Regulatory guidelines for Conducting Toxicity studies OECD

This presentation provides an overview of the regulatory guidelines established by the Organisation for Economic Co-operation and Development (OECD) for conducting toxicity studies. It covers key principles, study design, and compliance requirements for assessing chemical safety in pharmaceuticals, food additives, and environmental chemicals.

1. Regulatory guidelines for Conducting Toxicity studies OECD Submitted by: Sant Kumar M.Pharm (2 nd Semester) Department of Pharmaceutical science Gurugram University Submitted to: Prof. Dhirender Kaushik

2. Introduction OECD- Organisation for Economic Co-operation and Development The OECD has developed internationally accepted guidelines for toxicity studies. These guidelines ensure scientific reliability, regulatory compliance and ethical consideration in testing pharmaceutical, chemical and other substances.

3. Acute Toxicity Studies Purpose- Determines the toxic effects of a single dose of a substance within 24 hours. Establishes the lethal dose (LD50) and potential adverse effect. Key OECD Guidelines- OECD 420- Fixed dose procedure (FDP) OECD 423- Acute toxic class methods (ATC) OECD 425- Up and Down procedure Methodology Test animals (usually rats/mice) are administered a single dose. Observed for 14 days for signs of toxicity (weight loss, behavioral changes) Determines the dose response relationship.

4. Repeated Dose Toxicity Studies Purpose - Evaluate toxicity after prolonged exposure (14-90 days). Identifies target organs affected by the chemicals. Key OECD guidelines – OECD 407- 28 days (Subacute toxicity) OECD 408- 90 days (Sub-chronic toxicity) OECD 409- 1 year(Chronic toxicity) Methodology - Animals are exposed daily to different doses of the test compound Parameters monitored- Hematology and Biochemistry LFT & KFT Organ weights (Heart, Liver, Kidney,etc .) Histopathology (Microscopic examination of organs)

5. Genotoxicity studies Purpose - Assess a substances potential to cause DNA damage or mutation. Important for cancer risk evaluation. Key OECD guidelines – OECD 471- Ames test(Bacterial Reverse Mutation test) OECD 473- In vitro chromosomal Aberration test OECD 476- In vitro mammalian cell gene mutation test Methodology – OECD 471(Ames Test)- Uses bacteria (Salmonella) to detect mutations. OECD 473- Examines chromosomal Aberration in mammalian cells. OECD 476- Studies gene mutations in mammalian cell (e.g.- Chinese Hamster ovary cells)

6. Carcinogenicity Studies Purpose - Determines if long-term exposure leads to cancer. Essential for drugs used in chronic condition ( eg - diabetes, hypertension) Key OECD guidelines – OECD 451- Carcinogenicity study OECD 452- Chronic Toxicity study OECD 453- Combined chronic toxicity/Carcinogenicity Methodology – Conducted in rats/mice for 2 years (lifetime exposure) Parameters monitored- Tumour incidence and histopathology Genetic and molecular markers of cancers Biochemical changes (DNA damage, Oxidative stress)

7. Reproductive and developmental toxicity studies Purpose- Evaluate affects on fertility pregnancy and fetal developments Ensures drugs are safe for pregnant women. Key OECD guidelines OECD 414- Prenatal development Toxicity study OECD 415- One generation Reproduction study OECD 416- Two generation Reproduction study Methodology – OECD 414- Pregnant animals exposed to test compound; features examined for abnormalities. OECD 415- Assess effects on male and female fertility OECD 416- Studies multiple generation to detect heritable effects.

8. Eco-toxicity studies Purpose - Assess environmental Toxicity an aquatic and terrestrial organism. Ensure safe disposal of chemicals. Key OECD guidelines – OECD 201- Algal growth inhibition test. OECD 202- Daphnia acute Immobilization test. OECD 203- Fish acute toxicity test. Methodology – OECD 201- Measures growth inhibition in algae due to chemicals. OECD 202- Examines Immobilization and mortality in Daphnia(Water flea) OECD 203- Tests lethal effects on fish species.

9. Toxicokinetic Studies Purpose - Studies the absorption, distribution, metabolism and excretion (ADME) of a drug. Determines drug exposure levels in tissue and plasma. Key OECD guidelines – OECD 417- Toxicokinetics Methodology – Animals administered a radiolabeled drug. Blood, urine and tissue samples analyzed for metabolites profiling.

10. Ethical Considerations: Good Laboratory Practice (GLP) OECD GLP guidelines ensure- Reliability and reproducibility of studies Animal welfare (reducing suffering) Regulatory compliance with FDA, EMA, CDSCO. Alternative methods encouraged- OECD 431- In vitro skin corrosion test OECD 432- In vitro photo toxicity test

11. Conclusion The OECD toxicity study guidelines ensure human safety, environmental protection and regulatory approval. These studies are mandatory for drug development and help assess risks before clinical trials.

12. References OECD Guidelines for the Testing of Chemicals URL:-https://www.oecd.org/chemicalsafety/testing/oecdguidelinesforthetestingofchemicals.htm OECD provides standardized test methods for assessing chemical hazards, widely used by regulatory agencies globally. Good Laboratory Practice (GLP) – OECD Principles Reference: OECD, "OECD Principles of Good Laboratory Practice (GLP)", Series on Principles of GLP and Compliance Monitoring URL: https://www.oecd.org/chemicalsafety/testing/good-laboratory-practiceglp.htm Ensures quality and integrity of toxicity studies used in regulatory submissions.

13. OECD Test Guidelines for Toxicity Studies Covers acute, subacute, chronic, reproductive, and developmental toxicity tests. Full List: https://www.oecd.org/env/ehs/testing/oecd-guidelines-testing-chemicals-section4-health-effects.htm OECD Mutual Acceptance of Data (MAD) System. Reference: OECD "Mutual Acceptance of Data (MAD) in the Assessment of Chemicals“ URL: https://www.oecd.org/chemicalsafety/mutualacceptanceofdatamad.htm Ensures data generated in one OECD country is accepted by others, reducing duplication of animal testing .