Primary Observation (Irwin) Test in Rodents for Assessing Acute Toxicity of a Test Agent and its Effects on Behavior and Physiological Function

Sylvain Roux1, Evelyne Sablé1, Roger D. Porsolt1

1 Porsolt & Partners Pharmacology, Z.A. des Suhards, Le Genest‐Saint‐Isle
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 10.10
DOI:  10.1002/0471141755.ph1010s27
Online Posting Date:  January, 2005
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Abstract

The Irwin observation test is commonly used to evaluate the effects of a new substance on behavior and physiological function. The results of the Irwin test are used to determine potential toxicity and to select doses for specific therapeutic activity. The Irwin test can also be used in a safety approach for detecting untoward effects of a new compound on general behavior and for evaluating its acute neurotoxicity. In particular, data obtained in the Irwin Test can help to determine the dose range to be tested in other safety tests. Furthermore, the Irwin Test can furnish a first but pertinent orientation towards a specific therapeutic indication, a specific mechanism of action or a specific physiological function.

Keywords: Irwin test; general behavior; physiological function; safety pharmacology

     
 
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Table of Contents

  • Basic Protocol 1: Primary Observation (Irwin) Test in the Rat
  • Alternate Protocol 1: Primary Observation (Irwin) Test in the Mouse
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Primary Observation (Irwin) Test in the Rat

  Materials
  • Male Wistar (Han) rats, supplied by Elevage Janvier (http://www.janvier‐breedingcenter.com), 2 to 3 months old, 180 to 250 g
  • Test compound(s) (see recipe)
  • Macrolon cages (41 × 25 × 14 cm) with wood litter
  • Animal balance, accurate to 1 g (e.g., Sartorius model 1401.001.2)
  • Binocular lamp (Bausch & Lomb, × 2, supplied by Cambridge Instruments) for measuring pupil diameter
  • Digital laboratory thermometer (Physitemp Model BAT‐12) with rat rectal probe
  • 5‐ml Terumo syringes, type B5‐05S, to administer the test substance
  • 25‐G, 5/8‐in. (0.5 × 16 mm) Terumo needles for intraperitoneal and subcutaneous administration
  • Gastric probes with olive extremity for oral administration (length, 76 mm, ø, 3 mm; BIOSEB model FNS‐16‐2)
  • Double bar fixed on two vertical supports for traction measurement (27 cm length, 27 cm height (first bar), 40 cm height (second bar), and 0.4 cm diameter (both bars), custom made (see Fig. )
  • Metal forceps for measurement of analgesia (tail pinch)
  • A wire metal grid mounted on a wood frame (20 × 45 cm; grid units 2 mm), custom made, for measurement of grasping and akinesia

Alternate Protocol 1: Primary Observation (Irwin) Test in the Mouse

  • Male NMRI mice, supplied by Elevage Janvier (http://www.janvier‐breedingcenter.com), 18 to 25 g
  • Macrolon cages (32 × 14 × 13 cm) with wood litter
  • 1‐ml Terumo syringes, type BS01T to administer the test substance.
  • Digital laboratory thermometer (Physitemp Model BAT‐12) with mouse rectal probe
  • Gastric probes with olive extremity for oral administration (length, 38 mm, ø, 1.4 mm; BIOSEB model FNS‐22‐1.5)
  • Single metal bar fixed on two vertical supports for traction measurement (20 cm length, 18 cm height, and 0.4 cm diameter), custom‐made (Fig. )
For this protocol, follow steps to of the protocol 1 substituting the abovementioned mouse strain for the rats and substituting the abovementioned materials for their counterparts in the protocol 1, with the following modifications at the indicated steps.
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Figures

Videos

Literature Cited

Literature Cited
   Irwin, S. 1968. Comprehensive observational assessment: A systematic quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 13:222‐257.
   Moser, V.C., Cheek, B.M., and McPhail, R.C. 1995. A multidisciplinary approach to toxicological screening. Neurobehavioral toxicology. J. Toxicology Environ. Health 45:173‐210.
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