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Question: Describe the types of dose-harm relationships that are investigated in toxicology and explain their importance to hygiene standard setting

Exposure to any material can be either acute or chronic. An acute exposure typically occurs through a single high dose, such as in an industrial accident where factory workers are exposed. A chronic exposure is seen with small repeated exposures, such as residual pesticides in the food supply or in the drinking water. Small doses of a harmful material given over years can result in a serious health risk, as will a short exposure to a high dose of a chemical.

In terms of the dose of a given chemical, several different scenarios must be considered. For example, an industrial worker whose job is to produce an agrochemical used to grow apples will be working with very high levels of the chemical on a daily basis. Industrial hygiene practices are needed to protect the worker. The farmer who applies the chemical in a liquid form, spraying it on his or her trees once or twice a year, may receive a high acute inhalation dose if he or she does not wear appropriate personal protective equipment. An individual who eats the apple could potentially receive a small residual dose daily.

Once a chemical enters the body, several different variables come into play. Typically, the potency of any chemical is dependent on four factors: absorption, distribution, metabolism, and elimination (ADME). Absorption is the process by which a chemical passes through cells and enters the bloodstream. The route of exposure and the physiochemical properties of the chemical will determine the rate of absorption. For example, an inhalation exposure will typically result in a rapid absorption, as the blood vessels of the lungs are directly exchanging with the inhaled air. A dermal exposure will on average have a slower rate of absorption, as the layers of skin provide a relatively impenetrable barrier to the bloodstream.

Metabolism is primarily carried out by the liver, where a large family of cytochrome P450 enzymes is responsible for the oxidative metabolism of chemicals. The family of cytochrome P450 enzymes includes more than 20 subtypes. The overall objective of the metabolic enzymes is to transform the chemicals into a form that is more water soluble so the body can more easily eliminate the materials in the urine. Successive oxidations and hydrolysis reactions lead to metabolites that are more polar and more easily eliminated. The broad spectrum of enzymes can address the wide range of chemicals with which the body has contact.

Question:Explain the term biological half time (BHT). Using examples show how BHT influences the derivation of the threshold dose for adverse effects.8 OHSE6020 Course Outline

The biological half-life and elimination half-life agent is the time elapsing between the substance (eg, metabolite, medicaments, a signaling molecule, a radioactive nuclide or other material) to lose half of its pharmacological, or physiological activity as defined in radiological mesh. In a medical context, half-life may also be described as the time between the blood plasma ...
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