Toxicology Study Guide

TK Modeling, Target Organ Toxicity,

Toxicokinetic modeling

A way to quantify the amount and rate of chemicals moving through an organism

Pharmacokinetic modeling

the administrated dose of drugs rather than the concentration of contaminants in surrounding media

zero order kinetic process

when the rate of loss is constant over time

First Order kinetic process

When elimination is initially rapid but then slows

Elimination Models (2)

Derived form and Integrated form

Simplistic Model

Entire body is a single compartment

Constant Infusion Model

Accounts for chemicals coming into at the same time that its being eliminated/metabolized

Concentration in Organism (C_a)

The summed concentration of a given chemical in an organism

Media Concentration

The summed concentration of a given compound in all external compartments of the summed media

Parent Concentration (C_p)

Concentration of non-metabolized form of a given compound in the organism or surrounding media

Metabolite Concentration (C_m)

Concentration of a single metabolic product in the organism or surrounding area

Steady State Concentration (C_ss)

Concentration of a compound in an organism when uptake rate = elimination rate

Uptake Clearance Coefficient (K_u)

Amount of surroudning media that is completely cleared of compound per gram of organism per hour

Elimination Coefficient (K_e)

Rate of elimination of a given compound from an organism 

Function of Toxic Chemicals

Disruption of target molecule activity, destruction of target molecule activity, triggering an immune response, disruption of biological environment

Cellular Toxicity

Toxic agent, disrupts any number of cellular processes that could result in cell dysfunction/death

Narcosis

General disruption of cell membranes

Two Types of narcosis

Polar and non polar narcosis

Two Theories on Narcosis

Critical volume theory, protein binding theory

Respiratory Uncouplers

“Uncouple” two processes of electron transport and ATP production during cellular respiration

Respiratory Blockers

Interferes with cellular respiration at the electron transport chain

Respiratory Blocker Examples

Cyanide, carbon monoxide, rotenone

Mutagens 

Detrimental effect to genetic materials and processes

Reactive Oxygen Species 

Mutagens that react with DNA, RNA and proteins

Oxidative Stress

Formation of excess ROS during periods of stress from UV, heat, chemicals

Carcinogensis

Substance that cause cancer

Hepatotoxin

The liver is a major metabolic organ in vertebrates and serves many functions

Acinus

Metabolic functional unit of liver, Divided into 3 zones that differ in terms of blood oxygen concentration

Necrosis

Destruction of cells in living tissue

Aflatoxin

Produced by certain grain fungi

Microcystin

Produced by certain species of cyanobacteria

Hepatitis

Inflammation of the liver

Cirrhosis

Caused from longer term abuse of grain alcohol and characterized by the presence of scar tissue and regenerative lumps

Neoplasm

Growth of abnormal masses of tissue or tumors due to long term exposure to chemicals like vinyl chloride that can result in neoplasia

Jaundice/ hepatic steatosis

Two common symptoms: Yellowish skin and fatty liver

Nephrotoxins

Blood enters and exits the kidney via renal artery/ renal vein

Nephron

Functional unit of the kidney

Ways that toxins can damage kidneys

Mechanical damage, damage to nephron tubules, nephropathy

Nephropathy

Damage/ inflammation of neurons, chemicals can affect glomerular filtration rate, causing large proteins ot leak into urine

Neurotoxicity Mechanisms

Neuropathies, axonpathies, myelinopathies, neurotransmitter associated toxicity

Chemicals Stimulating Neurotransmitters

Acetylcholinesterase Inhibitor, plant/animal toxins, amphetamines, insecticides

Chemicals Inhibiting Neurotransmitters 

Alcohol, barbiturates/ benzodiazepine, antihistamines, muscle relaxants 

Tetratogenesis

Disruption of reproductive/developmental processes

Disruption of pre-zygotic

may inhibit speratogenesis, sperm/ egg can be destroyed

Disruption of Post Zygotic

Disrupting developmental processes occurring after successful formation of a zygote

Endocrine dysruption

Cause effects at different levels such as endocrine glands with incorrect hormone levels, blocking hormones, or mimicking endogenous hormones

Examples of Endocrine disruptors

Pesticides, ethinylestradoil, phthalates, bisphenol A, isoflavones