**Q. I noticed your message for quiz question 9. I chose Adipose tissues as they are the fat tissue and the most significant place where lipid-soluble toxicants are found. Is that really the case?
A. Yes, lipid tissues are where most of the lipophilic chemicals are stored. Interestingly, the brain is essentially a lipid tissue. The point of the quiz question was that they are stored just about everywhere. All the body's cell membranes are a "lipid bilayer" as is the endoplasmic reticulum within the cell.

**Q. Vinyl acetate is sometimes described to be a monomer. In the dictionary, it defines monomer as;
The simple unpolymerized form of a chemical compound Does this mean that the compound does not [?] with itself or other molecules, and does that have any effect on it's toxicity
A. Sure. A polymer has very different properties than the monomer. Vinyl chloride is a good example. By itself, it is quite toxic, causing liver cancer. In the polymer, polyvinylchloride, it is harmless. Some polymerizations proceed spontaneously; most require input of heat or a catalyst. For common chemicals that used in polymerizations, it is common to note that it is the monomer that is the toxic form. Otherwise the product would still appear as toxic even after it was converted to the non-toxic polymer.

**Q. I'm a little fuzzy on the "second messenger" concept. Are the functional changes within cells side effects of receptor-ligand reactions? Do they always ["always" is never the right answer].happen or just in certain circumstances?
A. The cell membrane (lipid bilayer) separates what is inside the cell from what is outside, and is key, if you wax philosophical, to what is life and what is not life. Almost nothing, except water and perhaps glucose, transfer freely between the inside of a cell and the outside. All transfers are tightly controlled. The common way for the body to get a cell to do something is to send a first messenger, often a hormone, to the blood where it distributes throughout the body. Only cells with the correct "cell surface receptor" will latch onto the hormone, the rest remains in the blood. These cell surface receptors usually penetrate the cell membrane and have a molecular gadget inside the cell. When the hormone binds to the external receptor (you could call it a ligand - at that time), it activates the gadget, usually by changing its shape. Next there must be some sort of signal from the gadget to the location in cell where the body wanted the cell to do something. The usually method for doing that is the activated gadget is actually catalyst that changes a molecule that was already freely circulating within the cell. The new molecule is now a "second messenger" which float to the location within the cell, where it tells that part of the cell to do something. Often this second messenger is itself a catalyst, that in turn changes other molecules, which in turn change others, in a cascade. Thus one molecule, a hormone in the blood, might change thousands or millions of molecules within the cell without ever crossing the cell membrane. For our purpose, you can image how one xenobiotic molecule that blocked or activate the cell surface receptor might do far more damage than you might expect from one molecule.

**Q. After reading the section a few times, I still do not understand the difference between active site and regulatory site. Can you explain more?
A. On a molecular scale, most enzymes are very large molecules, hundreds of amino acids containing thousands of atoms. The amino acids bend and fold into characteristic shapes. Typically, in the whole huge molecule, there is often only one little site, the catalytic site, where the substrate is changed into products. That site and its near surrounding is the "active site." It must be very strictly structured to do its catalytic work. Often its near surroundings are also closely structured to shoo the right molecules into the catalytic site. Competitive inhibitors "look" like the substrate, that is, they fit in the same catalytic site and block the proper substrate from getting there. A regulatory site is someplace other than the catalytic site where a molecule can bind and by binding there, change the shape of the enzyme, perhaps just a little, but enough to alter the active site. This alteration might make the enzyme work faster or slower. This site is a regulatory site. In fact some enzymes have many regulatory sites that different molecules can bind to.

*Q. When reading the section on nerve agents, I was interested in the relationship between Tabun (least deadly) and VX (most deadly). I know there isn't necessarily a correlation between volatility and its lethality. Which of the two chemicals is more volatile? I was unable to find this info. Is VX more volatile that Tabun? Also is Tabun naturally found in the environment?
A. Whoops! Tabun is very deadly. It is just less deadly than VX. The progression from most to least could be set in the lab with animals. Exposing animals to fixed concentrations of gas is more complex than you'd think, but it can be done, and that is where the data you were looking at probably came from. However when assess the toxicity of a warfare agent, you would need to look at the exposure. If it all evaporates immediately, it would expose those nearby only. If it evaporated more slowly, it would expose people over a longer time. Some agents are more toxic via the skin.

* Q.While doing a web search for information on 1,2-dichloropropane I came across a report of a "Gavage Study". I am not familiar with this type of study, can you explain?
A. "Gavage" refers to a method of dosing animals. "Oral" usually implies the animals eat or drink the chemical, usually by mixing with their food. In gavage, a tube is placed into the animals stomach and a precise quantity is placed directly into their stomach.

Q.I couldn't find this answer from the module. I did a search on Google to find more information and found this site: http://www.elmhurst.edu/~chm/vchembook/573inhibit.html
A. I've got to revisit that. Those metals are clearly not hormones or second messengers, so the only correct answers are competitive or noncompetitive. To be a competitive inhibitor, the heavy metals would have to bind to the same site as the normal enzyme substrate, i.e., if the enzyme were operating on some heavy metal. That seems unlikely. Anyway, right now I can't find where that question came from, so I need to change it.

Q. One of the chemicals I'm using in my MSDS project is 1,2-dichloroethane. This chemical, along with all of its cousins (TCE, PCE, DCE, etc.), seem to have some pretty severe environmental consequences, especially when they find their way into groundwater. I understand their primary uses are as solvents. Are there more environmentally friendly solvents out there? I'm guessing the two major drawbacks to using more environmentally friendly solvents are that they don't work as well and they cost more. Is this generally the case? I'm also trying to see if there are solvents that have less toxicity than 1,2-dichloroethane. Perhaps they cost more and don't work as well too? It seems that often times the nastiest stuff works the best and costs the least.
A. Yes and is also less flammable. Most of the chlorinated hydrocarbons do not burn since they are already oxidized by the chlorine. This same property makes them hard to oxidize by the bacteria that will burn other hydrocarbons. Careful with what you read about their toxicity. Most of those chemicals have been in high use for many years and also pretty well tested, i.e., their toxicity is known. The same is not true of many of the replacement solvents. What you ask, though, is really an ENVE 649-type question.

Q. Are there other common toxins that we run into in our everyday lives that act as noncompetive inhibitors other than lead mercury and chromium?
A. Alcohol. Most drugs, useful and otherwise. For a drug or anything to be a completive inhibitor, you need a lot of it, relative to the "endogenous" molecule for which that enzyme was designed to catalize. A non-competitive inhibitor, by binind to a regulatory site on the enzyme, might affect the enzymes function at a much lower concentration.

Q. I am noticing a long period from when some of these chemicals were no longer manufactured to when they were no longer permitted for use. Some span a time period of ten years or more. Is this normal for so much time to pass before controls take affect or perhaps unique to my chemicals?
A. Each has its own history. Sometimes a company will be considering dropping a product, but still has some people who like it. Often the replacement chemicals are more expensive and/or less efficient. When the company learns that the EPA is considering banning the chemical, they will take the chemical off the market and blame the EPA, when in fact it was not profitable for them. On the other hand, when a company finds out a chemical is a bona fide hazard, they will immediate start looking for a replacement product to sell, meanwhile they will try to promulgate the proper precautions.

Q. In doing research on my three chemicals, 1,1-Dichloro-1-fluoroethane was listed as a 'high volume chemical'. Another link told me that a chemical will be classified as that if production exceeds 1 million pounds per year. Does EPA designate a compound a 'high volume chemical'? If it is EPA, I'll assume it is listed on their TRI website. Is there any other website, company, agency that tracks 'high volume chemicals'? If could not find it.
A. It is certainly an EPA definition, but I could not find chapter and verse.