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5.1.2 Pengurusan dan Pentadbiran OrganisasiPengurusan program ke arah penambahbaikan dan pemantapanpembangunan sesebuah organisasi• Pengurusan dan Pelaksanaan Strategi-strategi Peningkatan Kualitidalam Perkhidmatan Awam• Pengurusan Mesyuarat dan Urusan Jawatankuasa Kerajaan• Pengurusan Manual Prosedur Kerja dan Fail Meja• Pengurusan Perhubungan Pelanggan5.1.3 Panduan Pengurusan Pejabat• Bahagian I - Pengurusan Am Pejabat• Bahagian II - Pentadbiran Sumber Manusia• Bahagian III - Keperibadian dan Ketrampilan• Bahagian IV - Pengurusan Perhubungan Awam• Bahagian V - Sistem Penyampaian Perkhidmatan• Bahagian VI - Urusan Surat Kerajaan• Bahagian VII - Pengurusan Fail• Bahagian VIII - Penyelenggaraan, Pemeliharaandan Pelupusan Rekod Awam• Bahagian IX - Pengurusan Komunikasi danTeknologi Maklumat• Bahagian X - Inventori dan Bekalan Pejabat5.1.4 Tatacara dan Peraturan Keselamatan pejabat• Keselamatan• Penghantaran• Penyimpanan• Pemusnahan maklumat terperingkat• Penyimpanan kunci-kunci keselamatan• Tanggungjawab pegawai terhadap pengawalan rahsia-rahsiakerajaan5.1.5 Pengurusan Kewangani. Pengurusan Akaun Awam• Terimaan• Bayaranii. Perolehan Kerajaan• Bekalan• Perkhidmatan• Kerjaiii. Pengurusan Aset• Inventori• Hapuskira• Pelupusan2

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSSCIENTIFIC PERSONNEL INVOLVED IN THE STUDYDr. RAJUL SAXENA, M.V.Sc.(Scientist Pathology)Dr. VIVEK SRIVASTAVA , M.V.Sc.(Research Associate)Ms. LITHA THOMAS, M.Sc.(Analyst)Mr. ALISHA N. SINGH , D.M.L.T.(Lab Technician)Page 4 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSINDEXS. No. Contents Page No.1. Quality Assurance Statement 22. Statement of Compliance with Good LaboratoryPractice33. Scientific personnel involved in the study 44. Summary 75. Introduction 86.7.ObjectiveTest Substance9108. Experimental design 119. Experimental procedure 1210. Animal groups and dosage level 1311.12.Clinical Laboratory studiesTerminal Studies151713. Observations18-1914. Result and Conclusion 20Page 5 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSOBJECTIVESTo assess the toxicological effects of 90 days oral administration of NHH 44Bt-Cotton seeds in comparison to the NHH 44 Non Bt-Cotton seeds andcontrol (only vehicle ) in rats so as to provide information on the possiblehealth hazards likely to arise from repeated exposure over a limited period oftime, based on ‘DBT guidelines for Toxicity and Allergenicity Evaluation ofTransgenic Seeds, Plants and Plant Parts’.Page 9 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSSTUDY LABORATORYSTRAIN AND SPECIESANIMAL SOURCESEXWEIGHT RANGEHUSBANDRYEXPERIMENTAL DESIGNDept. of ToxicologyShriram Institute for Industrial Research19, University Road, Delhi-110007 (INDIA)Wistar (albino) ratsLab animal facility, SRI, DelhiMale & Female120 ± 20 gmsAll animals were caged in a group of 5 according to sex inplastic cages fitted with wire mesh tops and havingsterilized paddy husk bedding. Water and standard ratdiet were provided ad libitum.ENVIRONMENTALCONDITIONSAGE OF ANIMALSRoom temperature : 22 ± 3°CRelative humidity : 30 – 70 %Air exchange : 15 air changes / hourLighting condition : 12 hrs light and 12 hrs dark cycle6-8 weeksACCLIMATIZATION PERIOD7 daysDATE OF COMMENCEMENTOF STUDYDURATION OF STUDY19.12.200690 daysDATE OF TERMINATION OFSTUDY18.03.2007NECROPSY DATE Terminal Sacrifice : 19.03.200720.03.200721.03.2007Page 11 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSEXPERIMENTAL PROCEDURESample preparationPowdered samples of NHH 44Bt-Cotton seeds and NHH 44Non Bt-Cottonseeds were freshly prepared every day in corn oil (vehicle) for repeated oraladministration for 90 days.Total 60 healthy adult male and female (30+30) rats were acclimatized for 7days and animals were caged in a group of 5 according to sex in plasticcages fitted with wire mesh tops and having sterilized paddy husk bedding.The rats were randomized and assigned to 3 groups of 10 male and 10female rats each and identified by cage tag and individual marking.The first group was kept as control and was given only the vehicle i.e. cornoil. Second and third group was administered with NHH 44Bt-Cotton seedsand NHH 44Non Bt-Cotton seeds at the dose level of 1000 mg/kg B.wt.respectively.The rats were observed daily for behaviour, appearance and toxicologicalsigns and symptoms, if any.Page 12 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSMortalities : If any, subjected to detailed macroscopicexamination and tissue samples werepreserved for histopathological examination.The following clinical laboratory determinations were made in all theanimals of each group after termination of the experiment. The organs wereweighed and subjected to detailed macroscopic / microscopic examinations.Page 14 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSBiochemistryFollowing estimation were performed on control and treated rats usingBoehringer Mannheim diagnostic kits:(a) Blood sugar(b) Blood urea nitrogen (BUN)(c) Total protein (TP)(d) Albumin(e) Serum glutamic oxalo acetate transaminase (SGOT)(f) Serum glutamic pyruvic transaminase (SGPT)(g) Serum alkaline phosphatase (SAP)(h) CholestrolPage 16 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSTERMINAL STUDIESAutopsy : After completion of treatment period all animals fromeach group were sacrificed and subjected to detailedmacroscopic examination.The following organs were weighed :Heart, kidneys, liver, lungs, spleen, adrenals, testis, ovaries, uterus and brain.Histopathology: Microscopic examination of the followingtissues from all animals from each groupwere carried out :StomachBrainIntestineHeartLungsKidneysLiverAdrenalsSpleenTestisUterusOvariesAny other macroscopically abnormal tissue.BIOSTATISTICAL METHOD USEDAll the data were analysed by using standard student’s t- test of analysisPage 17 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSOBSERVATIONSMortality and toxic signsNo mortality was observed in any of the test groups including the controlgroup of animals. No toxic signs and symptoms were noticed in any of thetwo dose groups and the control group of animals.Mean body weightsNo significant differences were observed in the body weight gain(Appendix -1) pattern of the test groups when compared to the controlgroup of animals.Feed ConsumptionThe feed consumed by the rats in all the test groups was similar to thatconsumed by the animals of control group (Appendix-2).Haematological evaluationsNo significant changes were noted among the test groups and control groupof animals with respect to haematological findings (Appendix-3) as all theparameters fell within the accepted limits of normal variations for albinorats.Page 18 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSClinical Biochemistry evaluationsSerum Biochemistry evaluations (Appendix-4) disclosed no significantdifferences in the tests as well as the control groups of animals, as all theparameters fell within the accepted limits of normal variations.Organ WeightAbsolute organ weights and their ratios (relative organ weights) with theirrespective body weights are shown in Appendix-5. As there were nosignificant changes in the organ weights of the test animals, when comparedwith organ weights of control group animals, the test substance (NHH 44 Bt-Cotton seeds and NHH 44 Non Bt-Cotton seeds) was failing to suggest anyspecific target organ.Necropsy examinationsNecropsy examination of animals did not reveal any significant changes inboth the test groups i.e. NHH 44 Bt-Cotton seeds and NHH 44 Non Bt-Cotton seeds at the level of 1000 mg/kg B.wt when compared to its controlcounterparts, as shown in Appendix 6.Histopathological examinationNo significant histopathological changes (Appendix-7) were noticed in theanimals of NHH 44 Bt-Cotton seeds and NHH 44 Non Bt-Cotton seedsdosed at 1000 mg/kg B.wt when compared to its control counterparts.Page 19 of 93

SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCHPROJECT NO.PRODUCTSTUDYREPORT NO. : 000046990DATE : 18.5.2007: TOX- 355 B: NHH 44 Bt–COTTON SEEDS: SUB CHRONIC ORAL TOXICITYSTUDY IN RATSRESULT WITH CONCLUSIONUnder the conditions of this study, the 90 days repeated oral administrationof NHH 44 Bt-Cotton seeds at the dose level of 1000 mg/kg B.wt for fivedays/ week to wistar rats did not induce any treatment related observabletoxic effects, when compared to its corresponding NHH 44 Non Bt-Cottonseeds and the control group of animals treated with corn oil (vehicle) only.Hence, No Observable Adverse Effect Level (N.O.A.E.L.) = 1000 mg/kg.B.wt.The sample has been conducted as per DBT, Guidelines for Toxicity andAllergenicity Evaluation of Transgenic Seeds, Plants and Plant parts.Page 20 of 93