*** Q. What is the difference between effective does 50 and median lethal dose 50?  They seem to be measuring the same thing-the amount of a substance to cause 50 percent of a population to die.
A. The “effect” may be other than death.  If it is death, we use LD, if it is other than death we use ED. 

**Q. Shouldn't natural bodily mitigation of substances be allowed for in the definition of toxicity? (i.e. urination of excess water)
A. We'll spend a lot of time on that concept - the body's natural defenses. When a whole animal is tested, those natural defenses are integrated into the results.

** Q. What types of toxicity testing are performed on humans and why?
A. None, anymore. 50 years ago toxic effects were sometimes tested in volunteer prisoners, but this is now against the law. Drugs are tested for their beneficial effects in humans and toxic effects carefully noted, but it is considered unethical to test toxicity, as such, in humans. At least at levels where toxic effects are expected.

** Questions: Is my interpretation correct: i.e., Can LD50 be defined according to different scales (e.g., 96 hours, 14 days, etc.)? If so, how are different LD50's related to each other? Are they defined in terms of acute toxicity vs. 14 day lethality, etc.? And what would cause one to test in a time frame departing from the standard set by the CPSA?
A. It's easy for a scientist or engineer to make fun of the government. We are trying to find a truth about nature or design something, while they are trying to make a "bright line," i.e., an absolutely clear determination of what is legal and what is illegal. I'm guessing the 14 days was some sort of compromise long ago. It may, I'm guessing, give the animals a chance to die, but not enough time to build up defenses. But the variation of effects over time might be different for each and every of the 30,000 common chemicals or 2 million utilized chemicals, of which we have tested less than 500 in any detail. 96-hours is the standard for acute testing. Chronic testing usually lasts a lifetime, about two years for most lab animals. There are no rules, that I know about, that would let you compare a 96-hour test, with a 14 day test, with a 60 day test. They might all be very different.

**Q. What constitutes a "strain"? I gather it is more than just color. Does it also include the class? Species? Both?
A. Strain is a sub-division of species. Dogs are a species, while Dobermans and Poodles are strains. Species is a biological reality, while strain may be a matter of opinion, or marketing.

**Q. I am not clear on the explanation of the number of electrons associated with the radical molecule OH(with a dot) in quiz question 7.
A. Oxygen had 6 and hydrogen has 1, so OH must have 7. Now the hydroxyl ion, OH^- has an extra electron, that makes it a charged particle; it has 8 electrons. It often steals that electron from a different hydrogen, leaving that without any electrons, just a poor proton, H⁺

* Q. What other means, besides radiation bombardment, lead to the creation of free radicals?
A. Many, both biological and chemical. Our bodies make a free radical, O2(dot)- (aka, superoxide anion) constantly, but they are in turn used in other processes, and if they get loose, there are enzymes to neutralize them. We will revisit radicals later.

* Q. How does an overabundance of water rupture the cell membrane?
A. The cell membrane of higher animals and plants passes water freely, but does not pass salt ions, except through channels. If you take such a cell out of the bod and place it in pure water, it will swell and burst because of osmotic pressure.

* Q. I’ve always been taught in HAZWOPER training that the primary routes of entry into the body are inhalation, ingestion, injection, and absorption.  In the definition of “toxic” found in 15 US Code Section 1261, why aren’t substances that have the capacity to produce personal injury or illness to man through injection included?  Or would injection be included under “absorption through any body surface”?
A. I’ve never heard of injection as a hazwopper issue.  Generally things that get injected are due to an “accident” that is, a “safety concern,” which is different than an “exposure” which is a health concern.  I go into that a little in another course, ENCE 649, Hazardous and Toxic Waste Management.  But here is a page from that site that gets into that distinction.
http://www.faculty.uaf.edu/ffrap/EQE_649/Module_01/1C_Risk_and_Safety/RiskandSafety_1.html

*Q. To extend off of the discussion about typical laboratory rat testing with chemicals, I’m curious if you know the basic procedure for human testing with pharmaceuticals.
A. Here’s a website with an overview and time line.  I did vet it, but it looks about right:
http://www.drugs.com/fda-approval-process.html

*Q. Do they start out by testing new pharmaceuticals with white rats, rabbits, etc?
A. Almost always.  They always test the toxicity with lab animals – the mouse is the most common.  But when they get close they use the rat.  The next step depends on the toxic reaction, or suspected toxic reaction.  If there is a suspicion that it will be toxic in a, say, a sheep, they will test that.  In order to be approved for use during pregnancy, they will use at least three species.  We will talk about that.
Next it will be “tested” with “volunteers,” usually the staff of the lab that is working on the drug.

*Q. Then, if you (human) have the condition that the drug is supposed to target (such as cancer, diabetes, AIDs, depression, etc), and if other approved drugs do not work does the physician then ask if you would like to become part of a trial run?
A. The next step is field trials.  Those are usually conducted by a hospital and physician that have contracted to perform this service.  Usually it is teaching hospital and the physicians are on the staff of the associated college.  Choosing the subjects, their medical conditions, and many other things are in fact a negotiation between the Food and Drug Administration and the drug developer.  These field trials take at least three years, often five and cost 20 million or more.
Generally they will not use test drugs if the patient is close to death. 

*Q. The do you sign release of liability papers, etc, and become part of the statistical analysis for future either approval or rejection of the drug?
A. Indeed, you sign “informed consent forms” and lots of stuff.  You often get paid something for your trouble.   There are ethical issues, if there are alternative drugs that work, but not well.  All the final tests are “double blind” with neither the physician nor the patient knowing if they are getting the test drug or a placebo.

Q. In Sub module 1B the point is made that any substance in the right amount can be considered a poison. The one chart showed Oxygen as being a potential cause of birth defects. I recognized the other four examples, even water causing cell breakage, but don't remember hearing about Oxygen. Under what circumstances would Oxygen cause a birth defect?
A. High pressure oxygen is directly toxic, that's why it isn't used for divers. There is some evidence that maternal hyperoxia can cause birth defects in the fetus.

Q. Question #8 in the quiz addresses the definition of "Highly Toxic" and the type of rat used in the testing. Re-reading the definition, I agree it only says laboratory white rat. In Stine, however, in discussing the LD50, they refer to the white Norway rat as being the standard laboratory animal used. In the question you refer to "strain" of rat used. I gather that there are different strains of Norway rat? After re-reading the biology portions, I'm not sure I fully understand breeding of strains of animals.
A. Turns out that "Norway Rat" is a species, Rattus norvegicus. Most lab rats are technically some strain of the Norway Rat. Note many have been bred for many generations for some special characteristics and might appear very different than the archetype Norway Rat, and from other strains.