[unificationengine]

Hello, I'm doing some independent studies on the Flumist vaccination out of curiousity, however unfortunately I know practically nothing about chemistry!  Thusly, I can't claim to fully understand much of the research I am doing, if one of you folks could clarify some things for me that would be excellent! 

So, each pre-filled refrigerated FluMist sprayer contains a single 0.2 mL dose. Each 0.2 mL dose contains three live strains of the H1N1 virus attenuated with EDTA.
.2 mg monosodium glutamate,
2.00 mg/dose hydrolyzed porcine gelatin,
2.4 mg/dose arginine,
13.7 mg/dose sucrose
2.3 mg/dose dibasic potassium phosphate
1 mg/dose monobasic potassium phosphate

In my research of the components of the spray, my biggest concern is the presence of arginine, as according to Hasan Mukhtar in "Skin Cancer:  Mechanisms and Human Relevance" p.148,  "arginine may lower blood pressure because it is involved in the formation of nitric oxide.  Nitric oxide combines with oxygen in the blood to form nitrogen peroxide, Once it metabolizes into  Dinitrogen tetroxide and dinitrogen trioxide, it is known to induce powerful pneumonia and edema."

Following that line of investigation lead me to a paper by Hye Chin Chung, So Hee Kim, Myung Gull Lee, and Sang Geon Kim  "Increase in Urea in Conjunction with L-Arginine Metabolism in the Liver Leads to Induction of Cytochrome P450 2E1 (CYP2E1): The Role of Urea in CYP2E1 Induction by Acute Renal Failure."  In that work they state that "L-arginine, which is irreversibly hydrolyzed to urea and ornithine by arginase, also induced hepatic CYP2E1.The results of the present study provided evidence that increases in plasma urea in conjunction with L-arginine metabolism leadto the induction of CYP2E1 in theliver. "

Continuing I encountered a work on CYP2E1 which stated "

CYP2E1 induced bioavailability of acetaminophen, arcrylonitrile, benzene, carbon tetrachloride, chloroform, dichloromethane, 1,2-dichloropropane, ethylene dibromide, ethylene dichloride, ethyl carbonate, halothan, nitrosodimethylamine, styrene, trichloroethylene, and vinyl chloride.   "Casarett and Doull's toxicology: the basic science of poisons"

CYP2E1 Can activate acetaminophen to the hepatoxic metabolite, N-acetylbenzoquinoneimine.  This substance binds with proteins throughout the body, inhibiting function.  (this is one of my major concerns, as well!  A cursory browsing of the VAERS reports for flumist indicate that frequently people use Tylenol with the intent of lessening the headache and other side effects of the drug, is this dangerous?)
 By Louis J. Casarett, Curtis D. Klaassen, John Doull p.242"



Oxidative metabolism of TCE yields the primary metabolites, chloral,
TCE oxide, and dichloroacetyl chloride (Fig. 1). Chloral, a predominant
TCE metabolite, is rapidly converted to chloral hydrate
(CH), which then undergoes oxidation and reduction by aldehyde
dehydrogenase and alcohol dehydrogenase to form trichloroacetic
acid (TCA) and trichloroethanol (TCOH), respectively (Green and
Prout, 1985; Dekant et al., 1986). Dichloroacetyl chloride subsequently
undergoes decomposition to form dichloroacetic acid (DCA),
which can also be formed from dechlorination of TCA (for review, see
Lash et al., 2000).  "PULMONARY BIOACTIVATION OF TRICHLOROETHYLENE TO CHLORAL HYDRATE: RELATIVE CONTRIBUTIONS OF CYP2E1, CYP2F, AND CYP2B1
Poh-Gek Forkert, R. Michael Baldwin, Brandie Millen, Lawrence H. Lash, David A. Putt, Michael A. Shultz, and Kathy S. Collins"

So given this data the questions I would like to pose are:

If individuals are exposed through their environment to the substances which cyp2e1 makes bioavailable such as TCE and VC, are they at greater risk for adverse side effects?  For example, my town has an established TCE plume due to a dry cleaning operation, with levels of TCE significantly higher than the accepted limits - what effects would this have on the flumist inhalation?

Given that urea production is greatly increased as a result of arginine metabolism, how would that interact with the oxidizing agents in the mist?

Are there any more contaminants naturally present within the modern human bloodstream which would cause a reaction of concern?  I refer to fluoride, heavy metals, other solvents, etc. 

Would the acids produced in the metabolism of the mist react in any way with the sugar or potassium phosphate?

So, I think thats all I have to ask for now, any explanations would be deeply appreciated!  Thanks for your time.

[renge ishyo]

I wouldn't be too concerned about a mere 2.4 x10^-3g of arginine being present in a flu vaccine. You probably ingest hundreds to thousands of times that amount when you eat a small Burger King hamburger. Out of all the contents in the vaccine, the virus as the active component of the vaccine is by far the most dangerous component for the human body. If the virus vector inserts itself into the middle of a gene for instance it can cause disease or cancer instantaneously...this is the reason why you have to sign a waver before you get a flu vaccine. However, the probability that this will happen is very very small. Fortunately (unlike Burger King hamburgers) we don't take vaccines very often so all of these dangers don't pose a general threat to human life.

Arginine is actually needed by your body all the time for many essential functions (see the wiki for just a short list of positive functions: http://en.wikipedia.org/wiki/Arginine). In fact, your body synthesizes a large amount of it from the food you eat although some must be taken in from the diet to meet your body's demands. When we are talking about the danger of a chemical to the body in general you need to consider two things:

1. Amount of the chemical. If you ingest too large an amount of *any* chemical at any one instant then yes, that chemical can kill you...even water or anything else essential to life. The determining factor to the danger of a chemical is *how much* of the chemical can we  ingest in a short period of time before it becomes toxic? This partly determines the danger of the chemical. The other part is that if we ingest some man-made chemical like ethylene dibromide we are in far more danger than if we ingest arginine because our body has mechanisms to both make and dispose of arginine and all its metabolic byproducts (the reason for the increase in urea is that your body just excretes the extra arginine as its waste product ureas if we happen to ingest a larger amount than what is needed). The body doesn't have anything to deal with ethylene dibromide hence the former is much more dangerous at much lower concentrations. It is also more dangerous if the chemical can't be disposed of by our body easily and just "sits" in there allowing a smaller concentration of the ingested chemical to reach the toxic amount the next time around.

2. Duration of exposure. This is the far more serious threat to our health, and unfortunately because humans tend to work at jobs that use chemicals this is also the threat we will have the hardest time avoiding. Even a small excess of a chemical in our environment can build up in our bodies over time and lead to problems later on. So it might not be a good idea to live next to a toxic waste plant, but driving by one probably won't expose you long enough to do any long term damage.

Now to address your questions, the real problem is that everything kills. It just depends on those two factors above. Even if no dry cleaner existed to release chemicals that could potentially react with our pee (urea); the urea in and of itself can be oxidized by the air to nitrous oxide radicals that can be inhaled by the body and wreak havoc. So if you went to a sewage plant and breathed in the air (smell that country fresh!) for a long time you can develop health issues just from inhaling natural human waste. The scary thing about the chemicals the dry cleaner is releasing is that they are "man-made" which brings up the whole "in what concentration is this safe" debate that goes along with any man-made chemical. However, keep in mind dosage and exposure. If you wanted to argue that increased pee in an area where a dry cleaner operates can be hazardous to human health you might want to consider regulating the amount of arginine in the hamburger restaurant up the street rather than the tiny amount present in the once-in-20-years flu shot that people take. My two cents anyways.

[JGK]

From what liitle I've read on the web doses of up to 2000 mg (2 g) Arginine per day are not considered harmful so the 2.4 mg in the vaccine administered once are unlikely to induce irreversible arginine toxixity.

As a toxicologist, I must say that quoting the articles the way you have done is scaremongering at its worst. There is no indication of dosages, or whether or not the effects are seen after chronic or acute exposure.

In a similar fashion I could equally well say that hand cream is fatal to humans (It is if you drown in a vat of the stuff)In normal use is unlikely to have a fatal effect, it's all a matter of scale.

As paracelsus said "everthing can be a poison, what matters is the dose"

[unificationengine]

Thanks for the replies.  Know that I am not an anti-vaccinationist by any stretch of the leg, and I understand the sensitive nature of the question well.  I have a fair understanding of the vast spectrum of chemical contaminants we are all exposed to on this planet and know that, as goes the cliche, it is the dose that makes the poison.  It is a desire for a greater understanding that motivated the questions and not a desire to instill fear in anyone, which is why I came to a forum specializing in chemistry to request some incite as to the nature of chemical processes.  Understanding is fears bane, I always say.  In any case I appreciate your replies, they have been very helpful!