Comment

Comment on Svarch-Pérez et al. Methods for a Non-Targeted

Qualitative Analysis and Quantification of Benzene, Toluene,
and Xylenes by Gas Chromatography-Mass Spectrometry of
E-Liquids and Aerosols in Commercially Available Electronic
Cigarettes in Mexico. Int. J. Environ. Res. Public Health 2024,
21, 1308
Roberto A. Sussman 1, * , Humberto Gómez-Ruiz 2 and Konstantinos Farsalinos 3

1 Institute of Nuclear Sciences, National Autonomous University of Mexico (UNAM), Alcaldía de Coyoacán,
Mexico City 04510, Mexico
2 Department of Analytical Chemistry, Faculty of Chemistry, National Autonomous University of
Mexico (UNAM), Alcaldía de Coyoacán, Mexico City 04510, Mexico; [email protected]
3 Laboratory of Molecular Biology and Immunology, Department of Pharmacy, University of Patras,
26500 Rio-Patras, Greece; [email protected]
* Correspondence: [email protected]

The authors of a study recently published in IJERPH quantified levels of benzene,

toluene and xylenes (BTXs) in e-liquids and aerosols in a sample of 20 disposable e-cigarettes
collected in Mexico City [1]. They conclude that these concentrations exceed the concentra-
Academic Editors: Joshua Muscat and
Paul B. Tchounwou
tions of these compounds given by the Threshold Limit Values (TLVs), Permissible Exposure
Limit (PEL) and Short-Term Exposure Limit (STEL) of the California Occupational Safety
Received: 26 February 2025
Revised: 17 May 2025
and Health Administration (Cal/OSHA) [2].
Accepted: 17 June 2025 This article exhibits severe methodological flaws and serious analytical and interpre-
Published: 30 June 2025 tive errors that invalidate its findings and render its conclusions misleading.
Citation: Sussman, R.A.; The major issues, addressed in detail below, are the following:
Gómez-Ruiz, H.; Farsalinos, K. 1. The authors erroneously converted Cal/OSHA PEL values from ppm to µg/L by
Comment on Svarch-Pérez et al.
multiplying the ppm by 1000, overlooking the established conversion formula that
Methods for a Non-Targeted
Qualitative Analysis and
considers the molecular weight of a substance in order to make the conversion. They
Quantification of Benzene, Toluene, also failed to notice that the Cal/OSHA PEL document, which they cite, had already
and Xylenes by Gas Chromatography- included values in mg/m3 (which is the same value when expressed in µg/L) for
Mass Spectrometry of E-Liquids and toluene and xylenes [2].
Aerosols in Commercially Available
2. They compared e-cigarette BTX emissions in µg/L of aerosolized e-liquid with
Electronic Cigarettes in Mexico. Int. J.
Cal/OSHA PELs expressed in µg/L of ambient air, which is scientifically mean-
Environ. Res. Public Health 2024, 21,
1308. Int. J. Environ. Res. Public Health
ingless. We note that 1 L of ambient air corresponds to two breaths, while 1 L of
2025, 22, 1049. https://doi.org/ aerosolized liquid corresponds to 200–250 days of e-cigarette use, as explained below.
10.3390/ijerph22071049 3. The presentation of the comparison with tobacco cigarettes is also wrong because
Copyright: © 2025 by the authors.
their source reported the values in ppb [3]. Therefore, the same error as with PELs
Licensee MDPI, Basel, Switzerland. was made in converting the values to µg/L. Furthermore, there is no scientific basis
This article is an open access article in comparing values in tobacco cigarettes that represent the amount per L of smoke
distributed under the terms and inhaled (representing fewer than two cigarettes, as explained below) with values
conditions of the Creative Commons
in e-cigarettes that represent the amount per L of liquid aerosolized (representing
Attribution (CC BY) license
200–250 days of consumption).
(https://creativecommons.org/
licenses/by/4.0/).

Int. J. Environ. Res. Public Health 2025, 22, 1049 https://doi.org/10.3390/ijerph22071049

Int. J. Environ. Res. Public Health 2025, 22, 1049 2 of 4

4. Even beyond occupational settings, BTXs are ubiquitous in an indoor environment,

and the recommended exposure limits for indoor spaces (just breathing air at home)
result in far higher exposure from breathing air at home than from e-cigarette use, as
calculated below.
In detail, it is well-established that concentrations expressed in ppm in ambient air
can be converted to mass per volume of air only after considering the molecular weight of
each compound, using the formula [4]

µg/L = (ppm × molecular weight)/24.45

In fact, the Cal/OSHA document, which Svarch-Pérez et al. cite in their article [2],
already provides both ppm and mg/m3 (which the latter being the same value when
expressed in µg/L) for toluene (10 ppm, 37 mg/m3 ) and xylenes (100 ppm, 435 mg/m3 ).
The mg/m3 (i.e., µg/L) values reported in the document are in agreement with the formula
provided above and, obviously, are very different from the conversion made by Svarch-
Pérez et al. Therefore, all comparisons between e-cigarette emissions and environmental
safety limits are invalid.
Additionally, Svarch-Pérez et al. compared PELs expressed in µg per L of working-
environment air with e-cigarette aerosol concentrations expressed as µg per L of aerosolized
e-liquid. This is a scientifically unjustified comparison. An amount of 1 L of e-liquid rep-
resents approximately 200 to 250 days of consumption, based on vaper surveys, which
have reported an average daily consumption of 4 to 5 mL [5,6]. In contrast, the PEL con-
centrations represent exposure from breathing 1 L of air. This corresponds to a maximum
of two breaths considering that the average tidal volume for adult humans under resting
conditions is 500 mL. Therefore, Svarch-Pérez et al. compared two breaths in an occupa-
tional setting with 200–250 days of e-cigarette consumption. In addition to the already fatal
flaw of incorrect conversions from ppm to µg/L, such a comparison makes their study
discussion and conclusions invalid.
The comparison between tobacco cigarettes and e-cigarettes is also problematic. The
authors used data from a Korean study on BTX concentrations in tobacco cigarette smoke [3].
However, that study reported levels in ppb. Thus, Svarch-Pérez et al. made the same error
as for PELs when converting ppb values to µg/L. An additional problem is that the
reported concentrations represent the amounts of BTX per L of smoke inhaled by a smoker.
Considering the average smoke volume per puff of 55 mL (as per the Health Canada
Intense puffing regime), 1 L of smoke represents approximately 18 puffs. Thus, the authors
compared 18 puffs of a tobacco cigarette (fewer than two cigarettes smoked) with tens of
thousands of e-cigarette puffs taken during 200–250 days of use. Therefore, the comparison
between tobacco cigarettes and e-cigarettes is also invalid.
Beyond environmental exposure assessment, BTXs are ubiquitous in indoor environ-
ments. Benzene is present in indoor spaces at levels of 0.5 to 2.2 µg/m3 [7]. The proposed
residential maximum exposure limit for benzene is 0.6 µg/m3 for long-term exposure [7].
Toluene levels in indoor spaces have been reported to range from 5.5 to 24.7 µg/m3 , and
the recommended residential maximum exposure limit is 2.3 mg/m3 [8]. For xylene, the
typical levels measured in indoor air range from 0.4 to 17.3 µg/m3 , while the recommended
exposure limit (reference concentration—RfC) is 150 µg/m3 , adjusted by a total uncertainty
factor of 300 from the NOAEL to accommodate for interspecies and intraspecies variation,
addressing exposure to more sensitive population subgroups such as children [9].
To understand the magnitude of the errors in the comparisons made by Svarch-Pérez et al.,
we made the correct unit conversions for toluene and we compared daily exposure from
the 20 samples reported by the authors (using an average of 5 mL liquid consumption) with
Int. J. Environ. Res. Public Health 2025, 22, 1049 3 of 4

8 h of exposure in a working environment with toluene at the PEL (10 ppm, 37 µg/mL)
using the EPA-defined inhalation rate of 0.027 m3 /min for moderate activity [10]. We
found that daily exposure from e-cigarette use ranged from 0.58 to 653.09 µg, while an 8-h
working shift would expose a worker to 488,332.8 µg of toluene. Therefore, e-cigarette use
would result in 748 to 844,866-fold lower toluene exposure compared to working in an
environment with toluene levels at the PEL. When compared with residential recommended
maximum exposure limits (for 24 h of exposure), the respective difference was 30- to
34,380-fold lower exposure to toluene from e-cigarette use, even when underestimating
indoor exposure by assuming the unrealistic condition of only a resting respiratory rate for
the whole 24 h period (8.6 m3 /d breathing volume, instead of the guideline-recommended
volume of 20 m3 /d). The respective difference for xylenes was 1.6 to 324-fold lower from
e-cigarette use, while only for benzene the differences were from 2-fold lower to 10-fold
higher exposure from e-cigarette use compared to the strict residen-tial exposure limits.
Such differences are so large that exposure would be far lower from e-cigarette use than
from indoor exposure even for population subgroups with lower ventilation rates, such as
minors, or with extreme e-cigarette consumption.
Finally, we have detected several potential problems in the analytical methodology
and in the results presentation, which we will present only briefly:
1. Tables 2–4 in the original manuscript report BTX concentrations in g/L, which would
imply levels hundreds of times above the solubility of these compounds in water. This
may have been a typographical error, but such a glaring issue casts serious doubt on
the quality control during peer review.
2. The authors collected aerosol from 2 e-cigarette puffs only, a puffing procedure that
prevents statistically reliable outcomes (due to inter-puff variability in emissions) and
grossly deviates from the recommended experimental standards [11].
3. There is significant ambiguity in the experimental methodology. The use of different
columns and extraction techniques (water vs. methanol), the inconsistent descrip-
tions of purge and trap versus thermal desorption, and the lack of procedural detail
undermine the reproducibility of the work.
4. The internal standard used for quantification is not identified in the main manuscript.
No calibration data is presented.
5. The authors identify a dozen compounds with their retention times (in page 5 of their
manuscript), but they had to report two retention times for each compound since they
reported having used two columns.
Even if we assume that further and sufficient clarification would be provided by the
authors concerning their analytical methodology, the mistakes in converting units from
ppm to µg/L, the scientifically unjustified comparison between two breaths in a working
environment and 200 to 250 days of e-cigarette consumption, and the erroneous compar-
isons between tobacco cigarettes and e-cigarettes make a large part of the manuscript,
including the results, discussion/interpretation, and conclusions of the study, invalid.
Characteristically, five out of the eight paragraphs in the Discussion section and two out of
the four paragraphs in the Conclusions section refer to comparisons between BTX exposure
from e-cigarettes and tobacco cigarettes or PELs, comparisons which are demonstrably
wrong. Based on the above, we believe that the manuscript cannot be corrected and re-
vised. The whole manuscript would need to be rewritten and resubmitted for peer review,
focusing only on presenting the analytical results, clarifying the methodological issues we
raised, clearly stating that they report amounts per L of aerosolized liquid, and not making
comparisons with tobacco cigarettes and PELs. Therefore, we ask the editors to consider
retracting the study.
Int. J. Environ. Res. Public Health 2025, 22, 1049 4 of 4

Conflicts of Interest: The authors declare no conflict of interest.

References
1. Svarch-Pérez, A.; Paz-González, M.V.; Ruiz-Juárez, C.; Olvera-Chacón, J.C.; Larios-Solís, A.; Castro-Gaytán, S.; Aldeco-Pérez, E.;
Alcocer-Varela, J.C. Methods for a Non-Targeted Qualitative Analysis and Quantification of Benzene, Toluene, and Xylenes by
Gas Chromatography-Mass Spectrometry of E-Liquids and Aerosols in Commercially Available Electronic Cigarettes in Mexico.
Int. J. Environ. Res. Public Health 2024, 21, 1308. [CrossRef]
2. Occupational Safety and Health Administration. Web Page, Table AC-1: Permissible Exposure Limits for Chemical Contaminants,
Permissible Exposure Limits and Short Term Exposure Limit. Available online: https://web.archive.org/web/20240730020210
/https://www.dir.ca.gov/title8/5155table_ac1.html (accessed on 16 February 2024).
3. Pandey, S.K.; Kim, K.H. Determination of hazardous VOCs and nicotine released from mainstream smoke by the combination of
the SPME and GC-MS methods. Sci. World J. 2010, 10, 1318–1329. [CrossRef]
4. Centers for Disease Control and Prevention. The National Institute for Occupational Safety and Health (NIOSH). Safety Checklist
Program for Schools. Conversion Calculator. Available online: https://www.cdc.gov/niosh/docs/2004-101/calc.html (accessed
on 10 December 2024).
5. Farsalinos, K.E.; Romagna, G.; Tsiapras, D.; Kyrzopoulos, S.; Spyrou, A.; Voudris, V. Impact of flavour variability on electronic
cigarette use experience: An internet survey. Int. J. Environ. Res. Public Health 2013, 10, 7272–7282. [CrossRef] [PubMed]
6. Farsalinos, K.E.; Romagna, G.; Tsiapras, D.; Kyrzopoulos, S.; Voudris, V. Characteristics, perceived side effects and benefits of
electronic cigarette use: A worldwide survey of more than 19,000 consumers. Int. J. Environ. Res. Public Health 2014, 11, 4356–4373.
[CrossRef] [PubMed]
7. Government of Canada. Proposed Residential Indoor Air Quality Guidelines for Benzene. Available online: https://www.canada.
ca/en/health-canada/programs/consultation-proposed-residential-indoor-air-quality-guidelines-benzene/document.html
(accessed on 5 May 2025).
8. Health Canada. Residential Indoor Air Quality Guideline: Toluene. Available online: https://www.canada.ca/content/dam/
canada/health-canada/migration/healthy-canadians/publications/healthy-living-vie-saine/toluene/alt/toluene-eng.pdf
(accessed on 5 May 2025).
9. Health Canada. Residential Indoor Air Quality Guidelines for Xylenes. Available online: https://www.canada.ca/content/
dam/hc-sc/documents/services/publications/healthy-living/residential-indoor-air-quality-guidelines-xylenes/residential-
indoor-air-quality-guidelines-xylenes.pdf (accessed on 5 May 2025).
10. Environmental Protection Agency. Chapter 6—Inhalation Rates. In Exposure Factors Handbook; EPA/600/R-09/052F; U.S.
Environmental Protection Agency: Washington, DC, USA, 2011. Available online: https://www.epa.gov/sites/default/files/20
15-09/documents/efh-chapter06.pdf (accessed on 14 December 2024).
11. CORESTA Recommended Method No 81. Routine Analytical Machine for e-Cigarette Aerosol Generation and Collection—
Definitions and Standard Conditions. 2015. Available online: https://www.coresta.org/sites/default/files/technical_documents/
main/CRM_81.pdf (accessed on 14 December 2024).

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.