ETOX 80e Midterm 1 Key

 

1.  Define:  Bioaccumulation, biomagnification, biotransformation, bioavailability

(16 points total)

 

Bioaccumulation (2 points)

            Process by which a substance concentrates in an organism to a higher level than in the    organism’s environment

 

Biomagnification (2 points)

            Process by which a substance reaches progressively higher concentrations in organisms as         it moves up the food chain.

 

Biotransformation (2 points)

            Process in which an organism chemically converts a substance into another form, or a completely new substance.  Substances are usually converted into less toxic forms by biotransformation, however it can also result in a more toxic compound.  This process is also referred to as metabolism, and is often a mechanism to convert lipophilic substances to more hydrophilic substances which can be more easily excreted.

 

Bioavailability (2 points)

            A measure of how readily a substance can be absorbed or taken up by a cell or organism. 

 

 

Provide an example of two different forms of a toxic agent which vary in their bioavailability, being sure to give which is more bioavailable, and why. (8 points)

 

            One answer could be the case of methyl mercury(CH3Hg+) and ionic mercury (Hg2+).  Methyl mercury is more bioavailable because it has a lower formal charge and an organic constituent, both of which make it more lipophilic than ionic mercury.  While ionic mercury must be actively taken up in order to enter cells, which isn’t likely since it has no known biological requirement, methyl mercury by its more lipophilic nature is believed to be able to passively diffuse into cells, where it can then cause damage.  Because methyl mercury is more lipophilic it is stored in fatty tissue, and is more readily biomagnified, making it more bioavailable at each trophic level transfer.

            Any answer must refer to differences in bioavailability as determined by chemical structure and cellular uptake mechanism.

 

 

 

 

 

 

2. Draw a cell membrane with the two primary types of ion channel/transporters, then list the routes of cellular input by each of the following classes of molecules across a cell membrane

      (16 points total):

             Charged (e.g., Hg2+)

             Polar (e.g., acetone – C3H6O)

             Organo-metallic (e.g., CH3HgCH3)

             Nonpolar organic(e.g., propane – C3H8)

 

            Possible figure (from www.omedon.co.uk/ionchan) with transmembrane protein for facilitated diffusion (such a porin) on the left, and an active uptake ion channel on the right. Figure(s) must include bilipid layer, or must have hydrophilic and hydrophobic regions of membrane labeled.

(4 points for each)

 

             Charged:          Active uptake, facilitated diffusion. (2 points)

             Polar:               Active uptake, facilitated diffusion. (passive diffusion accepted) (2 points)

             Organo-metallic:           Passive diffusion, facilitated diffusion. (2 points)

             Nonpolar organic:        Passive diffusion, facilitated diffusion. (2 points)

 

 

3. Discuss what factors affect toxicity (10 points).

           

(2 points for each factor listed up to max of 10 points)

            Factors affecting toxicity include intrinsic toxicity, magnitude of dose, duration of exposure, interspecies variation, individual sensitivity/genetic variation, gender, age/stage of development, nutritional status, status of immune system, uptake pathway, efficiency of metabolism, bioavailability, synergistic or potentiating interactions, chemical structure and potential to mimic other substances.

 

 

 

 

 

 

 

4. What is the linear no threshold model?  What are its limitations?  Give three examples of when it is not appropriate to use the linear no threshold model (20 points total).

 

(5 points) The linear no threshold model attempts to predict the dose response relationship for a given system at low concentrations or doses by extrapolating results determined at high concentrations or doses.  Implicit in this model is that the dose-response relationship is linear, that the relationship holds at all doses down to zero, and that there is no threshold of exposure below which there is no response, or the response ceases to be linear.  The first figure below shows an example of a linear no threshold model applied to experimental data. 

 

 

 

 

(5 points) The limitations for the linear no threshold model are:  (1) it predicts a response at all dose exposures, namely that there is no threshold below which a response does not exist; (2) it assumes the dose-response relationship is always linear; and (3) it assumes that the nature of the response is the same at all dose, which is to say the response can not change from a positive one to a negative at some small dose.  These assumptions implicit to the model are limitations because the model can not be accurately applied to substances or dose-response relationships which do not exhibit these attributes.

 

(5 points for figure(s), which must have axes labeled)

 

(5 points)  It is not appropriate to apply the linear no threshold model to all systems.  Three examples of when the linear no threshold model would inaccurately predict the dose-response relationship at low doses are the cases of:

 

1.      A threshold exists, below which there is no response, as shown in the Figure 1 below.  This could be for any toxicant which is detoxified at low concentrations by an enzyme, but when the process becomes saturated at some higher concentration adverse effects are manifested.

Figure 1.  Case of threshold
 

 

2.      The response at low doses is non-linear, as shown in the Figure 2 below.  An example of this could be the incidence of cancer caused by dioxins.

 

Figure 2.  Case of sub-linear response
 

 

 

3.      The system exhibits hormesis, as shown in the Figure 3 below.  An example of this is data from some studies showing positive effects of radiation at very low doses.

 

Figure 3.  Case of hormesis
 


5. Explain the differences in three plots of the same data below and give the advantages of each of them (20 points total).

Year

# of cadmium poisoning cases

2003

1000

2004

100

2005

300

 

 

 

 

 

 

(6 points) In the first figure (above) the scale of the y-axis is much greater that the largest data value.  The acts to make the magnitude of the number of toxic cadmium cases appear smaller than it would had the scale only been from zero to 1000.  This scaling would be an advantage were you attempting to make the number of toxic cadmium cases seem small or insignificant.  The data is plotted as the number of toxic cadmium cases per year, and is thus straight forward and easy to interpret. 

 

(8 points) In the second figure the data is plotted as percent change of toxic cadmium cases from the previous year.  The figure is useful in tracking any relative yearly changes, but doesn’t show the absolute number of cases.  This type of graph has the advantage of showing the change as a percentage, which may be substantial even if the absolute values involved are not.  This is the only graph of the three in which the value of the data plotted is greatest in the year 2005, and thus to the untrained eye could imply that cadmium toxicity has become more of a problem in the past year. However, the figure is showing the percent change from year to year, and not the absolute number of cases.  So while the absolute number of cases in 2003 was 1000 compared to only 300 cases in 2005, the graph only presents the decrease in cadmium cases of 90 percent from 2003 to 2004, and the following increase of 200 percent between 2004 and 2005.

 

      (6 points) The third and final figure shows the number of cases plotted again as a percentage over time, but here it is a percentage of the number of Cd cases relative to the number of cases in 2003, and not as the percent change of toxic cadmium cases from the previous year, as in the second figure above.  An advantage of this figure is that unlike Figure 1 above, the scale of this graph permits the data to be spread out over the entire y axis, allowing for a better visualization of the changes involved.  Again this figure doesn’t show any absolute numbers, but does permit a graphical comparison of the changes relative to a benchmark, in this case the year 2003, which would be directly proportional to the absolute values involved.

 

6. Draw a dose-response curve for a nutrient and a toxicant. Discuss similarities and differences, label important points, and provide a specific example of a compound that belongs in each category (32 points).

(from lecture notes and 10/6/05 handout and website)

 

 

12 points for 2 figures (2 curves @ 2 axes each, plus curve shape for each)

 

14 points:

Nutrient                                    Toxicant

NOEL                                      NOEL

LOEL/LOAEL             LOEL/LOAEL

Example                                   Example

(_D50                                        _D50)

 

 

6 points combined for:

Similarities

Toxic at high dose range

NOEL/LOEL/_D50 possible for both

 

Differences

Low dose region—nutrients are toxic (deficiency) while non-nutrients aren’t

Nutrients are essential, so they have an “optimum range” while non-nutrients don’t
7. What criteria should be considered in assessing the credibility of scientific reports (16 points)?

(from lecture notes and website)

 

 

Author(s) credentials

·         Degrees

·         Institution

·         Publications

Publication credentials (including internet)

·         Peer-review

·         Ranking

Publication Date

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

8. Which form of chromium is an essential trace nutrient, and which form is currently believed to only be a toxicant (4 points)? 

(from lecture notes and website)

 

Cr(III) is an essential trace nutrient

Cr(VI) is a toxicant

 

 

 

 

 

9. List 5 reasons contributing to declining amphibian populations (10 points).

(from 9/22/05 handout and subsequent class discussion)

 

Habitat depletion and modification

Increased UV due to ozone depletion

Natural population flux

Increased predation

Fungal/bacterial infections and other diseases

Diminished food supply (can be indirect UV)

Competition with non-native/invasive species

Pollution (acid rain, pesticides, industrial chemicals…)

Endocrine disruption

Over-harvesting for food

 

 

10. Discuss, including four different reasons in your answer, why animal testing should be used in the biological or medical fields (16 points).

(from 10/4/05 handout and subsequent class discussion)

 

 

Enables scientific progress in the identity of disease and routes of infection that is otherwise unattainable because this information is unknown in humans

Enables scientific progress on the treatment of disease that is otherwise unattainable because testing on humans is impractical, unethical, and technically illegal

Animals are effective models that can be used to hone techniques and optimize treatment options

Allows scientists to discover information about the whole-organism response to disease

Allows scientists to discover information about the whole-organism response to treatment for disease

Cell cultures cannot adequately represent the whole organism response

We need a “first pass” test with organisms before testing on humans
What are four principal exposure pathways for lead (8 points)?

(from 10/11/05 handout)

 

Paint

Automobile Emissions

Water (lead in water leached from lead pipes)

Food (crops due to agricultural automobile emissions, as well as lead soldered cans)

Certain occupational exposures (also hobbyists)

Medications/folk remedies

Pottery and pottery glazes

 

12. Define and describe (20 points): (from text Ch. 3, pp 58-60)

Absorption

What is taken up by the body upon exposure to a chemical.  Absorption occurs at the point of entry, if the person suffers anything greater than a local effect.  Absorption refers to how the body is “introduced” to a toxicant upon exposure.  Absorption can be via inhalation, ingestion (oral), or dermal routes

 

Distribution

Describes what happens to a chemical after it is absorbed by the body.  This refers to how it is distributed throughout the body, which usually occurs via the blood.  Distribution provides for delivery of the (toxic) compound to target tissues or organs.

 

 

Metabolism

How the body biotransforms (metabolizes) toxicants in an effort to get rid of (excrete) these foreign compounds.  The body usually biotransforms compounds to increase water solubility and therefore decrease toxicity, although sometimes the body’s metabolism of a compound results in a biotransformed/metabolized compound which is more toxic than the original parent.

Excretion

      How the body gets rid of a compound, which is typically through urine (water soluble) or feces (less water soluble).  Sometimes other routes of excretion are utilized (e.g. exhaling, mother’s milk), based on the chemical properties of the biotransformed/metabolized toxicant.

 

 

13. What are the three principal acids present in acid rain?  What are the sources of acid rain?

      (from lecture notes and website)

 

      HNO3, H2SO­4, and HCl

Source(s): Industrial emissions and fossil fuel combustion byproducts in rainwater which are not neutralized.