Repeated dose toxicity in rodent

Aim: Assess tolerability and toxicity profile of the test item after repeated dose administration (various routes available) to rodents.

Background information: Repeated dose toxicity studies are part of the nonclinical safety studies recommended by Regulatory Authorities for the evaluation and registration of pharmaceuticals (ICH M3 (R2)). The goals of the nonclinical safety evaluation include a characterization of potential toxic effects with respect to targets organs, dose dependence, relationship to exposure, and, when appropriate, potential reversibility.

The information gained from preliminary non GLP studies allows determining the Maximum Tolerated Dose (MTD) and provides the basis for the selection of dose levels for subsequent pivotal GLP repeated dose toxicity studies.

In this assay, groups of animals are daily administered at different dose levels of the test item or the formulation vehicle (control group). The safety assessment is based on a series of in-life observations and terminal procedures at end of the treatment period.

While GLP-compliance will not be made for the study, the used laboratory procedures will be consistent with International Standards of GLP and will be performed in accordance with Welab Barcelona Standard Operating Procedures (SOPs) and Working Instructions (WIs).

Animal species: mice or rats

Compound requirement: according to test species & dose levels

Turnaround time: 4 weeks after experimental completion date (includes histopathology)

Experimental procedure

  • 3 to 5 animals/sex/group, dosed test item or formulation vehicle
  • Route of administration: as per clinical use
  • In-life observations:
  • Clinical signs
  • Body weights
  • Food consumption
  • Clinical pathology: haematology, biochemistry and coagulation
  • Necropsy procedures:
  • Macroscopic examination of organs and tissues
  • Organ weights
  • Histopathology (selected tissues)
  • Proof of exposure (parent and/or metabolites): toxicokinetics group
  • Formulation analysis: on request

Delivered results

  • Determination of the Maximum Tolerated Dose
  • Assessment of potential adverse effects and target organs of toxicity
  • Proof of exposure (toxicokinetics)