Environmental Science 102 W Fall 2005
Set I

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Exercises, problems, and questions highlighted in green are your assignments in addition to the reading.  Unless I indicate that these are to be turned in, they are to be treated as exercises to help you learn the material.

Words in bold type are terms you should remember for definitions, fill in the blanks. Warning: I'm not saying that a term or definition can't be asked about unless it's in bold type. The bold type to help you see the important terms.

First assignment: Please send me an email (wyman@mcneese.edu) saying you've made it to this point.

FYI Second assignment: Browse these sites. I have briefly annotated them. There is no written assignment for you to send in for this; this is just orientation.

USEPA pages. The following annotation is my review of www.epa.gov for the journal Choice, which appeared in the April 1998 issue:

2. Louisiana Department of Environmental Quality. Despite what you may have heard, Louisiana has a strong environmental protection agency.

3. Sites with long lists of other environmental quality sites.

• The Environmental Professional's Page

• MSU library guide to environmental information

Web lecture material starts here:

Introductory material: basic scientific background to environmental problems

Fundamental units, examples

1. Length: meter

2. Mass: gram

3. Time: second

4. Temperature: Fahrenheit, Celsius, Kelvin. F and C are relative scales; the Kelvin scale expresses absolute temperature. In the Kelvin scale, 0 means zero temperature; not so with the F and C scales. Ask question.

Derived units
Area = length x length, e.g. meter x meter = square meter (m2)

Volume = length x length x length, e.g. meter x meter x meter = cubic meter (m3)
                Liter a volume unit = 0.1 m x 0.1m x 0.1 m = 0.001 m3= 1.0 liter
                Therefore 1.0 m3 = 1000 liters
                The above comes from this: (0.001 m3) * 1000 = 1.0 liter * 1000

Density = mass/volume, e.g., grams/m3 or milligrams/liter

Unit prefixes:

Pollutant concentration expressions

1. mass of pollutant/volume of water, e.g. 4 mg lead/liter of water

2. mass of pollutant/volume of air, e.g. 3 mg particulate matter/liter of air

3. mass of pollutant/mass of soil, e.g. 7 grams of iron/kilogram of soil

4. volume of pollutant/volume of air, e.g. 2 liters of carbon monoxide/cubic meter of air

Note that the amount of pollutant is always in the numerator and the amount of the environmental medium (air, water, soil) is always the denominator of the concentration ratio.

Concentrations are expressed per single unit of the environmental medium. For example, if there are 4 milligrams of zinc in 8 kilograms of soil, the concentration is expressed as 0.5 mg zinc per one kilogram soil, 0.5 mg Zn/kg soil.

Example: see the U.S. Environmental Protection Agency drinking water standards. The MCL in the table stands for Maximum Contaminant Level, MCLG stands for Maximum Contaminant Level Goal. Don't worry about these regulatory terms for now; just notice that the standards are given as mg/L, which is milligrams (of the chemical) per liter of (drinking) water. Look down the table for fluoride. Its standard is 4.0 milligrams of fluoride per liter of drinking water. You see, then, that if you drank 0.25 liter of water, it should contain no more than 1.0 milligram of fluoride?
Ask question.

Questions:

1. What is an “environmental medium”?

2. List three examples of an environmental medium.

3. In a concentration expression, is the amount of the pollutant in the denominator or the numerator?

4. In a concentration expression, is the amount of the medium in the denominator or the numerator?

5. If 50 mg of lead are found in 10 kilograms of soil, the preferred concentration expression is

   a. 10 kilograms of soil per 50 mg of lead

   b. 50 mg of lead per 5 kilograms of soil

   c. 5 mg of lead per kilogram of soil

Problem set #1

This assignment is for units practice. Ask question.

Assignment:
1. Contrast the F, C, and kelvin scales in terms of the freezing point of water.
2. You weigh 1.2 liters of water and the scale reads 1.3 kilograms. What is the density of water, in grams per liter?
3. Air volume is expressed in cubic meters. If an air pump works at 2.5 liters per minute for one hour, how many cubic meters of air has the pump moved?
4. If there are 56 liters of carbon monoxide in 2 cubic meters of air, express as a) liters CO/m3 of air and b) liters CO/liter of air.
5. What is the Maximum Contaminant Level for nitrite, in mg/L? (You've got the web link.)

Answers
1. 32 F, 0 C, 273 K
2. 1.3 kilograms = 1300 grams. 1300 grams divided by 1.2 liters of water = 1083.3 grams per liter
3. 2.5 liters per minute times 60 minutes = 150 liters of air. 150 liters of air times 1 cubic meter per 1000 liters = 0.15 cubic meters.
4. a) 56 liters of CO in 2 cubic meters of air = 28 liters of CO in 1 cubic meter of air.
b) 2 cubic meters of air times 1000 liters per 1 cubic meter = 2000 liters of air. 56 liters of CO in 2000 liters of air = 0.028 liters of CO in 1 liter of air.
5. 1 mg/liter for nitrite. For nitrate, 10 mg/liter.

Chemistry
This is only a short list of basic terms and definitions. The definitions are not meant to be rigorous, but are a rough and ready review for our present purposes.

• Elements - fundamental building blocks of the material world. 103 have been identified. Can't be broken down into smaller components and still retain their properties.

• Atoms - smallest units of elements.

• Compounds - chemical substances made up of two or more elements. E.g. two hydrogen atoms and one oxygen atom, H2O.

• Molecules - smallest units of compounds. Water molecule, H2O.

• Mixtures - Combinations of two or more compounds. They are not chemically bound, but can be separated physically. Much of the natural world  (the atmosphere, water bodies, soil) is composed of mixtures. Therefore, pure air, pure water, and pure soil are misnomers: they are complex mixtures and can't be "pure" substances in the sense of being all "air", all "H2O", etc. Distilled, deionized water (pure water) is only found in the laboratory. Most pollutants in the air, water, or soil are part of a mixture.

Chemistry links: (FYI)
General Chemistry Basics
General Chemistry Tutorial

What is pollution?

Pollution is not self-defining.
1. Nature is not pure. See the mixtures discussion above.
2. Natural emissions of many chemicals that we call pollutants exceed human emissions of those pollutants. But human emissions are more localized and concentrated than are natural emissions, which are released all over the planet, mainly by bacteria and vegetation. Each natural emission point (e.g.,one bacterium) releases an infinitesimal amount, but the number of natural emission points is very large. When summed over the entire planet, natural emissions of some chemicals then exceed those from human activities. The natural emissions do not reach concentrations that would be considered polluting levels. Again, contrast this with human emissions, which can cause excessive concentrations when they are released from urban/industrial areas (localized and concentrated).

Synthetic organic compounds, as we use the term here, are chemicals created and produced by human activity and that do not exist in nature. It is possible that a compound that exists in nature will be synthesized (manufactured) by humans copying the natural molecule. For example, vitamin C can be extracted from citrus fruits or ascorbic acid (vitamin C) can be created from basic chemical building blocks in a laboratory or manufacturing setting. In this case the molecules made by nature and those made by man are the same.

Back to synthetic organics. These mostly contain carbon, hydrogen, and chlorine atoms and are also called chlorinated hydrocarbons. If these chemicals, which do not exist naturally, are found in the environment they are an indicator of human emissions.

Why are synthetic organic compounds troublesome? One, they are toxic at elevated concentrations, both to wildlife and to humans. Two, they are persistent in the environment, i.e., they remain present in the soil, air, or water for extended time periods compared with natural chemical compounds. Three, the synthetic organics can be bioaccumulated in wildlife and can be biomagnified in the food chain.

Bioaccumulation versus biomagnification.
Bioaccumulation is the increase in concentration of a chemical in the body of an organism from the organism's contact with or intake of soil, water, or air. The amount of the chemical increases in the organism if the intake exceeds the decomposition or excretion of the chemical.

Biomagnification is the increase in concentration of a chemical in the bodies of organisms as one goes up a food chain. The source of the chemical in biomagnification is food, as opposed to bioaccumulation, which involves the direct uptake of the chemical from soil, water, or air.

How bioaccumulation and biomagnification work.
Chemicals that bioaccumulation or are biomagnified possess two important properties that allow them to increase in concentration in an organism. These are a long half life and high fat solubility. A long half life means that the chemical is persistent in the environment, that it does not decompose readily. Synthetic organic chemicals have long half lives in the environment because the decomposers (mainly bacteria) don't (can't) use these chemicals as a food source; i.e., they don't possess the digestive enzymes necessary to break the molecules apart to gain energy. The absence of the enzymes is explained by noting that these synthetic molecules are not found, have never been found, in nature so organisms do not recognize them as food sources.

The second property is high fat solubility. This means that the chemical is soluble in, will be stored in, the fat (lipid) tissues in an organism, either plant or animal. If the chemical is stored in the fat, it is outside of active metabolism and therefore will not be broken down in the body, nor will it be excreted from the body. Therefore, and this is important to biomagnification, the chemical will be present in the body (stored in the fat) of an organism if another organism higher in the food chain eats the pollutant-containing organism. Now the chemical is present in the body of the next organism in the food chain and the chemical is stored in that organism's fat, and so on up the food chain. The concentration takes place because organisms eat large amounts of food relative to the increase in body mass. For example, a growing organism may eat 10 kg of food and only increase body mass by 1 kg. The other 9 kg are used for maintenance metabolism or are excreted. But if all of the food contains the synthetic organic compound, say at a concentration of 10 mg per kg, then 10 kg of ingested food would mean an increase in the body of the organism of 100 mg (10 mg per kg times 10 kg). Remember, the synthetic chemical can't be used as a food source and will not be excreted because it is stored in the fat.

Persistence in the environment
Synthetic organic compounds are not degraded (broken down) as rapidly in the air, water, or soil as natural organic compounds because they do not serve as a food source for the decomposer organisms (see above). We describe a chemical's persistence in the environment (or inside an organism) as its half life, which is the length of time it takes for one-half of the chemical present at the beginning of the time period to be broken down or transformed into other chemicals. Therefore, if a chemical has a half life of three days in soil, then if 60 ppm are present at time zero, 30 ppm will be present after 3 days, 15 ppm present after 6 days, 7.5 ppm present after 9 days, etc. (Theoretically this exponential decay process never goes to zero). Compounds with long half lives are more likely to be present in air, water or soil pathways by which an organism (including humans) will receive a dose of the chemical. Higher doses, higher (potentially adverse) responses.

Chlorinated hydrocarbons have half lives in years; natural chemicals will be in hours, days, weeks, or, at times, months/years. An example of the longer half lives would be tree trunks, bark.

Note that a long half life for a pesticide is seen as good by the farmer. Why?
Ask question.

Bioaccumulation and biomagnification review. Know the difference between bioaccumulation and biomagnification, how they occur.

Questions:

1. What two properties of a chemical cause the chemical to be bioaccumulated and biomagnified?

2. If the half life of chemical Z in soil is 10 days and the soil concentration of Z immediately after Z is added to soil is 50 ppm, what is the concentration of Z in the soil after 30 days?

3. Why is high fat solubility important to a chemical's residence time in the human body?

4. Why do synthetic chemicals have longer half lives in the environment?

Toxicology glossary

Definitions of pollution
1. Too much of something in the wrong place for too long. Too much is an excessive concentration of a chemical. Wrong place means that the concentration exists in the environment where it can be absorbed by a living creature (the organism can receive a dose from the the chemical concentration in the environmental medium). Too long means that the concentration persisted long enough for an excessive exposure (dose) to occur. Examples: A concentration of 180 mg of arsenic per liter of water, the water located in an aquifer supplying the drinking water for a human population, and the high concentration existing in the aquifer for long enough such that the population ingests enough contaminated water to receive an excessive dose of arsenic.
2. An undesirable change in the physical, chemical, or biological characteristics of the air, water, soil (food) that can harmfully affect living organisms.

Examples
Physical characteristics: air or water temperature, sound levels, ionizing and nonionizing radiation
Chemical characteristics: the types and amounts (concentrations) of natural or human-source chemicals
Biological characteristics: the levels of pathogenic (disease-causing)bacteria, protozoa, viruses, fungi, molds
Emphasis on chemical contaminants

Concentration: the amount of chemical in a given amount of an environmental medium (air, water, soil, food).
Dose = concentration x amount
12 mg of iron per liter of water times 10 liters of water = 120 mg of iron

Dose and dose rate
Dose rate = concentration x amount/time
12 mg of iron per liter of water times 10 liters of water per week = 120 mg of iron per week.

Why dose rate is a better expression than dose
If we calculate that someone drank 3 liters of water, each liter containing a concentration of 30 milligrams of arsenic per liter, the amount of arsenic ingested from drinking the water is 30 mg of arsenic per liter times 3 liters equals 90 mg of arsenic. Is this harmful or not? It depends the time period during which the arsenic was ingested. If the 3 liters were consumed over ten years, during which much less than a drop of water was taken each day, then there wouldn't be an adverse effect. However, if the 3 liters were drunk during one afternoon, poisoning would occur.

Dose rate from a chemical taken in by several routes of exposure: water, air, food
Air: 0.5 mg of iron per cubic meter times 20 m3 air per day = 10 mg iron
Water: 12 mg of iron per liter times 2 liters water per day = 24 mg iron
Food: 3 mg of iron per kilograms of food (say this is the average iron content) times 1 kg food per day = 3 mg iron
Therefore, 10 + 24 + 3 = 37 mg iron per day.

Remember: The chemical concentration, i.e., how many parts per million, is important, not the mere detection of the chemical. A chemical may be detectable at some extremely low level, e.g. one thousandth of one part per million (one part per billion), but the possible dose would be too low to have any adverse effect.

To determine hazard:
1. Get dose (dose rate):

• Measure (know) concentrations in environmental media

• Measure (assume) amounts (or amounts per time) taken in by an organism

2. Use dose-response relationship

3. Determine human exposure and absorption of the chemical

Concentration expressions: mass/mass, volume/volume, etc.
For common units, concentration as a ratio. To use these ratios the numerator and the denominator must be in the same unit: both mass (same unit) or both volume(same unit). For example gram/gram, liter/liter.

Concentration as a percent, as ppm, examples
1 gram of arsenic per 1 million grams of soil is 1 part per million = 0.000001 gm arsenic per one gram of soil
Parts per million are the same type of convenience term as per cent (parts per hundred). If I want a quick way of communicating the fraction 1/100 or 0.01 I say 1 percent. I get this by multiplying the fraction by 100. For example 0.075 is 7.5 percent.
For pollutant concentrations, the ratio of pollutant to the environmental medium is usually much lower than percent. Therefore we don't use percent as shorthand but ppm. Example: the aluminum content of soil is 75 grams aluminum per million grams of soil or 0.000075 grams aluminum per one gram of soil. Instead of using percent as a shorthand (0.0075 percent) I want to be able to use a whole number so I multiply by one million to get 75 ppm.

More examples:

*Corrected 9/2/2003

1 gram of X in 100 grams of soil = 0.01
0.01 times 100 = 1 part per hundred (percent)

A useful equality to remember is that one percent is equal to 10,000 ppm. (as in the last row in the table above). Do you see why 1% is the same as 10,000 ppm?

10,000 grams of X in 1,000,000 grams of soil = 0.01 gram of X in one gram of soil. Multiply by 1,000,000 for ppm = 10,000 ppm.

Questions:

1. How many ppm is 3.5%?

2. If soil contains 20,000 ppm of a pesticide, how many grams of the pesticide are present in 1000 grams of soil?

3. To convert a decimal fraction to ppm, I multiply by what factor?

Ask question.

FYI Another explanation of Parts per million.

Applications. Problem set #2:
1. Convert 0.0008 gram lead per one gram of soil to ppm
2. Convert 0.00005 kg lead per gram of food to ppm
3. Convert 3 milligrams of chromium per liter of water to ppm. The density of water is 1000 grams per liter. Hint: get to common units!

Answers:
1. Multiply the ratio 0.0008 gram lead/1.0 gram of soil by 1,000,000 = 800 ppm

2. 0.00005 kg lead per gram of food. Convert to common units. 0.00005 kg times 1000 grams/kg = 0.05 gram. Therefore we have 0.05 gram of lead per gram of food. Now multiply by 1,000,000 for ppm = 50,000 ppm.

3. 3 mg chromium(Cr)/liter of water times liter of water/1000 grams = 3 mg Cr/1000 grams water. Now convert mg Cr to grams of Cr. Multiply 3 mg Cr/1000 grams water times 1 gram Cr/1000 mg Cr = 3 grams Cr/1,000,000 grams water. This decimal fraction equal 0.000003. For ppm, multiply by 1,000,000 = 3 ppm

Dose = concentration x amount. For example 3 mg of A per 1.0 cubic meter (m3) of air times 10 m3 air breathed = 30 mg A inhaled.
Dose and dose rate. Dose rate is amount per time.
Dose rate = concentration x amount/time, example 3 mg lead/kg of potato x 1.5 kilogram potatoes consumed/day = 4.5 mg lead/day from potato consumption.

Dose-response relationships
Dose- (adverse) response relationship
What is the adverse response being observed? Different responses have different severities and therefore require different doses. For example, the dose causing death would be higher than the dose causing a pain in the stomach. Therefore, the dose-response relationship changes with the choice of what is considered an adverse response. The experimenter/observer chooses the adverse response to look for when administering a dose.

Toxicology: the science of poisons.
Paracelsus, founder of toxicology. Paraphrase of his famous quote: "The dose makes the poison."
Dose-response curves. Dose or dose rate on x axis, response on y axis.

Exercise: Draw a dose response curve using the following data points. Label the axes of your graph.
Graph shown below.

Data to use for the graph:

What your graph should look like:

Response is the change/effect being looked for in the study. This is called the endpoint.
Endpoint: the biochemical, physiological, or behavioral change used as an indicator of a(n) (adverse) response or effect. The experiment/observer chooses the endpoint.

Determining toxicity: animal, human data; acute, chronic data

1. Acute animal: LD50, which is lethal dose for 50 percent of the test organisms. LD50 data are useful in a relative sense; i.e., comparing LD50s for chemicals can show their relative toxicity. But note that this type of comparison can be misleading. Note that the lower the LD50, the more toxic.

2. Acute human: volunteers, accidents. Volunteers give their informed consent. Many safeguards are in place when performing experiments using human volunteers.

3. Chronic animal: rodents. If cancer is the response being studied, e.g., sacrifice animals at end of life and examine for tumors. Use tumor-prone strains. Compare numbers of tumors to control group.

4. Chronic human: epidemiology , which is the study of disease patterns in human populations. Occupational groups are studied often because they receive the highest routine exposures to the chemicals they are working with.
     Our department has an upper level course in Environmental Epidemiology.

Problems with epidemiology data.
1. Need to wait (decades?) before results.
2. Not a controlled experiment.
3. Need adverse effects (body count) before knowing there's a problem.
4. Humans, obviously, receive many other exposures during the years of observation and tracking.

Problems with animal toxicology data.
1. Species extrapolation. Animals not humans.
2. Dose extrapolation. Animal doses high. Dose extrapolation to much lower doses experienced by humans.
3. Body size extrapolation. Rodent mass v. human mass, or use relative surface areas.

Body size extrapolation.
No observed adverse effect level (NOAEL): highest dose causing no adverse effect.
Body size extrapolation from NOAEL in rat to human. Can use body mass or surface area extrapolation.
Body mass example: an NOAEL in a rat of 10 mg/day is observed. To scale by body mass use human mass of 70 kg and rat mass of 1 kg; scale up 10 mg/day by multiplying 10 mg/day by 70kg (man)/1 kg (rat) to get 700 mg/day NOAEL for humans.

Surface area example: an NOAEL in a rat of 10 mg/day is observed. To scale by surface area use a human surface area of 1.8 m2 and a rat surface area of 0.04 m2; scale up 10 mg/day by multiplying 10 mg/day by 1.8 m2/0.04 m2 to get 450 mg/day NOAEL for humans.

Question: Which of the two body size extrapolation methods is the most cautious (conservative in the sense of allowing a smaller dose)? The USEPA uses surface area scaling; why do you think they chose this method?
Answer: Surface area scaling gives a lower allowable human dose and the USEPA errs on the side of caution in its standard setting.

Carcinogens
Another way to determine toxicity of a chemical, if carcinogenicity (cancer-causing potential) of a chemical is to be measured is mutagen screening, a very common one being the Ames test. A chemical is added to petri dish with bacteria. This strain of bacteria can't grow on the nutrient agar in the dish unless they mutate. If the bacteria grow after exposure to the chemical, they have mutated. Assumption is that the chemical caused the mutation. Ames test quick and cheap compared with animal carcinogen testing. Used as a screening test. Ames only correctly predicts animal carcinogens about 70 percent of the time.

FYI More on the Ames test.

FYI And more.

Mutagen link to carcinogen. Cancer theory (much evidence) says that tumors start with a mutated cell. The cell mutation causes the cell to lose its growth control, becoming a mass of dividing cells (a tumor). Several parts of the DNA may need to mutate to actually cause a tumor.

Cancer as an older-age disease. Cancer risk increases with age for almost all cancer types. This fits the theory of cancer being caused by the accumulation of genetic damage over time.

Dose routes: ingestion, inhalation, skin absorption
Absorption factor (0-1) and fraction delivered to target organ (0-1). Absorption factor is the fraction, between 0.0 and 1.0 (0 to 100%), of a chemical that when inhaled or ingested is actually absorbed into the body. Fraction delivered to target organ is the fraction, between 0.0 and 1.0 (0 to 100%), of an absorbed chemical that is actually transported within the body to the area where damage can most readily occur. For some chemicals this will be the liver; for others, the brain; others, the kidneys, etc. Different dose routes have different absorption factors.

Questions:

1. If Anne drinks 3 liters of water containing 10 mg of chemical X per liter, and the absorption factor is 0.1, how many mg of are absorbed by Anne's body?

2. Of the three dose routes, which is the least voluntary, i.e., hardest to avoid?

Threshold, the lowest (non-zero) dose causing what is considered to be an adverse effect. If a threshold, can set a standard to result in a dose below the threshold level.

Carcinogens assumed to have no threshold. The high to low dose extrapolation is drawn as a dose-response curve that goes through the graph's origin. Therefore, any dose above zero corresponds to some expected adverse response.
The federal government generally assumes that carcinogens have no threshold dose.
Example of a dose-response curve showing no threshold; i.e. any dose is associated with some response (risk of cancer).

Dose routes: ingestion, inhalation, skin absorption
Response
Remember the definition of endpoint (the biochemical, physiological, or behavioral change used as an indicator of a(n) (adverse) response or effect. The experiment/observer chooses the endpoint.). Remember how choice of endpoint changes response rate.
The progression of adverse effects . (This hand means read this material carefully but the main thing to know is what an endpoint is and how it can vary.)

Adaptive response. First, an adaptive response is not adverse. Example: if elevated body temperature could eventually cause heat stroke and death, the first (adaptive) response to a higher body temperature is increased perspiration, more blood near the surface of the skin, all working to cool the body.
Physiological adaptive responses. Body temperature regulation as above.
Metabolic adaptive response. If a quart of vodka taken in over a short period of time could cause death, smaller doses are metabolized away before an excessive dose (blood level) can be built up. As long as the vodka is ingested at a rate that the body's metabolism can match, intoxication will not occur.

The liver is the main site in the body where metabolism of potentially toxic chemicals takes place. The enzymes (biological catalysts) in the liver mediate (allow to happen more readily) these biochemical reactions.

Overall, metabolic change of a chemical is to a less toxic form. Note that it is possible that metabolism will "activate" a chemical first to a more toxic form, and then further metabolism will lower the toxicity. This happens often with carcinogens. In this instance the chemical that we call a carcinogen does not increase tumor risk in its original form (i.e., the chemical that is ingested or inhaled) but when the body metabolizes the chemical it is changed to one that is mutagenic or carcinogenic. We will discuss this further in a later unit.

The other main metabolic change of a chemical is to increase water solubility, therefore excretion.
For example, benzene is metabolized to phenol, which is more water soluble and thus more excretable.

Dose rate can overwhelm adaptive response. For example, taking two aspirin every four hours can be effective for pain relief, but taking two aspirin every four minutes will lead to the severe poisoning or death.

Genetic makeup is connected to metabolism of chemicals by enzymes. Enzymes are proteins. Proteins are composed of amino acids. Amino acids are coded for by genes. Therefore, some people may inherit the inability to make certain enzymes that are required for the metabolism of certain chemicals. This means that they will be more susceptible to the chemical's adverse effects because they will be unable to detoxify and excrete the chemical.

Entry and fate of chemicals in the body. (This hand means to read the material carefully, but the main things to know here are the paths by which a chemical enters the body and the changes occurring to a chemical after it enters the body.)

Questions:

1. If the body can ward off toxic effects with a successful adaptive response, then why does anyone get harmed by pollutant exposure?

2. Metabolism of chemical changes its water solubility. Is the chemical more water soluble or less water soluble after metabolism?

Threshold dose
No observed adverse effect level
The two graphs below illustrate a threshold dose-response curve, and a D-R curve for a required nutrient.

Example of a D-R showing a threshold. The threshold dose is 4 mg/day, because a (small) fraction showed an adverse response. At 2 mg/day, there was no adverse response. Remember, the experimenter chooses the response to score as adverse.

Below is an example of a D-R curve for a required nutrient. Here, a zero dose is bad (the chemical is required) and a too-high dose is bad also (toxic effects)

No threshold chemicals.
Why are certain chemicals assumed to have no threshold.? Chemicals that are suspected of causing (increasing one's risk of) cancer are assumed to have no threshold. Because the mechanism of cancer causation is only poorly understood and that, in theory, only one cell needs to be transformed (mutated) to start the growth of a tumor, the U.S. government regulatory agencies, e.g. the USEPA, assume that any dose of a carcinogen increases the lifetime risk of cancer; i.e., there is no threshold below which we can expect no chance of an adverse effect.

Difficulty of drawing a D-R for humans from animal tumor data.
Experiments with animals involve administering extremely large doses of a chemical to an animal during its short life. If a chemical causes a significantly greater number of tumors in the dosed animals compared with the control group, then the chemical may be labeled an animal carcinogen. Does this mean that the chemical causes tumors in humans? We can't be sure. The doses that humans will receive are much smaller and the test system is an animal (a mammal, but one with a smaller body, different metabolism, a shorter life, etc.).

See the hyperlink for an overview of carcinogenicity (more later)
No threshold chemicals are assigned risk factors by the USEPA.

Using risk factors:
Dose (rate) = concentration x amount
Lifetime risk = dose x risk factor
Example: Let a chemical have a dose of 2 mg of the chemical per day and a risk factor of 2 x 10^-6 (0.000002) per 1.0 mg/day.
Lifetime risk = 2 x 10^-6 per 1.0 mg/day times 2 mg/day = 4 x 10^-6, which means that if someone is exposed to the chemical at a constant rate of 2 mg/day for a 70-year lifetime, then he has a 4 in one million chance of a cancer from that chemical at that dose rate, given the risk factor.

Application problem: If the risk factor is 1.5 x 10^-6 per 1.0 mg/day and the acceptable lifetime risk is 1 in 100,000, what is the allowable dose, in mg/day?
Answer: 1/100,000 divided by 1.5 x 10^-6 per 1.0 mg/day = 6.7 mg/day

So what's happening here is that the dose rate times the risk factor = lifetime risk, which is just a probability, the chance, according to the USEPA's methodology, of a cancer arising if one is exposed at the dose rate his entire life.

Sensitive groups, factors determining:
Age, health status, nutritional status, genetic makeup, exposure to other chemicals

Genetic makeup connection to metabolism of chemicals by enzymes.

Setting an environmental standard.
Standard written in terms of allowable ambient concentration.
Steps in standard setting:
1. Define endpoint.
2. Determine threshold or NOAEL (will be in the susceptible group).
3. Set ambient concentration to avoid harmful dose.
Dose= concentration x amount, so figure concentration using chosen acceptable dose and assumed amount of the environmental medium.

Example of standard setting, using a water pollutant.
Assume that the acceptable dose rate is 6 mg of the chemical daily. Use an assumed water consumption of 2 liters per day. Therefore, water concentration should be equal to or less than 3 mg/liter. Calculation: 6 mg/day divided by 2 liters per day = 3 mg of the chemical per liter.

Questions:

1. In the example above, is the threshold dose higher or lower than 6 mg per day?

2. Persons with liver disease are harmed if their dose rate exceeds 50 mg of chemical X per day. Jane has liver disease. John, who is free of liver disease, works with the chemical and is exposed to an average of 600 mg of chemical X each day. Jane gets a dose of 30 mg of chemical via her water supply. Which one is more susceptible to X?

If measurements of area air or water quality indicate concentrations over the standard, then the area is labeled as polluted. The interpretation of information that an area is polluted involves measured concentrations, endpoints, susceptible groups, and frequency of high readings.

Exercise: Go through the toxicology tutor at the National Institutes of Health

Risk assessment background.
FYI Some examples of environmental standards

Chemicals enter the environment as

• Emissions (from production or use)

• Waste (industrial/municipal, nonhazardous/hazardous)

• Products (accidental spills)

Usual concentrations of emissions, waste, and product.
Emissions will contain generally less than 10% pollutants (i.e. maybe 10 percent of the exhaust gases from a smokestack will be what we consider to be air pollutants: the rest will be carbon dioxide, oxygen, nitrogen, water vapor), pollutants can also be present at the low percent level down to the ppm or even parts per billion (ppb) level.

Wastes may contain 0-maybe 30% pollutants. Many hazardous wastes are labeled "hazardous" because they contain levels of certain chemicals greater than 10-100 ppm (nowhere near even one percent!) Contrast these low concentrations with the concentration of a chemical product moving in commerce. Products are shipped in an almost pure form. Ammonia moving in a tank car will be 99.9% pure.

The message here is that in terms of spills (accidents, not routine releases as out of a smokestack), products are much more dangerous, being almost 100% pure, not diluted as is waste.

Chemical regulation, from preproduction to disposal of waste. You want to know the name of the statute that governs each of the various stages of a chemical's "life". Environmental laws (statutes) are enforced and administered by regulatory agencies. The one agency with the greatest enforcement responsibility is the U.S. Environmental Protection Agency. Note that other agencies are also involved. Also know that this list is an overview and is not exhaustive.

• Preproduction: Toxic Substances Control Act, Federal Insecticide, Fungicide, and Rodenticide Act. USEPA administers both. In both cases the USEPA needs to approve the chemical before it can be produced or used.

• Design/safety: Consumer Product Safety Act. Administered by Consumer Product Safety Commission. Here the design of lawn mowers, toys,etc. are reviewed and safety measures are required.

• Production: Occupational Safety and Health Act (Occupational Safety and Health Administration), Clean Air Act (USEPA), Clean Water Act (USEPA). Either the workers (the group most heavily exposed to any chemical is those involved in the production of the chemical) or the public exposure to the air and water pollutants that are discharged off the industrial site.

• Transport: Hazardous Material Transportation Act (Department of Transportation). The DOT controls the safe design of tanker trucks, barges, and rail cars that carry chemicals in commerce.

• Consumer: No specific statutes. Labeling, safety & environmental education. It's up to the consumer to do the right thing.

• Waste disposal: Resource Conservation and Recovery Act (USEPA). The regulation of municipal waste, construction waste, nonhazardous industrial waste, hazardous waste is all under the Resource Conservation & Recovery Act.

• From production to disposal: Spills cleaned up by authority of Comprehensive Environmental Response, Compensation, and Liability Act. This act is also known as the Superfund, named for the money from a tax levied under this statute. The tax is dedicated to waste cleanups. (USEPA). These spills/releases/leaks could be from a rail tank car or from an old landfill.

Questions:

1. What law governs the safe transport of chemicals on Interstate 10?

2. Which law requires an assessment of a chemical's hazard before the chemical can be produced?

3. Which law regulates waste disposal?

4. Which law defines the actions necessary to clean up chemical spills?

The administrative agencies (USEPA for example) are called upon by the statutes to write regulations to implement/enforce the statutes' provisions. The idea is that the Congress doesn't know how to write the detailed rules necessary to control air pollution, e.g., so it gives the USEPA the power via the statute to write the detailed rules for air pollution control. For example, a regulation limiting carbon monoxide gas concentrations in a smokestack from a steel mill to 100 ppm would be written by the USEPA under the authority of the Clean Air Act (the statute).

Now, the administrative agencies are part of the Executive branch of the government and constitutionally it's a bit problematic for an executive agency to be writing laws (regulations). Since the 1930s, we have lived with this hybrid system, with the Congress delegating regulatory power, including the writing of the regulations the agencies enforce, to the agencies.

An important safeguard to this process is the Administrative Procedure Act, which governs regulations drafting (called notice and comment rulemaking). The agency must write regulations as a public process. The regs must first be published in a draft form in the Federal Register. Then the agency must take comments from any interested party on the regulations and must respond to all reasonable suggestions (at least telling why they did not take someone's suggestion). After the comment period is over, the agency will issue the regulations in a final form. All current regulations are compiled each year in a multivolume set called the Code of Federal Regulations. Examples:

Here are two examples of regulations:
The Federal Register from October 5, 1997 had an entry on pesticide regulation.
This is an example of an entry on pesticide applicator certification from the Code of Federal Regulations, Title 40, Part 171.

Note again the legislative aspect of regulations writing: proposal, comments, response. This is quite similar to what happens in a legislature. Therefore, one can lobby for a certain type of law at the statutory levels (changes to the Clean Air Act) and one can participate in the notice and comment regulations process (as the USEPA writes regulations under the authority of the Clean Air Act). Industry and environmental groups participate heavily in both processes.

Questions:

1. What law requires adminstrative agencies to publish draft regulations?

2. Where would you find the regulations proposed by the USEPA in the last month?

3. What publication contains all of the regulations in force at the end of a year?

4. In what publication would one find the final form of a regulation that was published last week?

Risk
I. Top Causes of death, U.S., 1900 and 2000*

*Source for 2000 death data: http://www.cdc.gov/nchs/fastats/deaths.htm
**Some sources rank heart disease as number 1 in 1900; differing definitions and record keeping influence these statistics, but the drop in infectious disease mortality remains.

Why the shift in causes of death, 1900-present? Improvements in public health: clean water, sewers, waste disposal. Also, improvements in diet, housing, standard of living. The change was NOT caused by medical care or drugs. See the charts that follow, which prove that medical care or drugs did not cause the drop in the death rates shown:

What this chart shows is the decline in tuberculosis deaths from the middle of the 19th century to the present in the British Isles.  The cause of tuberculosis is a microorganism called the tubercle bacillus. This organism was not identified until 1882 by the great microbiologist, Robert Koch. Streptomycin, a drug effective against TB, was not available until around 1950. An effective vaccine against TB was developed in the late 1950s. Clearly the great decline in TB deaths occurred long before effective treatment of TB was in use. The same curve with a different scale results when plotting the change in TB deaths in New York City. The same type of chart results when plotting deaths from other infectious diseases: scarlet fever, measles, etc.

II. Average death rates do not equal age-specific or sex-specific death rates.
Example: the average death rate in the U.S. is 8 per 1000 per year. Eight of every 1000 Americans die each year. But look at the risk of death by age group:

Top causes of death for U.S. do not equal top causes for various age groups. Although the top causes of all deaths are heart disease, cancer, stroke, and accidents, the top causes of death for 15-24 year olds in the U.S. are, in order:
1. Accidents
2. Homicide
3. Suicide

Now remember that the overall risk of death for 15-24 year olds is only 1 per 1000 annually. But if someone this old dies in the U.S. the top three causes are as above.

The more you know about an individual the better you can estimate his risk of death. Age is by far the best predictor. But sex is important too. Look at the 15-24 death rates, including males v. females. (I intend to update this table, bu more recent data reflect the same differences.)

So males are far more likely to die than females. This is true for all age groups, newborns to 90 year olds, by the way.

III. Life expectancy, changes during 20th century in U.S.
This table shows the average life expectancy at the beginning of the 20th century in the US and now. Do not picture that people born in 1900 withered up and died around 1947. This is the average age of death. In 1900, many more children died than die today. This is an average. If one averages these ages of death: 1, 3, 5, 70, 75, 67, 88, one will get 44 years old. This is how the average of 47 was produced. Therefore, as we have "conquered" many infectious diseases (big killers of children) we have greatly lengthened the average age of death at birth. But look at the average number of years left at age 70 for 1900 versus now. Not very much progress here; i.e. not much progress in terms of increased years of life against the diseases of old age such as heart disease, cancer, and stroke.

IV. Risk perception
Risk is a combination of probability and consequence
Examples: can be combination of low probability, low consequence, not much to worry about. Or a low probability event may have a catastrophic consequence and the "What if?" causes (legitimate) concern.

Numerical risk estimates not a good guide to risk perception/acceptability. This means that just because one risk calculates as lower doesn't mean that it is more acceptable: One may balk at taking off in an airplane in a storm and not worry about the automobile drive to the airport although the statistical calculations may show that the car drive is more dangerous.

Dimensions of risk that are important to its acceptability. It's not just the calculation that matters, but the context, as illustrated by these aspects:

1. Voluntariness: more voluntary, more acceptable

2. Location in time and space: deaths grouped together are viewed as worse than those that are scattered. Ex.: airline crash killing 200 people makes headlines while 200 people died that day in auto crashes around the country. Both are transportation related, but the airline crash may be seen as the less acceptable risk.

3. Identification of benefits. We'll accept risks of certain therapeutic drugs or medical procedures if they might cure a disease.

4. Identity of victim(s). It is easier to accept the death of 50 strangers in muggings than the killing of one person you know.

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Copyright © 1998-2005, Bruce Wyman, Ph.D.
Last modification 8/23/2005
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