In the Consideration of "The Children" with Regard to Vaping...

“The state must declare the child to be the most precious treasure of the people. As long as the government is perceived as working for the benefit of the children, the people will happily endure almost any curtailment of liberty and almost any deprivation.”


― Adolf Hitler, Mein Kampf

"USP" Nicotine

There is yet more to this story.

The term "USP" has meaning in and of itself. There is a scale from seven (7) to one (1) for purity. One (1) being the most pure, seven (7) the least.

USP is number three (3): "A chemical grade of sufficient purity to meet or exceed requirements of the U.S. Pharmacopeia (USP); acceptable for food, drug, or medicinal use; may be used for most laboratory purposes."

Hence any nicotine that is of "USP" purity would be considered by established science to be a product usable in any context for which that chemical is appropriate. By this I mean that it is considered "pure nicotine" and not some FDA-defined mish-mash of tobacco alkaloids.

These are scientific standards that apply to all manner of chemicals covered by the US Formulary, not just nicotine. (Look up the USP formulary web sites.)

Now if one inspects a site such as nicSelect we see this claim "NicSelect doesn’t just meet – it exceeds U.S. Pharmacopeia standards."  Below you'll see a list of chemicals, the maximum specific level of impurity required by the standard, and how nicSelect exceeds them (has fewer impurities).

I will argue that while the FDA could attempt to argue that, for example, nicSelect nicotine is "derived from tobacco" such an interpretation would imply that any USP-grade chemical that was sufficiently pure for a USP designation would not be what it was but in fact what it was derived from.

More absolute nonsense as I originally postulated.

So while one can argue nano- and micro-gram amounts of nicotine in second hand smoke or vapor, for example, these standards are simply not applicable here.

Effectively the FDA would have to single out nicotine as somehow "magical" in the sense that only it remained a tobacco product once it was sufficiently pure to receive a "USP" designation.

More importantly bypassing the intent of the legislature which specifically identifies the formularly.

I find it hard to imagine, and in fact in the legislation linked above it is not present, there would be any special meaning for nicotine outside the actual statutes.

So while the FDA and Mr. Zeller can say whatever they like they would have to undo a lot of established science to create the fiction that USP nicotine was somehow a tobacco product.

So, as they say, stick that in your pipe and smoke it...

Family Smoking Prevention and Tobacco Control Act/Food Drug and Cosmetic Act can not Regulate Nictone

As it turns out, upon reading the various acts you see the following:

See:

U.S. Code › Title 21 › Chapter 9 › Subchapter II › § 321
21 U.S. Code § 321 - section (g)1 -
(g)
(1) The term “drug” means
(A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and [nicotine is listed in the National Formulary]

and

(rr)
(1) The term “tobacco product” means any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part, or accessory of a tobacco product).

(2) The term “tobacco product” does not mean [ my underline ] an article that is a drug under subsection (g)(1), a device under subsection (h), or a combination product described in section 353 (g) of this title.

The Family Act amends (1) and (2) as

TITLE I—AUTHORITY OF THE FOOD
AND DRUG ADMINISTRATION
SEC. 101. AMENDMENT OF FEDERAL FOOD, DRUG, AND COSMETIC ACT.
(a) DEFINITION OF TOBACCO PRODUCTS
.—Section 201 of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321) is amended
by adding at the end the following:
‘‘(rr)(1) The term ‘tobacco product’ means any product made
or derived from tobacco that is intended for human consumption,
including any component, part, or accessory of a tobacco product
(except for raw materials other than tobacco used in manufacturing
a component, part, or accessory of a tobacco product).
‘‘(2) The term ‘tobacco product’ does not mean an article that
is a drug under subsection (g)(1), a device under subsection (h),
or a combination product described in section 503(g).

So, as I originally postulated and as is confirmed here the "Family Smoking Prevention and Tobacco Control Act" would not seem to include the regulation of nicotine "derived" from tobacco because nicotine is something that already exists outside of the tobacco plant, i.e., just like water or chloropyll.

Reductio ad absurdum - Nictone cannot be "derived" from Tobacco

So in the context of proposed FDA regulation of electronic cigarettes we see that bad old nicotine is probably a significant target.  After all, it, in a legal sense under, say the "The Family Smoking Prevention and Tobacco Control Act of 2009" (FSPTCA), is "... any product made or derived from tobacco that is intended for ..."

And, in the context of vaping, the intention of "deeming" regulations is to include nicotine.

So let's think carefully about this.

Tobacco is a plant to so by definition it contains chlorophyll and water as well as many other things, like alkaloids, amino acids, proteins, carbohydrates, starches, and pigments.   There are many lists and discussions of this (for example here and here) - this is not rocket science and the understanding of what constitutes of plant is hopefully not in question.

So if I were to "grind up" a tobacco leaf what might I find?

Things like water, chlorophyll, dextrose, ammonia, and pectin (from the second link).

Are these things addictive?

No.

Are these things unique to tobacco in the sense that they can be derived from no other source?

No.

I can derive these things (water, chlorophyll, dextrose, ammonia, and pectin), as well as many others, from tobacco.

I can also buy them at Walmart.

So I think we can also agree that the authors of the FSPTCA did not intend the FDA nor anyone else to "regulate" these items.

It would be absurd.

Now there are many alkaloids such as anabasine which are present only in tobacco.

Hence to obtain this alkaloid I would be required to derive it specifically from a tobacco plant.

This chemical is a pyridine (cyclical organic compound) and is relatively poisonous.

But this chemical, derived from tobacco, is unregulated by the FDA though I think it is clear that, by "derived," the authors of the FSPTCA would intend the FDA to regulate this chemical.

But they do not.

So if we divide up what we find in tobacco we have three classes of constituent: the first I will call a common constituent, something like water, which occurs naturally outside tobacco.  The second I will call a "derivative" which is something which is a constituent but, unlike the first class, can only be derived from tobacco.

And then there is nicotine, alone in its own class.

Nicotine as I have written previously in this blog is available from many sources besides tobacco such as peppers, tomatoes, and potatoes.

Like water and chlorophyll nicotine can be derived from tobacco.

Unlike anabasine it can also derived from peppers, tomatoes, and potatoes.

Nicotine's sin regarding regulation, then, must be its addictive properties?

Well, the FDA does not believe that nicotine is addictive (see their own web site),  where they say "although any nicotine-containing product is potentially addictive, decades of research and use have shown that NRT products sold OTC do not appear to have significant potential for abuse or dependence. [underline mine]"

Dextrose, which is sugar, is potentially addicting too (at least WebMD thinks so).

So under what logic, or specifically how from the perspective of the FSPTCA, can nicotine be singled out for regulation.

It is both logically and legal inconsistent.

The only reason would appear to be that historically nicotine was "thought" to be addictive.

The FDA's new "deeming" apparently fails to reflect the FDAs own thinking - more or less analogous to keeping laws regarding slavery on the books because your thinking on slavery hasn't changed since the passing of the 14th amendment.

If we look at copyright law, for example, its clear what a derivative work is, i.e., what it means to derive.  Congress passed both copyright law and the FSPTCA.

Basically a clear link between an original work and the derivative - something that retains the unique aspects of the original, analogous to anabasine being only found in tobacco.

Tobacco is the "original work" and "anabasine" is the derivative - it is in some sense a subset of tobacco and uniquely derivable from it.

Nicotine, water and chlorophyll are not derivatives in this sense.  They can be derived from anything that contains them, e.g., potatoes.

They are effectively constituents of tobacco but not derivatives.

So we are now faced with an absurdity:

Since I can derive water and pectin from tobacco they must be, by definition because they can be derived from tobacco, regulated under the FSPTCA.

After all pectin is found in jams and jellies - and "intended for human consumption."

So is water.

And finally: Is the water derived from tobacco somehow different that water from other sources?

Yet another absurdity.

Of course not.

Water is water - regardless of the source.

Water squeezed out of a tobacco plant is just like water from any other source.

If we believe that the FSPTCA is intended to regulate the constituents of tobacco then by definition virtually the entire planet would be regulated by this law.

But that's not what the law says.

It says "tobacco" and clearly there exists a class of things which are uniquely derivable from tobacco.

Since tobacco contains virtually all amino acids did the FSPTCA intend to include those as well?

The animals we eat all contain the same amino acids, hence the FDA would be required to regulate all animals that humans might consume as well.

But in fact there are other laws, such as laws related to supplements, to address those constituents.

So if the FSPTCA did not intend to regulate water or chlorophyll how can it regulate nicotine, a chemical with the same properties as water or chlorophyll?

The Congress clearly differentiates between "derivatives" and "constituents" in many areas.

The FDA is taking the law into their own hands and creating a magical new class of tobacco "constituent" - nicotine.
 

Discriminating Against Smokers/Vapers is in fact Racism...

From this.

From my read of the linked article what's going on with smoking and electronic cigarettes is very simple.

Nicotine metabolizes into cotinine - available, by the way, from Santa Cruz Biotechnology.

The process is basically applying either UV light or hydrogen peroxide to nicotine.

Cotinine was once supposed to be marketed as an antidepressant called "Scotine." (See this link - image from link at the right.)

So Cotinine is

  - a cognitive enhancer;

  - something that reduces anxiety and fear in at least the mouse model of PTSD;

  - something that extinguishes fear; and

  - positively affects mental illness such as depression or schizophrenia.

More here.

Basically it does much of what cigarette smokers claim cigarettes in fact do.

Your reaction to cotinine is very likely genetic and can be influenced by ethnicity.

There are specific genes and variations of those genes that determine your reaction to cotinine (see the linked article at the top of the page).

Which makes smoking or vaping, at least in my book, a genetic disorder, i.e., people with certain genes are predisposed to become smokers.

Would you discriminate against a woman with the breast cancer gene BRCA?
Hence singling out smoker is an act of racism.

So the FDA singles out smokers as an ethnic group - a group with specific genes - an discriminates against them.

How is this different than any other form of racism?

I have posted more detail here on the ECF.

Nicotine - Not Addictive

So I have been vaping nicotine professionally for sometime (over six months, in fact).

I haven't had a single issue of addiction - no desire to vape compulsively, no urges to pick up the vape, nothing.

So I started to wonder why I was not falling victim to the "great satan nicotine."  After all, at least according to the NY Times (see this) and Wikipedia, nicotine is more addictive than cocaine or heroin.

I've seen the consequences of these other drugs - not much fun.

But no addiction - no withdrawal when I leave the vape home, even for days.

Nothing...

So what's up with this?

First off I found this link at Discover Magazine. (EDIT: I have contacted the author for specific references to these studies.)

Its kind of an interesting article where you find things like this "In 2005, for instance, researchers at the University of California, Irvine, found that animals self-administer a combination of nicotine and acetaldehyde, an organic chemical found in tobacco, significantly more often than either chemical alone. In 2009, a French team found that combining nicotine with a cocktail of five other chemicals found in tobacco — anabasine, nornicotine, anatabine, cotinine and myosmine — significantly increased rats’ hyperactivity and self-administration of the mix compared with nicotine alone. "

And "...it’s almost impossible to get laboratory animals hooked on pure nicotine..."

So alone (and its alone in your vape because anabasine and friends are not present there) the nicotine your vape probably produces no addictive effect unless mixed with other chemicals.

This is not the only article.

Another, here,  which says “Studies have shown that none of the nicotine replacement therapies — chewing gum, inhalers, patches — none of those are addictive.”

What?  No addiction?

In fact, the professor who the article was about “I presented this position to 20 of the world’s experts,” he said. “And though some were shocked and insulted, no one could argue that my case was untrue.”

How interesting is this?  Sounds like the same crap the discoverers of H. Pylori (the bacetria the create stomach uclers) when through.  No one believed that the bacteria could live in the stomach of a human, much less cause ulcers.

As I recall and perhaps have written about in one of my posts, they had to resort to infecting themselves with H. Pylori to cause themselves to get ulcers and then curing themselves because no one would believe them.

Ultimately, in 2005, they won the Nobel Prize for their discovery.

Sounds like the same bogus science model - start with a forgone conclusion, e.g., nicotine is addictive, and conduct a study that shows you are correct.

ADDITIONAL STUDIES:  Here is a Nation Institute of Health document with many detailed references to studies showing that its not nicotine alone (as found in vaping relative to other whole tobacco alkaloids) that is addictive.

Another study from Israel (Dr. Reuven Dar) showing that smoking is a habit and not a nicotine-related addiction (Reference here.).

An earlier study from 2005 by Dr. Dar showing similar results.

Another study from New Zealand implicating whole tobacco alkaloids as an important element when combined with nicotine: "The conclusions were that non-nicotinic components have a role in tobacco dependence and that some tobacco products could have higher abuse liability, irrespective of nicotine levels."

UPDATE: The FDA says here, regarding its approved patches and gums, that "although any nicotine-containing product is potentially addictive, decades of research and use have shown that NRT products sold OTC do not appear to have significant potential for abuse or dependence."

Diacetyl - What's the Real, Objective Danger?

This post posits that diacetyl alone may not be the killer that popular culture suggests.  Certainly I am not any sort of official "health" scientist but I think there are a lot of very, very "loose" ends which need a better explanation.

The question I want to ask is simple: is diacetyl really dangerous?  And what about someone vaping something that might contain minute traces of diacytel, i.e., from a flavor provider that might not label their ingredients properly.

In researching this post I discovered a DuPont 1936 patent on the details of an industrial process to create diacetyl (or butane-2,3-dione).

Diacetyl has been used in the food industry since, as best I can tell, at least the 1930's and probably well before.  Its used in brewing beer (see this and this as examples) and is naturally created by fermentation.  In 1983 the FDA deemed diacetyl as GRAS (Generally Regarded as Safe).

From this web site (defendingscience.org) we find a rough timeline of how Bronchiolitis obliterans (popcorn worker's disease) was discovered (after roughly five decades of diacetyl used commercially):

Timeline:
 
March 12, 1985: NIOSH investigators visit an Indiana facility that produces flavors for bakeries, where two young, previously health, nonsmoking employees have been diagnosed with severe fixed obstructive pulmonary disease (consistent with bronchiolitis obliterans). Diacetyl is one of the chemicals commonly used at the facility.

February 16, 1993: Researchers for the German company BASF finish conducting a study in rats underwent a single 4-hour exposure to diacetyl vapors; all of them died at diacetyl concentrations > 23.9 mg/l.

May 19, 2000: Missouri Department of Health notifies OSHA that ten workers from one popcorn plant have bronchiolitis obliterans and asks OSHA to inspect the facility.

May 23, 2000: OSHA inspector visits the plant, but samples cannot be analyzed by OSHA’s laboratory.

August – November 2000: NIOSH investigates Missouri microwave popcorn facility; findings indicate that workers exposed to flavorings at the microwave popcorn plant are at risk for developing fixed obstructive lung disease.

December 2000: NIOSH issues interim recommendations to the Missouri microwave popcorn plant on ways to control workers’ exposure to the artificial butter flavoring

September 2001: NIOSH investigators return to the Missouri factory they studied to distribute materials describing investigation results, ongoing activities, and worker precautions.

September and December 2001: Attorney representing sick workers files complaints with OSHA, noting that worker health continued to decline after plant took measures recommended by NIOSH.

April 26, 2002: Scientists from NIOSH and the Missouri Department of Health publish an article in CDC’s Morbidity and Mortality Weekly Report describing their investigation; the article notes that "recent reports to CDC document bronchiolitis obliterans cases in the settings of flavoring manufacture" and that "preliminary animal studies at CDC suggest severe damage to airway epithelium after inhalation exposure to high air concentrations of a butter flavoring."

...

Fast forward to December of 2007.  Here we find this very interesting article in the Seattle-PI: "Flavor additive puts professional cooks at risk."

Now what's interesting is the assertions about the danger levels of diacetyl.

Let's look first at the EPA (see in the "The Pump Handle Blog" on diacetyl).

Here we see a fellow who eats two bags of microwave popcorn a day acquiring a case of bronchiolitis obliterans.  About six paragraphs down we see this "The exposure levels in his home were 0.5-3 parts per million after he popped the bags. This is comparable to levels in popcorn factories and evidently enough to damage his lungs."

0.5 to 3 ppm - So let's remember that.

(BTW - 1 ppm is roughly 1 drop in 13 gallons, 1 ppb (billion) is 1 drop in 13,000 gallons.)

Going back to our Seattle-PI article we find the following analyzing 22 of "the more popular cooking products. LabCor, a Seattle-based certified analytical laboratory frequently used by the Environmental Protection Agency."  (Note this is the level of "diacetyl in air samples captured from a heated skillet in which the products were tested.")

• Two real butters were analyzed and diacetyl was found in a range of 7 ppm to almost 16 ppm.
  
  
• In all the margarine and shortening products, levels of 7 ppm to almost 180 ppm were present.
  
• A butter-flavored cooking spray released more than 164 ppm of diacetyl.
  
• Butter-flavored cooking oils used by professional cooks ranged from 23 ppm to 234 ppm.
  
• Two brands of oil for popping corn came in at 1,062 ppm and 1,125 ppm.

So these number vastly exceed the 0.5-3 ppm found in the home popcorn case.  (You can google others who have done similar studies - I found this detailed FDA report.)

Its fairly easy to find any number of sites that talk about the range (in ppm) of diacetyl in various popcorn and flavoring preparation plants (see this and this and this as an examples).  All relate values similar to the 0.5 to say 98ppm.  The last link (this) claiming "exposure of mice to 200 and 400 ppm diacetyl via inhalation for 6 hours per day over 5 days caused death."

Note this "200 to 400 ppm" is in line with the exposure level in the kitchen for butter flavored cooking oils and oils for popping corn indicated with Seatle-PI.

So why aren't the cooks and theater workers dying?

Well, for one thing a human male, on average, might weigh around 50kg (from this), or 50,000g as compared to a mouse at maybe 15g (see this).

Thus a human weighs about 3,333 times more than a mouse.

Since there are no vast die-offs in the kitchens (with perhaps 3.5 million cooks) and untold numbers of teenagers working in movie houses selling popcorn one has to believe that this difference in scale means much more diacetyl is probably necessary to kill humans.

So 3,333 x 3 ppm would be 10,000 parts per million or a 1% atmosphere of diacetyl.  Makes perfect sense (in the case of pop corn workers) you could inhale this much if you are bent over a large heated tank.

At least that's one explanation.

Another issue is if, according to the FDA report above, the Ridgeway plant, which started making microwave popcorn in 1986 apparently never had any evidence of health issues until 2002 (when the investigation was conducted). 

Now maybe there were issues and no one noticed - though there were no mysterious deaths or other activities to draw attention.

Or maybe something else changed in the plant (remember diacetyl has been in use since at least the 1930s) that in concert with diacytel began causing problems.

So the more interesting question is this: what is the objective danger of diacetyl?

Subjectively everyone can scream in panic that "diacetyl is killing us..." - but what is the real danger?

Clearly from 1986 to 2002 when the problems began there were no reported issues.

As best I can tell diacetyl has killed "a few scores of people" - some in the Netherlands and others in the US (see this OSHA publication).  Interestingly all around the same period of time.

Perhaps something changed in the industry relating to how microwave popcorn was made?  A sort of "new best practice?"

But back to diacetyl.

Automobiles kill about 100 a day (based on the best research I could do).

The CDC says 443,000 a year (or about 1,200 a day) die from smoking.

Objectively, at least compared other causes of death, diacetyl kills in the range of a rounding error on automobile deaths.

So what about vaping?

It gets more interesting here.

The other day I spoke with someone who mentioned that rigorous testing for diacetyl was a requirement in the new, proposed FDA vaping regulations.

There are two ways to look at this.

One, millions of people exposed to relatively large (objective ppm values) diacetyl every day do not get sick or die and have not for decades.

If vaping provides diacetyl at or below the levels seen in normal, everyday cooking then it seems unlikely, excluding other issues which I will mention below, that diacetyl is an issue.

If, on the other hand, vaping provides diacetyl at a rate above these cooking levels this it seems that it should be a concern.

Another concern is less is known about diacetyl substitutes (which are derived from, what else, diacetyl).  What would be used if no diacetyl is present?  A substitute of course.

Diacetyl is also present in cigarettes at high levels.  Is less diacytel better than more? (Yes, its burnt there so perhaps its not related - though no one has suggested its related to, say, cancer of the lungs...)

Other compounds such as acetoin can convert into diacetyl, i.e., there are compounds that may contain compounds that convert into diacetyl.

Another interesting issue is that much of this seems tied to very little initial work at the popcorn plants other than simply collecting data.

Much of diacetyl has supposedly been removed from various cooking products as a result of this investigation.  

Though potentially contradicting this is this link suggests biochemists are busily genetically engineering microbes to produce diacetyl.

(The BASF study isn't necessarily meaning full - many things breathed in a 1% atmosphere will kill you.)

My guess is that in the panic to find the "witch" for trial the real culprit escaped notice:  something to do with diacetyl, e.g., an interaction with another chemical, heating, a process change, etc.  Certainly problems were detected in other diacytel-using plants.  But there doesn't appear to be a uniform distribution of problems - both over time and location.