Test 2 Review

1. Explain how experimental data from animal studies are extrapolated to people.

by mg/kg body weight: on a body weight basis, humans are generally 10-times more susceptible than animals
by surface area: related to body weight2/3: determine surface area by empirical formula:
m2= K W2/3 /100, K=species specific factor (rats=9; 70 kg human=10.6), W = body weight in kg.

2. What is the advantage of using an animal’s surface area as a dose criterion?

Estimates amount of absorption

3. Why are high doses of chemicals used in animal studies?

a minimum of 30,000 animals would be required to detect a 0.01% incidence of cancer (20,000 in 200,000,000) and
mathematical low-dose extrapolation methods are then employed to estimate human risk associated with lower, “real
world” chemical exposures....

4. Does a short-term acute animal study accurately predict all types of toxicity?

NO. goals are to determine potency relative to other toxicants, identify target organs, and determine if reversible

5. What is a carcinogen? Are all carcinogens “created equal”?

bstance, radionuclide, or radiation that is an agent directly involved in causing cancer. NO. different levels

6. How are carcinogens ranked in the IARC classification scheme?

CONFIRMED, probable, possible, not classified, probably not

7. Explain how you would conduct an Ames assay, including all assay components.

Rat liver (S9)

His Salmonella DNA
Test Chemical
Top agar

MIX and POUR. Incubate at 37C for 48 HRS, count his colonies

8. Describe the process of risk assessment and risk management.

9. Identify and describe the three major types of epidemiology studies, and their advantages and disadvantages.
Case-control or “retrospective”—what are the cause(s) of the observed disease?
Cohort or “prospective” “longitudinal” – what disease(s) will be caused by an exposure?
Cross-sectional- “horizontal” – what is the exposure and outcome of a population at a single time point?

10. What are the Hill’s Criteria for Causation?

Association is strong --- higher relative risks being more likely to indicate cause…,
Risk increases or decreases with exposure in a dose-responsive gradient
Consistent findings in several studies with different investigators, different populations, and different designs
Exposure (cause) precedes the disease
It is biologically plausible that exposure could cause the disease;
The association is specific between exposure and a single disease
Epidemiologic findings fit coherently with information with other types of research and other epidemiologic studies.

11. Explain how data from animal studies are extrapolated to determine risk to “real world” doses of chemicals people
are typically exposed to.

12. What is a reference dose, and how is it calculated?

RfD = NOAEL / Uncertainty Factor. These standards represent “safe” exposure limits that won’t result in an excess
incidence (usually > 1/106) of adverse health effects

1. arbitrary—by definition must be one of the experimental doses selected

2. once selected, rest of dose-response is ignored
3. experiments using fewer animals result in higher NOAEL values…
4. may not be available or reliable
5. depends on experimental design

13. When is benchmark dose used to determine risk?

BMD = BMDL/UF

14. What is the difference between a reference dose, an acceptable daily intake and a threshold limit value?

A reference dose is the United States Environmental Protection Agency's maximum acceptable oral dose of
a toxic substance

Acceptable daily intake or ADI is a measure of the amount of a specific substance (usually a food additive, or a residue
of a veterinary drug or pesticide) in food or drinking water that can be ingested (orally) on a daily basis over a lifetime
without an appreciable health risk

The threshold limit value (TLV) of a chemical substance is a level to which it is believed a worker can be exposed day
after day for a working lifetime withoutadverse health effects

15. What are some factors that determine the uncertainty factor?

Extrapolation: animal-to-human
• Extrapolation: human-to-human
• Experimental inadequacies:
o Less-than-lifetime exposure in animal studies
o Variations in NOAEL, LOAEL between studies
o Absence of NOAEL (extrapolation from LOAEL)
16. Define the “Precautionary Principle,” and explain its impact environmental toxicology.

precautionary principle or precautionary approach states that if an action or policy has a suspected risk of causing harm
to the public or to the environment, in the absence of scientific consensus that the action or policy is harmful,
the burden of proof that it is not harmful falls on those taking the action. Preponderance of evidence

17. What is a biomarker? Give four examples of chemical biomarkers and explain how they arise in the human body.
Based on the chemical itself, a metabolite of the chemical, a biochemical endpoint of toxic effect

Aniline methemoglobin blood

Toluene Hippuric acid urine
Toluene Toluene blood
Toluene o-cresol urine

18. What is the TRI?

Toxic Release Inventory

19. What is a PBT chemical, and why is it important?

Persistent, Bioaccumulative, and Toxic

1. Name four factors influencing chemical adsorption to soil. Name four factors influencing chemical evaporation from
water.

surface area, presence of charged sites, hydrogen bonding sites, hydrophobic areas

Surface area of soil, degree of ionization of chemical, soil type, sand binds poorly, evaporation, leeching, introduce
organic mulch to contain spills, water can displace chemicals from soil, excavate quickly

Octanol water coefficient, concentration, temperature, vapor pressure, degree of ionization

2. Why does a weak acid like the pesticide 2,4-D bind poorly to clay?

Acidic pesticide would be repelled from cation exchange sites. Positive charges bind to clay.

3. Calculate the theoretical proportion of the herbicide amitrole (pK = 3.0) that would bind to kaolinite clay at pH 6.

Amitrole is a base. At pH 6, will be neutral

4. Describe how the following chemical characteristics affects evaporation from soil: vapor pressure, temperature, soil
moisture and soil type.

Vapor pressure – higher vapor pressure evaporates more quickly

Temperature – vapor pressure increases with temperature
Soil moisture – wetter soil evaporates chemical more quickly
Soil type – dark, rich soil binds chemical due to more cation exchange sites, lots of ring groups/R-groups

5. Why aren’t chemicals with a low Kow biomagnified significantly?

Biomagification requires being lipid soluble. Have higher half-life in general and higher half-life in animals.

6. How does a chemical’s H value affect its evaporation from water?

H = Pv/S S = water solubility of chemical Pv= vapor pressure of the chemical
High Solubility of a chemical lowers henry’s law gas constant
Vapor pressure is proportional

7. How is EM calculated, and how does it relate to chemical Kow?

Ecological magnification (concentration in organism vs concentration in water) predictor for biomagnification in

environment

concentration in organism/concentration in water

8. What is the Farm Pond, and how is it used to predict biomagnification?

Mini ecosystem with plants, animals

9. What is the theoretical maximum body burden of lead assuming a constant daily exposure of 0.02 mg, and a first
order excretion rate of 10-4/day.

Xmax = k1/k2
t0.5 = 0.693/k2

Xmax k1/k2 0.02 x 1E4 485 days to plateau max burden achieved over 7 half lives 200 mg
Plateau occurs because of equil reached between intake and excretion

10. You are attempting to clean-up 5800 gallons of aniline on US Hwy 89, 5 miles east of Logan. The majority of the spill
is on the road shoulder adjacent to the Logan River near the intake for the city’s water supply. Aniline (pK= 5) has an
appreciable vapor pressure. The soil on the spill site is a sand/clay mixture (pH 6.5) but little organic matter; easterly
(i.e., towards town) winds, warmer temperatures and probable rain showers are forecast. In detail, a) what are your
immediate steps to reduce harm to people?;

b) assess the chemodynamics that will determine the movement of aniline from the immediate site (consider all routes);

c) detail the best course of action you would take to contain the spill, to minimize the spread of contamination to the
local environment as well as to the inhabitants of Logan.