***Q. [this question regarded if an employer was ethical, if he didn't report all the chemiclas in the shop.] does that make the business, unethical, since it is their reasonability to inform their workers on all the different hazards and such of a chemical?

•  A. To harm an employee or the public with your chemicals is always immoral – to me.
• To expose an employee or the public to a chemical would only be immoral if you believed the exposure would bring some measurable harm, or if your actions were reckless.
• To expose an employee or the public to a chemical would be illegal if the exposures were above a “bright line” established by law (regulations are laws).
• In America, today, there is a law that requires employers to communicate the hazards of chemicals to which employees may be exposed, on purpose or in a reasonably foreseeable accident.
• Ethical, in this sense, as I interpret it, for me, is to both obey the law and to protect people, both employees and the public, from harm due to my actions or inactions.
• As a practical matter, Ethics often deals with risk, the probability and severity of some harm, rather than actual harm.  So if there is no “bright line,” at what point is the probability and severity so low that it is ethical to expose people?  As human being who likes to think of himself as “moral,” and would like others to think that of me, I should rely on my conscious.  As a scientist, the answer is simple, “more research is needed.”

***Q. Lesions on the skin or in the organs seem to be a common symptom of chemical insult. What is happening at the cellular level that creates the lesion? My question comes from a broader interest in knowing why it is a discrete location and not more generalized tissue breakdown.
A. “ Lesion” is a very general word for damage to tissue. It might be a wound, sore, ulcers, tumor, cataract, or any other damage, caused by injury or disease. The damage has a focus or foci, usually visible, at least under a microscope. The term can even be used to damage at the molecular level, a mutation might be called a lesion on DNA. Regarding cancer, the answer to your question is probably just probability. All the cells in the liver (or in a zone of the liver) are being exposed to the insult, but only a few become cancerous. For other types of lesions, I am not sure why they tend to happen at foci, rather than be distributed.

***Q. I just want to make sure I understand this: When blood passes through kidneys, only a certain percentage actually gets filtered. Which means that the toxicant could circulate several times before being removed/eliminated by the kidneys.
A. To be technical, it is not “blood” that is filtered, but “filtrate,” which is blood minus all its components heavier than about 28,000 Daltons. Yes, it could circulate longer than that. The toxicant would have to stay in the filtrate when it is filtered, that is, not be reabsorbed in the proximal tubules.

**Q. I do have one question pertaining to the liver. In the course of doing the homework on liver and kidney effects from a chemical, the chemical I selected, dieldrin, was associated with a reduction of serum protein concentrations in the liver [or blood] . I had to do additional searching to find information on what this meant, in order to be able to explain it in plain English. I learned that the liver produces two types of proteins, albumin and some types of globulins. Albumin is essential in preventing blood from leaking out of the blood vessels. Globulins apparently fall into three types, alpha, beta, and gamma globulins, some produced in the liver and some by the immune system. What I didn't find was information on which types of globulins are produced in the liver, versus elsewhere in the body, and what the roles are played by globulins produced in the liver. In other words, how would our heath be affected by suppression of liver proteins?
A. The liver makes lots of proteins. Most people that die from liver failure die from low blood pressure, the blood and fluid just leak out of the blood vessels. “Globulins” is somewhat an archaic term. Most globulins are antibodies that are mostly made in the immune system. The liver makes many transport proteins besides albumin, and lipoproteins that transport lipids, etc. To name a few. The fatty liver is caused by a deficiency in lipoprotein production in the liver.

**Q. My question this week is about the code of ethics which so many professional associations have. I am member of the Alaska Association of Environmental Professionals (AAEP), and we too have a code of ethics.Firstly I'd be interested in knowing who comes up with these codes? Are they created by the members of the organization? Or are they created by the board of the association? Is there a formal process for having the code “approved” or “accepted”? Also is the code just drafted up off the top of someone's head or are they adopted from another similar organization?
A. Volunteers run most of these organizations. They may have a small paid staff, but mostly, if work needs to be done, members must be found to do it. So, usually, sometime early in the history of the organization, a committee of volunteers drafted the code. Certainly they used other codes as a starting point. It was sent out to review by the members, their suggestions considered, and a final version approved by the membership. Same process for amendment of the code.

**Q. The part B to my question(s) is what happens if you are a member of an organization and you are found to be in violation of the code of ethics? Will you be dropped as a member? Can there be any legal recourse?
A. Most organizations will boot out members who are found in violation of the code. However, for the reasons above, the organizations lack the resources to investigate allegations of unethical behavior. So, they often must wait until someone else investigates and publishes their findings. Then the org forms a committee, which makes a recommendation, and the general membership votes to oust the offenders. Certainly the disciplined former members can sue organizations, but usually the suits are not successful, IF the organization followed its own guidelines for such actions. These are often spelled out in their articles of incorporation or “bylaws.”

**Q. Can a damaged liver be almost completely regenerated? Could surgery be performed to remove the bulk of the liver to regenerate to a healthy organ, assuming one could control their diet to remove the need for the liver's function? Or does its capability to regenerate become hindered by disease?
A. My guess in a healthy person, a lot of liver could be removed and it will regenerate. It does in rats. However, in humans, such liver surgery is almost always performed on very sick people. There are often many complications.

**Q. You note that most toxic agents damage the liver. Just how resilient and regenerative is the liver? How much damage can the liver sustain before we experience serious health affects?
A. At the “clinical” (physician's) level there are two kinds of liver diseases, “compensated” and “uncompensated.” In compensated, the liver has enough capacity to do pretty much what it is supposed to do. Once the damage progress to a point where it can no longer keep up, signs and symptoms of liver disease show up. The uncompensated liver damage is very bad, but if the stressor, usually alcohol, is taken away, the liver can regenerate enough to go back to the “compensated” status.

**Q. According the Sunmodule 8A- Hepatic Toxicology, we know the liver can store nutrients, sugar and fats . Still in the former research, we also know a slight increase in liver fatty change in the high-dose group at 78 mg/kg-day dose of acrylic acid.So I think there are a little damage for the liver. Because I think the ability of liver , the ability of storing fats, were changed.Is it right?If it is right, I have a question why it did not considered as the adverse effects when the liver's fat changed ?For me, I think it is only a little damage for liver but it do not make any changes on the histopathological examination. So it do not make any the adverse effects for the liver.Is it right?
A. The phrase “a slight increase” is not quantitative. It implies they observed something, but it was not significant. This is sometimes an ethical dilemma; do you report everything, or just what you consider important? For quantitative results, it is possible to demonstrate “statistical significance.” For qualitative, this is often not possible.
If there were a “significant increase” in fatty changes, it would definitely be an “adverse effect.” The liver stores fat, but only a certain amount, then it exports the rest of the fat presented to it. In “fatty changes” the liver is not making the proteins necessary to export the fat, probably due to some damage or stress on the liver cells.

**Q. I don't mean to sound racist, but assuming the stereotype is true about natives having a lower tolerance to alcohol (is that true?), what is the science behind that? I would guess after reading the module that perhaps they have fewer P450 enzymes. Am I on the right track?
A. Alcoholism is a difficult topic. It cause or causes are unlikely related to the amount of P450 enzymes. Clearly it is a behavioral problem, in the sense that if one does not drink, there is no problem with alcohol. It is also, clearly, a genetic problem. There is no doubt that at least 50% of the problem is inherited, but this is the same as many genetic diseases. The issue of how much behavior in general is genetic is a deep topic, both philosophically and scientifically. Clearly the incidence of alcoholism is much more prevalent in some ethnic groups, as one goes north from the Sahara, the incidence of alcoholism increases. It is much higher in Scandinavians and Russians than in Italians. A well known genetic aberration leads to the other result – sobriety. Many Chinese lack the proper ADH enzymes and aldehydes quickly build up, if they drink any ethanol.

**Q. In the 7 rules for success in risk communications the point saying: Meet the media's needs
My question is that I don't understand which media is it (propaganda media OR the public). If propaganda media then why should a risk communicator meet their needs. He will directly communicate to public.
I mean it's not clear as to what needs and what kind of media is spoken about here.
A. Excellent question. The "needs" are usually known by the PR (public relations) person at your company or agency. They often have another name, but the function is the same, be the point of contact with the media. If you are on your own, there is no problem with calling them yourself. Some needs of the media are,

• Deadlines. Schedule events so key media have time to meet their day's deadlines
  
• Graphics. For TV and such, make sure your graphics are visible.
  
• "Press Releases." Always prepare a release or "fact sheet" with all the key data, especially numbers, so that the reporters do not have to rely on their notes. Always prepare copy such that the reporter can use it verbatim, if they want.
  
• Access. Give the reporters special places in the auditorium, or other space so they can do their work - space with auditory and/or visual access to the talk, debate, etc.

**Q. My question has to do with a portion of the text in the module. There is a statement that "there 20-40% of the blood is "filtered," meaning it leaves the blood and enters the nephron." I think I understand the concept of the kidneys, but something here doesn't make sense.
A. "Filtered" in this case is just a word that means it enters the nephron. At the beginning of the nephron, the fluid is called the "filtrate." The large molecules that remain in the blood have charges or hydrophilic centers, so some of the watery blood remains in the capillaries and does not enter the nephron.

** Question: I found out that aflatoxin is produced by fungi that
are natural contaminants of agricultural products such as peanuts, but what
exactly does it do the liver to produce cancer?
A. There are lots of kinds of Aflatoxin, B1 being the most toxic, or at least best known toxic. It is a reactive compound capable of damaging many organs, but there are typically only very small quantities of AFB1 in food. AFB1 is metabolized in the liver to an expoxide, which is an electrophilic species. It then binds to DNA (It also binds to RNA and proteins). The chemical binding to DNA, making an adduct, is likely to lead to a mutation. Enough of the "right" mutations make cancer.

**Q. One thing I wasn't sure about was the ability to predict alcohol metabolism by Michelis-Menten kinetics. It appeared the Km and Vmax were always the same. How does body weight or other variable such as physicology, etc. influence this rate of metabolism? It is truly always the same in each human?
A. Vmax is expressed in per kg basis, so body size is accounted for. The authoritative book I checked gave Vmax as 124 +/- 10 mg/kg hr or about a 10% variation. That seems reasonable, on the average. Heavy alcohol users will have a higher rate, based on the induction of P450s, but then may have a lower rate with damage to the liver.

**Q. Sandman claims that Risk = Hazard + Outrage. Right.  The public perception of risk has two components, the scientific evaluation of risk, which he calls hazard, and the public’s outrage at the situation.   This seems to inject a very difficult item into any analytical approach to risk management.  [Yes, but think what you are saying – the public’s perception is a difficult item.  Yup!] The outrage is a sociological and potentially more [or completely] subjective aspect. While outrage should not be dismissed, it seems that including it in the risk computation creates more problems than it solves. (widespread panic and pandemonium withstanding)  Perhaps outrage should be considered from the public relations point of view, and other risks dealt with in an analytical engineering approach.  Thus there is first a separate consideration of each aspect of the crisis. Then the two results are considered in the context of a dynamic and subjective interaction as they relate to public sensibilities. This is different from the   explicit relation that Sandman makes when he presents these two items in an equation.
Would you please comment on this statement?
A. Twenty years ago I would have agreed completely.  Today I don’t.   See the first two pages of  
http://www.faculty.uaf.edu/ffrap/ENVE_651/Module12/Submodule_12A_RMandPublic/Submodule_12A_1.htm

Q. How quickly does the liver repair itself? For instance, if someone is an alcoholic and has liver damage and hasn't reached the "point of no return".
A. Once an organ is inflamed and had dead tissue (necrosis) it is partly repaired by connective tissue. So the organ, at best, looses function. Because most of our organs are working at a small percentage of their capacity, especially the liver, they are far-gone before the damage is obvious. Then, conversely, it might not take much repair to restore minimal function that the person can perform again. Unlike most organs, the liver can regenerate almost completely. However this regeneration process is characterized by much "mitogenesis," which makes the regenerating liver susceptible to mutagens causing cancer. In lab animals, part of the liver is removed, and then the remainder regenerates. During this process some test chemicals are much more carcinogenic, indicating the role of mitogenesis.

* Q. Your thoughts on hepatic steatosis. What in your opinion is the reason for the accumulation of fat following the consumption of alcohol? What has broken down in the liver's cycle to allow the buildup of fat? Is there a breakdown in communication between the liver and gall bladder so that bile is not getting where it needs to be? Some type of allosteric site is blocked perhaps. Does alcohol induce a sort of cholestasis?
A. No, not cholestasis, but a derangement of fat handling. It was thought that it was due to malnutrition, but not anymore. There is a decrease in the production of lipoproteins that move fat out of the liver and into the tissues.

*Q. I found the link: http://www.chemcases.com/alcohol/alc-07.htm really interesting. I read, that alcohol is more a women problem. And I found out, that I could consume 12 drinks every Saturday night, maybe more because I'm heavy, without major health problems (if I don't drive by car after that). Right?
A. Several students commented on the gender differences, for which the author did not have a good explanation, nor do I. One thought about this. Here we have a very simple chemical, ethanol, that we know lots about, that we know the toxic effects of, that there is lots of money to study, and we do not have a good explanation of some important effects, in this case, related to gender. How then can we (I , toxicologists, industry) be expected to make detailed scientific pronouncements, i.e., prove beyond all reasonable doubt, anything related the possible effects of a chemical. Such gender differences in sensitivity are common in testing and that is one reason both sexes are tested, and the data recorded separately.

During the calculation for finding the safe limits for a working place:
1. Are the chief organs effected the only means of concluding whether the fractions should be added or not. If they damage the organ.
A. Yes. Some chemicals might slow down or speed up the metabolism of other chemicals.

2. Since we are dealing in fractions and decimals (very small numbers) shouldn't other target organs effected also be means of understanding the correlation between chemicals.
A. See above. In general, no damage to an organ is acceptable in the workplace. However many organs may be damaged, but not severely enough to have the damage detected.

3. Should there be a mathematical model (taking into consideration the target organs of the chemicals separately) to find out about the additive effects of chemicals upon the safe limits of a workplace.
A. There are lots of models, but you would have to know the dose response effect at each organ in order to make the model work. We seldom know that.

Q. From medical-toxicological point of view how usefull/harmfull is to eat beef/pork liver and kidneys?
I am asking, because I really like beef kidney dishes, I know how to cook it right to taste good. But I am not sure this is good for my health.
A. Certain toxic metals are concentrated in the liver and kidneys. It's a good question to ask. Beef cattle are fed a standard diet and are unlikely to have much toxic metal. It can be easily checked.

Q. I have another question sort of off topic. I have come across the topic of water toxicity several times, in military training and sport literature. Water toxicity boils down to consuming too much water, which dilutes your electrolytes and can affect the functioning of your muscles and some organs. This doesn't seem to be "toxic" in the same sense as we refer to the xenobiotics studied in class. There is no target organ, no carcinogenicity, no RfC or RfD.
A. If you drink a lot of water, your blood pressure increases. This tells the kidney to keep the valves shut in the ascending loop of Henle and excrete more urine. It does this via a feedback loop that goes from the kidney to the blood to the hypothalamus back to the kidney. (I didn't design the system.) The dilute urine from the kidney carries salt. The bod has a mechanism of doing this but still conserving salt, but it only does this if your blood pressure drops. So as long as you drink enough water to keep you blood pressure high, you will urinate salt. When you excrete enough salt, which is mostly sodium, but has some potassium, you will run low on potassium, usually first, and suffer from that. It takes a lot of water. Put salt in your beer if you are really concerned.

Q. I thought that it was interesting that adverse effects in woman were documented in moderate drinkers, specifically the definition of moderate being 7-13 drinks per week.
A. May be a body weight function.

Q. First page of submodule 8A: When the oxygen rich blood from the heptatic artery mixes with the oxygen poor blood from the portal vein and bile where does it go next and how does it get unmixed?
A. The bile ducts are not connected to the blood vessels and the bile is not mixed with blood. The blood is never unmixed.

Q. I have a question on translating the presence of Heinz bodies and iron deposits. I am also wondering what is generally made of organ enlargement. I can see it as bad since it indicates something unusual going on, puts pressure on other systems and generally knocks things out of whack. For the organ itself, with out histopathology, is there something inherently bad with being larger than usual. Also how do they determine absolute and relative enlargement? So they somehow weight the organs at the start of the experiment?
A. The last question I can answer, it is with respect to controls. Most strains of lab animals are inbreed, so all of the same sex and age should be close to the same weight. In general, it is very easy to weigh an organ. If it is lighter or heavier than it is supposed to be, that is a flag for microscopic examination. Microscopic examination, histopathology, is expensive. Just having a small statistical increase in weight is not an indication of toxicity; this is called hypertrophy or hyperplasia, if there is no change in cell type: