Paper on Natural Parabens by Anthony C. Dweck

References

Safety of Parabens

Expert Comments

(regarding latest reports on parabens and breast cancer)

The Cosmetic Directive

Curriculum Vitae

1. In a data sheet from Nipa Laboratories received from Malcom Irvine Dec 1994.
   "Parabens - the natural preservatives".

In the plant world 4-hydroxybenzoic acid and its derivatives are commonly found in various vegetable foods, such as barley, strawberries, black currants, peaches, carrots, onions, cocoa-beans, vanilla; further in foods prepared from fruit plants such as grapes and fruit juices, yeast extract, wine vinegar and also in cheeses. The distribution of the acid in plants, as derivatives of alkaloids, natural colourings etc. was reviewed by Banfield 1. Tomaszewski 2 investigated 122 plant species and found the acid present in all the plants. Billek 3 concluded that 4-hydroxybenzoic acid is the most widely distributed aromatic organic acid in the vegetable kingdom. Baardseth 4 showed that the Scandinavian cloudberry contained benzoic acid, sorbic acid, salicylic acid, 2-hydroxybenzoic acid, as well as methyl and propyl parabens, which accounted for the superior resistance of cloudberries to microbial spoilage.

The total organic acids were present at a level of 600 ppm.

Recently, Schafers 5 reported an elegant technique (GC/MS) for the detection of methyl and ethyl esters of hydroxybenzoic acid in vegetable and potato peelings.

In the animal kingdom, Schildknecht 6 found Dytiscus marginalis, the yellow beetle, produced in the secretion of its glands a disinfecting mixture of benzoic acid, 4-hydroxybenzoic acid, 4-hydroxybenzaldehyde and methyl paraben, which protected the glands from bacterial infection. Staddon 7 likewise found methyl paraben in the stink gland secretions of the British water bug, Ilyocoris cimicoides.

The presence of 4-hydroxybenzoic acid in urine of healthy, normally fed human beings 8,9 has been known for many years and is due to the decomposition of the amino acid, tyrosine, and from dietary sources.

Goodwin 10 identified methylparaben in the vaginal secretions of female dogs in oestrus. It was proposed that methylparaben was an essential part of the complex odour profile generated by the secretions of the vaginal glands. It is more likely, as in the water bug and yellow beetle examples, that methylparaben was produced as antimicrobial protection 11 of the microbiologically labile odoriferous components of the secretions.

Research worker suspected a vital role for 4-hydroxybenzoic acid. Davis 12 found it an essential growth factor (bacterial vitamin) for E. coli and as sulphonamides were an antagonist to 4-aminobenzoic acid (bacterial vitamin H), so methyl paraben was to its parent acid. Many other workers 13 supported these findings, culminating in Simonart & Wiaux 14 detecting the occurrence of 4-hydroxybenzoic acid in Penicillium griseofulvum which emphasized the fundamental importance of this acid in biochemistry.

It was eventually resolved 3,5-19 that 4-hydroxybenzoic acid was the precursor building block for ubiquinones (coenzyme-Q) which is essential for the oxidative phosphorylative process in all respiring organisms. Ubiquinones were found in microbes, in the heart muscle and in the normal skin 20. It was concluded that:-

"All respiring vegetable and animal species require 4-hydroxybenzoic acid. Without it there are no ubiquinones and hence no respiration. 4-hydroxybenzoic acid is a natural vital ingredient of aerobic life, it is no foreign substance to them."

Bose 21 reported that 4-hydroxybenzoic acid exhibited marked synergy with auxins, in promoting root growth of chrysanthemums, tomatoes and marigolds. Another interesting report by Kickuth 22 isolated and identified nine aromatic compounds from the rhizomes of bullrushes S. lacustris which had microbiocidal activity (especially against E. coli and Salmonella spp.) and therefore would make these plants important in maintaining water quality and protecting against pollution from disease producing organisms. The nine compounds identified were derivatives of benzaldehyde, 4-hydroxybenzoic acid and cinnamic acid (0.025 wt % of rhizomes). The aromatic acid function had the greatest activity and had bactericidal activity against E. coli at concentrations as low as single ppm levels.

Da & Vialle 23 studied the flavour components of natural vanilla extracts. They showed that, unlike the Bourbon vanilla, the Tahiti vanilla contained methyl paraben as one of the four major flavour components. Harbourne 24 found methyl paraben a constituent of lignin in some gymnosperms and woody dicotyledons.

Aldrich 25,26, studying the 7th-8th ventral abdominal gland secretions of adult males of the leaf-footed bugs, Leptoglossus and related species, found a preponderance of aromatic compounds, contrasting sharply with the aliphatic compounds which comprise the metathoracic gland defensive secretions of male and female leaf-footed bugs. It was later found that methyl paraben was a major component of the ventral abdominal gland secretion.

Perkins 27, investigating the major components of the rectal glandular secretions of male fruit flies found methyl, ethyl and propyl parabens. He found that the glandular extracts of the S.E. Asian fruit fly (Dacus albistrigatus) was rich in methyl paraben. In another Dacus zeugodacus sp. (a large unidentified Malaysian fruit fly) the glandular extract contained 66% ethyl paraben. Dacus cucurbitae, the melon fly, is the major fruit fly pest of melon and other cucurbits. Analysis of the rectal gland secretions showed ethyl paraben as the major component and propyl paraben as a minor one. Hancock 28, studying African cucurbit pests, found Dacus vertebratus Bezzi to be highly attracted to methyl paraben. This discovery was initially observed when the fly was attracted to a locally manufactured cosmetic product.

Methyl paraben has now joined three other previously identified fruit fly attractants, "Cue-lure" [4-(4-acetoxyphenyl)butan-2-one], "Willison's lure" [4-(4-hydroxyphenyl) buutan-2-one] and methyl eugenol. Methyl paraben has been called "Vert-lure".

The article continues with a discussion of the biodegradability and the 4-hydroxybenzoic acid biocycle.

It was concluded that 4-hydroxybenzoic acid and derivatives have a well reported and proven biocycle and are intrinsic and fundamental to all respiring and anaerobic life.

See the reference list in the data sheet.

2. Niels K. Veien, Thais Hattel and Grete Laurbergg:
   Oral challenge with parabens in paraben-sensitive patients.
   Short communications: Contact Dermatitis 1996, 34, 433.

Parabens used to preserve medicaments and cosmetics may sensitise and cause contact dermatitis at the site of application. It has been suspected that persons sensitised to parabens may experience flares of dermatitis from parabens in food and systemic medicaments.

From 1.1.90 to 31.12.94 we performed a placebo-controlled oral challenge with a mixture of 100 mg methyl p-hydroxybenzoate and 100 mg propyl p-hydroxybenzoate in 14 patients with least a+ positive patch test to the paraben mixture in the European Standard Series. 7 of the patients had hand eczema; 1 also had dermatitis of the face and 1 also had axillary eczema. 3 patients had dermatitis of the lower legs, 3 had dermatitis of the face and/or scalp, and 1 had dermatitis of the forearms.

The capsules containing the paraben mixture or a placebo were given an interval of 1 week. This interval was longer if there was a flare of dermatitis after the 1st. capsule. The sequence of capsules was randomized. The oral challenge was carried out when the dermatitis was quiescent. The patients themselves recorded whether or not aggravation occurred following the oral challenge.

2 of the 14 patients had flares of their usual dermatitis after challenge with the paraben mixture but not after the placebo. Both had hand eczema of the recurrent, vesicular type. Both had a severe erutpion of vesicles on the sides of the fingers within 24 hours of ingesting the paraben capsule. 1 of the patients also has a flare at a paraben patch test site on the back. 1 patient had doubtful reactions to both the paraben mixture and the placebo, while 11 patients did not have any reaction to the oral challenge.

The 2 patients with specific reactions to the challenge were informed about food and medicaments that may contain parabens. These preservatives are permitted in amounts up to 300 mg/kg of foods such as mayonnaise and ready-to-serve salads containing mayonnaise, water-based ice cream, preserved fish, preserved vegetables, including ketchup and mustard, marmalade, fruit and vegetable juices and cider as well as candy and cakes.

At follow-up visits after the patients had attempted to avoid the above-mentioned food items for a period of 1 to 2 months, neither patient of physician could see that the dermatitis had improved as a result of the diet.

Using the method described in the current study, we have not found oral challenge with parabens to be a useful test procedure in patients sensitive to the paraben mix. Although specific reactions were seen in 2 paraben-sensitive patients with recurrent vesicular hand eczema, the significance of this finding remains uncertain.

The European Cosmetic Toiletry and Perfumery Association COLIPA stated that the Routledge work was 'irrelevant' as 'Parabens are hydrolysed in the skin and we have data to show that none are entering the blood stream', and said that the Industry had no plans to follow up the work.

Further information is attached for a considered opinion

We are aware of the new research published by Dr Phillippa Darbre and the concern this may cause to consumers (1). The research does not find a causal link between underarm cosmetics containing parabens and breast cancer.

Parabens are preservatives that are used in cosmetics because of their excellent safety profile. They are very rarely used in deodorant and antiperspirant products because these products are, essentially, self-preserving. However, where parabens are used in cosmetic products they are declared in the ingredient listing by the name ‘paraben’.

Dr Darbre reports finding parabens in samples of human breast tumour tissues but she also found quantities of parabens in “blank” samples that did not contain any tissue at all. Thus, the significance of her results is not easy to ascertain. Extensive independent research has previously shown that any traces of parabens that might enter the skin are completely broken down by skin cells to harmless substances that cannot pose any risk of breast cancer.

According to a number of leading cancer research organizations, there is no plausible biological mechanism by which antiperspirants and deodorants could cause breast cancer. Other risk factors, including smoking, drinking and obesity, are well known to have an impact on the rising incidence of breast cancer.

Dr Chris Flower of the CTPA said “Extensive research available to our members continues to indicate that there is no proven link between rising breast cancer rates and the use of antiperspirants or deodorants. Dr Darbre’s research is based on an extremely small sample of 20 breast tumour cases and does not include any reference samples from normal tissues.”

Safety is the number one priority for CTPA members who manufacture antiperspirants and deodorants. Parabens are officially approved for use under the Cosmetics Directive (76/768/EEC), the European legislation that regulates all cosmetics and toiletries. We can reassure the public that all cosmetic and toiletry products containing parabens may continue to be used safely.

CF/eoc
e/state/ingr/parabens 12.1.04

(1) Concentration of Parabens in Human Breast Tumours. P.D. Darbre, A. Aljarrah, W.R. Miller, N.G.Coldham, M.J.Sauer and G.S.Pope. J. Appl. Toxicol. 24 : 5-13 (2004)

Expert comments

“The findings of parabens in tumour samples are additional results in line with the general hypothesis that there may be a link between oestrogenic compounds commonly used in underarm cosmetics and other consumer products and breast cancer. The results alone, however, do not suggest that these chemicals caused the tumours in these patients. Darbre et al.’s findings invite several questions: how did the parabens get into the breast, are they persistent and could they do harm? The answers require further research.”

Philip W. Harvey and David J. Everett

“We are all exposed to all kinds of chemicals but it doesn’t mean that they all cause cancer. The question is here whether the chemicals would have an impact on the hormones, and also what level you would see in a healthy breast tissue. A causal link has by no means been proved.”

Karol Sikora, Professor of Oncology at Imperial College London

The Observer
Sunday, 11 th January 2004

“Although this is an interesting study the sample size is very small. No causal link has been found between underarm cosmetics containing parabens and breast cancer. There is also no robust population-based evidence to suggest a link. Should any notional risk exist it would be insignificant when compared to other avoidable environmental risks for the disease, such as obesity.”

Dr Richard Sullivan, Head of Clinical Programmes at Cancer Research UK

The Sun, The Star, Daily Mail, The Independent, The Observer
Monday, 12 th January 2004

“This extremely small study does not demonstrate a direct or causal link between deodorant or anti-perspirant use and developing breast cancer. Further research is needed to establish the source of the chemicals found in the breast tumour samples and what, if any, the relationship is to breast cancer.”

Delyth Morgan, Breakthrough Breast Cancer

Daily Mail, Daily Mirror

Monday, 12 th January 2004

“We conclude from our results that the above mentioned paraben esterase III of keratinocytes (a skin enzyme that breaks down parabens) is sufficient to completely hydrolyse the traces of parabens that may enter the skin from topically applied ointments.”

C. Lobermeier, C. Tschoetschel, S. Westie and E. Heymann

Hydrolysis of parabens by extracts from differing layers of human skin.
Biol.Chem. 377(1): 647-651 (1996)

The Cosmetics Directive 76/768/EEC

Annex VI specifically permits 4-hydroxybenzoic acid and its salts and esters (the parabens) for use as preservatives in all cosmetic products. The maximum authorised concentration is 0.4% (as the acid) for any one ester and no more than 0.8% (as the acid) for mixtures of esters.

Anthony C. Dweck BSc, C.Sci, CChem, FRSC, FLS, FRSH, has worked for Smith & Nephew, S.C. Johnson, Marks & Spencer, and Peter Black (now PB Beauty). In 1998 he formed Dweck Data in order to devote more time to the study of botanicals and their chemistry.

He is a twice Past President of the Society of Cosmetic Scientists (a Medal Lecturer to the Society in 1995), and was Organiser and/or lecturer on the SCS Intensive Residential course in Cosmetic Science for many years. He was also the Associate Editor of the International Journal of Cosmetic Science. He was made an Honorary Member of the Society in 2004. He is the Technical Editor for the Personal Care Magazine (Asia Pacific) and is a member of numerous scientific advisory boards.

Author of over a hundred articles and papers on various aspects of the Cosmetic and Toiletry industry and numerous book chapters, Anthony is also a frequent lecturer on his favourite topic of botanicals/medicinal plants and has presented over 80 papers at conferences all over the world. He is a regular organiser of the conference programme for PCIA (Personal Care Ingredients Asia) and the honorary organiser for the SCS Spring Symposium 13-15th May 2007 “the 100% Natural Conference” at Staverton Park, Northants.

Anthony has a unique library of over 600 volumes on medicinal plants and their uses as well as a unique computerised data base on over 80,000 species of plants.