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Bilastine: Environmental risk assessment
Abstracts / Toxicology Letters 196S (2010) S37–S351
magna (static method) by performing statistical analysis of the data. This study aims to evaluate if DTOX could be used to monitor Cr(VI) in water. DTOX detected the toxicity of the tested solutions before the first 24 h. The mean times required to define state of attention (the first sign of unusual water quality that differs from an established baseline data) and contamination (the definitive sign of unusual water quality that is indicative of a contamination) were respectively 385 and 414 min. The Mann–Whitney statistical test confirmed for all tested concentrations the earliness of the attention states than contamination ones (p < 0.05). The comparison between two methods, calculated using a logistic regression with Probit model, demonstrated a statistical significant difference between the respective Cr(VI) concentration that produced immobilization in 50% of test organisms (EC50 ). The confidence intervals at 95% of EC50 were between 0.36 and 0.39 mg/L for static method and between 0.26 and 0.32 mg/L for DTOX. Despite statistical data concerning EC50 , the results demonstrate that the analysis of D. magna behavior with DTOX has considerable potential as a preventive tool to monitor Cr(VI) in water at concentrations between 0.20 and 0.49 mg/L. doi:10.1016/j.toxlet.2010.03.430
P108-030 Bilastine: Environmental risk assessment F. Ledo 1 , M.L. Lucero 1 , B. Seyfred 2 , M. Weissenfeld 2 , W. Megel 2 , A. Peither 2 , P. Roulstone 2 , T. Schoop 2 , E. Kiefer 2 1
Faes Farma S.A., Spain, 2 Harlan Laboratories Ltd., Spain
This study evaluates the potential risks to the environment after treatment of patients with Bilastine, a novel second generation H1 antagonist. The environmental risk assessment consists of two phases. Phase I covers the calculation of the Predicted Environmental Concentration (PEC). In Phase II (Tier A), information on physico-chemical and ecotoxicological properties are evaluated in relation to the extent of exposure of the environment. Biodegradability Test. In an OECD 301 B test Bilastine was classified as not readily biodegradable according to the test criteria. Transformation in aquatic sediment systems. The degradation and distribution in two aquatic systems (river and pond) incubated under aerobic conditions were investigated following test guideline OECD 308. Bilastine dissipated from the water phase with a DT50 of 6–7 days. Bilastine is partioning into the sediment and accounted for more than 10% of applied at day 14 and later sampling intervals. Respiration Inhibition Testing. Bilastine exhibited no inhibitory effects (3 h NOEC3 100 mg/L) on the respiration rate of activated sludge in an OECD 209 test. Algal Growth. The influence on the growth of Pseudokirchneriella subcapitata was investigated in a 72-h static test (OECD 201). The overall NOEC for algae is orders of magnitudes above the PEC SURFACE WATER. Fish Early Life Stage. The effects on zebra fish was investigated in an early life stage toxicity test (OECD 210).The NOEC was clearly above the PEC SURFACE WATER. Reproduction of Aquatic Invertebrates. The effect on the survival and reproduction of Daphnia magna was investigated in a semistatic test over 21 days (OECD 211). The NOEC was clearly above the PEC SURFACE WATER. Conclusion: No adverse aquatic or terrestrial environmental effects are expected to be associated with the use of Bilastine as a
S123
drug for treatment of patients with symptoms of allergic rhinoconjunctivitis and urticaria. doi:10.1016/j.toxlet.2010.03.431
P108-031 Biochemical biomarkers in Oreochromis niloticus exposed to mixtures of benzo[a]pyrene and diazinon E. Alves De Almeida, C.P. Trídico, D.C. Da Silva, L. Nogueira, A.C. Ferreira Rodrigues IBILCE - UNESP, Brazil There are several works describing the effects of the organophosphate pesticide diazinon (DZ) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) in classical fish biochemical biomarkers, like the activities of acetylcholinesterase (AChE), 7-ethoxyresorufin-O-deetilase (EROD), carboxylesterase (CbE), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH) and glutathione S-transferase (GST). However, little is known about the combined effects of both contaminants is such biomarkers. Thus, the aim of this work was evaluate how DZ and BaP alone or in mixtures affect the biochemical parameters listed above. Two sets of experiments were done, where tilapias (Oreochromis niloticus) were pre-exposed for three days to BaP and then DZ was added to uncontaminanted and BaP pre-exposed aquariums for two and seven additional days. In the first experiment, BaP and DZ doses were the same, 0.5 mg/L. In the second experiment, the DZ dose was increased to 1 mg/L. BaP alone caused the induction of phases I and II enzymes, and DZ caused CbE and AChE inhibition. No significant modulation was observed in antioxidant enzymes. When in combination with BaP, DZ caused a significant decrease of BaPinduced EROD and GST induction. Inhibition of SOD, CAT and GPx by the combination of BaP and DZ were also observed for the second experiment. These data indicates a significant interference of DZ in responses activated by BaP. doi:10.1016/j.toxlet.2010.03.432
P108-032 Evaluation of biochemical biomarkers in Nile tilapia exposed to metals and benzo[a]pyrene L.R. Maschio, D. Caetano Da Silva, E. Alves De Almeida UNESP - São Paulo State University, IBILCE, Brazil As the human population and industrial production increases, the contaminant input to the environment increases as well, causing substantial impact to the aquatic ecosystem, which represent a final receptor for most of these pollutants. To determine whether the pollutants affect the aquatic ecosystem, biochemical and genotoxic biomarkers can be assessed in sentinel organisms. The aim of our work was to evaluate the effects of metals (Fe, Cu, Cd and Pb) and benzo[a]pyrene alone or in combination on biochemical biomarkers of Nile tilapia (Oreochromis niloticus). The concentration of compounds tested were based on the maximum level allowed by the Brazillian legislation for (resolution 357/2005 – CONAMA), for “Class 2” waters, as follows: Fe (0.3 mg/L), Cu (0.009 mg/L), Pb (0.01 mg/L), Cd (0.001 mg/L), and Benzo[a]Pireno (0.05 g/L). These concentrations were established based on studies concerned to the protection of animal life, but were studied separately, and no information exists if these contaminants together at the limit of
magna (static method) by performing statistical analysis of the data. This study aims to evaluate if DTOX could be used to monitor Cr(VI) in water. DTOX detected the toxicity of the tested solutions before the first 24 h. The mean times required to define state of attention (the first sign of unusual water quality that differs from an established baseline data) and contamination (the definitive sign of unusual water quality that is indicative of a contamination) were respectively 385 and 414 min. The Mann–Whitney statistical test confirmed for all tested concentrations the earliness of the attention states than contamination ones (p < 0.05). The comparison between two methods, calculated using a logistic regression with Probit model, demonstrated a statistical significant difference between the respective Cr(VI) concentration that produced immobilization in 50% of test organisms (EC50 ). The confidence intervals at 95% of EC50 were between 0.36 and 0.39 mg/L for static method and between 0.26 and 0.32 mg/L for DTOX. Despite statistical data concerning EC50 , the results demonstrate that the analysis of D. magna behavior with DTOX has considerable potential as a preventive tool to monitor Cr(VI) in water at concentrations between 0.20 and 0.49 mg/L. doi:10.1016/j.toxlet.2010.03.430
P108-030 Bilastine: Environmental risk assessment F. Ledo 1 , M.L. Lucero 1 , B. Seyfred 2 , M. Weissenfeld 2 , W. Megel 2 , A. Peither 2 , P. Roulstone 2 , T. Schoop 2 , E. Kiefer 2 1
Faes Farma S.A., Spain, 2 Harlan Laboratories Ltd., Spain
This study evaluates the potential risks to the environment after treatment of patients with Bilastine, a novel second generation H1 antagonist. The environmental risk assessment consists of two phases. Phase I covers the calculation of the Predicted Environmental Concentration (PEC). In Phase II (Tier A), information on physico-chemical and ecotoxicological properties are evaluated in relation to the extent of exposure of the environment. Biodegradability Test. In an OECD 301 B test Bilastine was classified as not readily biodegradable according to the test criteria. Transformation in aquatic sediment systems. The degradation and distribution in two aquatic systems (river and pond) incubated under aerobic conditions were investigated following test guideline OECD 308. Bilastine dissipated from the water phase with a DT50 of 6–7 days. Bilastine is partioning into the sediment and accounted for more than 10% of applied at day 14 and later sampling intervals. Respiration Inhibition Testing. Bilastine exhibited no inhibitory effects (3 h NOEC3 100 mg/L) on the respiration rate of activated sludge in an OECD 209 test. Algal Growth. The influence on the growth of Pseudokirchneriella subcapitata was investigated in a 72-h static test (OECD 201). The overall NOEC for algae is orders of magnitudes above the PEC SURFACE WATER. Fish Early Life Stage. The effects on zebra fish was investigated in an early life stage toxicity test (OECD 210).The NOEC was clearly above the PEC SURFACE WATER. Reproduction of Aquatic Invertebrates. The effect on the survival and reproduction of Daphnia magna was investigated in a semistatic test over 21 days (OECD 211). The NOEC was clearly above the PEC SURFACE WATER. Conclusion: No adverse aquatic or terrestrial environmental effects are expected to be associated with the use of Bilastine as a
S123
drug for treatment of patients with symptoms of allergic rhinoconjunctivitis and urticaria. doi:10.1016/j.toxlet.2010.03.431
P108-031 Biochemical biomarkers in Oreochromis niloticus exposed to mixtures of benzo[a]pyrene and diazinon E. Alves De Almeida, C.P. Trídico, D.C. Da Silva, L. Nogueira, A.C. Ferreira Rodrigues IBILCE - UNESP, Brazil There are several works describing the effects of the organophosphate pesticide diazinon (DZ) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) in classical fish biochemical biomarkers, like the activities of acetylcholinesterase (AChE), 7-ethoxyresorufin-O-deetilase (EROD), carboxylesterase (CbE), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH) and glutathione S-transferase (GST). However, little is known about the combined effects of both contaminants is such biomarkers. Thus, the aim of this work was evaluate how DZ and BaP alone or in mixtures affect the biochemical parameters listed above. Two sets of experiments were done, where tilapias (Oreochromis niloticus) were pre-exposed for three days to BaP and then DZ was added to uncontaminanted and BaP pre-exposed aquariums for two and seven additional days. In the first experiment, BaP and DZ doses were the same, 0.5 mg/L. In the second experiment, the DZ dose was increased to 1 mg/L. BaP alone caused the induction of phases I and II enzymes, and DZ caused CbE and AChE inhibition. No significant modulation was observed in antioxidant enzymes. When in combination with BaP, DZ caused a significant decrease of BaPinduced EROD and GST induction. Inhibition of SOD, CAT and GPx by the combination of BaP and DZ were also observed for the second experiment. These data indicates a significant interference of DZ in responses activated by BaP. doi:10.1016/j.toxlet.2010.03.432
P108-032 Evaluation of biochemical biomarkers in Nile tilapia exposed to metals and benzo[a]pyrene L.R. Maschio, D. Caetano Da Silva, E. Alves De Almeida UNESP - São Paulo State University, IBILCE, Brazil As the human population and industrial production increases, the contaminant input to the environment increases as well, causing substantial impact to the aquatic ecosystem, which represent a final receptor for most of these pollutants. To determine whether the pollutants affect the aquatic ecosystem, biochemical and genotoxic biomarkers can be assessed in sentinel organisms. The aim of our work was to evaluate the effects of metals (Fe, Cu, Cd and Pb) and benzo[a]pyrene alone or in combination on biochemical biomarkers of Nile tilapia (Oreochromis niloticus). The concentration of compounds tested were based on the maximum level allowed by the Brazillian legislation for (resolution 357/2005 – CONAMA), for “Class 2” waters, as follows: Fe (0.3 mg/L), Cu (0.009 mg/L), Pb (0.01 mg/L), Cd (0.001 mg/L), and Benzo[a]Pireno (0.05 g/L). These concentrations were established based on studies concerned to the protection of animal life, but were studied separately, and no information exists if these contaminants together at the limit of