Our Response to Metal Study in eliquid aerosols from Johns Hopkins University

There have been headlines in the news media recently concerning ‘toxic heavy metals in eliquid vapours’ based on a study at the Johns Hopkins University.

A report on the study is posted on the University’s website, the following is an excerpt from that.

‘Study: Lead and Other Toxic Metals Found in E-Cigarette ‘Vapors’


Significant amounts of toxic metals, including lead, leak from some e-cigarette heating coils and are present in the aerosols inhaled by users, according to a study from scientists at Johns Hopkins Bloomberg School of Public Health.

In the study, published online in Environmental Health Perspectives on February 21, the scientists examined e-cigarette devices owned by a sample of 56 users. They found that significant numbers of the devices generated aerosols with potentially unsafe levels of lead, chromium, manganese and/or nickel. Chronic inhalation of these metals has been linked to lung, liver, immune, cardiovascular and brain damage, and even cancers.’

You can read the full report at the following link.


I have read the actual paper published in Environmental Health Perspectives, Environ Health Perspect; DOI:10.1289/EHP2175.

The first glaring problem is that the study is fraught with methodological flaws. They also used environmental safety limits for metals in air that cannot be applied to real vaping conditions at all.  Conclusions made from studies like this especially with sensationalised headlines by the media will have negative impact on smokers who are looking to alternatives to quit smoking.

Let us investigate in order to highlight the potential problems in this study.


The cardinal principles for all analytical work include Replication and Validation, these were not done. In any scientific experiment, if you cannot replicate your results with similar set of experimental conditions you have insufficient evidence to say that they are valid. If you haven’t validated your method there is no way of knowing it is fit for purpose.

Without full validation work it is impossible to have confidence in the results even with good QC results. An example for this is matrix blank was used to determine matrix effect in this study. This does not necessarily tell you if actual metal concentration results will be affected by the matrix unless you analyse a matrix blank spiked with a known amount of the metal of interest. We found out this when we validated our method.

Exposure Limits

Understanding how exposure limits are calculated is the key here. The numbers do not mean anything unless one exactly knows how they were calculated. A small number does not necessarily mean more ‘protective’ if this is for a longer period of exposure time compared to a higher one with a shorter period of exposure. The amount of air used to calculate environmental limits are many orders of magnitude higher than amount of air breathed in as a result of vaping. Just to give an example, the amount of air we breathe in per day is around 13000 L (DOI:10.1007/978-0-387-68909-8_6) and the total amount of air from vaping per day using the topography used in this study is ~ 34 L (assuming 500 puffs per day, Equation 1).

Here are a few examples how environmental limits are determined. EPA bases its Chromium limit based on occupational studies (NIOSH REL – 8-10 hours, OSHA PEL 8 hours, https://www.epa.gov/sites/production/files/2016-09/documents/chromium-compounds.pdf. The Nickel (Ni) limit used by the authors (ASTDR, MRL) is based on a no observed adverse effect level (NOAEL) of 0.06 mg Ni/m3 and a LOAEL (lowest-observed-adverse-effect level) of 0.11 mg Ni/m3 for chronic active lung inflammation in rats exposed to nickel sulfate 6 hours/day, 5 days/week for 13 weeks. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (non-carcinogenic) over a specified duration of exposure. Generally, ATSDR uses the no observed adverse effect level/uncertainty factor (NOAEL/UF) approach to derive MRLs for hazardous substances. They are set below levels that, based on current information, might cause adverse health effects in the people most sensitive to such substance-induced effects. MRLs are derived for acute (1-14 days), intermediate (>14 – 364 days), and chronic (365 days and longer) exposure durations, and for the oral and inhalation routes of exposure https://www.atsdr.cdc.gov/mrls/index.asp.

All inhalation safety limits take into account both the amount of air (volume) a person breathes and the duration (time) this happens. As there are no readily available health safety limits for metals in eilquids or eliquid aerosol, the best approach will be to adopt USP or ICH Permissible Daily Exposure (PDE) limits for metal impurities in medicines via the inhalation route. This leads to a simple straight forward comparison of the amount (in microgram of metal per day). Based on this, if we say an average vaper breathes in 400-500 inhalations per day, the amount of metal the person will likely be exposed to per day can be calculated by the total volume of air vaped (4-500 X Volume per puff).

The daily intake of metals by a vaper, based on this study will be

6.67×10−5 m3/puff multiplied by 500 puffs = 0.03335 m3                                Equation 1 

Concentration of metal multiplied by this volume gives the total amount of metal a vaper will be exposed per day.

Table 1. Comparison of heavy metal concentrations from the study with ICH metal impurities limit.


Amount per day (mg/m3) *Amount per day (mg) Amount per day (µg) **ICH limit (µg per day)
Ni 0.000444 1.48074E-05 0.0148074 6
Cr 0.0000846 2.82141E-06 0.00282141 2.9
Mn 0.0000197 6.56995E-07 0.000656995 N/A***
Pb 0.000106 3.5351E-06 0.0035351 5


*Multiplying by total volume of puffs per day (0.03335 m3)

**ICH Permissible Daily Exposure limit (PDE) http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/Q3D_Step_4.pdf

***No guideline limit set.

As you can see from the above table, even based on the results from this study the metal concentrations in the aerosol are nowhere near an appropriate health safety limit, such as ICH Q3D.

However, we cannot be complacent, further investigations on health impacts from metals from long term use need to be carried out and testing for heavy metals for all eliquid products that come in contact with heavy metals during manufacturing, bottling storage and vaping should be done as part of both regulatory and quality control frameworks, using properly designed and validated methods.

David Dawit (PhD)

CSO, Eosscientific

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