TOXICOLOGY AND TOXICANTS
Sep 19 - 25, 2011
Toxicology (from a Greek word toxicos "poisonous" and logos) is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms or the dynamic interaction of chemicals with living systems.
It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people.
Toxicity is the degree to which a substance can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ, such as the liver. Toxicologists' investigations explore how chemicals interact with biological systems by focusing on the adverse effects and outcomes caused by such interactions.
There are various specialized sub-disciplines within the field of toxicology that concern diverse chemical and biological aspects of this area. For example, toxicogenomics involves applying molecular profiling approaches to the study of toxicology.
Other areas include aquatic toxicology, chemical (pharmaceutical) toxicology, ecotoxicology, environmental toxicology, forensic toxicology, and medical toxicology.
Toxic chemicals may be referred to as either toxins (toxic chemicals produced by living systems such as plants or animals) or toxicants (the remainder of toxic chemicals). The location within the body where chemicals interact to cause adverse effects is often referred to as the target tissue or the site of action.
With any single chemical, there can be one or more site of action. For example, a chemical may affect the liver and the heart. The potency of a chemical, or how toxic it is, depends upon its movement through the body to the target site (toxicokinetics); its ability to interact with the body to cause harm (toxicodynamics); and the dose the body receives (exposure level), which is in turn modified by the toxicokinetics and toxicodynamics of the chemical.
The amount of chemical that reaches the target tissue is a result of all three of the above. Both the kinetics and dynamics depend upon the current biochemical status of the organism. A toxic agent is anything that can produce an adverse biological effect.
It may be chemical, physical, or biological in form. For example, toxic agents may be chemical (for example, cyanide), physical (radiation), and biological (snake venom). A distinction is made for diseases due to biological organisms. Those organisms that invade and multiply within the organism and produce their effects by biological activity are not classified as toxic agents. An example of this is a virus that damages cell membranes resulting in cell death.
If the invading organisms excrete chemicals, which are the basis for toxicity, the excreted substances are known as biological toxins. These organisms, in this case, are referred to as toxic organisms. An example is tetanus. Tetanus is caused by a bacterium, Clostridium tetani. The bacteria C. tetani itself does not cause disease by invading and destroying cells. Rather, it is a toxin that is excreted by the bacterium that travels to the nervous system (a neurotoxin) that produces the disease. Toxicant, toxin, and poison are often used as a general term in toxicology, there are subtle differences as indicated below:
Toxicants substances that produce adverse biological effects of any nature may be chemical or physical in nature effects may be of various types (acutes, chronic, etc.) Toxins specific pretiens produces by living organisms (mushroom toxin or tetanus toxin) Poisons in very small amounts most exhibit immediate effects toxicants that cause immediate death of illness when experienced
A toxic substance is simply a material, which has toxic properties. It may be a discrete toxic chemical or a mixture of toxic chemicals. The exact chemical identity (the 'species') of a substance can make a very big difference as regards its toxicity. This concept is called 'speciation'. For example, asbestos is a complex chemical compound containing atoms such as potassium, sodium, magnesium, aluminum, silicon and others, which in a different context, would have a much lower toxicity than they exhibit in the compound of asbestos. Asbestos is a toxic material that does not consist of an exact chemical composition but a variety of fibers and minerals.
Chromium in the hexavalent state (Cr VI) is a human carcinogen (as in the orange colored potassium dichromate or bi-chromate) while trivalent chromium (Cr III) (as in the green colored chromium III chloride) appears not to be.
If the chromium is in the Cr III form and oxidation to Cr VI is prevented, exposure should present no cancer risks. Nickel tetracarbonyl is a highly toxic gas inflicting severe damage to the lungs and heart, while nickel carbonate (NiCO3) is a solid which is much less hazardous. Metallic nickel probably poses no cancer risk at all while nickel subsulfide is almost certainly a very highly carcinogenic and dangerous compound which has been responsible for many sad deaths.
Toxic substances may be systemic toxicants or organ toxicants. A systemic toxicant is one that affects the entire body or many organs rather than a specific site. For example, potassium cyanide is a systemic toxicant in that it affects virtually every cell and organ in the body by interfering with cells' ability to utilize oxygen. An organ toxicant may affect a specific type of tissue (for example, connective tissue) that is present in several organs.
The toxic site is then referred to as the target tissue. Toxicity to germ cells can cause effects on the developing fetus (such as birth defects, abortions). Toxicity to somatic cells causes a variety of toxic effects to the exposed individual (for example, dermatitis, death, and cancer).
Toxicants may also affect only specific organs while not producing damage to the body as a whole. These specific sites are known as the target organs or target tissues. Benzene is a specific organ toxin in that it is primarily toxic to the blood-forming tissues. Lead is also a specific organ toxin; however, it has three target organs: the (central nervous system, the kidney, and the hematopoietic system).
TOXICANTS EFFECTS ON SPECIFIC ORGANS:
* 'Heavy' metals e.g. Pb (lead) Cd (Cadmium) and Hg (mercury) have a propensity to bind sulfur and indeed in nature in the earth's crust are often found as sulfides. they tend to bind to sulfhydryl groups -SH in enzymes and other proteins and cause damage in various parts of the body
* The lungs are often the subject of damage e.g. paraquat poisoning.
* Cardiovascular effects include arrhythmias e.g. caused by trichloroethane or by carbon disulphide.
* A very specific effect of exposure to some poisons such as the organophosphate insecticides (e.g. malathion, parathion) relates to their anticholinesterase effect.
* Synaptic transmission from a nerve cell to another cell such as a muscle cell in many situations relies on acetyl choline. The enzyme acetylcholinesterase in nerve endings catalyses the hydrolysis of acetylcholine to choline and acetylCoA, thus determining a very short action of acetylcholine.
* Organophosphate and carbamate pesticides inhibit acetylcholinesterase and lead to accumulation of acetylcholine at sites of neuromuscular transmission causing weakness of muscles, and paralysis including of respiration.
* Endocrine mimicking agents can act as endocrine disrupters.
TOXICODYNAMICS - or what poisons may do to the body (a general terminologies)
* Acute effects refer to the short term consequences of exposure
* Chronic effects relate to a much longer time scale, while sub-acute are in between acute and chronic)
* Some effects may be dose related - the higher the exposure the worse it gets e.g. irritant effects on the skin, asthma, asbestosis etc
* Other effects are 'all or none' and for a given exposure there is an element of chance (stochastic) as to whether or not the disease develops e.g. the development of cancer teratogenesis)
* detergents may remove fat from the skin and cause dermatitis.
* cement dust being alkaline may irritate the skin, or cause more severe damage (chromates within cement may also cause sensitization and allergic dermatitis).
* respiratory irritation may be caused by low concentrations of formaldehyde vapor.
* (carcinogenesis) or some forms of developmental damage to the fetus (More serious inflammation: more toxic agents and/or higher exposures may be associated with damage resulting in inflammation for example of terminal bronchioles and alveoli leading to a chemical pneumonitis and pulmonary oedema (e.g. from nitrogen dioxide NO2)
CORROSIVE EFFECTS: Severe local effects by contact e.g. caustics such as sodium hydroxide, or acids such as sulfuric, nitric or hydrochloric acid.
NARCOTIC AND ANESTHETIC EFFECTS: Fat soluble solvents will behave as anesthetics and cause drowsiness, nausea, headache, unconsciousness and death e.g. vapors from organic solvents such as ether or trichloroethylene.
ASPHYXIATION EFFECT: Various gases can cause asphyxia by interfering with oxygen transport. Examples: Carbon monoxide, Hydrogen cyanide, Hydrogen sulfide. Carbon monoxide reacts with hemoglobin (Hb) to form COHb, which cannot carry oxygen. At low concentrations these gases poison cytochromes and cause the rapid onset of headache, dizziness, vomiting and confusion. At high concentrations they are very rapidly lethal.
TOXICOKINETICS - OR HOW THE BODY HANDLES POISONS
ABSORPTION INTO THE BODY: As a general rule, fat soluble liquids are readily absorbed through the skin and fat soluble vapors are readily absorbed through the lungs. Notably these routes apply to organic solvents such as hexane, toluene, trichlorethylene and many others.
DISTRIBUTION WITHIN THE BODY
* Many factors affect the distribution of a toxic substance but water or fat solubility is very important. Thus, for example water soluble compounds of lead are found (amongst other places) in the red blood cells, while fat soluble ones concentrate in the central nervous system (CNS).
METABOLISM/ BIOTRANSFORMATION OF TOXIC SUBSTANCES
* Toxic substances may be converted into other substances (metabolites) by organs such as the liver and kidneys
* Thus non-polar and therefore not water soluble organic compounds tend to be oxidized within the liver e.g.: trichloroethane oxidised to trichloroethanol trichloroacetaldehyde and trichloroacetic acid, dichloromethane (methylene chloride CH2Cl2) oxidized to carbon monoxide (CO)
* Water soluble metabolites are then more easily excreted by the kidney (see below)
* Metabolism or biotransformation does not necessarily result in less toxic compounds. For example, benzene may be oxidized to an epoxide which then inflicts damage on the DNA in genes, i.e. it is genotoxic and thence carcinogenic
ROUTES OF ELIMINATION OF TOXIC SUBSTANCES / OR THEIR METABOLITES
* Kidneys - especially water soluble substances.
* Lungs - especially fat soluble vapors e.g. - alcohols, or gases such as carbon monoxide.