Repeated-dose 90-day Oral Toxicity Studies on Whole ... - Europabio
Repeated-dose 90-day Oral Toxicity Studies on Whole ... - Europabio
Repeated-dose 90-day Oral Toxicity Studies on Whole ... - Europabio
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1. Defining toxicologically<br />
relevant differences<br />
• As per guidance, relevant endpoints, c<strong>on</strong>sistent with OECD TG<br />
408, will be m<strong>on</strong>itored.<br />
– TG 408 specifies that each test animal will be m<strong>on</strong>itored <strong>on</strong> >200 individual<br />
endpoints.<br />
– Ensures a thorough examinati<strong>on</strong> of the whole animal and that known<br />
mechanisms of toxicity will be evaluated.<br />
• Toxicologists will review the data for c<strong>on</strong>sistent trends in related<br />
endpoints associated with toxic mechanisms.<br />
– ↑ serum ALT, ↑ liver weight, histopathological altera<strong>on</strong>s of liver ssue.<br />
– ↑ serum ALT, in the absence of other indica<strong>on</strong>s of liver damage, is of equivocal<br />
importance.<br />
• To reach scientifically valid c<strong>on</strong>clusi<strong>on</strong>s, the weight of evidence<br />
must be c<strong>on</strong>sidered to determine if the difference observed is<br />
treatment-related.<br />
11
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