Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

I F Nam,V V Zhuk

doi:10.1088/1757-899x/81/1/012092

Abstract

Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

Highlights

According to the rules governing medical products in Russian Federation the novel active pharmaceutical ingredient and all pharmaceuticals based on it are liable to toxicological studies
Toxicological studies consist of general toxical action studies and specific toxicities
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short space of time during a 24 hours [2]

Summary

Introduction

According to the rules governing medical products in Russian Federation the novel active pharmaceutical ingredient and all pharmaceuticals based on it are liable to toxicological studies. Toxicological studies consist of general toxical action studies and specific toxicities. Toxicity studies involve wide range of tests in different species with regular monitoring for physiological or biometrical abnormalities observed in long-term administration of the drugs. General toxical action of the drug determined in acute and subacute toxicity studies. The aim of acute toxicity studies is to estimate no observed adverse effect dose, maximum tolerated and lethal doses and get experimental animal mortality analysis. Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short space of time (usually less than 6 hours) during a 24 hours [2]

Objectives

Methods

Results