Toxicity studies

Toxicity studies

1. Toxicity studies Submitted by , Pavithra.P (117011101298) Pavithra.T (117011101299) Pooja.K (117011101300) 03-04-2020 B.Tech (biotechnology) 1

2. Toxicity: Any adverse effect that a chemical or physical agent might produce within a living organism. Toxicity studies are carried out on all putative new drugs,largely via testing in animals . 03-04-2020 B.Tech (biotechnology) 2

3. History of toxicity studies: Paracelsus (Father of Toxicology) determined specific chemicals responsible for the toxicity of plants and animals. “All substances are poisons;there is none which is not a poison.The right dose differentiates a poison and a remedy”. Mathieu orfila (Father of modern toxicology) determined relationship between poisons and their biological. 03-04-2020 B.Tech (biotechnology) 3

4. Necessties : Benefit-risk ratio can be calculated Prediction of therapeutic index Therapeutic index = maximum tolerated dose minimum curative dose Smaller ratio ,better safety of the drug. 03-04-2020 B.Tech (biotechnology) 4

5. Types of toxicity: Acute toxicity Sub-acute toxicity Sub-chronic toxicity Chronic toxicity 03-04-2020 B.Tech (biotechnology) 5

6. Acute toxicity: It refers to those adverse effects occurring following oral or dermal administration of a single dose of a substance , or multiple doses given within 24 hours . Objective: To determine Maximum Tolerated Dose(MTD) and No Observable Effect Level (NOEL ). To Identify parameters for clinical monitoring. To identify potential target organs for toxicity. 03-04-2020 B.Tech (biotechnology) 6

7. Duration : Few days to 2 weeks after a single dose Test system: 2 species required – Mice,Rats or sometimes rabbits or dogs. Dose Administration: Oral Inhalation Intravenous Intranasal Intradermal 03-04-2020 B.Tech (biotechnology) 7

8. Parameters : Mortality Clinical pathology Weight change Gross necropsy Signs of toxicity 03-04-2020 B.Tech (biotechnology) 8

9. Sub acute toxicity: It resembles acute toxicity except that the exposure duration is greater,from several days to one month . Objective: To determine toxicity after repeated administration of the test material. To help establish doses for sub-chronic studies. Duration : 14 days Test system: 2 species required: Mice,Rats,Rabbits,Dogs. 03-04-2020 B.Tech (biotechnology) 9

10. Dose administration: 3 to 4 doses given by the same routes as previous toxicity tests. Parameters : Histopathology Clinical pathology Weight change Mortality 03-04-2020 B.Tech (biotechnology) 10

11. Subchronic toxicity: It is the toxic exposures repeated or spread over an intermediate time range (1-3 months) Objective: To establish a “no observable effect level”(NOEL) To identify and characterize specific organs affected after repeated administration To predict a reasonable and appropriate dose for chronic exposure studies Duration: Commonly 90 days,but varies from 2 weeks to 6 months or upto 10% of species lifespan. 03-04-2020 B.Tech (biotechnology) 11

12. Test system: 2 species required : Rodents, dogs Dose administration: At least 3 doses given by the same routes as previous toxicity tests;the lowest producing no apparent toxicity and the highest producing toxicity but less than or equal to 10% mortality. Parameters: Mortality Weight change Clinical pathology Signs of toxicity 03-04-2020 B.Tech (biotechnology) 12

13. Chronic toxicity: It is the exposures (either repeated or continuous ) over a long period of time(greater than 3 months). Objectives: To evaluate the cumulative toxicity of chemicals. To assess carcinogenic potential Test system: 2 species required: Rodents , dogs 03-04-2020 B.Tech (biotechnology) 13

14. Duration : Rodents – 6 to 24 months Non-rodents – 12 months or longer upto 10% of species lifespan. Length depends on intended period of human exposure. Dose administration: As in subacute/ subchronic toxicity studies Parameters : Pathology and histopathology Weight change Clinical pathology of all animals Mortality 03-04-2020 B.Tech (biotechnology) 14

15. Reference: Biopharmaceutical second edition – Gary Walsh 03-04-2020 B.Tech (biotechnology) 15

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