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David B.V.,International Institute of Biotechnology and Toxicology
Pestology | Year: 2015

The history of GLP (Good Laboratory Practice) has been traced and the FDA and OECD principles of GLP have been outlined. The Indian scenario that was responsible for enactment of the Insecticides Act 1968 and the Rule 1971 and the subsequent developments that have necessitated the importance of GLP in India have been highlighted. The various steps taken for India becoming a full member of OECD principles of GLP have been brought out. There are 36 laboratories accredited by the National GLP compliance Authority (NGCMA), Department of Science & Technology till date. Suggstions for future have been given.

Anupama M.,International Institute of Biotechnology and Toxicology | Seiler J.P.,ToxiConSeil | Murthy P.B.,International Institute of Biotechnology and Toxicology
Archives of Toxicology | Year: 2010

Fluoroquinolones (FQ) are broad-spectrum antibacterial agents widely used for the treatment of infections with various types of gram negative and gram positive bacteria. Specifically, gatifloxacin (GFX) is under development as a component in a new antituberculosis fixed-dose drug combination. In the context of this project, GFX was also tested for genotoxic activity in human peripheral lymphocytes, and the induction of chromosomal aberrations by GFX in PHA-M stimulated cultured human lymphocytes, investigated under conditions of conventional and increased expression times, was further compared to the analogous effects induced by some other second- and third-generation FQ antibacterial agents, namely ofloxacin (OFX), ciprofloxacin (CFX) and sparfloxacin (SFX). OFX did not induce any significant chromosomal aberrations in human lymphocytes. CFX and SFX exhibited slight to moderate clastogenic potential at cytotoxic concentrations (150, 175, 200 and 225 μg/ml), and GFX, a third-generation FQ, induced a clear, concentration-dependent increase in the frequency of chromosomal aberrations at cytotoxic concentrations (150, 200 and 250 μg/ml). These effects were not apparent when metaphases were analysed at the conventionally used sampling time of 24 h, but only after prolongation of the expression time between treatment and harvesting to a sampling time of 36 h (4 h exposure and 32 h expression period). Also, an increased incidence of numerical aberrations (polyploidy and endoreduplication) was seen with GFX at non-cytotoxic concentrations (12.5, 25, 50 and 75 μg/ml). These effects can be attributed to the slight cross-reactivity of FQs between their inhibitory activity towards their intended targets, the prokaryotic type II topoisomerase enzymes DNA gyrase and topoisomerase IV, and the analogous mammalian enzyme topoisomerase II. We have also observed the formation of polycentrics, i.e., chromosomes with five to six centromeres, a rarely reported structural aberration, in GFX-treated cells. The significance of these observations with respect to the conventional conduct of such studies and to the interpretation of the effects is discussed. © 2010 Springer-Verlag.

Rajini A.,Sathyabama University | Revathy K.,University of Madras | Chitrikha T.,International Institute of Biotechnology and Toxicology
Indian Journal of Science and Technology | Year: 2016

Daphnia magna is ubiquitous link in ecological food chain; they are small planktonic crustacean used in ecotoxicological acute tests and chronic reproduction studies. Daphnia species are very sensitive to xenobiotics and very low concentrations will affect their survival. The objective is to investigate the toxicity and reproductive effect of Daphnia magna exposed to different concentrations of combination pesticide in M4 medium in accordance to OECD 211 guideline and in exposure water. To maintain the water hardness within the range in the exposure water as per the OECD guideline reverse osmosis water and drinking well water was blended 1:1 ratio. Twenty one days semi-static exposure was conducted with 10 daphnia held individually in each treatment and control. Daphnids were exposed to 0.0000134, 0.000134, 0.00134, 0.0134, 0.134, 1.34 and 13.4 μg/L of Chlorpyrifos 50% + Cypermethrin 5% EC. 10 μL of alga and yeast were fed with for daphnia of water and only alga was provided M4 medium during the semi-static 48 hour medium change. Agilent QQQ GC-MS/MS, Electron Impact Ionization mode was used for active content analysis. Stock solution of 13.4 μg/L was analyzed for its active content chlorpyrifos and cypermethrin. At 0 hour it was 89.7%, 87.5% and at 48 hour it was 85.3%, 72.4%, respectively. 0.0000134 μg/L was below limit of quantification level. Statistical analysis was performed with ECOSTATS program version 2012.06.03 (SAS Version 9.3, SAS Institute Inc., Cary, NC, USA, 2002-2010). EC50 calculated was 0.012 μg/L for M4 medium and 0.003 μg/L for exposure water at the end of 21 days. Parental mortality of daphnia and reproduction rate decline of off-springs collected in M4 medium and exposure water was found to be dose dependent. Significant change (P < 0.05) in off-spring reproduction was observed in M4 medium and exposure water by ANOVA Student-Newman-Keuls test. Based on the EC50 it is concluded that the pesticide is toxic to daphnids exposed in water than M4 medium exposure. Pesticide mixture effects and its interactions within mixtures is an area of concern to public and regulatory authorities, hence the combined actions of pesticides need to be addressed in the risk assessment process since mixtures of these chemicals may cause higher toxicity effects than those expected from the single compounds. Endocrine disrupting chemicals are compounds that alter the normal functioning of the endocrine system of both wildlife and humans and the tested pesticide active ingredient is considered as endocrine disruptor no reliable data is available on the reproduction effect of the combination pesticide and this experiment throws light that exposure water can also be used to assess contamination of pesticide like M4 medium which is used regularly in ecotoxicological studies for pesticide toxicity assessment.

Muralikrishna G.,International Institute of Biotechnology and Toxicology | Pillai S.K.,International Institute of Biotechnology and Toxicology | Kaleem S.,Integral University | Shakeel F.,King Saud University
Bulgarian Chemical Communications | Year: 2014

The malignant cells in tumor are known to exhibit high rate of glycolytic activity leading to high production of lactic acid. The anticancer drug cyclophosphamide has been reported to have a highly promising anticancer activity against fibrosarcoma bearing rats. In the present investigation, the effect of the energy metabolism of sarcoma-180 (S-180) on the mode of action of cyclophosphamide, as well as the effect of cyclophosphamide on the mitochondrial and cellular respiration of S-180 cells was studied. The effects of glucose utilization, pyruvate utilization and lactate formation were studied on whole S-180 cells and S-180 cell-free homogenate. The levels of glycolytic enzymes such as hexokinase and lactate dehydrogenate (LDH) were estimated. The utilization of glucose and pyruvate was found to decrease which resulted in decreased formation of lactic acid. The mitochondrial respiration was also found to decrease significantly after treatment with cyclophosphamide treated cells. The activity of glycolytic enzymes and mitochondrial respiration were also found to decrease. In conclusion, cyclophosphamide affects both cellular and mitochondrial respiration, leading to reduction of cellular energy pool and thereby resulting in a loss of viability of S-180 cells. © 2014 Bulgarian Academy of Sciences, Union of Chemists in Bulgari.

Maheswari S.T.,International Institute of Biotechnology and Toxicology | Ramesh A.,International Institute of Biotechnology and Toxicology
International Journal of Environmental Research | Year: 2012

Adsorption of anilofos was studied in four soils (topsoil from alfisol, inceptisol, oxisol and vertisol). The order of adsorption of anilofos was Vertisol > Oxisol > Alfisol > Inceptisol. The soil sorption coefficient K and the soil organic carbon sorption coefficient Koc are the basic parameters used for describing the environmental fate of the herbicides. In top soil the calculated K values were 5.43, 3.35, 9.41, 11.73; Koc values were 1086.00, 1288.46, 1191.14, 771.71 and Kc values were 9.05, 33.5, 20.02 and 36.66 from Alfisol, Inceptisol, Oxisol and Vertisol respectively. Field experimental plots with no previous history of anilofos were selected and studied the degradation of anilofos in top soil collected from Alfisol and Inceptisol. The halflife of anilofos in topsoil from Alfisol: T 1- 3.17 days and T 2 3.67 days and in Inceptisol: T 1-3.91 days and T 2- 4.55 days. The degradation of anilofos followed first order kinetics. Anilofos persisted for a longer duration in Inceptisol than in Alfisol. The combination of degradation data (t 1/2- soil) and organic carbon based sorption (K oc) data of herbicides have been used to assess the pesticide environmental impact in soils through Gustafson Ubiquity Score (GUS). The GUS values were found to be 0.48 in top soil from alfisol and 0.53 in inceptisol.

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