Toxicity and Sensitivity Risks of Some Common Skin Care Preservatives

This new thread was started to answer some questions from Jina (see below) about commonly used cosmetic preservatives. Because Jina is not one to shy away from deeper levels of scientific evidence, I thought we would try something different here. I am going to collect some of the most recent published scientific literature on the substances in question, and either link to it or paste in some abstracts (I cannot give you the whole article as they are copyrighted). l may annotate the abstracts, and give you my brief perspective on what they say. I would appreciate feedback from you readers in terms of whether this is too deep or what.

The first substance to discuss is Phenoxyethanol (PE). It is a commonly used preservative, and was originally touted as the replacement for formaldehye (which is quite toxic). It has replaced formaldehyde in medical pathology labs (preserving cadavers, samples, etc).

The problem is stated as sensitivity and toxicity which are two different things. Toxicity has to do with inherent properties of the chemical e.g. it’s propensity to cause damage to cells, at the DNA level, metabolic, or some other mechanism. Sensitivity has to do with your immune system having decided that this substance is an enemy, whether it is inherently toxic or not. Your skin can become sensitive to otherwise nontoxic molecules (e.g. pollens) which makes it quite problematic for you, but not for everybody. Proteins are especially prone to cause sensitivities or allergies, but any chemical can be sensitizing. Very sensitive people (we call them atopic in the allergy realm) can be easily sensitized to any number of chemicals. But even non-atopic people can be sensitized to chemicals like preservatives by seeing them over and over again.

The problem with Phenoxyethanol is that is is present in so many skin care products. One of the abstracts below (#1) shows it in 3541 “leave on products” Lots of opportunities to be exposed. If you are a skin care “junkie” you may be seeing this substance more often than you think.

Dosing is also important, especially for toxicity. The “acceptable range” (FDA-speak) of concentrations is quite large. Interestingly, it is effective in doses low as 1/20th of the allowed. (#2). For hypersensitive skin, even low concentrations could be a problem, but lower dosing would help a lot.

So, what about toxicity. Abstract #3 below is hot off the press. PE was tested along with two different parabens, benzyl alcohol, and ethylhexyl glycerine. At concentrations of 1% (quite high) cytotoxicity and genotoxicity (DNA alteration) was present for all, with parabens being worse than PE for genotoxicity. Again, higher concentrations than you would normally see in a product. But it does tell us that these chemicals are not without risks.

My own take on this is that PE has a reasonably low risk profile (compared e.g. to parabens) at usual product concentrations, but that lowering concentrations further would be a quite good thing. But, for anyone who thinks they are sensitive to PE, you need to be aware of just how ubiquitous it is these days. Beware that not every chemical in the bottle is on the label.

I am considering a totally “preservative free” version of a product line we are working on. But, you would have to keep it refrigerated to maintain its sterility. It would arrive in a dry ice package. Would there be enough sensitive users out there willing to put up with that inconvenience? Please tell me what you think.

Abstract #1

Contact Dermatitis. 2011 Sep;65(3):167-74

Risk of sensitization to preservatives estimated on the basis of patch test data and exposure, according to a sample of 3541 leave-on products.

Schnuch A, Mildau G, Kratz EM, Uter W.

BACKGROUND:

The risk of sensitization cannot be derived from the frequency of sensitization to allergens alone, but exposure should be considered.

 

OBJECTIVE:

To estimate the risk of sensitization to selected preservatives.

METHODS:

The occurrence of preservatives in 3541 leave-on products based on the labelling of the ingredients was documented. Frequency of sensitization to preservatives was analysed on the basis of Information Network of Departments of Dermatology data for 2006-2009. As an estimate of sensitization risk, the sensitization exposure quotient (SEQ) was calculated as the quotient of the relative frequency of sensitization and the relative frequency of use.

RESULTS:

The SEQs varied greatly, offering a ranking regarding risk of sensitization: phenoxyethanol (SEQ: 0.06), benzyl alcohol (0.30), parabens (0.35), sorbates (0.92), benzoates (1.35), formaldehyde-releasers (1.6), methylisothiazolinone (MI) (1.7), iodopropynyl butylcarbamate (3.4), methylchloroisothiazolinone/MI (9.0), and 2-bromo-2-nitropropane-1,3-diol (13). There was a good correlation between the ranking of substances according to potency (hazard) and the ranking of the SEQ (risk).

CONCLUSION:

High frequencies of sensitization may be put into perspective by the frequent use of certain preservatives. Despite infrequent use, others (with higher potencies or too high use concentrations) may turn out to be associated with an increased risk. Hazard assessment should be supplemented by risk assessment.

Abstract #2

Int J Cosmet Sci. 2011 Apr;33(2):190-

Low-level efficacy of cosmetic preservatives.

Lundov MD, Johansen JD, Zachariae C, Moesby L.

Preservation using combinations of preservatives has several advantages. This study shows that the concentration of some of the most frequently used allergenic preservatives can be markedly lowered when they are combined with phenoxyethanol. The antimicrobial efficacy of cosmetic preservatives and known allergens of various potency [diazolidinyl urea, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), methylisothiazolinone (MI) and phenoxyethanol] was tested alone and in various combinations of two or three preservatives together. The preservatives were tested for minimum inhibitory concentration (MIC) values and possible synergy using fractional inhibitory concentration. MCI/MI was the only preservative showing low-level MIC against all four tested microorganisms: Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. Different combinations of the preservatives indicated additive effects against the microorganisms. No combination of preservatives showed any inhibitory action on each other. Challenge tests with different concentrations and combinations were performed in a cosmetic cream. Diazolidinyl urea and MCI/MI alone were ineffective against C. albicans in a challenge test at concentrations up to 16 times higher than the observed MIC values. When combining phenoxyethanol with either one of the allergenic preservatives diazolidinyl urea, MCI/MI or MI, the cosmetic cream was adequately preserved at concentrations well below the preservatives’ MIC values as well as 10-20 times below the maximum permitted concentrations. By using combinations of preservatives, effective preservation can be achieved with lower concentrations of allergenic preservatives.

Abstract #3

Int J Cosmet Sci. 2011 Nov 28. Accepted.

In vitro induction of apoptosis, necrosis and genotoxicity by cosmetic preservatives: application of flow cytometry as a complementary analysis by NRU.

de Carvalho CM, de Menezes PF, Letenski GC, de Oliveira Praes CE, Feferman IH, Lorencini M.

Preservatives are used in cosmetics to prevent microbial contamination; however, some preservatives are not free of allergenic and cytotoxic potential. Allergenicity and cytoxicity potentialvaluesare major aspects of preservative safety, which determine limitations and maximum concentration dose in a cosmetic product. The purpose of this study was to investigate and compare the in vitro apoptosis, necrosis and genotoxicity-inducing potential of five different types of preservatives: Phenoxyethanol (PE), Propylparaben (PP), Methylparaben (MP), Benzyl Alcohol (BA), and Ethylhexyl Glycerine (EG). In vitro experiments were carried out on human dermal fibroblasts by a quantitative flow cytometry method, using specific cell markers (Annexin V, Propidium Iodide and H2A.X). We compared the resulting cell viability by means of Neutral Red Uptake (NRU) and established the IC(50) . Our results showed that PE, PP, MP and BA have similar cytotoxic mechanisms (high apoptosis and necrosis levels only at the test concentration of 1%), while EG showed only an apoptosis pathway. For genotoxicity, both parabens yielded the highest values. Results obtained by flow cytometry for necrosis were comparable to those produced by NRU; however, NRU does not distinguish apoptosis from necrosis.

 

24 Comments

  1. Jina says:

    Hi science guys,
    From my understanding in the last few days there has been a strong ongoing battle with EGFs. I guess there will be more on this issue in the future, but in the mean time if your time permits, I and perhaps others who scour these sites over cup of tea in the norning before the day begins., if you could put up any information regarding the good the bad and the ugly on phenoxyethonal, parabens, lavender oil and the new player radish root. These are preservatives that we are trying to avoid but are in many products. I should also mention alcohol as that was the bane of my flare up last week. Radish root is a new player and I don’t see much information on this ingredient, so wondering if you know much about it’s potency. Keep up the hard work and hope to here about your cutting edge products in the future. By the way, the face you have on your site, may I say is a beautiful girl, besides the fact she has freckles or if you call it pigmentation. When I look at the whole picture I only see beauty. If we can only bring up our children to see the beauty in others and not focus on what we or marketing thinks is not acceptable or whatever perfect is.

    Regards

    • drjohn says:

      Hi Jina. OK. We will take a look at those chemicals & botanicals soon. I love your comments on our BFT girl, and agree with your assessment. The message it portrays is pure, naked faced beauty on the one hand, and yet the concern on the other than those cute freckles could be the harbingers of something else — solar aging. The melanocytes there producing pigment spots are actually a defense system. But it has its limits, especially as we age. Its beauty preserved, for now, but the stresses that will show up later have already begun. Sort of a yin-yang. More later. Dr.J.

  2. Jina says:

    Hi,
    I’m still trying to understand the above but what you are saying is that it is less irritating to use PE, MI/MCI and alcohol together as a preservative? Again depending on each individuals tolerance and what percentage. I have read somewhere that MI/MCI are neurotoxins. They affect the brain and may lead to alziehmers if true, should we avoid such ingredients? I have also read lavender oil can lead to cell death. Is this also true. What’s the science about that, my goodness if true there goes the economy of south o France. Are there any other oils we should watch out for? Looking forward to your reply.

    • drjohn says:

      Hi Jina. Glad you are here. You always ask such interesting (and deep) questions. I’m going to need to split this into parts. Each really needs a post of its own. Let’s start with lavender oil. The source of the rumor about cell death is Paula Begoin. Here is what she published: Research also indicates that other components of lavender, specifically linalool, can be cytotoxic, meaning that topical application causes skin-cell death (Source: Cell Proliferation, June 2004, pages 221–229). The reference is a good one, and does demonstrate cytotoxicity in vitro (that means in a test tube). Add to that the more recent literature showing benefit for linalool as an anti-cancer agent by sensitizing cancer cells to chemotherapy, and its proven value as an anti-fungal agent. It’s chemically a terpenoid which as a class can be skin irritants. A lot of other essential oils also contain terpenoids, and they all like to attach to cell membranes and affect metabolism. So the news for the South of France is both bad and good. Their skin care ingredients business may be in trouble, but they could probably launch a whole new pharmaceutical industry based on this stuff.

      We shall get to the other questions later. Remember, ANY ONE PERSON CAN BE SENSITIVE TO ANY CHEMICAL. It’s a rule of immunology. Some chemicals are more prone to cause poroblems, some people are more prone to be sensitive to lots of chemicals.

      References
      Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle. Zore GB, Thakre AD, Jadhav S, Karuppayil SM. Phytomedicine. 2011 Oct 15;18(13):1181-90
      Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors. Gu Y, Ting Z, Qiu X, Zhang X, Gan X, Fang Y, Xu X, Xu R. Toxicology. 2010 Jan 31;268(1-2):19-24.
      Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells.Ravizza R, Gariboldi MB, Molteni R, Monti E. Oncol Rep. 2008 Sep;20(3):625-30.

    • drjohn says:

      The article above was actually making the point that MI/MCI have a reasonably high likelihood of causing sensitivity reactions, and the reason may be both frequent exposure (present in a large number of products) as well as properties of the chemicals themselves. The MI part of MI/MCI (Methylisothiazolinone) is a neurotoxin when tested in developing neurons in vitro. Prolonged exposure to low levels of MI and related compounds may have damaging consequences to the developing nervous system. See full text article here . As far as I know its never been tested in adults of any species, so the Alzheimer’s association is speculative, but not wildly so. Your question of “should we avoid” is a tough one. The problem is one of context — we are exposed to so many chemicals in so many ways, products and otherwise, every single day, including a number of neurotoxins. The only way to avoid them altogether would be to become a bubble boy (or girl). But then, in a more perfect world, we would have better preservatives, proven safe, zero risk, and highly effective. The problem is that nobody want to spend the money to get there. Products would double in price. Cheap knocks offs (with 10x the toxins) would sweep in and dominate the market. So, in some ways, its an economic issue, and a human behavior issue. Guessing that you, Jina, choose to avoid as much of that stuff as you can, I think you are doing the right thing for yourself. Reading labels, assessing the safety of ingredients, seeking out answers to tough questions, making careful selections. What I think would help would be a simple rating system that the average consumer could understand. The problem is that if government regulators got involved they would likely mess the whole thing up. So my advice is continue doing what you are doing, and be well informed and selective.

  3. Jina says:

    Hi, and thank you for your prompt reply. The only product my skin can tolerate at the moment is organic sesame and evening primrose oil with a drop of chamomile oil. I use this as my barrier cream. The latter helps the redness dissipate. My question with that is that being a terpenoid, will it bring skin cell death in the future from prologue use? I also spray my skin with chamomile hydrosal. And yes as soon as I pick up a product, there is the lavender oil. It seems to be in a lot of products. Drug store, department store and whole foods.

    • drjohn says:

      Sesame oil is safe according to the cosmetic ingredient review folks (see below). But I should point out that it is such a good skin barrier penetrant that it is being used as an effective carrier for methadone delivery via the scalp– into the brain! Makes me worry about essential oils in hair care. Also means you probably want to make sure your skin is totally clean before putting it on your face, to make sure unwanted chemicals don’t get dragged in with it (theoretically possible). Its also known in children to be an IgE mediated allergen, possibly as common as peanuts. Some protein they share in common. Chamomile oil has no issues I am aware of. BTW –are you by any chance allergic to peaches?

      Reference
      Int J Toxicol. 2011 May;30 (3 Suppl):40S-53S.

      Amended safety assessment of Sesamum indicum (sesame) seed oil, hydrogenated sesame seed oil, Sesamum indicum (sesame) oil unsaponifiables, and sodium sesame.

      Sesamum indicum (sesame) seed oil and related cosmetic ingredients are derived from Sesamum indicum. Sesamum indicum (sesame) seed oil, sesamum indicum (sesame) oil unsaponifiables, and hydrogenated sesame seed oil function as conditioning agents. Sodium sesameseedate functions as a cleansing agent, emulsifying agent, and a nonaqueous viscosity increasing agent. These ingredients are neither skin irritants, sensitizers, teratogens, nor carcinogens at exposures that would result from cosmetic use. Both animal and human data relevant to the cosmetic use of these ingredients were reviewed. The CIR Expert Panel concluded that these ingredients are safe in the present practices of use and concentration as described in this safety assessment.

      Indian J Pharm Sci. 2009 May;71(3):264-9.

      Transcranial route of brain targeted delivery of methadone in oil.

      The unique anatomical arrangement of blood vessels and sinuses in the human skull and the brain, the prevalence of a high density of skin appendages in the scalp, extracranial vessels of the scalp communicating with the brain via emissary veins and most importantly, the way that the scalp is used in Ayurvedic medical system in treating diseases associated with the brain show that a drug could be transcranially delivered and targeted to the brain through the scalp. …The results indicate that the transcranial brain targeted delivery of methadone base in the form of a [sesame] oil based non aqueous solution results in statistically significant antinociceptive effects under experimental conditions. Therefore, it is possible to deliver central nervous system drugs through the proposed transcranial route when suitably formulated.

      • Jina says:

        Hi, I guess will keep applying my potion this winter as my barrier cream. I have also read elsewhere that the more oils or moisture applied., the skin recognizes that it’s lubricated and stops that function. Interesting theory. Unless something spectacular comes across I will keep the nasties such as PE/MI/MCI for my serums. But would the sesame oil transport any nasties from my peptide serums. Ah! But that is another topic I want to eventually cover. Sorry guys I know you have more important things to do but answer my “but why questions”. Who knows by the end of this quest I may have my own potion line happening. I kind of like the name Truthinpotions! And no I am not allergic to any peaches that I know of, but do love and eat a lot of fruit. Hope that’s not bad for me too. Oh is that the glycation theory I feel coming up. That has to be explained to me too. Can’t live without my fruit. Ahh another topic.

        • drjohn says:

          No, not glycation, although that does have a lot to do with wrinkles. Rather, there is a constellation of protein allergies including skin sensitivities for which peach allergy is a “sentinel”. Truthinpotions sounds like a worthy cause. If you google on “sensitive skin blog” the top listing is a site whose front page says “Tuesday, January 20. 2004 posted in in Skin Conditions”. I think that is rather stale. So obviously somebody needs to step up to the plate. Why not you? We’ll support you on the science side. Now, which peptide serums are you using? That will offer more slues about what is happening, dermatologically speaking.

  4. Jina says:

    Hi, point taken, I’m not a scientist and thanks for the suggestion but it is something I would have to think about.

    Regards

  5. ChicGeek says:

    As far as sensitivity goes, I pretty much have to rely on the irritation potentials often listed on charts of comedogenicity. I’m a pretty good guinea pig for that, unfortunately, too. A new shave gel by a big manufacturer left me with a spectacular case of contact dermatitis, and I’m afraid that’s more the rule than the exception with my family. My husband’s actually worse–he gets the most spectacular hives from most scented laundry products, whereas my skin, if it reacts at all, mostly just gets reddened, irritated, and itchy.

    Your readers should realize that you really can develop reactions to almost ANYTHING. I have exercise-induced anaphylaxis. (It’s actually quite manageable, and I work out a number of times a week, but I have to watch my anaphylaxis threshold–learn to recognize the signs of an impending reaction, etc.) Some people react to WATER (though it’s not technically an allergy): http://en.wikipedia.org/wiki/Aquagenic_urticaria

    So while sometimes things can cause nasty reactions in a decent percentage of people, just because something causes a reaction in a very few people doesn’t mean it’s bad for everyone.

  6. Kristina says:

    I would absolutely be willing to put up with the refrigeration if that meant no nasty preservatives and chemicals on my skin. I asked a few friends and they agree too.

  7. lyonella says:

    Arent there any alternatives to PE that dont cause cell death tho? I prefer some type of antimicrobial agent in my products just because I dont live in a totally sterile environment and dont want contamination of products that go on my skin. Thx

    • drjohn says:

      The consensus amongst the pros is that PE (in the right doses) is both effective and safe. No cell death unless you exceed those limits. There are alternatives, including some so-called “natural” ones. But they don’t have enough of a track record to assure the guys who formulate and do quality testing and antimicrobial challenge testing. So for now I accept that PE is the best alternative to (much more problematic) parabens.

  8. Firefox7275 says:

    I have sensitive, eczematous skin which became remarkably less sensitive and eczematous after eliminating sulphates surfactants from my routine. Did so after reading of the small aqueous cream study published in 2010. I have used products requiring refrigeration before but found they created as many problems as they solve.

    I am interested in more ‘natural’ or multifunctional preservatives, by which I mean taking advantage of the bacteriostatic or otherwise antimicrobial properties of ingredients such as zinc oxide or coconut oil/ lauric acid. I would feel more confident purchasing a product preserved in this way because I know I have eaten or handled coconut many times and used zinc oxide in sunscreens. Not sure how realistic this route is for formulators! Another technique I employ is to emulsify an oil-based substance and water-based substance in the hand immediately before applying – this potentially reduces the need for preservatives, buffers, stabilisers or emulsifiers. Again probably not practical for innovative formulators.

  9. Deb says:

    Are parabens used as preservatives? Or are parabens and preservatives two different things?

  10. Brad says:

    Hello, I have a question related to plant memory and the possibility of utilizing their cells/properties in human hair….

  11. Helena says:

    Thank you so much for all the info! I might have missed it – what is your personal final take on Methylparaben, used in almost every Asian cosmetic brand? Thank you!!!

    • drjohn says:

      Parabens are probably safe in doses we see in cosmetics. It depends on the degree of caution you want to exercise. There are other preservatives without that baggage, so we don’t use them.

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