Toxicology

█ JUDYTH SASSOON

The science of toxicology is concerned with the adverse effects of chemicals on biological systems and includes the study of the detection, action and counteractions of poisons. Toxicologists today generally use the techniques of analytical chemistry to detect and identify foreign chemicals in the body, with a particular emphasis on toxic or hazardous substances. Toxins can be simple metal ions or more complex, inorganic and organic chemicals, as well as compounds derived from bacteria or fungi and animal-produced substances such as venoms. Poisons can range in their effects from a low-level debilitation to almost immediate death. Many drugs used to counter diseases can also be poisons at higher concentrations.

One of the most significant historical figures in the development of the science of toxicology was the Swiss physician and alchemist Paracelsus (1493–1541). He realized that there was a need for proper experimentation in the field of chemical therapeutics and distinguished between the therapeutic and toxic properties of substances, recognizing that they are indistinguishable except by dose. Paracelsus realized that it is not possible to categorize chemicals as either safe or toxic and laid the foundations for a key principle in toxicology known as the dose-response relationship. There is a graded dose-response relationship in individuals and a quantal dose-response relationship in a population. The quantal "all or none" dose-response is used to determine the median lethal dose (LDm), which estimates what percentage of the population, would be affected by a dose increase. Estimation of LDm involves the use of at least two different animal species and doses of the chemical under test are administered by at least two different routes. Initially most of the test animals die within 14 days. Subacute exposure is then tested for a period of 90 days and long-term exposure testing takes a further 6 months to 2 years. Mathematical extrapolation is used to generalize results from animal testing to human risk incidence.

Another significant figure in toxicology was Spanish physician Orfila (1787–1853) who contributed to the specialty known as forensic toxicology. He devised methods of detecting poisonous substances and therefore provided the means of proving when criminal poisoning had taken place. After Orfila, toxicology developed further to include the study of mechanisms of poison action.

Forensic toxicology involves the use of toxicological methods for legal purposes. There is a considerable overlap between forensic and clinical toxicology, criminology, forensic psychology, drug testing, environmental toxicology, pathology, pharmacology, sports medicine and veterinary toxicology. The work of a forensic toxicologist generally falls into three main categories: identification of drugs such as heroin, cocaine, cannabis; detection of drugs and poisons in body fluids, tissues and organs; and measuring of alcohol in blood or urine samples. Results of the laboratory procedures must then be interpreted and presented to the legal courts.

A forensic toxicologist is normally given preserved samples of body fluids, stomach contents, and organ parts along with a coroner's report containing information on symptoms and postmortem data. Specimens are generally divided into acidic and basic fractions for drug extraction from tissue or fluid. As an example, most of the barbiturate drugs are acid-soluble while most of the amphetamine drugs are base-soluble. After preliminary acidbase procedures, tissue or fluid samples are subjected to further laboratory tests consisting of screening tests and confirmation testing. Screening tests allow the processing of many specimens for a wide range of toxins in a short time and any positive indications from the screens are then verified with a confirmation test.

Laboratory methods used in toxicological analysis are various. Screening tests include (1) physical tests: testing the boiling point, melting point, density, and refractive index of a substance; (2) crystal tests: treatment of a substance with a chemical reagent to produce crystals; (3) chemical spot tests: treatment with a chemical reagent producing color changes; (4) chromatographic tests (thin layer or gas): these separate the mixtures under investigation. Confirmatory tests generally involve mass spectrometry in combination with gas chromatography. Every toxin has a characteristic mass spectrum that identifies it absolutely.

Drugs analysis in tissue samples can be very complicated and a substance under analysis must be subjected to rigorous tests with no margin for error. A range of screening tests employing color reactions exist for the detection of illegal drugs. Some commonly used color tests include the Marquis test for opium, Duqunois-Levine test for Marijuana, Van Urk test for LSD, Scott test for cocaine, and Dillie-Koppanyi test for barbiturates.

The challenges of modern science call on clinical and forensic toxicologists to expand their services. They are now encouraged to engage in research and development to meet a number of changing needs. Modern molecular biology has opened up a number of interesting possibilities for toxicologists. For example, genotyping for interpretation of potential toxic drug interactions and criminality testing is becoming a field of great interest. With the emergence of pharmacogenetics, genotyping may enhance rational drug therapy for better patient care, and may explain unexpected adverse or fatal drug reactions in postmortem analysis.

Expanding responsibilities for forensic toxicologists also derive from the greater threat of terrorism. Terrorism via weapons of mass destruction has moved out from war zones to civilian settings. Modern terrorist weapons may be in the form of nuclear, biological, and chemical devices. Recently, the possible use of chemical or biological weapons in the Middle East conflicts, the use of sarin gas in a Tokyo subway station, and the unregulated availability of nuclear fuel in some countries have all heightened the potential risks. Toxicologists must now be knowledgeable about the clinical pharmacology, safe samples processing, and possible screening and/or analysis of substances such as vesicants, cyanide, nerve agents, and riot control agents.

█ FURTHER READING:

BOOKS:

Bodziak, J., and Jon J. Nordby. Forensic Science: An Introduction to Scientific and Investigative Techniques. CRC Press, 2002.

Klaassen, C. D. Toxicology: The Basic Science of Poisons. McGraw-Hill Companies, 2001.

PERIODICALS:

Goldberger, B. A., and A. Polettini. "Forensic Toxicology: Web Resources." Toxicology 173 (2002): 97–102.

Maurer H. H. "Liquid Chromatography-mass Spectrometry in Forensic and Clinical Toxicology." J Chromatogr B Biomed Sci Appl. 713 (1998): 3–25.

Richardson T. "Pitfalls in Forensic Toxicology." Ann Clin Biochem. 37 (2000): 20–44.

Thormann, W., Y Aebi, M. Lanz, and J. Caslavska "Capillary Electrophoresis in Clinical Toxicology." Forensic Sci Int. 92 (1998): 157–83.

Wong, S. H. "Challenges of toxicology for the millennium." Ther Drug Monit. 22 (2000): 52–7102.

SEE ALSO

Chemical and Biological Detection Technologies
Chemistry: Applications in Espionage, Intelligence, and Security Issues
Drug Control Policy, United States Office of National
Forensic Science
Thin Layer Chromatography