Toxicology is a branch that studies toxins and poisons and their associated effect and treatment. Toxicity testing is an essential component of drug discovery and development. Toxicology (tox) study is crucial for developing new drugs and therapeutic products or extensions of existing molecules. The US FDA has stringent requirements for screening new molecules for their pharmacological activity and toxicity in animal models.
Drug toxicity can examine specific endpoints or adverse events related to cardiotoxicity, cancer, skin irritation, etc. Besides, tox studies are critical in calculating no observed adverse effect levels required to begin clinical investigations. Researchers study toxicity by evaluating accidental exposure, in vitro studies, and in vivo drug exposure in study animals.
The current article describes five surprising facts about toxicological studies.
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History of toxicity studies
The history of tox analysis starts with Paracelsus in 1493. He studied specific chemical effects of toxicity in plants and animals. He demonstrated the beneficial and harmful effects of toxins and established a dose-response association for drug effects. Paracelsus is regarded as the father of toxicology. On the other hand, another researcher, Mathieu Orfila, demonstrated a relationship between toxins and biological properties and showed specific organ damage caused by these toxins. He is often called the father of modern toxicology. Toxicity testing related to individual substances began in the mid-19th century, while environmental toxicity studies started in the mid-20th century.
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Range of different tests
Although toxicology is a single term, it encompasses several tests to evaluate the potential toxicity of a substance. A plethora of toxicity tests include:
- Acute toxicity testing
- Skin sensitization tests
- Repeated dose toxicity evaluation
- Mutagenicity testing
- Chronic and Subchronic oral toxicity testing
- Carcinogenicity testing
- Reproduction toxicity studies
- Toxicokinetic TK studies
- Pharmacokinetic/toxicokinetic (PK/TK) analysis
- Neurotoxicity studies
- Developmental toxicity studies
- Genetic toxicity studies
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Different classifications for toxins
Generally, researchers classify toxicants based on their mode of action, chemical nature, or class (use/exposure). The use class drugs can be classified as therapeutic drugs, pesticides, drugs of abuse, agriculture chemicals, plant toxins, cosmetics, and food additives. On the other hand, the exposure class divides toxins occurring in air, food, soil, or water.
Must Read: Benefits of Shared Good Practices in Laboratories Across Scientific Disciplines
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A dedicated, ethical committee
Before initiating tox studies in animal models or collecting animal samples, researchers should approve the experiment from the institute committee or a local governing body. The guidelines and recommendations for performing experiments and respective regulatory compliances may vary from region to region. Hence, scientists follow protocols and policies published by relevant authorities to maintain experimental animals.
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Animal toxicity studies
Animal toxicological studies started in 1920. It began when JW Trevan proposed using a 50% lethal dose test to identify the deadly levels of individual chemicals. After introducing this test, another FDA scientist, John Draize, developed a test for skin and eye irritation using rabbits. This method was later accepted for testing pharmaceuticals and chemicals on the skin and eye. The US National Cancer Institute later developed a test to determine carcinogenic toxins in mice and rats for two years. In the early 60s, several babies were born with weakening birth defects due to thalidomide. After this issue, regulatory bodies made determining toxicity profiles of pharmaceutical compounds compulsory before beginning clinical trials.
