Division of Toxicology

Toxicology division is a premier laboratory in the country in the field of biomaterial toxicology, and has a full-fledged facility for the pre-clinical evaluation of various materials and medical devices as per International Standards like ISO, USP and ASTM. The main aim of the division is the toxicity evaluation of materials, intended for the fabrication of medical devices and to investigate the potential biological hazards by careful observation for unexpected adverse reactions or events in humans during clinical use of the medical device. The Pre-clinical toxicity/biocompatibility/safety studies of medical devices, pharmaceuticals, nanomaterials and tissue engineered products are accredited by COFRAC France as per ISO 17025.

The development of an " In vitro pyrogen test kit" for the evaluation of pyrogenicity using human whole blood" project is in the stage of successful completion. This new development will be an ELISA method for pyrogen test and will be suitable for evaluating wide spectrum of applications to measure the undetected non endotoxin pyrogens, such as pyrogens of any chemical or biological nature.

A new project entitled "Evaluation of molecular toxicity of newly developed materials intended for biomedical applications" is ongoing under the support of Indian Council of Medical Research (ICMR), New Delhi. The objective of the project is to evaluate the molecular level toxicity of the six newly developed materials and their chemical leachants on mtDNA, antioxidant enzymes, lipid peroxidation and cytogenetic effects. The expected out come of the project will be a cardinal change in approach to biocompatibility evaluations leading to a paradigm shift in bringing in newer regulations for development of safer medical devices, implants and tissue engineered organs for life time application.

Faculty

Dr. Remya N. S.

Facilities

Small animal surgery theatre, full-fledged facility in conducting GLP studies for biocompatibility, material toxicity, nanomaterial toxicity, pyrogenicity, genotoxicity, short, long term toxicity studies, carcinogenicity, teratogenicity and chronic toxicity studies.

HPLC, Affinity Chromatography, Metafer for Chromosome analysis and Karyotyping, ELISA reader, PCR, Ultra speed Refrigerated centrifuge, Motorized Microscope, Computer attached Microscope, Inverted microscope, Incubators, CO2 incubator, Laminar benches, -20 and -80 deepfreezer, electronic balances, high sensitivity thermometer, computerized autoclave system, homogenizer, lyophilizer, semi automated biochemical analyzer.

Services

Following Toxicity testing services offered.

Accredited tests (ISO 10993, USP and ASTM protocols)

1. Closed patch test for delayed hypersensitivity
2. Maximization test for delayed hypersensitivity
3. Intracutaneous Test
4. Acute systemic toxicity test
5. Test for local effects after Implantation in muscle
6. Pyrogen Test
7. Vaginal irritation Test
8. Penile irritation test
9. In vivo Mammalian chromosomal Aberration test
10. In vivo Mammalian erythrocyte micronucleus test
11. Test for local effects after implantation in bone
12. Test for local effects after implantation in subcutaneous tissue
13. Animal skin irritation Test
14. Assessment of Haemolytic properties
15. Extraction of materials

Non accredited tests (ISO 10993, USP and ASTM protocols or as per study plan)

1. Subchronic toxicity in rats/mice
2. Chronic toxicity in rats/mice
3. Cracinogenicity in rats
4. Haemolysis
5. Intraperitoneal implantation
6. Knee joint implantation
7. Immunization study
8. Safety study in mice
9. Calvarial defects
10. Implantation in brain (rat)
11. In vitro chromosomal aberration using human blood
12. In vitro micronucleus test using human blood
13. Limulus Amebocyte Lysate test (LAL)
14. Physico-chemical analysis of potable water

Projects/Consultancies

As Principal Investigator

As Co-Investigator

Regulatory Studies as Study Director

1. Evaluation of Chronic toxicity (12 months) by intraperitoneal implantation of degradable Polycaprolactone (PCL) based scaffold in wistar rats.
   Status : Ongoing
2. 90 day sub-chronic toxicity by intraperitoneal implantation of degradable Polycaprolactone (PCL) based scaffold in wistar rats.
   Status : Ongoing
3. Evaluation of long term biocompatibity of degradable Polycaprolactone (PCL) based scaffold in albino rabbits.
   Status : Ongoing
4. Toxicity study of Stent materials
   Status : Completed
5. Evaluation of the hemostatic efficiency of Poly [ß-(1,4)-2-amino-2-deoxy-D-glucosamine], based Haemostatic dressing in albino rabbits
   Status : Completed
6. Acute, sub acute and sub chronic oral toxicity of a composite dug HIVS2004
   Status : Completed
7. Repeated dose 90 day Oral toxicity study of Polymeric nanoparticle - NMITLI -BST001 in rats
   Status : Completed
8. Biological evaluation of collagen based Biomaterials
   Status : Completed
9. Evaluation of the efficacy of Recombinant platelet-derived growth factor on healing of experimentally induced surgical wounds in Sprague dawley rats.
   Status : Completed

Publications

1. Mohanan PV, Leo Mavely, Ashish Pandya (2010). Toxicity and Haemostatic potential of Poly [ß- (1, 4)- 2-amino-2-deoxy-D-glucosamine] based haemostatic material on albino rabbits. Toxicology mechanisms and methods, USA (in press)
2. Mohanan PV, Siddarth Banerjee, Geetha CS (2010). An indigenously developed human whole blood assay for pyrogenicity: A comparative assessment. Toxicology letters, 196(S), S131 (doi: 10.1016/j.toxlet.2010.03.457)
3. Joseph J, Mohanty M, Mohanan PV (2010) Role of immune cells and inflammatory cytokines in regulation of fibrosis around silicone expander implants. J Mater Sci Mater Med. 21(5):1665-76.
4. Joseph J, Mohanty M, Mohanan PV (2010) Investigative study of myofibroblasts and cytokines in peri-implant tissue of silicone breast expander by rt-PCR in a rat model. J Biomater Sci Polym Ed. 2010;21(10):1389-402 .
5. Shekhar Nath, Bikramjit Basu, Mira Mohanty, PV. Mohanan (2009) In vivo response of novel calcium phosphate-mullite composites: results upto 12 weeks of implantation. J Biomed Mater Res. Part B: Appl Biomater 90(B), 547-557.
6. Sunny MC, Ramesh P, Mohanan PV, George KE (2009) Metallocene based polyolefin: a potential candidate for the replacement of flexible poly (vinyl chloride) in the medical field. Polym. Adv. Technol.(www.interscience. wiley.com) DOI: 10.1002/pat.1475.
7. Sumithra G, Mohanan PV (2009) Quantitative measurement of endotoxin, haemolysis and water extractable protein from four brands of surgical latex gloves. Toxicol. Int.Vol. 16 (1), 77-80
8. Reeja Rajab, Mohankumar C, Murugan K, Harish M, Mohanan PV (2009) Purification and toxicity studies of stevioside from Stevia rebaudiana Bertoni. Toxicol. Int.Vol. 16 (1), 49-54.
9. Sumithra G, Mohanan PV (2008) Cytotoxic potential and identification of dithiocarbamate from four brands of surgical latex gloves. J. Ecophysiol. Occup. Hlth. 8, 249-256
10. Sailaja GS, Mohanty M, Kumary TV, Mohanan PV, Ramesh P, Varma HK (2008) Surface Phosphorylated Copolymer promotes direct bone bonding. Tissue engineering Part A. (doi: 10.1089/ten.TEA, 2008.0454)

Patents

Development of an "In vitro pyrogen test kit" for the evaluation of pyrogenicity using human whole blood, By Mohanan PV, Siddharth Banerjee, Muralidharan CV, Lissy K Krishnan and Bhuvaneshwar GS (applied)

Research

Pre-clinical evaluation of various materials and medical devices as per International Standards such as ISO, USP and ASTM. The main aim of the division is the toxicity evaluation of materials, intended for the fabrication of medical devices and to investigate the potential biological hazards by careful observation for unexpected adverse reactions or events in humans during clinical use of the medical device.

The "development of an In vitro pyrogen test kit for the evaluation of pyrogenicity using human whole blood" project is completed and is under validation. This new development is an ELISA method for pyrogen test and will be suitable for evaluating wide spectrum of applications to measure the undetected non endotoxin pyrogens, such as pyrogens of any chemical or biological nature. The project is initially supported by DBT, New Delhi and now by the Institute.

A new project entitled "Evaluation of molecular toxicity of newly developed materials intended for biomedical applications" is ongoing under the support of Indian Council of Medical Research (ICMR), New Delhi. The objective of the project is to evaluate the molecular level toxicity of the six newly developed materials and their chemical leachants on mtDNA, antioxidant enzymes, lipid peroxidation and cytogenetic effects. The expected out come of the project will be a cardinal change in approach to biocompatibility evaluations leading to a paradigm shift in bringing in newer regulations for development of safer medical devices, implants and tissue engineered organs for life time application.

Research activities on short term and long term toxicity and immuno - toxicological effects of Dextran coated Ferrite and Hydroxylapitite nanomaterials are ongoing (supported by Nanomission, DST, New Delhi).

In Vitro alternative test system development for toxicity tests are another area of interest (supported by ICMR, New Delhi).

In vivo and in vitro genotoxicity studies on nanoparticles are established and regularly doing.

Toxicology of degradable material (scaffold) in wistar rats

Following research activities on biomaterials are ongoing;

Immunotoxicology using T and B lymphocyte proliferation assay.

Evaluation of Cytokines

Isolation of mtDNA and identification of DNA damage from whole blood and tissues using HPLC method..

The Development of National GLP Guidelines & Identification and selection of National Regulatory Guidelines for Testing and Evaluation of Medical Devices is ongoing. A Road map for this is made and action plan started. This is supported by the National GLP Compliance Monitoring Authority, Dept. of Science and Technology, New Delhi

Staff

Name, Designation

Hari Kumar G., Lab. Animal Attendant

Reeja Rani D.C., Sr. Technical Asst. (Lab)

Shaji S., Lab. Animal Caretaker - C

Sobhana Karumathil, Unit Helper - B