Saturday 2 March 2019

Limonene in vaporisers and e-cigarettes might induce health problems

I gave it a million thoughts before I even started imagining this post. Believe me, it was one of the hardest I wrote so far, and not because of the science on it, but because of the lack of science available on it!!! 

Even though there are million pages out there on the dangers associated to the use of limonene, as you already know, I'm not one willing to duplicate or replicate anyone else's work, especially if already presented with excellent content. 

I then decided to do it a tad different, and when I realised I wasn't writing a post on the toxicity of limonene anymore, I was writing a post on a very specific putative danger associated to its inhalation via e-cigarette/vaporiser.

But before progressing any further and for the sake of contextualisation, it is imperative to draw a few preliminary lines on the whole topic. For that matter I'll use some direct questions in order to make scientific sense of the info readily available on limonene. 

What is limonene?

Limonene, also known as Alpha-Limonene, Alpha-Limonène, Dipentene, D-Limonene, D-Limonène, L-Limonene, L-Limonène, Limonène, Limoneno, R-Limonene, R-Limonène, S-Limonene [1] is a low toxicity volatile organic chemical compound that can be found in the peels of citrus fruits, among other plants.

What is limonene used for?

The different industries realised that limonene has many applications. This compound has been used, for example, in the pharmaceutical industry in products that require improved skin penetration [2], in weight loss drugs and supplements [3], extensively used in immunooncology research [4, 5], in the food industry as flavouring [6], in house cleaning products due to its scent. In this sense the volatile nature of this product is often related to certain hazards, but if you need to know more I advise you to read this source [7] containing a great easy-to-understand summary on the dangers of inhalation of limonene, and consequently, formaldehyde. You don't know what formaldehyde is? Well, it is a product that in the specific case of the example we are hereby analysing, is generated by the reaction between ozone and limonene. If we consider that limonene is extensively used in air sprays or as a solvent, then we must also consider the large amounts of formaldehyde (a strong carcinogenic, irritant and corrosive substance) [8] that is being inhaled by people all over the globe. However, specialists at the World Health Organisation consider these to be of trace levels, and thus, irrelevant health-wise.

On the dangers associated to inhaling limonene... for fun... or out of habit:

Now imagine if you are one of those people that have replaced sucking on a cigarette (a terrible unhealthy habit I mastered from the age of 17 to the age of 27) by sucking on a device known as Electronic Cigarette (some with crazy shapes like dragons or butterflies). Many of those daily recreational users of electronic cigarettes or vaporizers tend to claim these are a safe option. But in reality there is still insufficient data to claim these devices and their contents are safe for human use. From the Herbert Gilbert's idea of an electronic cigarette back in 1967, to the first modern e-cigarette by the Chinese Hon Lik company in the year 2000, very little research on short-, long-term use inhalation of the numerous constituents of these inhaling solutions has been presented to public eye. No one can immediately state that electronic cigarettes and vaporisers are safe or less unhealthy a habit in comparison to the murderous predecessor cigarette.

I found an article that 'supports' the idea that people randomly vaporising my face (when I'm out there on the streets) is enough a reason to go bonkers and mentally imagine slapping that sh*t out of their faces. I never do it, but the rabid Dwayne Johnson in me clearly wants to come out seeking vengeance. The article I tell you about is the Clapp and Jaspers (2017) [9] where the authors produced a great review linking e-cigarettes to asthma. Something the public should be reflecting on. In their article they go on about, among other very important aspects, the possible impact of the potent TRPA1 agonist role of common electronic cigarette's/vaporiser's flavouring agents... such as LIMONENE (the one that offers that lemony scent). Meaning that these agents promote a strong pulmonary reflex response that might be involved in contributing to exacerbation of asthma, but is also related to exacerbation of oral lichen planus (a chronic inflammatory condition affecting oral mucous membranes [10]). In itself, oral lichen planus is not seen as a serious condition... until we realise that there is a 1% risk of developing into an oral cancer [11]. That's 1 in 100, 10 in a thousand, and so on and so forth.

In summary, there is so much more to know and research about these vaporisers that until we can actually assume full understanding of the impact of such agents on human health, a lot of studies must be adequately conducted. My question is, if so little was known about the short- and long-term use of these substances, how come were they so easily made legal for human consumption as inhalers? And if we go a bit deeper, most of the knowledge gathered so far, that actually excuses the use of substances like limonene in vaporisers and e-cigarettes, is based on single exposures... someone forgot to look into the combinatorial effects. A simple example is the one aforementioned: Limonene + Ozone = Formaldehyde!

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[1] Limonene, WebMD, [https://www.webmd.com/vitamins/ai/ingredientmono-1105/limonene], last visited on the 2nd of March 2019, last update unknown.

[2] Almirall, M. ,  Montaña, J. ,  Escribano, E. ,  Obach, R. ,  Berrozpe, J. D. (1996). "Effect of d-limonene, alpha-pinene and cineole on in vitro transdermal human skin penetration of chlorpromazine and haloperidol". Europe PMC, 46(7), pp. 676-680.

[3] Brudnak, M. A. (2002). "Weight-loss drugs and supplements: are there safer alternatives?". Medical Hypotheses, 58(1), pp. 28-33.

[4] Rodrigues, B. S., Ávila, R. I., Benfica, P. L., et al (2018). "4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells", Life Sciences, 203, pp. 141-149.

[5] Yu, X., Lin, H., Wang, Y. et al (2018). "d-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer". OncoTargets and Therapy, 11, pp. 1833–1847.

[6] Guneser, O., Demirkol, A., Yuceer, Y. K. (2017) "Production of flavor compounds from olive mill waste by Rhizopus oryzae and Candida tropicalis". Brazilian Journal of Microbiology, 48(2), pp. 275–285.

[7] What is limonene, cleansmart, [http://www.ukcpi.org/features/limonene], last visited on the 2nd of March 2019, last update unknown.

[8] Medical Management Guidelines for Formaldehyde, Agency for Toxic Substances, last visited on the 2nd of March 2019, last update on the 21st of October 2014.

[9] Clapp, P. W., and Jaspers, I. (2017). "Electronic Cigarettes: Their Constituents and Potential Links to Asthma". Current allergy and asthma reports, 17(11), pp. 79-101. 

[10] Shan, D., Long, H., Lai, W. 2017). "TRPA1 may contribute to the exacerbation of oral lichen planus through Koebner phenomenon". Oral diseases, Letter to the Editor.

[11] Oral Lichen Planus, British Asociation of Dermatologists, [http://www.bad.org.uk/shared/get-file.ashx?id=111&itemtype=document], last visited on the 2nd of March 2019, last update on May 2016.

Post image by Finn Gross Maurer on Unsplash.

***

https://www.rcplondon.ac.uk/projects/outputs/every-breath-we-take-lifelong-impact-air-pollution

http://www.ukcpi.org/features/limonene

https://www.who.int/ipcs/publications/cicad/en/cicad05.pdf?ua=1

https://www.bbc.co.uk/news/magazine-35281338

https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+1809

https://www.rcplondon.ac.uk/projects/outputs/every-breath-we-take-lifelong-impact-air-pollution

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