Various Concepts Flashcards
Define LD50. Define ED50.
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)
What is on the x-axis for an LD50 or ED50 curve?
What is on the y-axis?
X-Axis: concentration of chemical
Y-Axis: % endpoint
–for LD50, endpoint = death
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
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
List 5 factors that influence why individuals can have different responses when exposed to the same dose of a particular chemical.
- Age
- Lipid Content
- Body Weight
- Social Factors/Placebo Effect
- Genetic/Species Differences
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?
(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
What factor determines the order of solubility for different classes of organic compounds?
Which organic compounds are more soluble? Which are less soluble?
The order of solubility is based on polarity.
Alcohols > Aldehydes > Organic Acids > Ketones > Aliphatics > Aromatics > Chlorinated Compounds
What is the vapor pressure?
What does the vapor pressure indicate in terms of chemical fate and transport?
Vapor Pressure = pressure exerted by vapor onto the liquid
VP estimates ability of compound to volatilize.
State Henry’s Law.
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
What does Henry’s constant estimate?
What two factors is Henry’s constant a balance between?
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)
The biocentration factor estimates the ability of a substance to bioaccumulate in an organism. What is the ratio that describes the BCF?
BCF = [chemical] in organism / [chemical] in water
Kow = Octanol/Water Partition Coefficient
What does this coefficient approximate?
Kow = Co / Cw
What do Co and Cw stand for?
Kow approximates potential for bioaccumulation in fish and animal tissue
Kow = Co / Cw Co = [chemical] in octanol phase Cw = [chemical] in aq phase
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?
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
What are 3 ways in which organic materials can be biodegraded?
- organism uses chemical as food source
- cometabolism
- organism adapts to metabolize “xenobiotic” material
What is cometabolism?
Cometabolism is the simultaneous degradation of two compounds, in which the degradation of the secondary substrate depends on the presence of the primary compound.
What are 4 factors affecting transport across cell membranes?
1) lipid solubility
2) molecule size
3) concentration gradient
4) presence of transporters or channels
Define reference dose, LOAEL, and NOAEL.
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
To determine RfD, identify NOAEL for most sensitive species and endpoint. Then apply what (5) safety factors at 10x.
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
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.
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
Describe the concept of a toxicity “threshold.”
Threshold: minimum dose at which toxic effects are produced
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?
What does the cancer slope factor estimate?
What type of assays is the CSF based on?
What is the targeted precision?
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
Describe (3) conservative assumptions incorporated in calculation of CSF.
- 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)
What is the basic formula for calculating chronic daily intake (CDI)?
CDI = mg/kg per day of exposure over entire lifetime
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?
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.
