Toxicology

For the scientific journal, see Toxicology (journal).

Toxicology (from the Ancient Greek words τοξικός toxikos "poisonous" and λόγος logos) is a branch of biology, chemistry, and medicine (more specifically pharmacology) concerned with the study of the adverse effects of chemicals on living organisms.[1] It also studies the harmful effects of chemical, biological and physical agents in biological systems that establishes the extent of damage in living organisms. 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); the route of exposure, the species, age, sex and environment.

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.

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.[4]

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.[5]

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.[6] 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".[7]:30

Basic toxicology

The goal of toxicity assessment is to identify adverse effects of a substance.[8] 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.[9] Generally, different sets of experiments are conducted to determine whether a substance causes cancer and to examine other forms of toxicity.[9]

Factors that influence chemical toxicity:[7]

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).[10]

Animal testing methods

The classic experimental tool of toxicology is animal testing.[7] As of 2014, animal experiments provide information that is not available by other means about how substances function in a living organism.[11]

Alternative testing methods

While testing in animal models remains the best method of estimating human effects, there are both ethical and technical concerns with animal testing.[12]

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.[13][14]

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.[15]

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.[16] This work requires expert knowledge in molecular modeling and statistics together with expert judgment in chemistry, biology and toxicology.[16]

Dose response complexities

Most chemicals display a classic dose response curve – at a low dose (below a threshold), no effect is observed.[7]: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".[17] 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;[7]:85–90 these also receive special consideration.

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.[18] Within the Toxicology in the 21st Century project,[19][20] 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.[21][22][23][24]

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 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 more 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 wastewater.

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.

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. ↑ "Biography of Mathieu Joseph Bonaventure Orfila (1787–1853)". U.S. National Library of Medicine.
  5. ↑ 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.
  6. ↑ "Paracelsus Dose Response in the Handbook of Pesticide Toxicology WILLIAM C KRIEGER / Academic Press Oct01".
  7. 1 2 3 4 5 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.
  8. ↑ 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.
  9. 1 2 "Human Health Toxicity Assessment". United States Environmental Protection Agencies.
  10. ↑ 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.
  11. ↑ "The importance of animal in research". Society of Toxicology. 2014.
  12. ↑ "Existing Non-animal Alternatives". AltTox.org. 8 September 2011.
  13. ↑ "Alternative toxicity test methods: reducing, refining and replacing animal use for safety testing" (PDF). Society of Toxicology.
  14. ↑ Alan M. Goldberg. The Principles of Humane Experimental Technique: Is It Relevant Today? Altex 27, Special Issue 2010
  15. ↑ 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.
  16. 1 2 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.
  17. ↑ Ottoboni 1991, pp. 83-85.
  18. ↑ 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.
  19. ↑ 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 2675641. PMID 19357069.
  20. ↑ 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.
  21. ↑ "Toxicology in the 21st century Data Challenge" https://tripod.nih.gov/tox21/challenge/leaderboard.jsp
  22. ↑ "NCATS Announces Tox21 Data Challenge Winners" http://www.ncats.nih.gov/news-and-events/features/tox21-challenge-winners.html
  23. ↑ 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).
  24. ↑ Unterthiner, T.; Mayr, A.; Klambauer, G.; & Hochreiter, S. (2015) "Toxicity Prediction using Deep Learning". ArXiv, 2015.

Further reading

External links

Look up toxicology in Wiktionary, the free dictionary.
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