Closure sub-modules contain my responses to student questions and sometimes
other material related to that module, which I realize I missed the first time
around. The items that are important, in the sense they are part of course content,
are indicated by two or more asterisks (***) and have been grouped first. Items
that relate to administrative issues are grouped second. The answers to other
questions are grouped last. Some of this last group is my philosophical rambling,
which you might find interesting but of itself will not be on the tests unless
it is later presented again.
*** Q. In the Dose-Response experiment does Cheech
change the fishes for each dose experiment?
A. Yes, You would start with a new, unexposed batch of fish for each dosing
level. The lesson did not make that clear.
*** Q. In the toxicology submodule you refer to a dose that effects 90% of test
subjects as ED90, but in the homework you refer to the dose as EC90, are the
interchangeable?
A. I should have been consistent. The "D" in "ED" stands
for "dose," typically mg / kg of body weight. That is the terminology
used for oral and dermal exposure of test animals. For inhalation exposure of
land animals or water exposure of aquatic species, the term "EC" is
used and it means "effective concentration," typically in ppm or mg
/ m^3.
*** Q. (Several questions regarding the electronic quiz, question 1, and acute
exposure:)
A. Acute vs. chronic refers to the duration of the exposure, not the effect.
Regarding the Dartmouth researcher who was exposed to dimethyl mercury that
you read about, her exposure was seconds, but the effect, culminating in death,
took months. Many acute exposures have a "latency" period before the
effects are patent.
In the Law, the exposure specified as a one-time brief exposure to the chemical,
and thus acute. The effect is measured at 14 days. Or rather lack of effect,
if the animal is not dead before then. (See Blackboard announcement about hints.)
*** Q. "Are the terms "risk assessment" and "risk characterization"
interchangeable, or are there notable differences? The terms appear in the NAS
diagram.
A. Not exactly interchangeable. "Risk Assessment" refers to the entire
process of determining the probability and severity of harm. "Risk Characterization"
refers to the statement of the findings, which is the statement of the probability
and severity of the harm and the statement of uncertainties.
*** Q. 1 ppm for water equal to mg/L, for soil it would be 1 mg/kg. What about
gases? Is 1 ppm for gas equal to 1 mg/m^3?
A.. I avoid using ppm for water solutions. In order to use the term "parts
per million [parts]", both numerator and denominator must be in the same
units. If and only if one liter of the solution weighed exactly one kilogram,
1 ppm equals 1 mg / L. However, in many environmental measurements, the solution
is very dilute and one liter weighs just about one kilogram, so ppm and mg/L
are used interchangeably. For gases, I added a non-mandatory page about converting
ppm to mg / m^3. One ppm of a gas is different than 1 mg / m^3, usually
quite different.
Q. Will you leave all the modules posted on Blackboard throughout the semester?
Or will you pull them off as you add new one's?
A. Yes.
Q. In sub module 1C, the NOEL was noted at being the no observable effect level.
Therefore, I am to assume that any dose higher than the NOEL would produce an
effect and everything lower would have no observable effect. Does the
no observable effect include long latency periods (such as causing cancer years
later???)?
A. Very good questions, see above for part of my answer. You observed that the
Consumer Product Safety law for "highly toxic" had a definite cut-off
time for effects and only mentioned death as an effect. Lawyers, not toxicologists,
write this type of definition. I just put it in the lesson to illustrate how
those words were used and to get you to think about their meaning. For the definition
of "toxic" it had any harmful effect and no cut off time, so any harmful
effect at any time would require the toxic label. Of course there are no testing
protocols specified, either.
Q. Would the NOEL also be considered the threshold level?
A. We will talk more about NOEL and thresholds. They are often used synonymously,
but are not. The NOEL would refer to a particular experiment. These experiments
test a series of progressively higher doses, starting with zero dose called
the controls. The NOEL would be the highest of the doses that did not demonstrate
an effect. Long ago, toxicologists would state a "no effect level."
Since the philosophers tell us that any dose must have some effect, the terms
"no observable effect " became standard. Sometimes the matter is expanded
to "no observable adverse effect (NOAEL), which is more accurate. These
terms are common to regulatory toxicologists who have to come up with some definite
number. The terms would be meaningless, unless they are coupled with the particular
laboratory experiments that were used to determine them. For chemicals suspected
of being carcinogens, those protocols would specify observations for the lifetime
of the animals.
A threshold would be the largest dose that produced no effect. It is a scientific
concept that is not tied to any particular experiment, but would be stated for
a particular animal species and other protocols. There is much scientific debate
if carcinogens have thresholds. We will discuss this.
Q. What are the criteria for "effects" when an experiment is done
to determine the NOEL up to EC90? What if different individuals within a species
show different effects?
A. This is part of the reason that the choice of animal species is so important. Some strains of lab animals are inbred and most of the individuals will show the same effect. Other strains are outbred and there will be more variation in effect. You can also see why the choice of an "endpoint" is so critical. This is why death is such a convenient endpoint.
Q. Also, am I right to conclude that reversible effects are reversed
once exposure has stopped? Do irreversible effects include effects
that require intense medical treatment such as chemotherapy (in
other words, are does reversible effects include only those effects
which would naturally reverse on their own once exposure has ended?
Blurry vision might revert back to normal vision after exposure
whereas cancer may not be reversible if medical treatment is not
seeked and even if it was it still might result in death or may
eliminate someone's ability to reproduce.)
A. Again, reversible and irreversible are very general concepts. The effects
would have to reverse sometime in the future and not be permanent. Similar to
the question, is a seven-day test is chronic or acute, for an adverse effect
that slowly reversed itself for years, you would better presenting that explicitly
rather than trying to decide if it is reversible or irreversible. We will discuss
cancer in much greater detail soon.
Q. Is the effective dose affecting 10% of the population meaning
any type of observable effect except death.
A. You would include death as an "effect." Its just
that death is such an easily observed endpoint, it is often specified
and the LD is often used. Obviously ED is not very descriptive,
unless you specify the effect.
Q. Regarding the scented candle issue, what are the quantified
health risks associated with use of scented candles? Do the levels
presented in the abstract represent a serious health risk?
A. Deep questions, but so deep, I can give shallow answers. The
abstract about the candles presented no quantified health risk
for the candles. The author did a chemical analysis of soot and
other combustion products from a set of very different candles,
and not unsurprising found different chemicals. Then the author
presented the health effects from stated levels of these chemicals,
where they were known. For the biggest issue, candle soot, there
were no known health effects published, so the author used the
data from diesel exhaust, a completely different compound. What
the author presented were assumptions stacked on top of estimates
over a layer of extrapolations. We will often see this. My guess
is the original paper carefully stated all this. When you use
the words "serious health risk" you are trying to determine
the acceptability of the risk. In my house, the fire danger from
candles is thousands of time greater than any likely health effects.
Q "toxic" and "highly toxic" are both defined
in terms of human illness or death, but the homework question
referred to the results of a rat test. Can you infer a chemical
is toxic if rats are affected, or does there have to be direct
proof that humans will suffer?
A. In this case the law of the land defined the terminology required
to warn humans of the hazard in terms of animal testing. Almost
all toxicology testing is done in animals and the choice of the
correct "animal model" is most important. We will deal
much more with this issue in a few weeks.
Q. If, in Environmental Engineering "sticking to ethics"
is given a lot of importance then how would one defend the cruelty
imparted to animals used for studying the affects of various "poisons"?
A. Animal testing is an important issue. Economics dictates minimizing
animal testing, if in vitro testing will suffice. The animal quarters
where I did my graduate work were better than my graduate student
offices, better ventilation and climate control. Strict adherence
to animal welfare controls is an important part of experimental
procedures. If animals are stressed they may produce anomalous
experimental results. I have never witnessed or heard of any cruel
or base treatment of laboratory animals, other than what was required
by the experiments. As a practical matter, whole animal testing
is required for all foods, drugs, and cosmetics that people will
be exposed to, in order to determine if they are "poisons"
or better put, what the harmful dose is. It would be irresponsible
to purposefully expose consumers without prior animal testing.
For persons whose moral system puts humans on a higher plane than
animals, I do not perceive any moral issues with testing animals.
(A person who took pleasure in hurting mammals is rare, and this
type of behavior upsets other people, so it is anti-social.)
On the other hand, persons whose moral system puts animals and
humans on the same plane might have problems with animal testing.
Biomedical research is probably not a good career choice for persons
with this ethic.
Q. In the Minimata case, did Chisso Corporation ever pay the $100
million settlement suit?
A. I don't know. It is an interesting moral issue. Today, we regard
almost any pollution as a crime or at least anti-social corporate
behavior. That was not the case in the US until sometime in the
1960's. Engineers were taught, "The solution to pollution
is dilution." Almost everyone accepted that some contamination
was inevitable and required for economic progress. The situation
in Japan was worse, with most industries and infrastructure damaged
or destroyed by World War II. Now what happed (as I remember some
readings I have never researched this is depth) Chisso and the
government knew that they were polluting and the pollution was
not against any Japanese law. When it became apparent that there
might have been health effects, the government told the locals
to stop fishing in the Bay and stop eating the fish from the bay.
Chisso in turn paid the fishermen to not fish in the bay. The
fishers may have not stopped fishing, the fish outside the bay
may have had some contamination, and certainly some of the effects
may have been due to exposure before the restrictions. The same
is true of Love Canal in New York. Everything Hooker Chemical
Co. did was legal when they did it. In addition, when the site
was sold there was a deed restriction that should have prevented
housing and certainly the school being built on the dump. That
is one of the reasons that the RCRA law was passed.