Is the whole scandal with da and ap overblown? Some numbers inside

[Jode]

I'm under the impression that while fruit flavors may have diacetyl, the concentration is an order of magnitude lower than what is in butter/cream/custards. I'd be interested if anyone had more solid facts on this.

Nope, no facts here. I understand the same as you, but since strawberry was used as an example in the post I quoted I mentioned this other thread.

 

[sparkky1]

You cannot make this conclusion. Natural extract flavors are often full of diacetyl, which is a naturally occurring compound in diary and some fruits. Plus they can contain a lot of other things I personally would not want to inhale (lipids, proteins, polysaccharides, etc). They cost more because they are more expensive to make than mixing synthetic flavor compounds...or they charge what their market will tolerate, or both.

Plus, the term "natural flavor" does not have the definition most people think. It only means it is a compound that is also found in the food. Isoamyl acetate is a natural banana flavor, but it is synthesized in a lab.

I am a co-author on the Farsalinos DA/AP publication (Kistler). I am also deeply involved with all things chemistry in the e-liquid industry, mostly as a consultant for AEMSA. I can assure you that I know of several companies that do test for DA and AP, and that they have either removed or are in the process of removing these chemicals from their recipes. Some have even developed pure-flavor lines that are verified free of them, as in working with the flavor industry to formulate these flavors.

DA and AP are NOT considered flavor ingredients by the FDA. They are considered adulterants, since they carry a known risk of serious injury or death.

The mechanism of lung damage from DA or AP is not known. We don't know if it is purely a chemical interaction, or, what is being thought now, it triggers an autoimmune response where the body essentially rejects the lung. In many cases of BO followed by lung transplant, the new lung also gets BO and dies, even without further exposure to DA or AP. So it may be a particular biochemistry in a person's body that works with DA to create the disease.

The rat inhalation studies show that not just the lungs are affected, but also mucosa/nasal passages. This is true with AP as well.

Bad news: these are not the only vicinal diketones used in flavorings. There are also hexanediones and heptanediones with vicinal carbonyls, and which also show lung damage in rats.

When asked what the safe amount of DA or AP could be in an e-liquid, all toxicologists that we contacted answered ZERO AMOUNT. NIOSH is for workers that have no choice with exposure if they want to keep their jobs. Defending what is essentially just a luxury flavor in vaping is not the same thing at all. They don't need to be there, there is a known risk, and so they should not be there. I concur with this professional opinion.

The risk of a highly publicized law suit is not worth taking, regardless of its merit or the lack thereof. And companies that I work with simply do not want to sell e-liquids with these compounds, period, end of story. We were blind-sided and horrified when we found out that the term DA-free did not mean that at all in many instances. AT BEST, this meant that consumers were robbed of informed consent. Ideally it should be the flavor companies that do the tests, I agree, but I know of many e-liquid vendors that are doing this themselves so they KNOW the results.

And DA and AP are actually not that easy to test for. The limit of detection and/or quantification should be ideally about 1 ug/mL, but this is hard to create the assay for. Just squirting a bit onto a GC-MS without standard solutions to compare to will tell you they are present, but not accurately how much is present. Accurately measuring relevant levels in e-liquids is VERY hard, since there are a LOT of flavor compounds of similar size to these, and peaks overlap in the flavor matrix. I have seen commercial labs claim they will test these for cheap, but when pushed on their limits of detection do not respond. I have also seen tests from labs stating the compounds are not present, but their LOD is 100 ug/mL or more!

But these compounds are not illegal, and people are free to vape what they like. I mean that. If you want them, have at it. If you don't, you should be able to have the opportunity to buy flavors verified to be free of them. Not just words on a website, which are clearly meaningless, but lab results on finished products. This IS happening right now, and it will continue to increase, I expect. And I would support companies that are doing this. They have spent a LOT of money making sure you are getting products that are as safe as our current understanding allows.

Concentrated flavorings were never constructed with the intention of heating to vapor and inhaling, take a look at the health hazard of just one of the compounds : 2,3-Butanedione | 431-03-8

So it's substitute 2,3 Pentanedione was introduced but with it being a 5-carbon alpha-diketone produced the same results, so now we have an Ester being made from Butyric acid it might be great for chickens, fishing bait and stink bombs but highly doubt it was designed to vaporize and inhale.Some feel the risk out way's the reward, I am on the same page as most, were I am lost is, at what point can you truly say "these" new esters can be vaporized with no damage to the lung tissue ?
These are some of the chemicals in analogs, are they the cancer causing agents ? doubtful, do I feel e cigs are a safer alternative ? absolutely

 

[sparkky1]

Steve,

I'm drinking some right now and have a tank of diacetyl free AIV Cherry Blossom tea to go with it...
I actually don't get the custard thing. Is it just cool like Pluid used to be?

I'm right there with you on the tobacco thing, I love my Cohiba extracts / black cherry cigar flavorings but I think you have gotten your point across very well how you stand on CUSTARD ! let it go man ..........

 

[Kurt]

Something else that I believe is Worth Mentioning when NIOSH REL's are used in comparison to e-Cigarette Vapor.

And that is the what role the Relative Humidity of an Air Sample with Regards to the Impact on Possible Effects seen from Da and AP Exposures.

Not sure how that is relevant. If there is water present in a juice, then rel humidity of the vapor will be ~100%. Hydrates of aldehydes can form, but as far as I know that does not remove the toxicity in the lungs.

I think this was a question many people had in earlier topics.

I've seen "5" for the ug/ml limit of detection, etc. You have to know what the LOD is before you can even judge the results.

What do you think is the usual LOD that most labs are actually *able* to create the assay for?

Depends on the detection method, and details of the assay for a particular sample. Lower LODs will be achieved with standards for calibration curves. It also depends on the complexity of the flavor matrix of the sample, as I mentioned earlier. It is not always a simple matter of injecting the sample and getting a number your can trust. GC-MS with standards should be about the best, as long as the lab has the skills and patience to do it. Also GC-FID. Before paying for tests, its a good idea to check what their method is, if they are using calibration standards of the pure diketones, and what their LOD and LOQ are. And if they have done diketones before and have worked out the details to get low LODs and LOQs. If they've never done it, but say they can easily do it, I would be suspicious of that. Sorry no set answer to this.

i don't mean to nit pick but,from what i understand if DA and AP meet the governments
definition of an adulterant why are they even being sold as food additives?
why hasn't the FDA rammed seventh fleet sized enforcement and regulatory
actions down our throats and sent us all packing years ago?

just asking and regards
mike

Because they are safe to eat and drink, most likely. I don't know for sure. Maybe lobbying. There are now warnings on microwave popcorn bags to not inhale hot gasses from them soon after microwaving the popcorn. Up until now, this was really the only way a consumer could be acutely exposed. The FDA has not deemed any regulations on vapor products as yet. Maybe they are waiting to see what the industry does first. Enforcement is expensive. But again, I don't know.

Lawsuits like this tend to change things faster than enacting and enforcing laws: 'Popcorn Lung' Lawsuit Nets $7.2M Award - ABC News

 

[skoony]

Lawsuits like this tend to change things faster than enacting and enforcing laws: 'Popcorn Lung' Lawsuit Nets $7.2M Award - ABC News

you got that right.
regards
mike

 

[Kurt]

Simple synthetic ? How are they safer ?
Decomposition of what DA ?

Each flavor compound used in synthetic flavorings is a known entity with known inhalation safety standards. The vast majority are most likely fine for e-liquids. There are some however that have a bad track record, custard note diketones are just one type, but they seem to be the most dangerous. Meat flavorings can also cause problems, but those are not so popular in vaping.

Whole food extracted flavors, as I said, can have a whole host of biomolecules that the lungs are not good at expelling, and that can be very prone to thermal decomposition.

And decomposition of ANY organic compound, flavors, PG, VG, will create toxic aldehydes and possibly acrolein. And free radicals, which are also toxic. Partial combustion products, generally detected as dry-puff when their concentrations are high enough. If the coil gets too hot, stuff breaks down, and generally into things you don't want to inhale.

BTW, butyric acid is a carboxylic acid, not an ester. "Esters" is a term often used in brewing (incorrectly from a strict chemistry standpoint) to describe certain flavor compounds, including diacetyl, which is also not an ester. Some of these compounds are esters, but many strictly speaking are not, but its an old term in brewing and not likely to change soon.

 

[zoiDman]

Not sure how that is relevant. If there is water present in a juice, then rel humidity of the vapor will be ~100%. Hydrates of aldehydes can form, but as far as I know that does not remove the toxicity in the lungs.

...

What I was trying more to interject was the Effects of Air Humidity when the NIOSH Testing method 2557 is used.

And that a ppm REL for Exposure in Relative Humidity Air may not be Reflective of what the ppm REL should be for Direct Inhalation of Vapor containing either Da and or AP.

 

[sparkky1]

Each flavor compound used in synthetic flavorings is a known entity with known inhalation safety standards. The vast majority are most likely fine for e-liquids. There are some however that have a bad track record, custard note diketones are just one type, but they seem to be the most dangerous. Meat flavorings can also cause problems, but those are not so popular in vaping.

Whole food extracted flavors, as I said, can have a whole host of biomolecules that the lungs are not good at expelling, and that can be very prone to thermal decomposition.

And decomposition of ANY organic compound, flavors, PG, VG, will create toxic aldehydes and possibly acrolein. And free radicals, which are also toxic. Partial combustion products, generally detected as dry-puff when their concentrations are high enough. If the coil gets too hot, stuff breaks down, and generally into things you don't want to inhale.

BTW, butyric acid is a carboxylic acid, not an ester. "Esters" is a term often used in brewing (incorrectly from a strict chemistry standpoint) to describe certain flavor compounds, including diacetyl, which is also not an ester. Some of these compounds are esters, but many strictly speaking are not, but its an old term in brewing and not likely to change soon.

Butyric acid has been used for over a year in the 2 main Italian / German flavor labs not just the beverage company's.Not an ester ?

Eastman™ Butyric Acid, Food/Feed Grade
Methyl butyrate - Wikipedia, the free encyclopedia
Biochemistry of food flavorings | Dusengemungu Leonce - Academia.edu

 

[sparkky1]

That is why I used the word "the ester being made from"

 

[sparkky1]

Each flavor compound used in synthetic flavorings is a known entity with known inhalation safety standards. The vast majority are most likely fine for e-liquids. There are some however that have a bad track record, custard note diketones are just one type, but they seem to be the most dangerous. Meat flavorings can also cause problems, but those are not so popular in vaping.

Whole food extracted flavors, as I said, can have a whole host of biomolecules that the lungs are not good at expelling, and that can be very prone to thermal decomposition.

And decomposition of ANY organic compound, flavors, PG, VG, will create toxic aldehydes and possibly acrolein. And free radicals, which are also toxic. Partial combustion products, generally detected as dry-puff when their concentrations are high enough. If the coil gets too hot, stuff breaks down, and generally into things you don't want to inhale.

BTW, butyric acid is a carboxylic acid, not an ester. "Esters" is a term often used in brewing (incorrectly from a strict chemistry standpoint) to describe certain flavor compounds, including diacetyl, which is also not an ester. Some of these compounds are esters, but many strictly speaking are not, but its an old term in brewing and not likely to change soon.

There was a question that was actually directed towards you, I will rephrase it for you to better evaluate it.
At what point can you truly say "this" new "flavoring" can be vaporized with no damage to the lung tissue, so to my advise I would recommend not using X / Y / Z and just use T ?

 

[Kurt]

Butyric acid has been used for over a year in the 2 main Italian / German flavor labs not just the beverage company's.Not an ester ?

Eastman™ Butyric Acid, Food/Feed Grade
Methyl butyrate - Wikipedia, the free encyclopedia
Biochemistry of food flavorings | Dusengemungu Leonce - Academia.edu

Butyric acid is not an ester. It is an acid. Thus the name "acid". It is CH3CH2CH2CO2H (acid group in bold). An ester of butyric acid is different. Methyl butyrate is CH3CH2CH2CO2CH3 (ester group in bold). The -CO2H is now -CO2CH3. It is no longer an acid (has no acidic H on it). It is an ester.

Ester - Wikipedia, the free encyclopedia
Carboxylic acid - Wikipedia, the free encyclopedia

That said, certain food and beverage industries use the term ester more liberally than an organic chemist, like me, would. They can include other compounds into what they call "esters", diacetyl, for example.

You asked:
"There was a question that was actually directed towards you, I will rephrase it for you to better evaluate it.
At what point can you truly say "this" new "flavoring" can be vaporized with no damage to the lung tissue, so to my advise I would recommend not using X / Y / Z and just use T ?"

A bit of a loaded question, no? If you are referring to butyric acid, it is an irritant, which is largely person- and dose-dependent. Most sources talking about the problems it causes are referring to the pure compound. But as far as we know it is not TOXIC at the levels we use, nor does it kill lung tissue like diacetyl. It might cause irritation, mucus, depending on the person and amount present. I think that amount is generally very low in creams, however, since it takes very little to start tasting like vomit. But I am not aware of any studies that show it is damaging to the lungs at the levels we would be using it at. Chemically is it similar to acetic acid, vinegar, which is often used in liquids.

But our knowledge about AP is actually quite recent. People thought since it was not diacetyl, it must be much safer, like there is some evil incarnate to the diacetyl molecule. But it was found in recent rats studies that it is in fact as toxic as diacetyl, due to its similar chemical nature and structure.

Flavors are a big uncertainty, so blanket "this is perfectly safe" statements are not appropriate without more long term lung tissue studies with vapor. And we don't have a lot of long term data even anecdotally, other than some flavors causing mucus or irritation. So its a gamble, but I think the majority of flavor compounds out there are probably ok. That said, I do advocate using minimal flavors or vape unflavored, which I do most of the time. As we head into deeper and deeper lung penetration through very high wattage, we may start seeing more problems...which may not be toxicity problems, but irritation problems. If a flavor makes me cough a lot or causes a lot of mucus, I avoid it. Cinnamaldehyde (hot cinnamon) is a strong irritant, and has been known to cause throats to close up...but some have no issues at all with it. It does have a toxicity associated with it, but only in very high concentrations. SOMETHING in Capellas Milk Chocolate Toffee, maybe DA!, causes me to cough uncontrollably, so I avoid it.

Dr F has done some cytotoxicity studies on a limited number of flavored e-liquids, and most were not cytotoxic. Naturally extracted coffee did have low toxicity. None were even remotely as toxic as cigarette smoke.

And as I said, flavors have a range of thermal stabilities and some can easily decompose on a coil, which creates its own set of toxins, even if the flavor compound itself is benign. Any flavor that "gunks up" a coil is decomposing. So if a vape starts to taste "off", fix it, as it is probably decomposition starting from poor wicking to the coil. If a flavor causes any irritation problems for you, avoid it.

But even with all of this scary rhetoric about diacetyl and acetyl propionyl, we have an excellent track record for injuries, and no vaping deaths that I am aware of, knock wood. However, people should be aware that there is a lot we still don't know about vaping flavors. So pay attention to what your body tells you.

 

[sparkky1]

I think were going to learn an awful lot from the popcorn industry in the near future, what I mean is I don't think your going to see a ban on e liquid with said flavor compound and not ban it from being in popcorn as to then will the "safe" additive be known ?
I don't mind cutting out the bad to take in the good but it would be so nice to be able to honestly tell your friends / family / smokers / general public there is nothing bad in e luquid without hearing well personal injury lawyers have been searching for “the next asbestos”
Some things I didn't know, not just the article but notice the Orville redenbacher : Why Microwave Popcorn Is An Absolute Health Nightmare

And some food for thought :Deliciously Dangerous: Why Microwave Popcorn Can Be Terribly Harmful - NDTV Food
Guidance on Product Labels : Hazard Communication Guidance for Diacetyl and Food Flavorings Containing Diacetyl

 

[stevegmu]

The microwave popcorn manufacturers in the U.S. No longer use diacetyl. They haven't in years...

 

[Rossum]

The microwave popcorn manufacturers in the U.S. No longer use diacetyl. They haven't in years...

Did they switch to Acetyl Propionyl?

 

[stevegmu]

Did they switch to Acetyl Propionyl?

No idea, but after the lawsuit they no longer use it, according to some quick research. Probably a different chemical mix... Personally, I buy non flavored popcorn and pop it in a machine, rather than a microwave...

 

[MsLoud]

Hell, I cant win...

I just ordered $100 worth of flavors (I bought none that had the CAUTION! background) and have a huge box of Orville's in the pantry. Sigh

 

[Kurt]

What I was trying more to interject was the Effects of Air Humidity when the NIOSH Testing method 2257 is used.

And that a ppm REL for Exposure in Relative Humidity Air may not be Reflective of what the ppm REL should be for Direct Inhalation of Vapor containing either Da and or AP.

I think maybe you mean the diacetyl test method 2557? There is no 2257. 2557 analyzes for DA with GC-FID, and it does state that high relative humidity will cause underestimation of DA concentration. I think this is because in high humidity, diacetyl will react with water and form the hydrated forms, which will have a different peak in the GC-FID than anhydrous DA. But I am not sure about this, and NIOSH is evidently researching this.

I don't think this is applicable to the method we used, however, since we used a derivitized-HPLC method, which to put it simply, treats the anhydrous and hydrated forms equally, as well as acetals and hemiacetals that DA/AP can form with VG or PG. The reagent to react with the DA also reacts with these other forms, and all give the same product, and this is what is analyzed in the end. Same for AP.

But your question is very good, and may be important for labs using GC-FID to analyze for diketones. I will look into this to see if it is of significance, or is just a slight error in the reported GC-FID values. It may well be that pro labs using GC-FID are taking this into account already. But again, we do not use GC-FID for DA/AP analysis, and these other products of DA or AP are taken into account with our method.

 

[zoiDman]

I think maybe you mean the diacetyl test method 2557? There is no 2257. 2557 analyzes for DA with GC-FID, and it does state that high relative humidity will cause underestimation of DA concentration. I think this is because in high humidity, diacetyl will react with water and form the hydrated forms, which will have a different peak in the GC-FID than anhydrous DA. But I am not sure about this, and NIOSH is evidently researching this.

I don't think this is applicable to the method we used, however, since we used a derivitized-HPLC method, which to put it simply, treats the anhydrous and hydrated forms equally, as well as acetals and hemiacetals that DA/AP can form with VG or PG. The reagent to react with the DA also reacts with these other forms, and all give the same product, and this is what is analyzed in the end. Same for AP.

But your question is very good, and may be important for labs using GC-FID to analyze for diketones. I will look into this to see if it is of significance, or is just a slight error in the reported GC-FID values. It may well be that pro labs using GC-FID are taking this into account already. But again, we do not use GC-FID for DA/AP analysis, and these other products of DA or AP are taken into account with our method.

Sorry for the Confusion Kurt.

Your are Correct. I mean to type Testing Method 2557.

 

[Kurt]

Ok, follow up. I got information from a pro lab I work with. This NIOSH method 2557 is for air sampling, not for measuring AD/AP in an e-liquid. The humidity can affect the ability of the DA to adsorb into the solid trapping medium. This is not relevant to analysis of e-liquids directly, only air analysis that uses a solid trapping medium for DA.

 

[zoiDman]

Ok, follow up. I got information from a pro lab I work with. This NIOSH method 2557 is for air sampling, not for measuring AD/AP in an e-liquid. The humidity can affect the ability of the DA to adsorb into the solid trapping medium. This is not relevant to analysis of e-liquids directly, only air analysis that uses a solid trapping medium for DA.

Thank you Kurt.