Exam 1 Flashcards
The interaction of chemicals in toxicology includes all of the following except:
Subtractive
Paracelsus was an expert in all of the following professions except:
Astrophysicist
Which of the following is not considered a phase II biotransformation?
Epoxide hydration
Toxicology may be defined as the study of:
The adverse effects of chemicals in living systems
Toxicants may move across biological membranes by all of the following mechanisms except:
Aqueous hydrolysis
Which of the following statements best characterizes synergism?
Synergism occurs if two chemicals with a similar action, when given together, produce an effect that is greater in magnitude than the sum of the effects when the chemicals are given individually
Biotransformation reactions generally produce a product that is:
less lipid-soluble than the original chemical
A toxicant’s distribution to a specific tissue does not:
Increase for xenobiotics that are bound to plasma proteins
High-energy cofactors that are NOT involved in phase II reactions include:
Amino acids such as taurine and glycine
Now that you know that all chemicals are toxic, which of the following corollary statements is false?
Exposure limits may be set for all chemicals that will instill confidence that we are safe from chemicals
Toxicology testing in the 21st century will include in silico testing of chemicals. Advantages are numerous when compared with standard bioassasys, but some problems still need to be worked out. These problems include:
Predictive analyses, more informative, and efficient
True or False. Pesticides are ubiquitous and present to the environment in a diversity of 900 ingredients composing 35,000 commercial products with billions of pounds being being released to the global environment annually.
True
Which type of pesticide inhibits the acetylcholinesterase enzyme and with chronic exposure may result in neuropathy characterized by weakness or paralysis of the arms and legs?
Organophosphates
Which of the following statements is false?
A. glucuronide conjugates are excreted readily by the kidneys
B. a lipid-soluble xenobiotic metabolite will sequester in fatty tissue
C. acidification of the urine may help trap acidic drugs in urine
D. for a weakly acidic drug (pKa+3) at equilibrium, the ratio of nonionized to ionized drug (HA/A-) equals 1 when the pH of the medium is 3
C. acidification of the urine may help trap acidic drugs in urine
Induction of xenobiotic biotransformation by exposure to a toxicant will:
Result in increased amounts of enzymes in the ER
Steps for liver ridding body of toxins
- introduce oxygen (phase I)
- create charge separated species (bioactivation)
- Mechanisms try and force compounds to elimination
- Tripeptide (GSH) sucks up reactive oxygen compounds (phase 2)
- Result is R-O-Y, eliminated in feces
What is risk assessment?
quantitative estimate of the potential effects on human health to illuminate the significance of exposure to chemicals in the environment
What is a poison?
any agent capable of producing a deleterious response in a biological system
What is the difference between a toxin and a toxicant?
toxin- produced by biological system (plants, fungi, animals, bacteria)
toxicant- produced or by-product of anthropogenic activity
What are the three stages in the history of toxicology?
- antiquity
- Middle Ages
- Age of Enlightenment
Who developed a method for arsenic analysis?
Marsh, 1836
Who developed a method for separating As and Hg?
Reinsh, 1841
Who detected and identified phosphorus?
Stas-Otto, 1951
What is the Delaney Cause (1958)?
any chemical found to be carcinogenic in lab animals or humans could not be added to the food supply
What is regulatory toxicology?
determining whether a drug or chemical poses a low enough risk based on mechanistic and descriptive data
What is mechanistic toxicology?
identifies and investigates cellular, biochemical, & molecular mechanisms by which chemicals exert their influence
What is descriptive toxicology?
concerned with toxicity testing and evaluating the safety of certain substances
What are the responsibilities of legislation?
- protect human health and the env. from pesticides and waste disposal
- conserve energy and natural resources
- reduce generated waste, and ensure waste is managed in an environmentally sound manner
How are toxic agents classified?
- target organ (i.e. hematopoietic system)
- use (i.e. pesticides)
- source (i.e. toxin/toxicant)
- effects (i.e. cancer/liver injury)
What are some undesired effects of toxic agents?
- allergic reactions/hypersensitivity
- immediate vs. delayed toxicity
- reversible vs. irreversible effects
- local vs. systemic toxicity
- interaction of chemicals
- tolerance
What is a hapten?
a molecule combines with an endogenous protein to cause an allergic reaction
What are the four ways chemicals interact?
- Additive (1+1=2)
- Synergistic (1+1=>2)
- Potentiation (0+1>1)
- Antagonism (1+1
What are the multiple mechanisms for antagonism?
- functional
- chemical
- dispositional
- receptor
What are the major routes of chemical exposure?
- ingestion
- inhalation
- dermal
- parenteral routes
What is slope indicative of in a dose-response relationship?
half life
What does time to toxicity depend on?
- frequency of administration
- dose level
- time to recover between doses
What is a quantal dose-response relationship?
- “all or non”
2. at any dose, any individual in the population either does or does not responsd
What is hormesis?
xenobiotics may cause stimulatory effects at low dose but adverse effects at high doses
Where do ED, TD, and LD lie on a dose-response graph by comparison?
ED- left shifted
TD- center
LD- right shifted
What is potency?
the range of doses over which a chemical produces increasing responses
What is allometry?
the study of the relationship between body weight and physiology
What is NOAEL?
no observable adverse effect level
What are the major functions of the liver?
- maintain metabolic homeostasis
2. bile formation
Where does bioreactivation (R-O-Y)?
hepatocytes
What are the three zones of the acinus, or functional hepatic unit?
- closest to the entry of blood
- intermediate
- abuts the terminal hepatic vein
What cells act as macrophages in the liver?
Kupffer cells
What happens when the liver dysfunctions due to toxins?
- high secretios of metabolites
- inhibition of bilirubin uptake
- inhibition of clotting factor secretion
What are some types of injuries of the liver due to toxic chemicals?
- fatty liver
- cell death
- canalicular cholestasis
- bile duct damage
- sinusoidal disorders
- fibrosis and cirrhosis
- tumors
What do activated Kupffer cells secrete?
cytotoxins (ROS and RNS)
What are phase I reactions?
hydrolysis
reduction
oxidation
What are phase II reactions?
conjugation
What components in phase II reactions can cause organ damage?
charge separated species
What are the steps in benzo(a)pyrene activation?
- receptor (AhR) bind to BAP to form complex
- ARNT pulls complex into nucleus
- Complex sits on a promoter
- Complex initiates expression of CYP450
What leads to suppression of hematopoiesis in bone marrow?
CYP450 activation of benzene
What is the goal of toxicology?
- hazard identification
- dose-response assessment
- exposure assessment
- risk characterization
What are the three most commonly used forms of asbestos used commercially?
Chrysotile
Amosite
Crocidolite
What diseases do fleas carry?
Plague
Murine typhus
What diseases do lice carry?
Typhus
Relapsing fever
What diseases do sand flies carry?
Pappataci fever
Three-day fever
Sandfly fever
Phlebovirus
What diseases can mice carry?
Rat-bite fever
Weil’s disease
Hantavirus pulmonary syndrome
What molecules do organophosphates and carbamates inactivate?
acetylcholinesterase
What are the manifestations of developmental toxicology?
- structural malformations
- growth retardation
- functional impairment
- death of the organism
What are some human developmental toxicants?
Radiation
Infection
Maternal trauma and metabolic imbalances
Drugs/chemicals
What is the threshold phenomenon in developmental tox?
That a maternal dosage below which an adverse response is not elicited because some repair or defense system is able to combat exposure
What maternal factors affect fetal development?
Genetics Disease Nutrition Stress Placental toxicity Maternal toxicity
What is the Barker Hypothesis (Susceptibility Exposure Paradigm)?
the effects of early childhood exposure may not be apparent until later in life
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What is step one of the mechanisms of toxicology?
Delivery from the site of exposure to the targe
What are the two possible outcomes of step one of the mechanisms of tox?
Absorption
Pre-systemic elimination
What path does a first-path effect take?
Drug Digestive system Portal circulation Liver Extensively metabolized
Where does reabsorption of chemicals take place?
kidney
GI tract
What is involved with the toxification of numerous chemicals?
formation of electrophiles
What are there no efficient elimination mechanisms for?
nonvolatile, highly lipophilic chemicals
What does phase II metabolism eliminate to prevent its biotransformation?
the ultimate toxicant
What is the second step of the mechanisms of tox?
reaction of the ultimate toxicant with target molecule
What is the third step of the mechanisms of tox?
cellular dysfunction and resultant toxicities
What is step 4 of the mechanisms of tox?
repair or dysrepair
What happens when repair fails in the mechanisms of tox?
Tissue necrosis
Fibrosis
Carcinogenesis
