Repeated-dose 90-day Oral Toxicity Studies on Whole ... - Europabio

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Challenges in study design and conduct 1. Designing for appropriate power 2. Experimental design and conduct a) Practical aspects regarding cage location b) Variation controls 3. Housing conditions and impact on the Experimental Unit (ExpU) 4. Statistical power investigation 10
1. Defining toxicologically relevant differences • As per guidance, relevant endpoints, consistent with OECD TG 408, will be monitored. – TG 408 specifies that each test animal will be monitored on >200 individual endpoints. – Ensures a thorough examination of the whole animal and that known mechanisms of toxicity will be evaluated. • Toxicologists will review the data for consistent trends in related endpoints associated with toxic mechanisms. – ↑ serum ALT, ↑ liver weight, histopathological alteraons of liver ssue. – ↑ serum ALT, in the absence of other indicaons of liver damage, is of equivocal importance. • To reach scientifically valid conclusions, the weight of evidence must be considered to determine if the difference observed is treatment-related. 11
Page 1 and 2: Repeated-d
Page 3 and 4: Existing safety data and the weight
Page 5 and 6: Hazard Identification and multiple
Page 7 and 8: Section summary • EuropaBio Membe
Page 9: Part 1: Study design and conduct 9
Page 13 and 14: 1. Endpoints and effect sizes Endpo
Page 15 and 16: 1. Toxicological endpoints for powe
Page 17 and 18: 2. Experimental design • EFSA gui
Page 19 and 20: 2. Experimental design (continued)
Page 21 and 22: 2. Section summary/discussion • E
Page 23 and 24: 3. Group or single housing (continu
Page 27 and 28: 4. Endpoints and effect sizes Endpo
Page 29 and 30: 4. Average coefficients of variatio
Page 31 and 32: 4. Analysis details • For the 3-t
Page 33 and 34: 4. Results 1 animal/cage, 3 treatme
Page 35 and 36: 4. Results 2 animals/cage, 3 treatm
Page 37 and 38: 4. Provisos for power analyses •
Page 39 and 40: 4. Should males and females be anal
Page 41 and 42: Part 2: Study analysis and interpre
Page 43 and 44: 1. Toxicological interpretation •
Page 45 and 46: 2. Presentation of results on the s
Page 49 and 50: 3. Summary statistics and raw analy
Page 51 and 52: 3. Section summary/discussion • P
Page 53 and 54: References • EFSA. 2011c. Guidanc
Page 55 and 56: References • WHO. 2003. GEMS/FOOD

Repeated-dose 90-day Oral Toxicity Studies on Whole ... - Europabio

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