Format: MS WORD Chapters: 1-4
Pages: 63 Attributes: **
Toxicology is a branch of science that deals with toxins and poisons and their effects and treatment. Toxicological screening is very important for the development of new drugs and for the extension of the therapeutic potential of existing molecules. The US Food and Drug Administration (FDA) states that it is essential to screen new molecules for pharmacological activity and toxicity potential in animals (Parasuraman, 2011). The toxic effects of chemicals, food substances, pharmaceuticals, etc., have attained great significance in the 21st century. This brief review focuses on the historical importance of toxicological screening and alternative and specific methods using various experimental animal models. Toxicity tests are mostly used to examine specific adverse events or specific end points such as cancer, cardiotoxicity, and skin/eye irritation. Toxicity testing also helps calculate the No Observed Adverse Effect Level (NOAEL) dose and is helpful for clinical studies (Setzer and Kimmel, 2013).
1.2 History Of Toxicity Studies
The history of toxicity studies begins with Paracelsus (1493–1541), who determined specific chemicals responsible for the observed toxicity of plants and animals. He demonstrated the harmless and beneficial effects of toxins and proved dose-response relationships for the effects of drugs (Parasuraman, 2011). Paracelsus, who was a physician, alchemist, and astrologer, is widely regarded as the father of toxicology. The following statement of his is often quoted: “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.” Mathieu Orfila (1787–1853), a Spanish physician, determined the relationship between poisons and their biological properties and demonstrated specific organ damage caused by toxins. Orfila is referred to as the father of modern toxicology. Toxicological screening methods and toxicological research on individual substances developed in the mid-1900s, and environmental toxicological studies developed in the mid-20th century (Hunter, 2018).
The use of animals in toxicity studies began in 1920, when J. W. Trevan proposed the use of the 50% lethal dose (LD50) test to determine the lethal dose of individual chemicals. After the introduction of LD50, a FDA scientist John Draize developed a method for testing eye and skin irritation using rabbits, and this method was widely accepted for testing the effects of chemicals and pharmaceuticals on the eye and skin. Later, the US National Cancer Institute (NCI) developed a test to identify carcinogenic chemicals through the daily dosing of rats and mice for 2 years. In the early 1960s, thousands of babies were born with debilitating birth defects caused by thalidomide. After this, all the regulatory agencies concentrated on determining the toxicity profiles of all pharmaceutical substances available for regular patient use and made mandatory the submission of toxicity profiles of investigational new drugs (IND). In the late 1980s, the Organisation for Economic Co-operation and Development (OECD) and the International Conference on Harmonization (ICH) brought out the guidelines for toxicity testing of pharmaceutical substances (Parasuraman, 2011).
3.1 Acute Toxicity Testing
Acute toxicity testing is carried out to
determine the effect of a single dose on a particular animal species. In
general, it is recommended that acute toxicity testing be carried out with two
different animal species (one rodent and one non-rodent). In acute
toxicological testing, the investigational product is administered at different
dose levels, and the effect is observed for 14 days. All mortalities caused by
the investigational product during the experimental period are recorded and
morphological, biochemical, pathological, and histological changes in the dead
animals are investigated. Acute toxicity testing permits the 50% lethal dose
(LD50) of the investigational product to be determined. The LD50
was used as an indicator of acute toxicity previously. The determination of the
LD50 involves large numbers of animals, and the mortality ratio is
high (Parasuraman, 2011).
Booth, A., Amen, R. J., Scott, M. and Greenway, F. L. (2011). Oral dose-ranging developmental toxicity study of an herbal supplement (NT) and gallic acid in rats. Advances in Therapy, 27: 250–255.
Charnley, G. (2012). "Ames Test". Encyclopedia of Public Health, 5: 45.
Curren, R. D. and Harbell, J. W. (2016). In vitro alternatives for ocular irritation. Environmental Health Perspectives, 106: 485–92.
Derelanko, M. J. and Auletta, C. S. (2014), Handbook of Toxicology (3rd ed.), CRC Press, ISBN 978-1-4398-9014-1.
Diallo, A., Eklu-Gadegkeku, K., Agbonon, A., Aklikokou, K., Creppy, E. E. and Gbeassor, M. (2016). Acute and sub-chronic (28-day) oral toxicity studies of hydroalcohol leaf extract of Ageratum conyzoides L (Asteraceae). Tropical Journal of Pharmaceutical Research, 9: 463–7.
Eastmond, D. A., Hartwig ,A., Anderson, D., Anwarb, W. A., Cimino, M. C. and Dobrev, I. (2017). Mutagenicity testing for chemical risk assessment: Update of the WHO/IPCS Harmonized Scheme. Mutagenesis, 24: 341–9.
Ganiger, S., Malleshappa, H. N., Krishnappa, H., Rajashekhar, G., Ramakrishna Rao, V. and Sullivan, F. (2017).. A two generation reproductive toxicity study with curcumin, turmeric yellow, in Wistar rats. Food Chemistry and Toxicology, 45: 64–9.
Gholami, S., Soleimani, F., Shirazi, F. H., Touhidpour, M. and Mahmoudian, M. (2016). Evaluation of mutagenicity of mebudipine, a new calcium channel blocker. Iran Journal of Pharmaceutical Research, 9:49–53.
Gregory, C. W. (2014). Exposure classes, toxicants in air, water, soil, domestic and occupational settings. In: Hodgson E, editor. A textbook of modern toxicology. 3rd ed. New Jersey: John Wiley and Sons, pp345.
Hofmann, T., Horstmann, G. and Stammberger, I. (2012). Evaluation of the reproductive toxicity and embryotoxicity of insulin glargine (LANTUS) in rats and rabbits. International Journal of Toxicology, 21:181–189.
Hunter, P. (2018). A toxic brew we cannot live without. Micronutrients give insights into the interplay between geochemistry and evolutionary biology. EMBO Reports, 9: 15–8.
Jaijoy, K., Soonthornchareonnon, N., Lertprasertsuke, N., Panthong, A. and Sireeratawong, S. (2011). Acute and chronic oral toxicity of standardized water extract from the fruit of Phyllanthus emblica Linn. International Journal of Applied Science and Biology, 3: 48–58.
Kimm-Brinson, K. and Ramsdell, J. S. (2011). The red tide toxin, brevetoxin, induces embryo toxicity and developmental abnormalities. Environmental Health Perspectives, 109: 377–381.
Luzhna, L., Kathiria, P. and Kovalchuk, O. (2013). "Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond". Frontiers in Genetics, 4: 131.
Matsuura, I., Saito, T., Tani, E., Wako, Y., Iwata, H. and Toyota, N. (2015). Evaluation of a two-generation reproduction toxicity study adding endopoints to detect endocrine disrupting activity using lindane. Journal of Toxicological Science, 30: 135–61.
Mortelmans, K. and Zeiger, E. (2011). "The Ames Salmonella/microsome mutagenicity assay". Mutation Research, 455(1–2): 29–60.
Muralidhara, S., Ramanathan, R., Mehta, S. M., Lash, L. H., Acosta, D. and Bruckner, J. V. (2011). Acute, subacute, and subchronic oral toxicity studies of 1,1-dichloroethane in rats: Application to risk evaluation. Toxicological Science, 64:135–45.
OECD (Organization for Economic Cooperation and Development). (2011). Acute Inhalation Toxicity. Guideline for testing of chemicals, 2: 1-14.
Oliveira, C. D., Moreira, S. Q,. Marques de Sá, L. R., Spinosa, H. and Yonamine, M. (2011). Maternal and developmental toxicity of ayahuasca in Wistar rats. Birth Defects Research B, Developmental and Reproductive Toxicology, 89: 207–12.
Parasuraman, S. (2011). Toxicological screening. Journal of Pharmacology and Pharmacotherapy, 2(2): 74–79.
|BANKING AND FINANCE||11|
|CONSTRUCTION AND BIULDING||1|
|ELECTRICAL AND ELECTRONICS||1|
|ENGLISH LITERARY STUDIES||29|
|GEOGRAPHY AND PLANNING||1|
|HOM SCIENCE AND MANAGEMENT||3|
|LIBRARY AND INFORMATION SCIENCE||4|
|OFFICE TECHNOLOGY AND MANAGEMENT||21|
|SCIENCE LABORATORY TECHNOLOGY||19|
|SOIL AND ENVIRONMENTAL SCIENCE||1|
No data found...