Additional toxicological studies

Each new drug may have a lot of unfavorable and even dangerous adverse effects. One of these properties of the drug which are of concern to both a physician and a patient is its ability to cause toxic effect on human body. However before the drug may be used in clinical practice, laboratories should check out its safety and conduct the appropriate toxicological studies.

Goals and methods of chemical toxicological studies

It should be understood that not all drugs may cause acute intoxication. Development of sub-acute and chronic toxicity is also possible. Chemical toxicological studies are performed in laboratory animals to reveal the ability of a substance to cause these phenomena.

To evaluate the pathological influence of the drug on the organism of experimental animal the following methods are used:

  • general blood analysis (hematological and biochemical), urine analysis;
  • electrocardiography;
  • nervous system state diagnostics;
  • identification of locally irritating action;
  • evaluation of skin-resorptive effect;
  • determination of general animal state and state of separate organs and systems;
  • histopathological methods.

After conducting chemical toxicological studies the final decision about drug toxicity and possibility of its usage in clinical practice is made. Then additional chemical toxicological studies are carried out to accurate toxic and lethal doses, adverse effects and other unfavorable effects.

The appropriate chemical toxicological study that was properly conducted allows avoiding the use of toxic drugs in practice and providing complete safety of a patient throughout treatment.

Additional toxicological studies are performed in accordance with OECD protocols for testing of chemicals:

417 Toxicokinetics
424 Neurotoxicity Study in Rodents
426 Developmental Neurotoxicity Study
427 Skin Absorption: In Vivo method
428 Skin Absorption: In Vitro method
432 In Vitro 3T3 NRU Phototoxicity test
435 In Vitro Membrane Barrier Test Method for Skin Corrosion
440 Uterotrophic Bioassay in Rodents: Short-term screening test for the detection of estrogenic properties
441 Hershberger Bioassay in Rats: A Short-term Screening Assay for (Anti)Androgenic Properties
456 H295R Steroidogenesis Assay

 Сardiotoxicity assessment in guinea pigs by a method of ECG changes (ICH S7B; Current protocols in pharmacology, 2009)

Electrocardiogram parameters of healthy guinea pigs, М±m






HR/min 315±9 324±8
RR, msec 192±5 198±4
P, msec 43±2 45±3
P, mV 0.09±0.01 0.09±0.01
PQ, msec 62±2 64±2
QRS, msec 55±1 53±2
R, mV 0.47±0.03 0.48±0.02
S, mV 0.10±0.01 0.08±0.01
ST, msec 71±2 76±3
ST, mV 0.06±0.01 0.05±0.01
QT, msec 109±2 113±5