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Toxicology is the study of the adverse effects of various agents on human beings and other living organisms. A simple way to think about it is the science of poisons. Medical research has in particular expanded the knowledge of how toxic agents and toxic levels of otherwise non toxic agents do damage to the body’s cells, organs and biochemicals (the substances needed to maintain body functions). It is now widely recognized that virtually all toxic effects are caused by alterations in specific molecules in cells and biochemicals. The range of responses of exposure to toxins is from a subtle, slow alteration that manifest no symptoms for months or years to sudden death. Early man recognized poisonous animals and plants as by the time of the first recorded history, their extractions were being used with weapons. By 1500 BC, written recordings indicated that hemlock and opium arrow poisonings and certain metals were used in hunting, to poison enemies or for state executions. In 1500 AD, the work of Paracelsus determined that specific chemicals were the cause of the toxicity of an animal or plant. He determined through scientific methods that small doses of a substance might bring about a beneficial effect or at least be harmless whereas larger doses proved toxic. This is known as the dose-response relationship, to date a cornerstone concept of toxicology. Paracelsus said, “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” An example of this dose dependent effect can be made easily with Alcohol (ETOH) looking at ethanol blood levels which correlate directly with the amount ingested considering the size and overall health of the drinker. A non-toxic dose would produce an ethanol blood level of 0.05%, a toxic dose 0.1%, and a lethal dose 0.5%. As suggested by the ETOH example above, there are factors that influence toxicity. Dosage is the most important but there are several other influencing factors. For instance the form of the substance makes a difference such as if in a vapor, a liquid, or a solid form which would determine the exposure route, another important factor. The varying numbers of electrons and the varying chemical activity of substances determines lethality. Hydrogen cyanide binds to a biochemical resulting in all cells not being able to use oxygen thus bringing about sudden death. Less intense an example would be nicotine binding with certain receptors in the central nervous system altering nerve conduction and with increased dosing inducing gradual onset of paralysis. Other factors include presence of other chemicals in the areas of the body affected, ability to be absorbed by susceptible parts of the body, metabolism which is the changing of the substance within the body, distribution within the body as far as how many organs or cells have exposure to the substance and on how many levels, excretion of the substance or it’s metabolites which are the other chemicals produced when the original is actively changed in the body. Other factors are age, gender, and species. Toxicity is complex. Some substances may distribute widely throughout the body but only adversely affect a target organ and the target organ may change if the same substance has different dosing or length of exposure. A gas at high doses rapidly administered may damage the nervous system but at lower doses over a longer period of time may damage the liver and not affect the nervous system. An example of this is high doses of ETOH administered over a short period of time will profoundly affect the nervous system and cause depressed breathing and could cause death, but smaller amounts over a longer period of time and not necessarily at regular intervals will destroy cells in the liver that will be replaced by fibrosis, a scar like tissue that can not do the work of the liver cells. The route of exposure to a toxic substance is also important. Ingested chemicals may be completely neutralized by the liver, but the same substance inhaled would enter the blood stream directly, circulate throughout the body first before being detoxified by the liver. There can be different target organs depending on the route of exposure. Differing levels of toxicity to one chemical by different species is called selective toxicity. Insectacides will kill insects but be relatively harmless or cause harm in other ways such as damaging the reproductive system of various other sentient beings. Toxicity to the system of beings will not occur if contact is made and absorption does not take place. Ethanol alcohol is quickly absorbed from the gastrointestinal tract, but is very poorly absorbed if rubbed on the skin. Certain forms of heavy metals are readily absorbed from the gut, where others are not absorbed at all. Another major factor in determining the toxicity of a substance is the way it is metabolized and transformed in the body into other substances, the metabolites. This breaking down or changing of substances in the body is also called biotransformation. There are two forms : 1) detoxification where the chemical is transformed into a less toxic form. 2) bioactivation where the substance becomes more active and toxic. Toxicity is also dependent on how and at what rate of speed a chemical and/or it’s metabolites are excreted from the body. The kidney primarily as well as the bowels, lungs and skin serve this purpose. Toxins can also leave the body through milk, sweat, and tears. The presence of other chemicals can alter the toxic effects of a substance. Another chemical may make a toxic substance less toxic called antagonism, more toxic called synergism, or add another toxic effect called additivity. Antidotes function by antagonizing the toxicity of a poison. Exposure standards and guidelines are developed to protect the public from harm. Standards are legally acceptable exposure levels or controls issued as a result of governmental mandates at the congressional or executive level. They are legally enforceable. Violators are subject to punishment, including fines and imprisonment. Guidelines are recommendations of maximum exposure levels which are voluntary and not legally enforceable. Guidelines may be developed by regulatory and non-regulatory agencies, or by professional societies. Federal and state regulatory agencies have the authority to issue permissible exposure standards and guidelines. They include exposure standards and guidelines covering consumer products and environmental and occupational exposures. The rate of development of synthetic chemicals exploded (no pun) by the mid-twentieth century. There are notorious disasters from the toxic effects of the widespread use of some of these substances. Thalidamide, an anti-nausea drug given to pregnant women in the middle of the 20th century resulted in thousands of children being born with serious birth defects. Dioxins, some consider second only to radioactive waste in toxicity, are carcinogenic. Several studies show that workers exposed to high levels of dioxins in the workplace have an increased risk for cancers. It is felt by many in the scientific community to be in large part the cause of the dramatic rise over the last century in cancer rates, particularly hormonally based cancers. Industrial emissions have been reduced by more than 90% from the 1980’s levels and superfund sites work to eliminate the highest concentrations of these chemicals. The truth remains though that dioxins will NEVER be eliminated from the environment.
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