in lower pH. It may suggest that the character of reaction contributes to glyphosate’s mechanism of action. The aim of the study was to estimate the effect of glyphosate applied in incubation media of different pH value on the spontaneous motoric activity of rat isolated jejunum strips. The experiments were conducted under isotonic conditions. The application of glyphosate in every concentration was conducted twice in a non-cumulative manner. The obtained results revealed that glyphosate applied in the concentration range of 0.0027–1.7 g/L changes significantly, but not dose-dependently, the spontaneous motoric activity of jejunum strips. If applied in the lowest dose, glyphosate induces strong contractile response of jejunal smooth muscle during first treatment and only very weak contraction after repeated treatment. Glyphosate in the middle concentration (0.068 g/L) does not influence motoric activity of jejunum strips (applied for the first time) and next causes a contractile reaction (repeated administration). Eventually, glyphosate in the highest dose (1.7 g/L) induces the strongest miorelaxation of jejunal muscle after both applications. The administration of glyphosate dissolved in a medium of pH value 5.2 results in a permanent relaxation of jejunum strips, no contraction is observed. The force of the miorelaxation surpasses twice the size of the reaction evoked by glyphosate in a medium of pH value 7.4. http://dx.doi.org/10.1016/j.toxlet.2013.05.472
P17-17 Toxic effects of combined (tri)azole fungicides on prostate gland and testis in rats Flavia Schmidt 1 , Svenja Rieke 1 , Tanja Heise 1 , Mechthild Ladwig 1 , Wolfram Haider 2 , Karen Ildico Hirsch-Ernst 1 , Lars Niemann 1 , Rudolf Pfeil 1 , Philip Marx-Stoelting 1 Federal Institute for Risk Assessment, Berlin, Germany, 2 Institut für Tierpathologie, Berlin, Deutschland
1
The application of pesticides has changed over the last decades. In accordance with good agricultural practice, application of specific pesticide combinations at lower dose levels has become more common. Consequently consumers are exposed to “cocktails” of pesticides via the diet rather than to individual substances. Recent animal studies have shown that chemicals with the same mode/mechanism of action may act in a “dose additive” manner. Cumulative effects were observed even after exposure to doses close to their NOAEL. However, pesticide risk assessment is generally based on the evaluation of single substances but the authorities are currently developing regulatory approaches considering mixture effects. To deal with the huge amount of possible substance combinations, it is essential to define so-called cumulative assessment groups (CAGs) based on their toxicological profile. Triazoles share a common mode/mechanism of action and are consequently well suited to study potential mixture effects. To identify potential cumulative effects of triazoles, adult male rats were dosed for 28 days via diet. Ventral prostate and testis were examined as potential endocrine responsive target organs in regard to histopathological alterations and changes in gene expression by using quantitative real-time PCR and low density microarray. Based on preliminary results cyproconazole and epoxiconazole were selected to investigate mixture effects of these substances at three