On 2017 Feb 17, Andrey Khlystov commented:

Gentlemen, The problem with your arguments is that Brand II, though being the “cleaner” of the three we tested, still produces very high aldehyde emissions. Three out of five V2 liquids that we tested exceeded the one time (one time!) exposure limits in a single puff. They also produced higher emissions than non-flavored liquids used in more powerful Brand I and III e-cigarettes. Surely you can check that. Please see our reply to Farsalinos et al. letter to ES&T – there are other studies that found even higher aldehyde concentrations than we did. High aldehyde emissions are not limited to a single study or a single liquid. We also demonstrate that “dry puff” arguments that Farsalinos et al. use to dismiss all high aldehyde studies have absolutely no factual basis. I doubt I can add anything else to this discussion except for reminding you that the strength of science is not only in reproducing results, but also in not cherry-picking studies and data that fit one’s theories or expectations. I do appreciate your efforts in clarifying the benefits and risks of e-cigarette use and whish you success in this endeavor.

On 2017 Feb 13, Peter Hajek commented:

Dr Khlystov, I understand that your laboratory has a good track record. Your findings are potentially important, but they do need to be replicated so a possibility that they were an artefact of some part of your procedure is ruled out The reason for wanting to test Brand 1 liquids is as follows. If other liquids show no alarming toxicant levels (which is possible because in previous studies where dry puffs were excluded, no such levels were found), the next level of explanation will be that the levels may be low in other liquids, but they were high in the liquid you tested. It is of course possible that your results will be replicated, but if not, this would necessitate another round of testing of the liquids you used. Testing your Brand 1 liquids straight away would remove this potential expense and delay in clarifying the issue. Providing information on which liquids you used, if this is available, should be simple and uncontroversial.

On 2017 Feb 11, Konstantinos Farsalinos commented:

Dr Khlystov mentions that there is information about 5 samples tested in their study. Unfortunately he refers to the samples with the lowest (by far) levels of carbonyl emissions. In fact, only one of these samples had high carbonyl emissions, unlike Brand I samples which showed very high levels of toxic emissions (especially for 3 of the samples, the levels found were extreme).

Liquids from different batches may not be the same, but finding almost 7000 ug/g of formaldehyde compared to < 0.65 ug/g from an unflavored sample can be easily reproduced with reasonable accuracy even with different batches. A replication study finding levels of carbonyl emissions lower by orders of magnitude cannot be attributed to different batches.

As i mentioned in my ES&T letter to the editor, the levels found by Khlystov and Samburova could only be explained by dry puffs, but this has been excluded because of the findings in unflavored liquids. Also, previous studies with verified realistic (i.e. no dry puff conditions) have found aldehyde levels orders of magnitude lower compared to their study. This creates a crucial need to replicate the samples with the highest levels of carbonyl emissions, despite the reassurance about the laboratory quality. Replication is the epitomy of science. But the authors are not providing the necessary information for these liquids.

On 2017 Feb 11, Andrey Khlystov commented:

Dr. Hajek,

You have not read the paper carefully. As I said earlier, our paper has information on 5 liquids that should be enough to get anybody started in replicating the data. They are from Brand II, which is V2 Standard (see Table 1). The brand is very easy to find (www.v2.com). The other liquids were from local vape shops, but this is of little consequence for the study, see below.

You seem to miss the point of our paper. Please let me briefly summarize its message: flavors, especially at higher concentrations, appear to dominate aldehyde production. To check generality of our observations, all one needs to do is take any flavored liquid and test it at different concentrations and/or against unflavored liquids and see what happens.

Contrary to what you suggest, there is little value in testing exactly the same liquids. Testing specific liquids or flavors was not the point of our study. We observed that a fairly wide variety of randomly selected flavored liquids produce significant aldehyde emissions, with aldehyde profiles varying among different flavors. If only PG or VG were responsible for the majority of aldehyde emissions, there would be no differences among liquids that have the same PG/VG composition. Yet, we observed significant differences among such liquids.

I also doubt that liquids from different batches are exactly the same, especially from small-time operations. At the time of writing the paper, we did not measure concentrations of liquid constituents. Having understood their role, we are controlling for liquid composition in our on-going study. As we mentioned in the letter to ES&T, we see appreciable aldehyde concentrations in both mainstream and secondary aerosols for a wide variety of e-cigarettes and liquids that users bring to our study. High aldehyde emissions are not limited to the 15 liquids and 3 e-cigarette brands we tested in our original study, it appears; the problem seems to be quite universal.

As we stated in our letter to ES&T, we are calling for checking findings of ANY e-cigarette study. I would like to note, however, that if one doubts our measurements, he or she needs to come up with a plausible mechanism, other than the effect of flavors, that explains why unflavored liquids produced significantly lower emissions than flavored ones or why a diluted flavored liquid was producing less than a more concentrated one. Please note, this was observed for the same e-cigarette, the same power output, and the same experimental setup. As of now and as far as I know, nobody came up with a single credible reason to doubt our results. I would also like to stress that aldehyde measurements are not trivial. We have over 20 years of experience in these measurements with a solid track record of QA/QC. Please rest assured - we stand by the quality of our data.

On 2017 Feb 09, Peter Hajek commented:

Your paper does not identify the actual products. Can you let others know the product name and the online address where it was purchased? There is no point trying to clarify your finding with different e-liquids.

On 2017 Feb 08, Andrey Khlystov commented:

Please read our paper carefully. There is information on 5 liquids that can be easily ordered online. Good luck with your experiments.

On 2017 Feb 08, Peter Hajek commented:

In their just published response to Farsalinos et al. comment on these unexpected results, the authors acknowledge that replications are needed. Could they please respond to repeated requests to specify which e-liquids they used so a replication can be performed?

On 2016 Dec 12, Peter Hajek commented:

The authors are correct that other studies are needed to check this phenomenon. Can they specify which e-liquids they tested so a replication is possible?

On 2016 Dec 12, Peter Hajek commented:

The authors are correct that other studies are needed to check this phenomenon. Can they specify which e-liquids they tested so a replication is possible?

On 2017 Feb 08, Peter Hajek commented:

In their just published response to Farsalinos et al. comment on these unexpected results, the authors acknowledge that replications are needed. Could they please respond to repeated requests to specify which e-liquids they used so a replication can be performed?

On 2017 Feb 08, Andrey Khlystov commented:

Please read our paper carefully. There is information on 5 liquids that can be easily ordered online. Good luck with your experiments.

On 2017 Feb 09, Peter Hajek commented:

Your paper does not identify the actual products. Can you let others know the product name and the online address where it was purchased? There is no point trying to clarify your finding with different e-liquids.

On 2017 Feb 11, Andrey Khlystov commented:

Dr. Hajek,

You have not read the paper carefully. As I said earlier, our paper has information on 5 liquids that should be enough to get anybody started in replicating the data. They are from Brand II, which is V2 Standard (see Table 1). The brand is very easy to find (www.v2.com). The other liquids were from local vape shops, but this is of little consequence for the study, see below.

You seem to miss the point of our paper. Please let me briefly summarize its message: flavors, especially at higher concentrations, appear to dominate aldehyde production. To check generality of our observations, all one needs to do is take any flavored liquid and test it at different concentrations and/or against unflavored liquids and see what happens.

Contrary to what you suggest, there is little value in testing exactly the same liquids. Testing specific liquids or flavors was not the point of our study. We observed that a fairly wide variety of randomly selected flavored liquids produce significant aldehyde emissions, with aldehyde profiles varying among different flavors. If only PG or VG were responsible for the majority of aldehyde emissions, there would be no differences among liquids that have the same PG/VG composition. Yet, we observed significant differences among such liquids.

I also doubt that liquids from different batches are exactly the same, especially from small-time operations. At the time of writing the paper, we did not measure concentrations of liquid constituents. Having understood their role, we are controlling for liquid composition in our on-going study. As we mentioned in the letter to ES&T, we see appreciable aldehyde concentrations in both mainstream and secondary aerosols for a wide variety of e-cigarettes and liquids that users bring to our study. High aldehyde emissions are not limited to the 15 liquids and 3 e-cigarette brands we tested in our original study, it appears; the problem seems to be quite universal.

As we stated in our letter to ES&T, we are calling for checking findings of ANY e-cigarette study. I would like to note, however, that if one doubts our measurements, he or she needs to come up with a plausible mechanism, other than the effect of flavors, that explains why unflavored liquids produced significantly lower emissions than flavored ones or why a diluted flavored liquid was producing less than a more concentrated one. Please note, this was observed for the same e-cigarette, the same power output, and the same experimental setup. As of now and as far as I know, nobody came up with a single credible reason to doubt our results. I would also like to stress that aldehyde measurements are not trivial. We have over 20 years of experience in these measurements with a solid track record of QA/QC. Please rest assured - we stand by the quality of our data.

On 2017 Feb 11, Konstantinos Farsalinos commented:

Dr Khlystov mentions that there is information about 5 samples tested in their study. Unfortunately he refers to the samples with the lowest (by far) levels of carbonyl emissions. In fact, only one of these samples had high carbonyl emissions, unlike Brand I samples which showed very high levels of toxic emissions (especially for 3 of the samples, the levels found were extreme).

Liquids from different batches may not be the same, but finding almost 7000 ug/g of formaldehyde compared to < 0.65 ug/g from an unflavored sample can be easily reproduced with reasonable accuracy even with different batches. A replication study finding levels of carbonyl emissions lower by orders of magnitude cannot be attributed to different batches.

As i mentioned in my ES&T letter to the editor, the levels found by Khlystov and Samburova could only be explained by dry puffs, but this has been excluded because of the findings in unflavored liquids. Also, previous studies with verified realistic (i.e. no dry puff conditions) have found aldehyde levels orders of magnitude lower compared to their study. This creates a crucial need to replicate the samples with the highest levels of carbonyl emissions, despite the reassurance about the laboratory quality. Replication is the epitomy of science. But the authors are not providing the necessary information for these liquids.

On 2017 Feb 13, Peter Hajek commented:

Dr Khlystov, I understand that your laboratory has a good track record. Your findings are potentially important, but they do need to be replicated so a possibility that they were an artefact of some part of your procedure is ruled out The reason for wanting to test Brand 1 liquids is as follows. If other liquids show no alarming toxicant levels (which is possible because in previous studies where dry puffs were excluded, no such levels were found), the next level of explanation will be that the levels may be low in other liquids, but they were high in the liquid you tested. It is of course possible that your results will be replicated, but if not, this would necessitate another round of testing of the liquids you used. Testing your Brand 1 liquids straight away would remove this potential expense and delay in clarifying the issue. Providing information on which liquids you used, if this is available, should be simple and uncontroversial.

On 2017 Feb 17, Andrey Khlystov commented:

Gentlemen, The problem with your arguments is that Brand II, though being the “cleaner” of the three we tested, still produces very high aldehyde emissions. Three out of five V2 liquids that we tested exceeded the one time (one time!) exposure limits in a single puff. They also produced higher emissions than non-flavored liquids used in more powerful Brand I and III e-cigarettes. Surely you can check that. Please see our reply to Farsalinos et al. letter to ES&T – there are other studies that found even higher aldehyde concentrations than we did. High aldehyde emissions are not limited to a single study or a single liquid. We also demonstrate that “dry puff” arguments that Farsalinos et al. use to dismiss all high aldehyde studies have absolutely no factual basis. I doubt I can add anything else to this discussion except for reminding you that the strength of science is not only in reproducing results, but also in not cherry-picking studies and data that fit one’s theories or expectations. I do appreciate your efforts in clarifying the benefits and risks of e-cigarette use and whish you success in this endeavor.