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What are the three major routes of exposure in toxicology?
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What are the two types of time element in exposure?
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What factors affect the rate of absorption of chemicals?
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What is the general scheme of xenobiotic absorption?
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What governs the fate of a chemical in the body?
The ability of a chemical to move across biological membranes
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What are the components of biological membranes?
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What determines how well a chemical is absorbed?
The physicochemical properties of the molecule
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What is the role of membrane phospholipids in absorption?
They are amphipathic with polar and nonpolar components
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How does the chemical structure of a compound affect its behavior in the body?
It determines interaction with biological macromolecules
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What is the amphipathic nature of the lipid bilayer?
It presents a substantial barrier to movement of ionized highly polar compounds.
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What does a high partition coefficient indicate?
Greater lipophilicity of the compound.
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What is the formula for the partition coefficient?
\(K_{ow} = \frac{\text{concentration in octanol}}{\text{concentration in water}}\)
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What are the characteristics of a compound that crosses a biological membrane easily?
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What does the Henderson-Hasselbalch equation calculate?
The degree of ionization based on pH and pKa.
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How does pH affect the ionization state of weak acids or bases?
It can markedly change the ability to pass across membranes.
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What is the water solubility of P,p'-DDT?
0.003 ppm
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What is the partition coefficient of 2,4-D?
\(6.5 \times 10^2\)
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What is the water solubility of Phenoxyacetic acid?
12000 ppm
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What are the terms that describe lipid/water solubility?
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What does the term lipophobic mean?
Hates lipid.
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What does the term hydrophilic mean?
Likes water.
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What is illustrated in the cell membrane diagram?
Phospholipid bilayer, proteins, cholesterol, carbohydrate chains.
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What is the Henderson-Hasselbalch equation used for?
It relates pH, pKa, and the ratio of ionized to unionized forms of a compound.
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What does pKa represent?
The pH point where 50% of the test compound is ionized and 50% is unionized.
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What is the pKa of benzoic acid?
4
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What is the pKa of aniline?
5
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What type of compound is benzoic acid?
A weak acid and a proton donor.
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What type of compound is aniline?
A weak base and a proton acceptor.
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What is favored when pH is below pKa for weak acids?
Absorption is favored because the unionized form predominates.
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What happens to absorption when pH is above pKa for weak acids?
Absorption is not favored as the ionized form predominates.
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What is the effect of pH = 2 on the absorption of benzoic acid?
Absorption is favored, HA/A- = 100/1, anti-log = 100.
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What is the effect of pH = 5 on the absorption of benzoic acid?
Absorption is not favored, HA/A- = 1/10, anti-log = 0.1.
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What is the most important mechanism for movement of chemicals across biological membranes?
Passive transport diffusion.
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What factors affect the rate of diffusion across membranes?
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Why do ionized compounds not move readily by diffusion?
Due to low lipid solubility.
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What is the process of filtration in membranes?
Membranes have pores that allow low molecular weight compounds (< 100) to pass, e.g., water, ethanol. Larger molecules are filtered in the kidney via glomerular filtration.
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What are the two types of endocytosis?
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What is active transport?
A membrane carrier protein binds to a toxicant, ferries it across the membrane, and releases it on the other side. It requires energy (ATP) and can be rapid and saturable.
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What are the characteristics of active transport?
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Where are the vulnerable sites for absorption of chemicals?
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What are the layers of the skin?
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What does the epidermis do in terms of absorption?
The epidermis varies in thickness (0.1-0.8 mm) and is crucial for the absorption of toxicants. Different body areas show varying absorption abilities.
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What are the three major routes of exposure in toxicology?
What are the two types of time element in exposure?
What factors affect the rate of absorption of chemicals?
What is the general scheme of xenobiotic absorption?
What governs the fate of a chemical in the body?
The ability of a chemical to move across biological membranes
What are the components of biological membranes?
What determines how well a chemical is absorbed?
The physicochemical properties of the molecule
What is the role of membrane phospholipids in absorption?
They are amphipathic with polar and nonpolar components
How does the chemical structure of a compound affect its behavior in the body?
It determines interaction with biological macromolecules
What is the amphipathic nature of the lipid bilayer?
It presents a substantial barrier to movement of ionized highly polar compounds.
What does a high partition coefficient indicate?
Greater lipophilicity of the compound.
What is the formula for the partition coefficient?
\(K_{ow} = \frac{\text{concentration in octanol}}{\text{concentration in water}}\)
What are the characteristics of a compound that crosses a biological membrane easily?
What does the Henderson-Hasselbalch equation calculate?
The degree of ionization based on pH and pKa.
How does pH affect the ionization state of weak acids or bases?
It can markedly change the ability to pass across membranes.
What is the water solubility of P,p'-DDT?
0.003 ppm
What is the partition coefficient of 2,4-D?
\(6.5 \times 10^2\)
What is the water solubility of Phenoxyacetic acid?
12000 ppm
What are the terms that describe lipid/water solubility?
What does the term lipophobic mean?
Hates lipid.
What does the term hydrophilic mean?
Likes water.
What is illustrated in the cell membrane diagram?
Phospholipid bilayer, proteins, cholesterol, carbohydrate chains.
What is the Henderson-Hasselbalch equation used for?
It relates pH, pKa, and the ratio of ionized to unionized forms of a compound.
What does pKa represent?
The pH point where 50% of the test compound is ionized and 50% is unionized.
What is the pKa of benzoic acid?
4
What is the pKa of aniline?
5
What type of compound is benzoic acid?
A weak acid and a proton donor.
What type of compound is aniline?
A weak base and a proton acceptor.
What is favored when pH is below pKa for weak acids?
Absorption is favored because the unionized form predominates.
What happens to absorption when pH is above pKa for weak acids?
Absorption is not favored as the ionized form predominates.
What is the effect of pH = 2 on the absorption of benzoic acid?
Absorption is favored, HA/A- = 100/1, anti-log = 100.
What is the effect of pH = 5 on the absorption of benzoic acid?
Absorption is not favored, HA/A- = 1/10, anti-log = 0.1.
What is the most important mechanism for movement of chemicals across biological membranes?
Passive transport diffusion.
What factors affect the rate of diffusion across membranes?
Why do ionized compounds not move readily by diffusion?
Due to low lipid solubility.
What is the process of filtration in membranes?
Membranes have pores that allow low molecular weight compounds (< 100) to pass, e.g., water, ethanol. Larger molecules are filtered in the kidney via glomerular filtration.
What are the two types of endocytosis?
What is active transport?
A membrane carrier protein binds to a toxicant, ferries it across the membrane, and releases it on the other side. It requires energy (ATP) and can be rapid and saturable.
What are the characteristics of active transport?
Where are the vulnerable sites for absorption of chemicals?
What are the layers of the skin?
What does the epidermis do in terms of absorption?
The epidermis varies in thickness (0.1-0.8 mm) and is crucial for the absorption of toxicants. Different body areas show varying absorption abilities.
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