Module 2

**Q. How long is a "long paragraph?" Maybe, my assignment is too short. I will see it. A. No, it is just fine. I try to give an idea of the length, because some students feel they have to write 8 or 10 pages, while another feels one sentence is sufficient.

*Q. Is it required (by law!), to provide the MSDS and the proper training in an understandable language for the employee?
A. Very important point. I teach more about worker protection in ENVE 649, Hazardous and Toxic Waste Management. Briefly, it is the employer's obligation to sure each employee understands the hazards. The problem is that the employees will insist they understand English, when they may not. Also, without proper training, how will an English-speaking employee know who IARC is? Or what "hepatotoxic" means?

*Q. I have had basic organic chemistry presented I don't know how many times and I still get the names messed up. Have you ever seen a good one or two page cheat sheet/reference? They are inside the front cover of many organic chemistry textbooks.
A. Here's one from the web:
http://www.wikipedia.com/wiki/functional+group

*Q. According to US law: do scientific research or medical institutions have to report the newly obtained data on chemical's toxicity? If yes, where? To whom? Or is it a requirement for manufacturers to carry such research?
A. No they don't. When a manufacturer markets a new chemical they must prepare an MSDS sheet, but they do not need to do any research on it. They have a legal liability if anyone gets hurt; so most manufacturers do some investigation. Many new products are mixtures of several chemicals, and the properties of these constituents are known. These will be on the MSDS sheet. Medical or scientific labs might discover something but they are not required to report their discoveries.

*Q. In general words, how will I, common person, know how toxic might be a simple household chemical, if a manufacturer provides old data?
Consumer products, those that you buy in a supermarket, come under the Consumer Product Safety Commission regulations. These require labeling of toxicity, but only in the very general way. You will see most labels have an 800 number or address for more information, but I have not had any luck getting real toxicity information by this route. Most commercial products by major manufactures have been tested pretty well. The chemicals you use in the laboratory are not consumer products and do not need to be labeled.

*Q. I finally went to the department homepage that states that MSDS sheets should be obtained from the manufacturer for any chemical used in the lab. Based on the limited information in the database, this is a great idea, but they should not represent their database as containing MSDS info.
A. There is worker-OSHA issue in that statment. In the US you are allowed to use CD's and MSDS's from the web to inform your employees, but they have to be trained in this and the system must be readily available. You can't just tell employees, "you can find it on the web."

*Q. In addition to same MSDS sheets the companies or manufacturers mention about the purity of the chemical they are selling.
A. Because they don't have to. But that brings up an important point, often a minor impurity from a chemical standpoint, might be the major factor from a toxicological standpoint. 2,3,7,8 TCDD is a minor impurity of "agent orange" but was allegedly responsible for many effects.

Q: Are the rate of organic reactions generally faster or slower compared to the rate of inorganic reactions and why?
A. They are so variable that you could not categorize reaction rate by organic vs. inorganic. Most reactions rates are temperature dependent and biological reactions are limited to a narrow range of temperatures.

Q. Why don't companies and manufacturers follow one particular guideline for MSDS sheets for their products ?
A. They do, but the guideline, the OSHA regulation, is very broad.

Q. Do the majority of toxics affect tissue and organs or the CNS?
A. The CNS, central nervous system, is a branch or department of the organ system known as Nervous System. Most such branches of other organ systems are separate organs. For example the pancreas and liver are separate organs in the GI system. The CNS is really just one organ and the "system" part of the name is somewhat a misnomer. Almost all toxics that are interested do their damage at the cellular and biochemical level of organization. The "clinical significance" on the other hand, comes when this damage to individual cells becomes significant to an organ or organ system.


Q. That Tissues, Organs, Systems, Signals and Receptors Submodule seems like it could have been a whole lesson in and of itself. Do you have a eukaryote point of view on organelles?
A. Only eukaryotes have "membrane bound" organelles. Prokaryotes do have ribosomes.

Q. Also, are unsaturated oils better for you because of the physical properties (ie the slipperiness and shape) or because of the chemical properties (the double bond that may allow something)?
A. Both, but many of the details are beyond me. Note the location of the double bonds is apparently very important.

Q. In light of these different styles and qualities, was there a regulatory change at some point in the 1990s that dictated a uniform style to MSDS's.?
A. No. The ANSI standard is still voluntary. The ANSI standard was developed in 1993, long after the HAZ COM law, so some major players did not have theirs in ANSI format. They would also object to a change in the standard.


Q. Finally, have there been any proposals to establish regulatory oversight and review of MSDS quality, such that an incomplete MSDS would require rewriting if a review deemed it inadequate?
A. Not as far as I know. It takes a major push and about 10 years to change an OSHA regulation.


Q. I am very disturbed by the story of Dr. Wetterhahn. If DMM is that lethal, it seems to me that there should have been some very extensive training for not only Dr. W., but for everyone who worked in that lab and may have had the opportunity to come in contact with DMMe~. If the chemical was so dangerous, why didn't anyone know or tell Dr. W. about the latex gloves? Dr. W. was experiencing symptoms- shouldn't she have been under a special medical surveillance program? If she were working with radioactive isotopes, she would have been forced to wear film badges, protective clothing and get her thyroid checked twice a year. Was this just a fluke incident of compounding errors, or is there potential for similar incidences that we are not aware of?
A. Her employer, Dartmouth, was fined by OSHA. Training is a difficult issue in this case because Dr. W probably was the local expert on DMMe. Gloves and other backup systems are not tested until there is a mistake. She may simply have not spilled any on herself in the past. Her symptoms did not occur until several weeks after the exposure. This is an extreme case. In this tox class we have to break off learning about worker protection at some point, in the Hazardous and Toxic Waste course (ENVE 649) we spend much more time on those topics.


Q. In chemical engineering, the term kinetics is associated with how fast reactions occur and is invariably tied up with differential equations. I recall that this is also the case in biological reactions e.g. the Michaelis-Menten equation. Does toxicokinetics also rely on this mathematical approach?
A. Yes, We assume each compartment is a well-stirred continuous flow reactor. Elimination goes on in one or two selected compartments; this may be first order, M-M, or whatever. The compartments are linked by first order differential equations. Chemical engineers make good toxicokineticists.

Q. Just as an interesting note: Secondary and tertiary amines can also act as weak acids because the N-H proton can be removed by a strong base. For example the production of Lithium diisiopropylamide from Butyllithium and diisopropylamine (Organic Chemistry, McMurry).
A. McMurry is my textbook too. The key is "strong base" most biological bases and acids are weak. But thanks for the fine point.


Q. What is special about the composition of nerve tissue that makes it a good conductor of electrical impulses - at least more so than other tissues?
Q. It's specialized for that, and only that. Nerve cells (which are called neurons) that are designed to transmit long distances have insulating cells around them, called Schwann cells. We'll talk a little more about that in a few weeks.

Q. I was wondering if the [p] designation in the chemical name dibenzo[p]dioxin signifies the "para" orientation of the oxygen molecules to the chlorine atoms on the benzyl rings of the compound. In dibenzo[b,e][1,4]dioxin, what does the [b,e][1,4] indicate?
A. Go here: http://www.chem.qmw.ac.uk/iupac/fusedring/app2.html and look at item 63 and note l. [p] for para would take care of one of the para connections, but not the second.http://www.chem.qmw.ac.uk/iupac/fusedring/app2.html.

Q. What are/is the chemical receptors on the cell that the dibenzo[p]dioxins target?
A. We will do a little more on that, but it's called the Ah receptor, it seems to affect DNA quite a bit in some species, but no one is quite sure what the "natural" function of the Ah receptor was or why there is such an enormous species difference in it.


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