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The use of everted rat small intestinal sacs in vitro to estimate relative absorption potential of a series of alpha olefins
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Abstracts / Toxicology Letters 229S (2014) S40–S252
Conclusions: This structured approach to appraising the strengths and weaknesses of a toxicological literature review should be of use to readers of reviews, peer-reviewers at journals and as part of internal planning and review procedures of institutions engaged in production of literature reviews. http://dx.doi.org/10.1016/j.toxlet.2014.06.448 P-2.103 Expression of brain-derived neurotrophic factor (BDNF) and neuronal nitric oxide synthase (nNOS) in hypothalamus following subchronic malathion exposure Raja Rezg 1,3,∗ , Bessem Mornagui 2,4 , Melika Ben Ahmed 2 , Saloua El-Fazaa 1 , Najoua Gharbi 1 , Noomen Ben El-Hadj 4 1 Faculty of Sciences of Tunis, El Manar II, Tunisia, 2 Pasteur Institute of Tunis, Tunis, Tunisia, 3 High Institute of Biotechnology of Monastir, Monastir, Tunisia, 4 Faculty of Sciences of Gabes, Gabes, Tunisia
some countries, such as Brazil. Aware of this problem, Brazilian researchers have developed a new metallic-insecticide, which is under patent, as an effective alternative to the replacement of sulfluramid. This new compound is natural, bonded to a metal complex and has great efficacy in the control of leaf-cutting ants. This study aimed to evaluate the toxicity of the metallic-insecticide Mg6[Mg(5-methyl-phen)(hesperetin)(H2 O)2 ](CH3 COO) through chromosomal aberration assay and induction of micronuclei in root cells of Allium cepa (onion). Onion seeds were exposed to soil containing three different concentrations of the compound (0.5 mg/L, 1.0 mg/L and 2.0 mg/L), to control soil and positive controls (trifluralin and methylmethane sulfonate). Slides with cells from the meristematic region were made and the results were analyzed by Kruskal–Wallis statistical test. The statistical test showed that the three studied concentrations were not able to induce micronucleus formation and chromosome aberrations. Thus, the results suggest that this new compound was not genotoxic, since it does not alter the DNA of the test organism. Financial support: FAPESP (2012/12019-5).
Recent scientific literature revealed a large variety of human health problems caused by exposure to organophosphorus pesticides (OP) considered as major food chain contaminants. However, the impact of these xenobiotics on neurotrophins, especially on brain-derived neurotrophic factor (BDNF), is extremely limited. The aim of this study was to investigate the effects of subchronic exposure to malathion, an OP insecticide, on BDNF and neuronal nitric oxide synthase (nNOS) mRNA expression in rat hypothalamus. Malathion was administered to Wistar rats by gavage for 32 days at a dose of 100 mg/kg bw/day. RT-PCR was used to measure mRNA levels. The results demonstrate differences in the responses and showed that (nNOS) mRNA expression decreased, however, BDNF expression remained unchanged in malathion treated rats compared to control group. Interestingly, this anatomical region, hypothalamus, considered like the key element in the neuroendocrine response and which seems to possess a high degree of plasticity, remains still not affected by 32 days malathion exposure. However, NO is a key factor in the expression of proteins involved in neuroplasticity and it has been confirmed that expression of plasticity-related proteins depends on nNOS-derived NO, especially BDNF signaling, thus, we suggest that significant nNOS decrease will present a serious risk factor to synaptic plasticity in chronic exposure and requires more investigation. http://dx.doi.org/10.1016/j.toxlet.2014.06.449 P-2.104 Evaluation of the action of a new metallic-insecticide in genetic material of Allium cepa Raphael Souza 1,∗ , João Batista Fernandes 2 , Rose Maria Carlos 2 , Odair Bueno 1 , Carmem Fontanetti 1 São Paulo State University, Rio Claro, SP, Brazil, 2 Federal University of São Carlos, São Carlos, SP, Brazil
1
Brazil has 10 species of Atta (leaf-cutting ants) and this fact contributes to its classification as a major consumer of pesticides in the world. The only active ingredient that features high efficiency against such organisms is sulfluramid. However, its production and degradation involve perfluorooctane sulfonate (PFOS), toxic to many organisms. Thus, in 2009, the Stockholm Convention banned production of PFOS, but allowed its use in
http://dx.doi.org/10.1016/j.toxlet.2014.06.450 P-2.105 The use of everted rat small intestinal sacs in vitro to estimate relative absorption potential of a series of alpha olefins Robert Powrie 1,∗ , Mike Penman 2 , Clifford Elcombe 1 CXR Biosciences, Dundee, UK, 2 Penman Consulting, Brussels, Belgium 1
Higher olefins (HO) range from C6 to greater than C32 olefins with an alpha or internal double bond and with linear and/or branched carbon chains. To meet the extensive requirements of REACH, data read across was used for more than 30 HOs. A hypothesis of a category approach for HOs is that mammalian bioavailability decreases as molecular weight increases. If this was demonstrated experimentally, the case for read across would be strengthened, reducing the need for toxicity studies on all of the chemicals. This study determined and ranked the absorption potential of a series of alpha-olefins using an in vitro everted rat small intestinal sac model. Sacs were prepared (∼2.5 cm) from proximal small intestine and were filled with oxygenated Fed State Simulated Intestinal Fluid (FeSSIF, the serosal medium). Sacs were incubated (1 h, 37 ◦ C) in flasks containing FeSSIF saturated with individual alpha-olefins. The serosal fluids were extracted and analysed for olefin content using GC-FID. The absorption of 30 olefins (C6–C27) was investigated. Marked inter-compound differences in absorption were observed, with the degree of absorption decreasing with increasing carbon number. C6–C10 olefins were well absorbed, while those of C14 and above were either not absorbed or very poorly absorbed. Data such as these could be used to select representative compounds from a series to study further in vivo. Funded by the Higher Olefins and Polyalphaolefins Reach Consortium (HOPA), c/o Penman Consulting, Brussels. Reference Galia, et al., 1998. Pharm. Res. 15, 698.
http://dx.doi.org/10.1016/j.toxlet.2014.06.451
Abstracts / Toxicology Letters 229S (2014) S40–S252
Conclusions: This structured approach to appraising the strengths and weaknesses of a toxicological literature review should be of use to readers of reviews, peer-reviewers at journals and as part of internal planning and review procedures of institutions engaged in production of literature reviews. http://dx.doi.org/10.1016/j.toxlet.2014.06.448 P-2.103 Expression of brain-derived neurotrophic factor (BDNF) and neuronal nitric oxide synthase (nNOS) in hypothalamus following subchronic malathion exposure Raja Rezg 1,3,∗ , Bessem Mornagui 2,4 , Melika Ben Ahmed 2 , Saloua El-Fazaa 1 , Najoua Gharbi 1 , Noomen Ben El-Hadj 4 1 Faculty of Sciences of Tunis, El Manar II, Tunisia, 2 Pasteur Institute of Tunis, Tunis, Tunisia, 3 High Institute of Biotechnology of Monastir, Monastir, Tunisia, 4 Faculty of Sciences of Gabes, Gabes, Tunisia
some countries, such as Brazil. Aware of this problem, Brazilian researchers have developed a new metallic-insecticide, which is under patent, as an effective alternative to the replacement of sulfluramid. This new compound is natural, bonded to a metal complex and has great efficacy in the control of leaf-cutting ants. This study aimed to evaluate the toxicity of the metallic-insecticide Mg6[Mg(5-methyl-phen)(hesperetin)(H2 O)2 ](CH3 COO) through chromosomal aberration assay and induction of micronuclei in root cells of Allium cepa (onion). Onion seeds were exposed to soil containing three different concentrations of the compound (0.5 mg/L, 1.0 mg/L and 2.0 mg/L), to control soil and positive controls (trifluralin and methylmethane sulfonate). Slides with cells from the meristematic region were made and the results were analyzed by Kruskal–Wallis statistical test. The statistical test showed that the three studied concentrations were not able to induce micronucleus formation and chromosome aberrations. Thus, the results suggest that this new compound was not genotoxic, since it does not alter the DNA of the test organism. Financial support: FAPESP (2012/12019-5).
Recent scientific literature revealed a large variety of human health problems caused by exposure to organophosphorus pesticides (OP) considered as major food chain contaminants. However, the impact of these xenobiotics on neurotrophins, especially on brain-derived neurotrophic factor (BDNF), is extremely limited. The aim of this study was to investigate the effects of subchronic exposure to malathion, an OP insecticide, on BDNF and neuronal nitric oxide synthase (nNOS) mRNA expression in rat hypothalamus. Malathion was administered to Wistar rats by gavage for 32 days at a dose of 100 mg/kg bw/day. RT-PCR was used to measure mRNA levels. The results demonstrate differences in the responses and showed that (nNOS) mRNA expression decreased, however, BDNF expression remained unchanged in malathion treated rats compared to control group. Interestingly, this anatomical region, hypothalamus, considered like the key element in the neuroendocrine response and which seems to possess a high degree of plasticity, remains still not affected by 32 days malathion exposure. However, NO is a key factor in the expression of proteins involved in neuroplasticity and it has been confirmed that expression of plasticity-related proteins depends on nNOS-derived NO, especially BDNF signaling, thus, we suggest that significant nNOS decrease will present a serious risk factor to synaptic plasticity in chronic exposure and requires more investigation. http://dx.doi.org/10.1016/j.toxlet.2014.06.449 P-2.104 Evaluation of the action of a new metallic-insecticide in genetic material of Allium cepa Raphael Souza 1,∗ , João Batista Fernandes 2 , Rose Maria Carlos 2 , Odair Bueno 1 , Carmem Fontanetti 1 São Paulo State University, Rio Claro, SP, Brazil, 2 Federal University of São Carlos, São Carlos, SP, Brazil
1
Brazil has 10 species of Atta (leaf-cutting ants) and this fact contributes to its classification as a major consumer of pesticides in the world. The only active ingredient that features high efficiency against such organisms is sulfluramid. However, its production and degradation involve perfluorooctane sulfonate (PFOS), toxic to many organisms. Thus, in 2009, the Stockholm Convention banned production of PFOS, but allowed its use in
http://dx.doi.org/10.1016/j.toxlet.2014.06.450 P-2.105 The use of everted rat small intestinal sacs in vitro to estimate relative absorption potential of a series of alpha olefins Robert Powrie 1,∗ , Mike Penman 2 , Clifford Elcombe 1 CXR Biosciences, Dundee, UK, 2 Penman Consulting, Brussels, Belgium 1
Higher olefins (HO) range from C6 to greater than C32 olefins with an alpha or internal double bond and with linear and/or branched carbon chains. To meet the extensive requirements of REACH, data read across was used for more than 30 HOs. A hypothesis of a category approach for HOs is that mammalian bioavailability decreases as molecular weight increases. If this was demonstrated experimentally, the case for read across would be strengthened, reducing the need for toxicity studies on all of the chemicals. This study determined and ranked the absorption potential of a series of alpha-olefins using an in vitro everted rat small intestinal sac model. Sacs were prepared (∼2.5 cm) from proximal small intestine and were filled with oxygenated Fed State Simulated Intestinal Fluid (FeSSIF, the serosal medium). Sacs were incubated (1 h, 37 ◦ C) in flasks containing FeSSIF saturated with individual alpha-olefins. The serosal fluids were extracted and analysed for olefin content using GC-FID. The absorption of 30 olefins (C6–C27) was investigated. Marked inter-compound differences in absorption were observed, with the degree of absorption decreasing with increasing carbon number. C6–C10 olefins were well absorbed, while those of C14 and above were either not absorbed or very poorly absorbed. Data such as these could be used to select representative compounds from a series to study further in vivo. Funded by the Higher Olefins and Polyalphaolefins Reach Consortium (HOPA), c/o Penman Consulting, Brussels. Reference Galia, et al., 1998. Pharm. Res. 15, 698.
http://dx.doi.org/10.1016/j.toxlet.2014.06.451