Toxicology

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Toxicology is a discipline, overlapping with biology, chemistry, pharmacology, medicine, and nursing, that involves the study of the adverse effects of chemical substances on living organisms[1] and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage (and whether it is acute or chronic), route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning.

History

Lithograph of Mathieu Orfila

Dioscorides, a Greek physician in the court of the Roman emperor Nero, made the first attempt to classify plants according to their toxic and therapeutic effect.[2] Ibn Wahshiyya wrote the Book on Poisons in the 9th or 10th century.[3] This was followed up in 1360 by Khagendra Mani Darpana.[4]

Mathieu Orfila is considered the modern father of toxicology, having given the subject its first formal treatment in 1813 in his Traité des poisons, also called Toxicologie générale.[5]

In 1850, Jean Stas became the first person to successfully isolate plant poisons from human tissue. This allowed him to identify the use of nicotine as a poison in the famous Bocarmé murder case, providing the evidence needed to convict the Belgian Count Hippolyte Visart de Bocarmé of killing his brother-in-law.[6]

Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493–1541) (also referred to as Paracelsus, from his belief that his studies were above or beyond the work of Celsus – a Roman physician from the first century) is also considered "the father" of toxicology.[7] He is credited with the classic toxicology maxim, "Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist." which translates as, "All things are poisonous and nothing is without poison; only the dose makes a thing not poisonous." This is often condensed to: "The dose makes the poison" or in Latin "Sola dosis facit venenum".[8]:30

Basic principles

The goal of toxicity assessment is to identify adverse effects of a substance.[9] Adverse effects depend on two main factors: i) routes of exposure (oral, inhalation, or dermal) and ii) dose (duration and concentration of exposure). To explore dose, substances are tested in both acute and chronic models.[10] Generally, different sets of experiments are conducted to determine whether a substance causes cancer and to examine other forms of toxicity.[10]

Factors that influence chemical toxicity:[8]

  • Dosage
    • Both large single exposures (acute) and continuous small exposures (chronic) are studied.
  • Route of exposure
    • Ingestion, inhalation or skin absorption
  • Other factors
    • Species
    • Age
    • Sex
    • Health
    • Environment
    • Individual characteristics

Testing methods

Toxicity experiments may be conducted in vivo (using the whole animal) or in vitro (testing on isolated cells or tissues), or in silico (in a computer simulation).[11]

Non-human animals

The classic experimental tool of toxicology is testing on non-human animals.[8] An example of a model organism is Galleria mellonella, which can replace small mammals to study toxicology in vivo.[12] As of 2014, such animal testing provides information that is not available by other means about how substances function in a living organism.[13]

Alternative testing methods

While testing in animal models remains as a method of estimating human effects, there are both ethical and technical concerns with animal testing.[14]

Since the late 1950s, the field of toxicology has sought to reduce or eliminate animal testing under the rubric of "Three Rs" - reduce the number of experiments with animals to the minimum necessary; refine experiments to cause less suffering, and replace in vivo experiments with other types, or use more simple forms of life when possible.[15][16]

Computer modeling is an example of alternative testing methods; using computer models of chemicals and proteins, structure-activity relationships can be determined, and chemical structures that are likely to bind to, and interfere with, proteins with essential functions, can be identified.[17] This work requires expert knowledge in molecular modeling and statistics together with expert judgment in chemistry, biology and toxicology.[17]

In 2007 the National Academy of Sciences published a report called "Toxicity Testing in the 21st Century: A Vision and a Strategy" which opened with a statement: "Change often involves a pivotal event that builds on previous history and opens the door to a new era. Pivotal events in science include the discovery of penicillin, the elucidation of the DNA double helix, and the development of computers. ...Toxicity testing is approaching such a scientific pivot point. It is poised to take advantage of the revolutions in biology and biotechnology. Advances in toxicogenomics, bioinformatics, systems biology, epigenetics, and computational toxicology could transform toxicity testing from a system based on whole-animal testing to one founded primarily on in vitro methods that evaluate changes in biologic processes using cells, cell lines, or cellular components, preferably of human origin."[18] As of 2010 that vision was still unrealized.[19] As of 2014 that vision was still unrealized.[13]

In some cases shifts away from animal studies has been mandated by law or regulation; the European Union (EU) prohibited use of animal testing for cosmetics in 2013.[20]

Dose response complexities

Most chemicals display a classic dose response curve – at a low dose (below a threshold), no effect is observed.[8]:80 Some show a phenomenon known as sufficient challenge – a small exposure produces animals that "grow more rapidly, have better general appearance and coat quality, have fewer tumors, and live longer than the control animals".[21] A few chemicals have no well-defined safe level of exposure. These are treated with special care. Some chemicals are subject to bioaccumulation as they are stored in rather than being excreted from the body;[8]:85–90 these also receive special consideration.

Several measures are commonly used to describe toxic dosages according to the degree of effect on an organism or a population, and some are specifically defined by various laws or organizational usage. These include:

  • LD50 = Median lethal dose, a dose that will kill 50% of an exposed population
  • NOEL = No Observed Effect Level, the highest dose known to show no effect
  • NOAEL = No Observed Adverse Effect Level, the highest dose known to show no adverse effects
  • PEL = Personal Exposure Limit, the highest concentration permitted under US OSHA regulations
  • STEL = Short-Term Exposure Limit, the highest concentration permitted for short periods of time, in general 15–30 minutes
  • TWA = Time-Weighted Average, the average amount of an agent's concentration over a specified period of time, usually 8 hours.
  • TTC = Threshold of Toxicological Concern have been established for the constituents of tobacco smoke[22]

Types

Medical toxicology

Medical toxicology is the discipline that requires physician status (MD or DO degree plus specialty education and experience).

Clinical toxicology

Clinical toxicology is the discipline that can be practiced not only by physicians but also other health professionals with a master's degree in clinical toxicology: physician extenders (physician assistants, nurse practitioners), nurses, pharmacists, and allied health professionals.

Computational toxicology

Computational toxicology is a discipline that develops mathematical and computer-based models to better understand and predict adverse health effects caused by chemicals, such as environmental pollutants and pharmaceuticals.[23] Within the Toxicology in the 21st Century project,[24][25] the best predictive models were identified to be Deep Neural Networks, Random Forest, and Support Vector Machines, which can reach the performance of in vitro experiments.[26][27][28][29]

Toxicology as a profession

A toxicologist is a scientist or medical personnel who specializes in the study of symptoms, mechanisms, treatments and detection of venoms and toxins; especially the poisoning of people. To work as a toxicologist one should obtain a degree in toxicology or a related degree like biology, chemistry, pharmacology or biochemistry. Toxicologists perform many different duties including research in the academic, nonprofit and industrial fields, product safety evaluation, consulting, public service and legal regulation.

Requirements

To work as a toxicologist one should obtain a degree in toxicology or a related degree like biology, chemistry or biochemistry. Bachelor's degree programs in toxicology cover the chemical makeup of toxins and their effects on biochemistry, physiology and ecology. After introductory life science courses are complete, students typically enroll in labs and apply toxicology principles to research and other studies. Advanced students delve into specific sectors, like the pharmaceutical industry or law enforcement, which apply methods of toxicology in their work. The Society of Toxicology (SOT) recommends that undergraduates in postsecondary schools that don't offer a bachelor's degree in toxicology consider attaining a degree in biology or chemistry. Additionally, the SOT advises aspiring toxicologists to take statistics and mathematics courses, as well as gain laboratory experience through lab courses, student research projects and internships.

Duties

Toxicologists perform many duties including research in the academic, nonprofit and industrial fields; product safety evaluation, consulting, public service and legal regulation. In order to research and assess the effects of chemicals, toxicologists perform carefully designed studies and experiments. These experiments help identify the specific amount of a chemical that may cause harm and potential risks of being near or using products that contain certain chemicals. Research projects may range from assessing the effects of toxic pollutants on the environment to evaluating how the human immune system responds to chemical compounds within pharmaceutical drugs. While the basic duties of toxicologists are to determine the effects of chemicals on organisms and their surroundings, specific job duties may vary based on industry and employment. For example, forensic toxicologists may look for toxic substances in a crime scene, whereas aquatic toxicologists may analyze the toxicity level of water bodies.

Compensation

The salary for jobs in toxicology is dependent on several factors, including level of schooling, specialization, experience. The U.S. Bureau of Labor Statistics (BLS) notes that jobs for biological scientists, which generally include toxicologists, were expected to increase by 21% between 2008 and 2018. The BLS notes that this increase could be due to research and development growth in biotechnology, as well as budget increases for basic and medical research in biological science.

Etymology and pronunciation

The word toxicology (/ˌtɒksɪˈkɒləi/) is a neoclassical compound from New Latin, first attested circa 1799,[30] from the combining forms toxico- + -logy, which in turn come from the Ancient Greek words τοξικός toxikos, "poisonous", and λόγος logos, "subject matter").

See also

References

  1. ^ Schrager, TF (October 4, 2006). "What is Toxicology". 
  2. ^ Hodgson, Ernest (2010). A Textbook of Modern Toxicology. John Wiley and Sons. p. 10. ISBN 0-470-46206-X. 
  3. ^ Levey, Martin (1966). Medieval Arabic Toxicology: The Book on Poisons of ibn Wahshiyya and its Relation to Early Native American and Greek Texts. 
  4. ^ Bhat, Sathyanarayana; Udupa, Kumaraswamy (1 August 2013). "Taxonomical outlines of bio-diversity of Karnataka in a 14th century Kannada toxicology text Khagendra Mani Darpana". Asian Pacific Journal of Tropical Biomedicine. 3 (8): 668–672. doi:10.1016/S2221-1691(13)60134-3. PMC 3703563Freely accessible. PMID 23905027. 
  5. ^ "Biography of Mathieu Joseph Bonaventure Orfila (1787–1853)". U.S. National Library of Medicine. 
  6. ^ Wennig, Robert (April 2009). "Back to the roots of modern analytical toxicology: Jean Servais Stas and the Bocarmé murder case". Drug Testing and Analysis. England. 1 (4): 153–155. doi:10.1002/dta.32. PMID 20355192. 
  7. ^ "Paracelsus Dose Response in the Handbook of Pesticide Toxicology WILLIAM C KRIEGER / Academic Press Oct01". 
  8. ^ a b c d e Ottoboni, M. Alice (1991). The dose makes the poison : a plain-language guide to toxicology (2nd ed.). New York, N.Y: Van Nostrand Reinhold. ISBN 0-442-00660-8. 
  9. ^ Committee on Risk Assessment of Hazardous Air Pollutants, Commission on Life Sciences, National Research Council (1994). Science and judgement in risk assessment. The National Academic Press. p. 56. ISBN 978-0-309-07490-2. 
  10. ^ a b "Human Health Toxicity Assessment". United States Environmental Protection Agencies. 
  11. ^ Bruin, Yuri. et. al (2009). "Testing methods and toxicity assessment (Including alternatives)". Academic Press. ELSEVIER: 497–514. doi:10.1016/B978-0-12-373593-5.00060-4. 
  12. ^ Harding, Clare R.; Schroeder, Gunnar N.; Collins, James W.; Frankel, Gad (2013-11-22). "Use of Galleria mellonella as a Model Organism to Study Legionella pneumophila Infection". Journal of Visualized Experiments (81). doi:10.3791/50964. ISSN 1940-087X. 
  13. ^ a b "The importance of animal in research". Society of Toxicology. 2014. 
  14. ^ "Existing Non-animal Alternatives". AltTox.org. 8 September 2011. 
  15. ^ "Alternative toxicity test methods: reducing, refining and replacing animal use for safety testing" (PDF). Society of Toxicology. 
  16. ^ Alan M. Goldberg. The Principles of Humane Experimental Technique: Is It Relevant Today? Altex 27, Special Issue 2010
  17. ^ a b Leeuwen van.C.J.; Vermeire T.G. (2007). Risk assessment of chemicals: An introduction. New York: Springer. pp. 451–479. ISBN 978-1-4020-6102-8. 
  18. ^ National Research Council (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. National Academies Press. ISBN 9780309151733.  Lay summary
  19. ^ Krewski D, Acosta D Jr, Andersen M, Anderson H, Bailar JC 3rd, Boekelheide K, Brent R, Charnley G, Cheung VG, Green S Jr, Kelsey KT, Kerkvliet NI, Li AA, McCray L, Meyer O, Patterson RD, Pennie W, Scala RA, Solomon GM, Stephens M, Yager J, Zeise L. "Toxicity testing in the 21st century: a vision and a strategy". J Toxicol Environ Health B Crit Rev. 13: 51–138. doi:10.1080/10937404.2010.483176. PMC 4410863Freely accessible. PMID 20574894. 
  20. ^ Adler. S.; et. al (2011). "Alternative (non-animal)methods for cosmetic testing: current status and future prospects - 2010". Arch Toxicol. Springer-Verlag. 85 (1): 367–485. doi:10.1007/s00204-011-0693-2. 
  21. ^ Ottoboni 1991, pp. 83-85.
  22. ^ Talhout, Reinskje; Schulz, Thomas; Florek, Ewa; Van Benthem, Jan; Wester, Piet; Opperhuizen, Antoon (2011). "Hazardous Compounds in Tobacco Smoke". International Journal of Environmental Research and Public Health. 8 (12): 613–628. doi:10.3390/ijerph8020613. ISSN 1660-4601. PMC 3084482Freely accessible. PMID 21556207. 
  23. ^ Reisfeld, B; Mayeno, A. N. (2012). "What is Computational Toxicology?". Computational Toxicology. Methods in Molecular Biology. 929. pp. 3–7. doi:10.1007/978-1-62703-050-2_1. ISBN 978-1-62703-049-6. PMID 23007423. 
  24. ^ Hartung, T (2009). "A toxicology for the 21st century--mapping the road ahead". Toxicological Sciences. 109 (1): 18–23. doi:10.1093/toxsci/kfp059. PMC 2675641Freely accessible. PMID 19357069. 
  25. ^ Berg, N; De Wever, B; Fuchs, H. W.; Gaca, M; Krul, C; Roggen, E. L. (2011). "Toxicology in the 21st century--working our way towards a visionary reality". Toxicology in Vitro. 25 (4): 874–81. doi:10.1016/j.tiv.2011.02.008. PMID 21338664. 
  26. ^ "Toxicology in the 21st century Data Challenge". www.tripod.nih.gov. 
  27. ^ "NCATS Announces Tox21 Data Challenge Winners". www.ncats.nih.gov. 
  28. ^ Unterthiner, T.; Mayr, A.; Klambauer, G.; Steijaert, M.; Ceulemans, H.; Wegner, J. K.; & Hochreiter, S. (2014) "Deep Learning as an Opportunity in Virtual Screening". Workshop on Deep Learning and Representation Learning (NIPS2014).
  29. ^ Unterthiner, T.; Mayr, A.; Klambauer, G.; & Hochreiter, S. (2015) "Toxicity Prediction using Deep Learning". ArXiv, 2015.
  30. ^ Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster. 

Further reading

  • Caito, Samuel; Almeida Lopes, Ana Carolina B.; Paoliello, Monica M. B.; Aschner, Michael (2017). "Chapter 16. Toxicology of Lead and Its Damage to Mammalian Organs". In Astrid, S.; Helmut, S.; Sigel, R. K. O. Lead: Its Effects on Environment and Health. Metal Ions in Life Sciences. 17. de Gruyter. pp. 501–534. doi:10.1515/9783110434330-016. 
  • Andresen, Elisa; Küpper, Hendrik (2013). "Chapter 13. Cadmium toxicity in plants". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Cadmium: From Toxicology to Essentiality. Metal Ions in Life Sciences. 11. Springer. pp. 395–413. doi:10.1007/978-94-007-5179-8_13.  (subscription required)
  • Thévenod, Frank; Lee, Wing-Kee (2013). "Chapter 14. Toxicology of cadmium and its damage to mammalian organs". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Cadmium: From Toxicology to Essentiality. Metal Ions in Life Sciences. 11. Springer. pp. 415–490. doi:10.1007/978-94-007-5179-8_14.  (subscription required)

External links

  • Toxicology at DMOZ
  • National Library of Medicine's "Toxicology Tutor" provides basic information on the science of toxicology.
  • Toxipedia
  • Information Toxicology International
  • Society of Toxicology
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