Intro to Toxicology Flashcards
What is Toxicology?
The study of adverse effects of chemicals on the body
Chemicals can be considered…?
Poisons
Toxins
Toxicants
Xenobiotics
Poisons
Any agent capable of causing harm in a biological system
Toxins
Toxic substances produced BY a biological system
Types of Toxins?
Phytotoxins (plant-based)
Zootoxins (animal-based)
Bacteriotoxins (bacterium-based)
Toxicants
Toxic substances produced by human activity
Xenobiotics
Any substance not normally found within the body
Toxicity
The adverse effects that a chemical may produce
Dose
The amount of a chemical that gains access to the body
Exposure
Contact which provides the opportunity of obtaining a poisonous dose
Hazard
The likelihood that toxicity will be expressed
Over what percentage of poisonings happen at home?
90%
Household products implicated in most poisonings…
Cleaning solutions
Fuels
Medicines
Glue
Cosmetics
Certain animals secrete xenobiotic poison which we call _______ while others harbor _______?
Venom; infectious bacteria
Some ______ are poisonous to humans and animals
Household plants
A career in toxicology
involves evaluating the bodily effects of drugs, contaminants, and other toxins
Toxicology is carried out in what types of settings?
Government, private, industry, universities, and research settings
Toxicologists use many sophisticated tools to determine the risk of these chemicals, such as?
Computer simulations, molecular biology, cell culture, genetically-engineered laboratory animals, as well as many, many chemical experiments
What do toxicologists do?
most work to develop a mechanistic understanding of how chemicals affect living systems
What does toxicology work lead to?
Developing safer chemical products, developing safer drugs, determining risks for chemical exposures, developing treatments for chemical exposures, teaching
Mechanistic toxicologists
study how a chemical causes toxic effects by investigating its absorption, distribution, and excretion
They often work in academic settings or private industries and develop antidotes
Descriptive toxicologists
evaluate the toxicity of drugs, foods, and other products
They often work in a pharmaceutical or academic setting
Clinical toxicologists
usually physicians or veterinarians interested in prevention, diagnosis, and treatment of poisoning cases
Often work in hospitals or animals hospitals and have specialized training in emergency medicine and poison management
Environmental toxicologists
study the effect of pollutants on organisms, populations, ecosystems, and the biosphere
They usually work within a state or federal laboratory, or private organizations
Regulatory toxicologists
use scientific data to decide how to protect humans and animals from excessive risk
They usually work within regulatory agencies such as at the FDA and EPA
Some occupational exposure is controlled at a level beyond individual choice to avoid exposure
Regulatory toxicology
Groups that try to control exposures on a communal or global level
Communities or governments (leads to many regulatory agencies)
Who funds regulatory agencies?
Government
The research performed by these toxicologists also help establish the requirements by performing what?
Risk assessments
Regulatory toxicology provide assistance in the interaction between what?
Government and industry
“Virtually every medical achievement of the last century has depended directly or indirectly on research in animals”
U.S. Public Health Services
There are regulatory agencies put in place to prevent the mistreatment of animals used in research such as…?
the Institutional Animal Care and Use Committee (IACUC)
Any experimentation done on humans is first approved by…?
Institutional Review Board (IRB)
Forensic toxicologists
study the application of toxicology to the law
Use chemical analysis to determine causes and circumstances of death in a postmortem investigation
What do forensic toxicologists look for?
Look to see whether the level of substance present in the body at the time of death would be able to produce an altered state in the individual
Who do forensic toxicologists usually work within?
State or federal laboratory, or independently
Why is toxicology arguably the oldest scientific discipline?
Earliest humans had to recognize which plants were safe to eat
Most exposure of humans to chemicals is via what?
Naturally occurring compounds consumed from food (plants)
Humans are exposed to chemicals both _____ and _____
Inadvertently; deliberately
2700 BC
Chinese journals show the cataloging of food and fish poisons
1900 - 1200 BC
Egyptian documents have directions for the collection, preparation, and administration of more than 800 recipes, both medicinal and poisonous
800 BC
India writings contain Hindu medicines that show notes on both poisons and antidotes
50 - 100 AD
Greek physicians classify over 600 plant, animal, and mineral poisons via “De Materia Medica”
50 - 400 AD
Romans use poisons for executions and assassinations
Who was executed using hemlock for his teaching of radical ideas to the youth?
Socrates
1200 AD
Spanish rabbi, Maimonidies, writes a first-aid book for poisonings, Poisons and Their Antidotes
1493 - 1541 AD
Paracelsus!! Father of modern toxicology!
Who was the Father of Modern Toxicology?
Paracelsus
“All substances are poisonous; there is none which is not a poison. The right dose differentiates a poison from a remedy.”
1713 AD
Italian physician Ramazzini publishes De Morbis Artificium (Diseases of Workers)
What does De Morbis Artificium describe?
“asthma” caused by health hazards in workers that deal with certain dusts, fumes, and gasses
What Ramazzini described in De Morbis Artificium would be diagnosed as what today?
“Allergen-induced asthma” for bakers and horse riders
The lung disease that was suffered by the other workers would be “pneumoconiosis,” which is what?
A group of dust-related chronic diseases
1815 AD
Spanish physician, Orfila, establishes toxicology as a distinct scientific discipline
Who established toxicology as a distinct scientific discipline?
Mathieu Orfila (Spanish physician)
20th century (Ehrlich)
Paul Ehrlich develops staining procedures which assist in seeing toxicant influence on living organisms
20th century (Carson)
Rachel Carson publishes Silent Spring, which alarms public about the dangers of pesticides
Environmental toxicants (pollutants)
Substances harmful to humans and the environment
Pollutants (Enviro Toxicants) can be both _____ and _____?
Natural; man-made
Public perception tends to think that _____ toxicants are more serious, but the reality is that _____ can be very serious
Man-made; both
Many examples of diseases associated with specific occupations have been recorded in antiquity, but the seriousness was not evaluated because of societal concerns at the time
These include:
Miner’s Disease – 1533
Hill & Pott discoveries – 1761, 1775
Radium Dial Painters/”Aniline dye” workers – 1900
Shoe salesmen – 1950s
Industrial chemical workers – 1940s to present day
Miner’s Disease (1533)
Came from inhaling metal vapors, foundation for the field of chemotherapy
Which disease helped with the creation of Chemotherapy?
Miner’s Disease
Hill (1761)
Linked tobacco (snuff) to cancer
Pott (1775)
Linked soot (benzo(a)pyrene) to scrotal cancer in chimney sweeps
Radium Dial Painters/”Aniline Dye” Workers (1900)
Painters licked their brushes to pull them to a point, resulting in radiation
Shoe salesman (1950s)
Used a shoe-fitting fluoroscope, which resulted in repeated exposure for salesmen
Industrial Chemical Workers (1940s to present)
Workers are exposed to a great number of carcinogens for a greater period of time
These occupations present with a high risk of cancer
Healthcare workers
Pharmaceutical and laboratory workers
Refinery workers
Rubber workers
Furniture makers
Pesticide workers
Due the toxicology concerns, various governmental programs were established
1906 – Food and Drug Administration (FDA)
1961 – Society of Toxicology
1970 – Environmental Protection Agency
1970 – National Institute for Occupational Safety and Health (NIOSH)
1971 – Occupational Safety and Health Administration (OSHA)
What must occur for the chemical to present a risk?
Exposure
The magnitude of risk is proportional to both the _____ of the chemical and the _____?
Potency; extent of exposure
“The dose makes the poison”
Extent may mean concentration or length of time and the extent of the exposure/dosage is what makes something poisonous
Can a nontoxic chemical become toxic at a high enough dosage?
Yes
Highly toxic chemicals may also be life-saving when given in the appropriate doses
Poisons may not be harmful at a sufficiently low dose
Chemotherapy is an example!
Lethal dose
Dose which will cause death in the specimen (mice, humans, etc.)
Sugar lethal dose
3 quarts
Alcohol lethal dose
3 quarts
Salt lethal dose
1 quart
Herbicide lethal dose
One half cup
Nicotine lethal dose
one half teaspoon
Food poison (botulism) lethal dose
Microscopic
Arsenic lethal dose
1-2 teaspoons
Exposure can affect the toxicological response based on different what?
Routes of exposure
Frequencies of exposure
Durational of exposure (acute v. chronic)
Routes of environmental exposure
Ingestion
Absorption
Injection
Inhalation
Ingestion
water and food
Exposure is through the gastro-intestinal track, and may start as soon as the mouth
Absorption
through skin
Injection
bite, puncture, or cut
Inhalation
breathing, air particles
How are people able to protect themselves from environmental exposure?
by blocking these routes of exposure
What contributes to dose?
Both duration and frequency
What type of exposure is less than 24 hours in duration and usually entails just a single exposure?
Acute exposure
Repeated or chronic exposures are classified as what?
Subacute
Subchronic
Chronic
Subacute
repeated for up to 30 days
Subchronic
repeated for 30-90 days
Chronic
repeated for over 90 days
Chronic exposures usually involve _______?
smaller amounts of toxicant
Why is there a variety of responses among organisms that get the same dose of chemical?
Individual susceptibility
(also affected by caffeine intake and medication dosage…)
Xenobiotics
foreign chemicals that aren’t synthesized within the body
Xenobiotics may be naturally occurring chemicals produced by what?
plants, microorganisms, or animals
Xenobiotics may also be synthetic chemicals that ______ produce?
humans
Poisons are xenobiotics, but…
NOT all xenobiotics are poisons
How do some xenobiotics cause toxicity?
By disrupting normal cell function
How do xenobiotics disrupt normal cell function
Bind and damage proteins (structural or enzymatic)
Bind and damage DNA (mutations)
Bind and damage lipids (cell wall mechanisms)
React in the cell with oxygen to form “free radicals,” which damage lipids, protein, and DNA
Types of toxic effects
Organ damage
Mutagenesis
Carcinogenesis
Teratogenesis
Death
Mutagenesis
The change of genetic information which causes mutations
Carcinogenesis
The creation of cancers
Teratogenesis
The creation of malformations produced in an embryo or fetus
Target organ toxicity: Certain toxins affect specific organs, which results in organ damage, including:
Central nervous system – Lead
Immune system – Isocyanates
Liver – Ethanol, Acetaminophen
Respiratory tract – tobacco smoke, asbestos, ozone
Eye – UV light (sunlight, eclipses)
Kidney – metals
Skin – UV light, gold, nickel
Reproductive system – dibromochloropropane
How does the body prevent xenobiotic action?
Once the body is exposed to xenobiotics, it responds in the following pattern:
Redistribution
Excretion
Metabolism
Redistribution
Moving the poison to areas around the body for further action
Excretion
removing the xenobiotic by processes usually involving the kidney and liver
Excretion works mostly for what kind of compounds?
Water soluble compounds
Metabolism
Major mechanism for terminating xenobiotic activity
What is the single, most important determinant of duration and intensity of toxic response?
Metabolism
Metabolism involves which structures?
liver
kidney
lung
GI system
(and others)
Redistribution and excretion are highly dependent on what?
Metabolism
