Yyyy Toxicology

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- elucidates the cellular, molecular, and biochemical effects of xenobiotics

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Mechanistic toxicology

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- uses the results from animal experiments to predict what level of exposure will cause harm in humans

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Descriptive toxicology

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-combined data from mechanistic and descriptive studies are used to establish standards that define the level of exposure that will not pose a risk to public health or safety

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Regulatory toxicology

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- Is the study of adverse effects of xenobiotics in humans

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Toxicology

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- exogenous agents that can have an adverse effect on the living organism -e.g chemicals, drugs

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Xenobiotics

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- exogenous agents that have an adverse effect on a biological system; however, it is more often used when describing substances from animal, plant, mineral or gas

-e.g. Venoms from poisonous snakes or spiders, poisonous hemlock, arsenic, lead, and carbon monoxide

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Poisons

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- are endogenous substances biologically synthesized either in living cells or in microorganisms

-e.g. Botulinum toxin from Clostridium botulinum, hemotoxins from venomous snakes, and mycotoxins from fungus

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Toxins

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Routes of exposure

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1. Ingestion

2. Inhalation

3. Transdermal absorption

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**All substances have the potential to cause harm “The dose makes the poison” (Paracelsus,1493-1591)

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Dose-Response Relationship

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The lowest dose of a substance introduced by any route, other than inhalation, over any given period of time, and reported to produce any toxic effect in humans or to produce tumorigenic or reproductive effects in animals

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Toxic dose low (TDLO):

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: is the predicted dose that would produce a toxic response in 50% of the population

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Toxic dose 50 (TD50)

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: The lowest concentration of a substance in air to which humans or animals have been exposed for any given period of time that has produced any toxic effect in humans or produced tumorigenic or reproductive effects in animals

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Toxic concentration low (TCLO)

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: The lowest concentration of a substance in air to which humans or animals have been exposed for any given period of time that has produced any toxic effect in humans or produced tumorigenic or reproductive effects in animals

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Toxic concentration low (TCLO)

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: The lowest dose, other than LD50 of a substance introduced by any route, other than inhalation, which has been reported to have caused death in humans or animals

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Lethal dose low (LDLO)

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: A calculated dose of a substance which is expected to cause the death of 50 percent of an entire defined experimental animal population. It is determined from the exposure to the substance by any route other than inhalation

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Lethal dose fifty (LD50)

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: The lowest concentration of a substance in air, other than LC50, which has been reported to cause death in humans or animals

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Lethal concentration low (LCLO)

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: A calculated concentration of a substance in air, exposure to which for a specified length of time is expected to cause the death of 50 percent of an entire defined experimental animal population.

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Lethal concentration fifty (LC50)

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-it is the dose that would be predicted to be effective or have therapeutic benefit in 50% of the population

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Effective Dose 50 (ED50)

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-is the ratio of the TD50(LD50) to the ED50 , a parameter which reflects the selectivity of a drug to elicit a desired effect rather than toxicity.

-Drugs with a large therapeutic index demonstrate fewer toxic adverse effect

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Therapeutic index

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- relates to the individual’s health status as well as changes in xenobiotic exposure levels

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Individual dose-response relationship

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- describes the change in health effects of a defined population based on changes in the exposure to the xenobiotic

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Quantal dose-response relationship

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- associated with single, short-term exposure to a substance in which the dose is sufficient to cause immediate toxic effects

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Acute toxicity

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- associated with repeated and frequent exposure for extended periods of time (months to years) at doses that are insufficient to cause an immediate acute response

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Chronic toxicity

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Analysis of toxic agents **Samples:

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=24-hour urine sample

=serum

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relatively simple and inexpensive method for detecting drugs and other organic compounds

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Thin-layer chromatography (TLC)

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- widely used and well-established technique for qualitative and quantitative determination of many volatile substances

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Gas chromatography (GC)

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reference method for quantitative identification of most organic compounds

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Gas chromatography-Mass spectrophotometry (GC-MS)

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- most common and excessively consumed; AKA grain alcohol

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Ethanol

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-is a common lab solvent that is also found in many household cleaners

-AKA wood alcohol

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Methanol

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-AKA rubbing alcohol

-it is metabolized by hepatic ADH to acetone (primary metabolic end product)

-It has CNS depressant effects similar to ethanol

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Isopropanol

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-1,2-ethanediol

-is a common component of hydraulic fluid and antifreeze

-Ingestion by Children is relatively common because of its sweet taste

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Ethylene Glycol

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- is the established reference method for ethanol and can simultaneously quantitate other alcohols such as methanol and isopropanol

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Gas Chromatography

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-The affinity of ____ for Hb is 200-225 times greater than for oxygen (carboxyhemoglobin/COHb)

-Sources of _____ include gasoline engines, improperly ventilated furnaces, and wood or plastic fires

-_____ is colorless, odorless, and tasteless gas that is rapidly absorbed into the circulation

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Carbon monoxide

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- supertoxic substance that can exist as a gas, solid, or in solution

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Cyanide

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- is a metalloid that may exist bound to or as a priamry constituent of many different organic and inorganic compounds

-is also a common homicide and suicide agent

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Arsenic

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- it is a metal found in many industrial processes, with its main use being in electroplating and galvanizing. It is also commonly encountered during mining and processing of many other metals

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Cadmium

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causes basophilic stippling and cabot rings in RBC

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Lead

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-is a metal that occurs in 3 forms: elemental (liquid at room temp), inorganic salts, and component of organic compounds

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Mercury

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- commonly used analgesic, antipyretic, and anti-inflammatory drug -It decreases Thromboxane and prostaglandin formation through the inhibition of cyclooxygenase

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Acetylsalicylic acid/aspirin

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- Tylenol

-commonly used analgesic drug-overdose is associated with severe hepatotoxicity

-HPLC- is the reference method

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Acetaminophen

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Testing for Drugs of Abuse

1. _________- screening procedure

- Which allows the detection of parent compounds and congeners taht have similar effects

2. ___________- reference method for confirmation of most analytes

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Spot test

GC-MS

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are stimulants that speed up the body’s system. Many are legally prescribed and used to treat attention-deficit hyperactivity disorder (ADHD)

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Amphetamines

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- acts as both a stimulant and psychedelic, producing an energizing effect, distortions in time and perception, and enhanced enjoyment of tactile experiences. Adolescents and young adults use it to reduce inhibitions

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Ecstasy/ MDMA (Methylenedioxymethamphetamine)

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are synthetically produced variants of the naturally occurring male hormone testosterone that are abused in an attempt to promote muscle growth, enhance athletic or other physical performance, and improve physical appearance.

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Anabolic steroids

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- is a mind-altering (psychoactive) drug, produced by the Cannabis sativa plant. contains over 480 constituents

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Marijuana/Cannabis

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-is an intense, euphoria-producing stimulant drug with strong addictive potentia

-This results in a rapid-onset, intense euphoric effect known as a “rush.”

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Cocaine

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is a highly addictive non-synthetic narcotic that is extracted from the poppy plant, Papaver somniferum. The ______ poppy is the key source for many narcotics, including morphine, codeine, and heroin.

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Opium

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____ inhibits muscle movement in the bowels leading to constipation. It also can dry out the mouth and mucous membranes in the nose.

___ use leads to physical and psychological dependence, and can lead to overdose

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Opium

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is a non-synthetic narcotic with a high potential for abuse and is derived from opium. It is used for the treatment of pain

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Morphine

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is a highly addictive drug and it is a rapidly acting opioid

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Heroin

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is a potent synthetic opioid drug approved by the Food and Drug Administration for use as an analgesic (pain relief) and anesthetic. It is approximately 100 times more potent than morphine and 50 times more potent than heroin as an analgesic

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Fentanyl

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- is a potent hallucinogen that has a high potential for abuse and currently has no accepted medical use in treatment in the United States

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LSD(lysergic acid diethylamide)

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- Is an illicit drug with stimulant, depressant, anesthetic, and hallucinogenic properties - Adverse effects: agitation, hostility, paranoia

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Phencyclidine (PCP)