Various Concepts

Question 1

Define LD50. Define ED50.

Answer 1

LD50: dose (mg/kg body weight) required to kill 50% of an exposed test population.

ED50: dose required for 50% of exposed population to display measured endpoint (eg, sleep, excitability, birth defect)

Question 2

What is on the x-axis for an LD50 or ED50 curve?

What is on the y-axis?

Answer 2

X-Axis: concentration of chemical

Y-Axis: % endpoint
–for LD50, endpoint = death

Question 3

What is the type of exposure that corresponds to each of the following terms?

–single, one-time exposure

–repeated exposure at doses lower than can cause death

–long term exposure (90 days) at low dose

–long term exposure to levels not capable of causing immediate death

Answer 3

Acute Exposure
–single, one-time exposure

Subacute Exposure
–repeated exposure at doses lower than can cause death

Subchronic Exposure
–long term exposure (90 days) at low dose

Chronic Exposure
–long term exposure to levels not capable of causing immediate death

Question 4

List 5 factors that influence why individuals can have different responses when exposed to the same dose of a particular chemical.

Answer 4

1. Age
2. Lipid Content
3. Body Weight
4. Social Factors/Placebo Effect
5. Genetic/Species Differences

Question 5

What is the main factor determining a compound’s aqueous solubility?

What ratio does the Ksp represent for inorganic compounds?

Inorganic compounds are soluble in what form?

Answer 5

(Aq) solubility determined by polarity of compound.

Ksp: ratio of ionized (soluble) to un-ionized (insoluble) forms

Inorganic compounds are soluble in ionized form only

Question 6

What factor determines the order of solubility for different classes of organic compounds?

Which organic compounds are more soluble? Which are less soluble?

Answer 6

The order of solubility is based on polarity.

Alcohols > Aldehydes > Organic Acids > Ketones > Aliphatics > Aromatics > Chlorinated Compounds

Question 7

What is the vapor pressure?

What does the vapor pressure indicate in terms of chemical fate and transport?

Answer 7

Vapor Pressure = pressure exerted by vapor onto the liquid

VP estimates ability of compound to volatilize.

Question 8

State Henry’s Law.

Answer 8

Under eq conditions, the partial pressure of a gas above a liquid is proportional to the concentration of the chemical in the liquid

Pg = (H) x (C)
Pg = partial pressure of gas
H = Henry's constant
C = [chemical] in the liquid

Question 9

What does Henry’s constant estimate?

What two factors is Henry’s constant a balance between?

Answer 9

Henry’s constant estimates degree to which an organic compound will volatilize out of water into air.

Balance between vapor pressure and water solubility.
(H = (Pv) / (S)

Question 10

The biocentration factor estimates the ability of a substance to bioaccumulate in an organism. What is the ratio that describes the BCF?

Answer 10

BCF = [chemical] in organism / [chemical] in water

Question 11

Kow = Octanol/Water Partition Coefficient

What does this coefficient approximate?

Kow = Co / Cw

What do Co and Cw stand for?

Answer 11

Kow approximates potential for bioaccumulation in fish and animal tissue

Kow = Co / Cw
Co = [chemical] in octanol phase
Cw = [chemical] in aq phase

Question 12

Soil adsorption: the extent to which an organic chemical partitions itself between the solid and solution phases of saturated soil

Koc = soil adsorption coefficient

What 3 factors will promote soil adsorption?

Answer 12

3 factors to promote soil adsorption

• -high surface area/fine particle size
• -high organic carbon content
• -low water solubility

Koc = [chemical] in soil / [chemical] in water

Question 13

What are 3 ways in which organic materials can be biodegraded?

1. organism uses chemical as food source
2. cometabolism
3. organism adapts to metabolize “xenobiotic” material

What is cometabolism?

Answer 13

Cometabolism is the simultaneous degradation of two compounds, in which the degradation of the secondary substrate depends on the presence of the primary compound.

Question 14

What are 4 factors affecting transport across cell membranes?

Answer 14

1) lipid solubility
2) molecule size
3) concentration gradient
4) presence of transporters or channels

Question 15

Define reference dose, LOAEL, and NOAEL.

Answer 15

RfD = chronic daily lifetime dose (mg/kg per day) that is acceptable to all members of human population, at a high level of confidence; LOAEL = lowest dose at which adverse effects are observed; NOAEL = highest dose at which no adverse effects are observed

Question 16

To determine RfD, identify NOAEL for most sensitive species and endpoint. Then apply what (5) safety factors at 10x.

Answer 16

To determine RfD, identify NOAEL for most sensitive species and endpoint. Then apply safety factors at 10x:

• -general variability in humans
• -extrapolation of animal data to humans
• -using subchronic data for chronic
• -using LOAEL instead of NOAEL
• -additional margin

Question 17

Use basic math to describe concepts of additive effects, antagonistic effects, and synergistic effects. Provide (1) example of competing mechanism for antagonistic effect. Describe (3) modes of synergy and provide (1) pre-exposure synergy example.

Answer 17

Additive (1 + 1 = 2); Antagonistic (1 + 1 = 0) (alcohol + caffeine); Synergistic (1 + 1 = 25); increased bioactivation, increased potency, reduced excretion; ex: pre-exposure with C-Cl4 for isooctane

Question 18

Describe the concept of a toxicity “threshold.”

Answer 18

Threshold: minimum dose at which toxic effects are produced

Question 19

Describe the basic steps in carcinogensis. What is required to form a mutation? What is required for the pre-neoplastic cell to become a tumor?

Answer 19

Question 20

What does the cancer slope factor estimate?

What type of assays is the CSF based on?

What is the targeted precision?

Answer 20

CSF estimates excess cancer risk for every additional mg/kg per day of exposure

(CSF = change in risk / change in exposure)

based on animal bioassays; targeted precision is 1 in a million

Question 21

Describe (3) conservative assumptions incorporated in calculation of CSF.

Answer 21

1. extrapolates high dose lab animal exposures to low dose environmental exposures
   2) uses 95% upper CL at low dose
   3) lifetime and acute exposures treated the same (assumes additive risk)

Question 22

What is the basic formula for calculating chronic daily intake (CDI)?

Answer 22

CDI = mg/kg per day of exposure over entire lifetime

Question 23

What is the basic formula that explains the relationship between hazard quotient (HQ or HI), CDI, and RfD? Describe what the HQ tells us about the exposure related to the RfD. How are HQs used in an environmental risk assessment?

Answer 23

HQ = CDI / RfD; if HQ < 1, then exposure is below RfD; if HQ > 1, then exposure > RfD; in risk assessments, the HQs for a series of chemicals are added up, even though the effects of those chemicals aren’t necessarily additive.