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112 Cards in this Set

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Toxicity is complex with many influencing factors; what is the most important?
Toxicity is complex with many influencing factors; dosage is the most important.
Xenobiotics cause many types of toxicity by a variety of mechanisms. Some chemicals are ?. Others must be ? before they cause toxicity.
Xenobiotics cause many types of toxicity by a variety of mechanisms. Some chemicals are themselves toxic. Others must be metabolized (chemically changed within the body) before they cause toxicity.
Many xenobiotics distribute in the body and often affect only what?
Many xenobiotics distribute in the body and often affect only specific target organs. (Others, however, can damage any cell or tissue that they contact.)
The target organs that are affected may vary depending on what? Give an example.
The target organs that are affected may vary depending on dosage and route of exposure. For example, the target for a chemical after acute exposure may be the nervous system, but after chronic exposure the liver.
Toxicity can result from what kind of changes? List some examples.
Toxicity can result from adverse cellular, biochemical, or macromolecular changes. Examples are:


1. Cell replacement, such as fibrosis



2. Damage to an enzyme system



3. Disruption of protein synthesis



4. Production of reactive chemicals in cells



5. DNA damage
List three ways how xenobiotics may act indirectly.
xenobiotics may act indirectly by:


1. Modification of an essential biochemical function



2. Interference with nutrition



3. Alteration of a physiological mechanism
List 11 factors influencing the toxicity of a substance.
The toxicity of a substance depends on the following:

1. Form and innate chemical activity

2. Dosage, especially dose-time relationship

3. Exposure route

4. Species

5. Age

6. Sex

7. Ability to be absorbed

8. Metabolism

9. Distribution within the body

10. Excretion

11. Presence of other chemicals
The form of a substance may have a profound impact on its what? Give some examples.
The form of a substance may have a profound impact on its toxicity especially for metallic elements. For example, the toxicity of mercury vapor differs greatly from methyl mercury. Another example is chromium. Cr3+ is relatively nontoxic whereas Cr6+ causes skin or nasal corrosion and lung cancer.
The ? ? ? of substances also varies greatly. Some can quickly damage cells causing immediate cell death. Others slowly interfere only with a cell's function.
The innate chemical activity of substances also varies greatly. Some can quickly damage cells causing immediate cell death. Others slowly interfere only with a cell's function.
What is the most important and critical factor in determining if a substance will be an acute or a chronic toxicant?
The dosage is the most important and critical factor in determining if a substance will be an acute or a chronic toxicant. Virtually all chemicals can be acute toxicants if sufficiently large doses are administered. Often the toxic mechanisms and target organs are different for acute and chronic toxicity.
Exposure route is important in determining what? Explain and give 2 examples.
Exposure route is important in determining toxicity. Some chemicals may be highly toxic by one route but not by others. Two major reasons are differences in absorption and distribution within the body. For example:


1. Ingested chemicals, when absorbed from the intestine, distribute first to the liver and may be immediately detoxified



2. Inhaled toxicants immediately enter the general blood circulation and can distribute throughout the body prior to being detoxified by the liver
Frequently there are different what for different routes of exposure.
Frequently there are different target organs for different routes of exposure.
Toxic responses can vary substantially depending on the species. Most species differences are attributable to differences in what? Give examples.
Toxic responses can vary substantially depending on the species. Most species differences are attributable to differences in metabolism. Others may be due to anatomical or physiological differences. For example, rats cannot vomit and expel toxicants before they are absorbed or cause severe irritation, whereas humans and dogs are capable of vomiting.
What is selective toxicity?
Selective toxicity refers to species differences in toxicity between two species simultaneously exposed. This is the basis for the effectiveness of pesticides and drugs.
Give 2 examples of selective toxicity.
1. An insecticide is lethal to insects but relatively nontoxic to animals



2. Antibiotics are selectively toxic to microorganisms while virtually nontoxic to humans
Age may be important in determining what?
Age may be important in determining the response to toxicants. Some chemicals are more toxic to infants or the elderly than to young adults.
Give two examples of how age may be important in determining the response to toxicants.
1. Parathion is more toxic to young animals



2. Nitrosamines are more carcinogenic to newborn or young animals
Can toxic responses vary depending on sex?
Although uncommon, toxic responses can vary depending on sex.
Give 2 examples of toxic responses that vary depending on sex.
1. Male rats are 10 times more sensitive than females to liver damage from DDT



2. Female rats are twice as sensitive to parathion as male rats
What is essential for systemic toxicity to occur?
The ability to be absorbed is essential for systemic toxicity to occur.
The rates and extent of absorption may vary greatly depending on the what?
The rates and extent of absorption may vary greatly depending on the form of the chemical and the route of exposure.
The rates and extent of absorption may vary greatly depending on the form of the chemical and the route of exposure. Give 2 examples.
1. Ethanol is readily absorbed from the gastrointestinal tract but poorly absorbed through the skin



2. Organic mercury is readily absorbed from the gastrointestinal tract; inorganic lead sulfate is not
Metabolism is aka what?
Metabolism is also known as biotransformation.
Metabolism, also known as biotransformation, is a major factor in what?
Metabolism, also known as biotransformation, is a major factor in determining toxicity.
What are the products of metabolism known as?
The products of metabolism are known as metabolites.
There are how many types of metabolism? What are they?
There are two types of metabolism - detoxification and bioactivation.
What is detoxification?
Detoxification is the process by which a xenobiotic is converted to a less toxic form. This is a natural defense mechanism of the organism. Generally the detoxification process converts lipid-soluble compounds to polar compounds.
What is bioactivation?
Bioactivation is the process by which a xenobiotic may be converted to more reactive or toxic forms.
The what of toxicants and toxic metabolites throughout the body ultimately determines the sites where toxicity occurs?
The distribution of toxicants and toxic metabolites throughout the body ultimately determines the sites where toxicity occurs.
What is a major determinant of whether or not a toxicant will damage cells?
A major determinant of whether or not a toxicant will damage cells is its lipid solubility. If a toxicant is lipid-soluble it readily penetrates cell membranes.
What are the most common storage depots for toxicants in the body?
Fat tissue, liver, kidney, and bone are the most common storage depots.
What serves as the avenue for distribution of toxicants in the body?
Blood serves as the main avenue for distribution. Lymph also distributes some materials.
The site and rate of ? is another major factor affecting the toxicity of a xenobiotic.
The site and rate of excretion is another major factor affecting the toxicity of a xenobiotic.
What is the primary excretory organ? How else may xenobiotics be excreted?
The kidney is the primary excretory organ, followed by the gastrointestinal tract, and the lungs (for gases). Xenobiotics may also be excreted in sweat, tears, and milk.
A large volume of blood serum is filtered through the ?. Lipid-soluble toxicants are ? and concentrated in ? cells. Impaired ? function causes slower elimination of toxicants and ? their toxic potential.
A large volume of blood serum is filtered through the kidney. Lipid-soluble toxicants are reabsorbed and concentrated in kidney cells. Impaired kidney function causes slower elimination of toxicants and increases their toxic potential.
The presence of other chemicals may do what to the toxicity of a substance?
The presence of other chemicals may decrease toxicity (antagonism), add to toxicity (additivity), or increase toxicity (synergism or potentiation) of some xenobiotics.
The presence of other chemicals may decrease toxicity (antagonism), add to toxicity (additivity), or increase toxicity (synergism or potentiation) of some xenobiotics. Give 2 examples.
1. Alcohol may enhance the effect of many antihistamines and sedatives



2. Antidotes function by antagonizing the toxicity of a poison (atropine counteracts poisoning by organophosphate insecticides
What is a target organ?





An organ that stores the xenobiotic or its metabolite.




An organ that is damaged by the xenobiotic or its metabolite.




An organ that absorbs the xenobiotic.
A target organ is an organ that is damaged by the xenobiotic or its metabolite. There may be more than one target for toxicity for a particular substance. For example, the targets for alcohol are the central nervous system and the liver.
What are the important factors that influence the degree of toxicity of a substance?





Innate chemical activity and the dosage of the chemical.




Absorption, distribution, metabolism and excretion.




Exposure route, species, age, sex, and the presence of other chemicals.




All of the above.
Many factors can influence the toxicity of a substance. Some are chemical specific, such as innate chemical activity, dosage, and presence of other chemicals. Some are specific for the human or test animal, such as metabolism, age, sex, and species.
Metabolism of a xenobiotic:





Has no influence on whether it will cause toxicity.




May result in either detoxification (less toxic metabolites) or bioactivation (more toxic metabolites).




Always results in reduced toxicity of the xenobiotic.
Metabolism of a xenobiotic may result in either detoxification (less toxic metabolites) or bioactivation (more toxic metabolites). In some cases, a xenobiotic itself may not cause cancer but a metabolite of the xenobiotic may have carcinogenic potential. (This is a form of bioactivation).
The situation in which an antibiotic administered to humans kills bacteria in the human body but does not damage the human tissues is an example of:





Selective toxicity




Differences in absorption of the xenobiotic




Extremely fast elimination by the human
The situation in which an antibiotic administered to humans kills bacteria in the human body but does not damage the human tissues is an example of selective toxicity. Substances that are selectively toxic to one species, and not another, form the basis for drugs and insecticides.
The toxicity of pharmaceuticals to older persons and infants is generally:





Greater




Less




The same
The toxicity of pharmaceuticals to older persons and infants is generally greater. For this reason many pharmaceuticals come in reduced dosage specifically for use by infants and elderly patients.
Toxic effects are generally categorized according to the what?
Toxic effects are generally categorized according to the site of the toxic effect.
When a toxic effect occurs at only one site what is the site referred to as?
When a toxic effect occurs at only one site this site is referred to as the specific target organ.
Toxic effects may occur at multiple sites. What is this referred to as?
toxic effects may occur at multiple sites. This is referred as systemic toxicity.
List 6 types of systemic toxicity.
1. Acute Toxicity



2. Subchronic Toxicity



3. Chronic Toxicity



4. Carcinogenicity



5. Developmental Toxicity



6. Genetic Toxicity (somatic cells)
What is Acute toxicity?
Acute toxicity occurs almost immediately (hours/days) after an exposure.
What is a major concern in cases of acute exposures?
Death is a major concern in cases of acute exposures.
What is Subchronic toxicity?
Subchronic toxicity results from repeated exposure for several weeks or months. This is a common human exposure pattern for some pharmaceuticals and environmental agents.
Give 2 examples of subchronic toxicity.
1. Ingestion of coumadin tablets (blood thinners) for several weeks as a treatment for venous thrombosis can cause internal bleeding.



2. Workplace exposure to lead over a period of several weeks can result in anemia.
What is chronic toxicity?
Chronic toxicity represents cumulative damage to specific organ systems and takes many months or years to become a recognizable clinical disease.
Give 4 examples of chronic toxic affects.
1. Cirrhosis in alcoholics who have ingested ethanol for several years



2. Chronic kidney disease in workmen with several years exposure to lead



3. Chronic bronchitis in long-term cigarette smokers


4. Pulmonary fibrosis in coal miners (black lung disease)
What is carcinogenicity?
Carcinogenicity is a complex multistage process of abnormal cell growth and differentiation which can lead to cancer. At least two stages are recognized.
Carcinogenicity is a complex multistage process of abnormal cell growth and differentiation which can lead to cancer. At least two stages are recognized. What are they?
They are initiation in which a normal cell undergoes irreversible changes and promotion in which initiated cells are stimulated to progress to cancer. Chemicals can act as initiators or promoters.
The initial neoplastic transformation results from what?
The initial neoplastic transformation results from the mutation of the cellular genes that control normal cell functions. The mutation may lead to abnormal cell growth. It may involve loss of suppresser genes that usually restrict abnormal cell growth. Many other factors are involved (e.g., growth factors, immune suppression, and hormones).
What is a neoplasm?
A tumor (neoplasm) is simply an uncontrolled growth of cells.
What is the difference between a benign and a malignant tumor?
Benign tumors grow at the site of origin; do not invade adjacent tissues or metastasize; and generally are treatable. Malignant tumors (cancer) invade adjacent tissues or migrate to distant sites (metastasis). They are more difficult to treat and often cause death.
Developmental Toxicity pertains to what? This can result from what?
Developmental Toxicity pertains to adverse toxic effects to the developing embryo or fetus. This can result from toxicant exposure to either parent before conception or to the mother and her developing embryo-fetus.
List the three basic types of developmental toxicity are.
1. Embryolethality

2. Embryotoxicity

3. Teratogenicity
What is embryolethality?
Failure to conceive, spontaneous abortion or stillbirth.
What is embryotoxicity?
Growth retardation or delayed growth of specific organs.
What is teratogenicity?
Irreversible conditions that leave permanent birth defects in live offspring. (cleft palate, missing limbs, etc)
Chemicals cause developmental toxicity by two methods. Explain.
Chemicals cause developmental toxicity by two methods. They can act directly on cells of the embryo causing cell death or cell damage, leading to abnormal organ development. A chemical might also induce a mutation in a parent's germ cell which is transmitted to the fertilized ovum. Some mutated fertilized ova develop into abnormal embryos.
Genetic Toxicity results from what? This process is known as what?
Genetic Toxicity results from damage to DNA and altered genetic expression. This process is known as mutagenesis.
A genetic change is referred to as a ? and the agent causing the change as a ?.
A genetic change is referred to as a mutation and the agent causing the change as a mutagen.
List 3 types of genetic changes?
1. Gene mutation

2. Chromosome Aberration

3. Aneuploidy/Polyploidy
What is a gene mutation?
Change in a DNA sequence within a gene.
What is a chromosome aberration?
Changes in the chromosomal structure.
What is aneuploidy/polyploidy?
An increase/decrease in the number of chromosomes.
When is the effect of a mutation inheritable?
If the mutation occurs in a germ cell the effect is heritable.
If the mutation occurs in a germ cell the effect is heritable. There is no effect on the ?; rather the effect is ?.
If the mutation occurs in a germ cell the effect is heritable. There is no effect on the exposed person; rather the effect is passed on to future generations.
If the mutation occurs in a somatic cell what can it cause?
If the mutation occurs in a somatic cell, it can cause altered cell growth (e.g. cancer) or cell death (e.g. teratogenesis) in the exposed person.
List the types of organ specific toxic effects?
1. Blood/Cardiovascular Toxicity



2. Dermal/Ocular Toxicity



3. Genetic Toxicity (germ cells)



4. Hepatotoxicity



5. Immunotoxicity



6. Nephrotoxicity



7. Neurotoxicity



8. Reproductive Toxicity



9. Respiratory Toxicity
Blood and Cardiovascular Toxicity results from what?
Blood and Cardiovascular Toxicity results from xenobiotics acting directly on cells in circulating blood, bone marrow, and heart.
Give 4 examples of blood and cardiovascular toxicity.
1. Hypoxia due to carbon monoxide binding of hemoglobin preventing transport of oxygen



2. Decrease in circulating leukocytes due to chloramphenicol damage to bone marrow cells



3. Leukemia due to benzene damage of bone marrow cells



4. Arteriosclerosis due to cholesterol accumulation in arteries and veins
Dermal Toxicity may result from what?
Dermal Toxicity may result from direct contact or internal distribution to the skin. Effects range from mild irritation to severe changes, such as corrosivity, hypersensitivity, and skin cancer.
List 3 examples of dermal toxicity.
1. Dermal irritation due to skin exposure to gasoline



2. Dermal corrosion due to skin exposure to sodium hydroxide (lye)



3. Dermal hypersensitivity due to skin exposure to poison ivy



4. Skin cancer due to ingestion of arsenic or skin exposure to UV light
Eye Toxicity results from what? What are directly exposed to intoxicants?
Eye Toxicity results from direct contact or internal distribution to the eye. The cornea and conjunctiva are directly exposed to toxicants. Thus, conjunctivitis and corneal erosion may be observed following occupational exposure to chemicals.
What may cause conjunctivitis?
Many household items can cause conjunctivitis.
Chemicals in the circulatory system can do what?
Chemicals in the circulatory system can distribute to the eye and cause corneal opacity, cataracts, retinal and optic nerve damage.
Chemicals in the circulatory system can distribute to the eye and cause corneal opacity, cataracts, retinal and optic nerve damage. List 3 examples.
1. Acids and strong alkalis may cause severe corneal corrosion


2. Corticosteroids may cause cataracts



3. Methanol (wood alcohol) may damage the optic nerve
Hepatotoxicity is what?
Hepatotoxicity is toxicity to the liver, bile duct, and gall bladder.
Why is the liver particularly susceptible to xenobiotics?
The liver is particularly susceptible to xenobiotics due to a large blood supply and its role in metabolism. Thus it is exposed to high doses of the toxicant or its toxic metabolites.
List the 7 primary forms of hepatotoxicity?
1. Steatosis

2. Chemical hepatitis

3. Hepatic Necrosis

4. Intrahepatic Cholestasis

5. Hepatic Cancer

6. Cirrhosis

7. Hypersensitivity
What is Steatosis?
Lipid accumulation in hepatocytes.
What is chemical hepatitis?
Inflammation of the liver.
What is hepatic necrosis?
Death of hepatocytes.
What is intrahepatic cholestasis?
Backup of bile salts into the liver cells.
What is hepatic cancer?
Cancer of the liver.
What is cirrhosis?
Chronic fibrosis, often due to alcohol.
What is hypersensitivity?
Immuner rxn resulting in hepatic necrosis.
What is Immunotoxicity?
Immunotoxicity is toxicity of the immune system. It can take several forms: hypersensitivity (allergy and autoimmunity), immunodeficiency, and uncontrolled proliferation (leukemia and lymphoma).
The normal function of the immune system is to do what? How is this accomplished?
The normal function of the immune system is to recognize and defend against foreign invaders. This is accomplished by production of cells that engulf and destroy the invaders or by antibodies that inactivate foreign material.
Give 4 examples of immunotoxicity.
1. Contact dermatitis due to exposure to poison ivy



2. Systemic lupus erythematosus in workers exposed to hydrazine



3. Immunosuppression by cocaine



4. Leukemia induced by benzene
The kidney is highly susceptible to toxicants for what two reasons?
A high volume of blood flows through it and it filtrates large amounts of toxins which can concentrate in the kidney tubules.
What is nephrotoxicity?
Nephrotoxicity is toxicity to the kidneys. It can result in systemic toxicity.
Nephrotoxicity is toxicity to the kidneys. It can result in systemic toxicity causing what?
1. Decreased ability to excrete body wastes



2. Inability to maintain body fluid and electrolyte balance



3. Decreased synthesis of essential hormones (e.g., erythropoietin)
What is neurotoxicity?
Neurotoxicity represents toxicant damage to cells of the central nervous system (brain and spinal cord) and the peripheral nervous system (nerves outside the CNS).
List the 4 primary types of neurotoxicity.
1. Neuronopathies (neuron injury)



2. Axonopathies (axon injury)



3. Demyelination (loss of axon insulation)



4. Interference with neurotransmission
What does reproductive toxicity involve?
Reproductive Toxicity involves toxicant damage to either the male or female reproductive system.
Toxic effects due to reproductive toxicity may cause these 6 effects.
1. Decreased libido and impotence



2. Infertility



3. Interrupted pregnancy (abortion, fetal death, or premature delivery)



4. Infant death or childhood morbidity



5. Altered sex ratio and multiple births



6. Chromosome abnormalities and birth defects



7. Childhood cancer
What is respiratory toxicity?
Respiratory Toxicity relates to effects on the upper respiratory system (nose, pharynx, larynx, and trachea) and the lower respiratory system (bronchi, bronchioles, and lung alveoli).
List the 8 primary types of respiratory toxicity.
1. Pulmonary irritation

2. Asthma/bronchitis

3. Reactive airway disease

4. Emphysema

5. Allergic alveolitis

6. Fibrotic lung disease

7. Pneumoconiosis

8. Lung cancer
Toxic effects are primarily of two general types:





hepatic and nephrotoxic effects




carcinogenic or teratogenic effects




systemic or specific target organ effects
Toxic effects are primarily systemic or specific target organ effects. Systemic effects are those in which there may be numerous target organs. For example, some agents will produce cancer in multiple organs rather than one specific organ.
The primary difference between acute and chronic toxicity is:





Acute toxicity appears soon after an exposure whereas chronic toxicity occurs many months or years later.




Different organs are involved.




Acute toxicity occurs only after a single dose whereas chronic toxicity occurs with multiple doses.
The primary difference between acute and chronic toxicity is that acute toxicity appears soon after an exposure whereas chronic toxicity occurs many months or years later. The period of time between an exposure and onset of chronic toxicity is known as the "latency period."
Police respond to a 911 call in which two people are found dead in an enclosed bedroom heated by an unvented kerosene stove. There was no sign of trauma or violence, a likely cause of death is:





Excess oxygen generated by the combustion of kerosene.




Acute toxicity due to uncombusted kerosene fumes.




Acute toxicity due to carbon monoxide poisoning.
Police respond to a 911 call in which two people are found dead in an enclosed bedroom, which is heated by an unvented kerosene stove. Since there was no sign of trauma or violence, a likely cause of death is acute toxicity due to carbon monoxide poisoning. The binding of carbon monoxide to hemoglobin is 245 times as strong as oxygen. Thus 0.1% carbon monoxide in air will bind 50% of the hemoglobin (since air contains 21% oxygen).
When toxicity occurs following several years' exposure to a chemical, the effect is known as:





Acute toxicity




Subchronic toxicity




Chronic toxicity
When toxicity occurs following several years' exposure to a chemical, the effect is known as chronic toxicity. It represents cumulative damage to specific organ systems and takes many months or years to become a recognizable clinical disease.
The process whereby a normal body cell becomes a cancer cell is known as:





acute toxicity




teratogenicity




carcinogenicity




nephrotoxicity
The process whereby a normal body cell becomes a cancer cell is known as carcinogenicity. The first step in this process is known as "cell transformation."
The difference between a benign tumor and a malignant tumor is:





A benign tumor does not cause health problems whereas a malignant tumor does.




A benign tumor is a controlled growth of cells whereas in a malignant tumor there is no control on the cell growth.




A benign tumor grows only at the site of origin whereas a malignant tumor may invade surrounding tissues and migrate to distant sites where it can spread.
The difference between a benign tumor and a malignant tumor is a benign tumor grows only at the site of origin whereas a malignant tumor may invade surrounding tissues and migrate to distant sites where it can spread. Another term for malignant tumor is "cancer."
Birth defects (teratogenic effects) are usually the result of:





Death or damage to critical cells of the developing fetus.




Mutations present in the parent's germ cells.




Both of the above.
Both mutations present in the parent's germ cells and death or damage to critical cells of the developing fetus can cause birth defects.
The term used to denote a substance that causes a change in the DNA of a cell is known as a:





mutagen




teratogen




carcinogen
The term used to denote a substance that causes a change in the DNA of a cell is known as a mutagen. The agent responsible for changes in the DNA of a cell is called a "mutagen." The process whereby a substance damages DNA is known as "mutagenesis."
Allergy is due to:





toxicity of the kidney




toxicity of the immune system




dermal toxicity




neurological conditions
Allergy is due to toxicity of the immune system. Allergic reactions may be systemic (e.g., shock, edema) or specific to one site (e.g., asthma or skin hives).