EVALUATION     OF     HISTOPATHOLOGICAL     AND     BIOCHEMICAL     CHANGES     OF     TAMRA     BHASMA      (A     COPPER     BASED     MINERAL FORMULATION) REPEATED DOSE TOXICITY STUDY IN WISTAR ALBINO RATS Ravi Bhaskar * 1 , Doshi.M.A 2 , Shakunthala.R.Pai 3 , Ravishankar.B 4 . *1 PhD Scholor, Anatomy Department, Krishna Institute of Medical Sciences Deemed University, Karad, Maharashtra, India. 2  Prof & HOD,  Anatomy Department, Krishna Institute of Medical Sciences Deemed University, Karad, Maharashtra, India. 3    Prof   &   HOD,   Anatomy   Department,   Srinivas   Institute   of   Medical   Sciences   &   Research   Centre,   Mukka,   Mangalore,   Karnataka,   Director 4 ,   SDM   Research centre for Ayurveda and Allied Sciences, Udupi, Karnataka. Corresponding Author: Ravi Bhaskar, Department of Anatomy, Srinivas Institute of Medical Sciences and Research Centre, Mukka, Mangaluru, India. E-Mail:  drravibhaskarr@gmail.com ABSTRACT Objective:   The   objective   of   this   present   study   was   to   evaluate   safety   profile   of   Tam ra   Bhasma   with   main   emphasis   on   biochemical   and   histopathological changes in Wistar albino rats. Study   design:    The   toxicity   study   was   done   by   repeated   dose   on   Wistar   albino   rats.   Animals   were   made   into   three   different   categories   or   groups   which contains   ten   rats   in   each   group.   Group   I   administered   with   0.5%   CMC   &   considered   as   vehicle   control.   Group   II   &   III   administered   with   Tamra   Bhasma   1.98mg/kg   &   9mg/kg   respectively.   These   groups   were   administered   the   specific   drug   Tamra    Bhasma    for   28   consecutive   days.   On   28 th    day   after   one   hour   of last dosing, animals were sacrificed. Data sources and extraction:  The blood and important organs were subjected for biochemical and histopathological examinations. Results:    The   repeated   administration   of   Tamra   Bhasma    didn’t   produce   remarkable   toxicity   at   therapeutic   dose   level.   However   Tamra   Bhasma   at   five   times of   therapeutic   dose   produced   changes   in   biochemical   parameters   such   as   there   is   an   increase   in   the   serum   creatinine   level.   This   was   without   concomitant increase   in   serum   urea   level-   which   was   found   to   be   decreased.   Total   bilirubin   level   was   found   to   be   elevated.      Kidney   sections   from   Tamra   Bhasma   administered   at   5   times   of   TED   has   shown   necrotic   changes   in   the   tubular   epithelium,   vacuolization   oedema   in   the   interstial   tissue   and   focal   cell   infiltration however,   the   cyto-architecture   of   the   other   important   organs   were   not   affected   in   a   drastic   manner.   Conclusion:       The   repeated   administration   of   test   drugs at   therapeutic   dose   level   confirms   their   relative   safety;   however   at   high   dose   level   they   may   have   some   concern   related   to   renal   functioning   and   hence   the benefits of repeated administration of Tamra Bhasma  outweighed the toxic potential. 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