Preserving the faithA cosmetic formulators overview

John Woodruff

www.creative-developments.co.uk

John Woodruff: the personal stuff

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1960: joined Smith & Nephew Research1976: Co-founded Pava, responsible for all technical aspects, from formulation and development to manufacture and filling and originated many well-known brands.October 1988: Established consulting laboratory for formulation of cosmetics and toiletry products. Developed Creativity a unique programme written for formula creation and cosmetic manufactureTwo books and many articles published on cosmetic technology. Twice appeared as an expert witness, 3 times Chairman of the European UV & Sun Filters Conference, Twice chaired a technical session at In-Cosmetics 1990 – 1996: Cosmetics Consultant to Manufacturing Chemist1996 – Present: Regular contributions to Soap, Perfumery and Cosmetics (SPC)Supports the Distance Leaning Course run by the SCSLectures on product formulation at the Principles and Practice of Cosmetic Science When he is not working he is sailing.

The cosmetic product brief

• Product type

• Claims

• Product format

• Application

• Texture

• Colour

• Perfume

• Packaging

• Cost

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What about the preservative?

Preservatives are one of the last things that most chemists think about when formulating a product and one of the first things that are suspected when a problem occurs. They are important ingredients, the value of which is never noticed when functioning properly and which are worthless when not. Preservatives are much maligned and misunderstood within the cosmetics industry. Because of this, they are often over-dosed, under-dosed or improperly formulated even by experienced chemists

Cosmetic formulations require a delicate balance of a large number of raw materials. The preservative system should be among those materials considered when developing a new formula, not an afterthought

Schϋlke

• http://www.cosmetic-preservation.com/

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The legal stuffEU Cosmetics Regulation (EC) No. 1223/2009

Cosmetics must be resistant to microbial contamination

Preservative efficacy must be assessed experimentally to ensure microbial stability and preservation during storage and use

SCCS/1501/12 gives guidance for the testing of cosmetic substances and includes guidelines on microbiological quality of the finished cosmetic product

For cosmetics sold in Europe (EC) No. 1223/2009 lists a table of permitted preservatives as Annex V

This list was first compiled in 1982 and more than half are not in general use and there have only been two new ones added in the last decade

The prohibitive cost of gaining acceptance for any new ones will severely restrict any future additions

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The problem

A presentation from Inolex, Cosmetic Preservation, Market Review, makes

the very valid point that the internet gives voice to all, regardless of

qualification and that ……

“Real science” and “Junk science” are given the same credibility by an ill-

informed public

Consumer, environmental and political groups are capitalising on this to

move their cause forward

And so are cosmetic companies

And ingredient suppliers

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The result

For various reasons consumers do not like preservatives in general and parabens in

particular; this makes cosmetic preservation even more difficult

“The limited number of available preservatives increases the risk of developing

resistant strains of bacteria. It also increases the risk that consumers will develop

allergic reactions to the preservative and a diverse palette is needed” Valérie Murset

of the *EFfCI

“The biggest issue confronting the preservative market is the potential for

misinformation to impact a formulator’s choice in product preservation and imperil

consumers” Mark Miller, McIntyre

*EFfCI - European Federation for Cosmetic Ingredients

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The formulators challenge

Stay legal in all potential markets

lack of harmonisation between EU, USA, Japan, Brazil, Australia etc.

Please the marketing department

who are trying to please consumers

Provide adequate preservation throughout the life of the product

shelf life

period after opening

Watch out for next consumer or legislative target• Isopropylparaben, isobutylparaben, phenylparaben, benzylparaben and pentylparaben now banned

• Maximum concentration of propylparaben and butylparaben reduced from 0.4% when used individually

and 0.8% when mixed with other esters, to 0.14% when used individually or together – early 2015

• MCI/MI mix banned from leave-on products such as body creams July 2015

• Will methylisothiazolinone be next?

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The formulators frustrations

Parabens work but consumer perception is that they are “bad”

Organic acids do not work well but consumer perception is that they are “good”

Consumer perception is that chemicals are “bad” and petrochemicals are even worse yet benzyl alcohol is good. Also if benzyl alcohol is part of a perfume it is a potential allergen at 0.001% yet can be used as a preservative at up to 1%

Other materials that have this anomalous behaviour includes salicylic acid: listed in Annex V to be used at a maximum concentration of 0.5% as a preservative however it is permitted at 3% in rinse-off hair products and 2% in leave-on skin care with the provision that its primary purpose must not be the inhibition of micro-organisms and its purpose must be apparent from the presentation of the product!

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The formulators frustrations

What is good in Europe becomes bad in the USA or Japan etc. and visa –versa

Example: o-cymen-5-ol is closely related to thymol, which occurs naturally in many

plants including thyme, where it may represent 60% of its essential oil

Annex V: permitted at up to 0.1% in leave-on and wash-off products

The CIR Review shows it as safe at concentrations up to 0.5%

No upper limit in Japan provided the product is not intended for use on mucous

membranes. Perhaps we should add 1% thyme oil to our products. Many essential

oils have antimicrobial activity and suppliers are creating interesting mixtures that

circumvent Annex V

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Some answers

Convince the consumer that preservatives protect them from potential harm

Make products anhydrous

Formulate the product to provide an unfriendly environment to bacteria, yeasts

and moulds

Use permitted preservatives

Look for synergy between preservatives

Use materials that coincidently have an antimicrobial action

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Convince the consumer

• Present the facts

Scientific opinions by the SCCS and CIR reports

The CTPA simplifies reports and presents www.thefactsabout.co.uk/

The Personal Care Products Council www.cosmeticsinfo.org/

Cosmetics Europe www.cosmeticseurope.eu/

Chemical Watch https://chemicalwatch.com/

First convince the marketing department

Then convince beauty editors

Then educate the consumer

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Make products anhydrous

Lipsticks and pressed powders

Seal from the environment – aerosols; collapsible tubes;

certain pump dispensers

Powdered shampoos

Non-aqueous shower gels & bath additives

Solvent-based products e.g. Mascara; After-shave;

Toilet Waters

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Unfriendly environments: a.k.a. Hurdle technology

Reduce water availability

Lowering the water activity of the final composition is a possible route to avoid the use of traditional preservatives however it is rarely practical with an oil-in-water composition or with other water-based products

Materials used to achieve lower water activity include glycols such as glycerin and butylene and propylene glycols

Higher diols like pentylene glycol, 1,2-hexanadiol and caprylyl glycol appear to have an antimicrobial effect beyond their water-binding capacity but they also become less water-soluble

Unfriendly pH

Preservative-free & self-preserving cosmetics & drugs; Jon J Kabara, Donald S Orth

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Use permitted preservatives

(EC) No. 1223/2009 Annex V- permitted preservatives

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Benzoic acid and its sodium salt Glutaral

2-Bromo-2-nitropropane-1,3- diol (Bronopol) Hexamidine & salts

5-Bromo-5-nitro-1,3-dioxane Hexetidine

7-Ethylbicyclooxazolidine Imidazolidinyl urea

Benzalkonium chloride, bromide etc Iodopropynyl butylcarbamate

Benzethonium Chloride Kathon CG Mix

Benzyl alcohol Methenamine

Benzylhemiformal Methylisothiazolinone

Biphenyl-2-ol, and its salts o-Cymen-5-ol

Bromochlorophene o-Phenylphenol, sodium o-phenylphenatae etc

Cetrimonium Chloride etc Parabens

Chlorhexidine, Chlorhexidine diacetate p-Chloro-m-Cresol

Chloroacetamide Phenoxyethanol

Chlorobutanol Phenoxyisopropanol

Chlorophene Phenylmercuric salts

Chlorophene Piroctone Olamine

Chloroxylenol Polyaminopropyl biguanide

Chlorphenesin Propionic acid + salts

Climbazole Quaternium-15

Dehydroacetic acid, sodium dehydroacetate Silver chloride

Diazolidine urea Sodium Hydroxymethylglycinate

Dibromohexamidine Isethionate Sorbic acid and sorbates

Dichlorobenzyl Alcohol Sulfites

Dimethyl Oxazolidine Thimerosal

DMDM Hydantoin Triclocarban

Formaldehyde, Paraformaldehyde Triclosan

Formic acid, sodium formate Undecylenic acid and its salts

Zinc pyrithione

Annex V Simplified. 54 ingredients plus salts

Useful permitted preservatives

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Benzoic acid and its sodium salt Iodopropynyl butylcarbamate

2-Bromo-2-nitropropane-1,3- diol MIC/MI mix

Chlorhexidine, Chlorhexidine diacetate Methylisothiazolinone

Chloroacetamide o-Cymen-5-ol

Chlorophene Parabens

Chloroxylenol p-Chloro-m-Cresol

Chlorphenesin Phenoxyethanol

Dehydroacetic acid, Na dehydroacetate Phenoxyisopropanol

Diazolidine urea Polyaminopropyl biguanide

Dichlorobenzyl alcohol Quaternium-15

DMDM Hydantoin Silver chloride

Glutaral Sodium Hydroxymethylglycinate

Sorbic acid and sorbatesUndecylenic acid + salts

Annex V Very Simplified. 26 ingredients plus salts

Useful permitted preservatives

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Benzoic acid & Na benzoate (0.5% in Leave-on)

Iodopropynyl butylcarbamate

2-Bromo-2-nitropropane-1,3- diol MIC/MI Mix

Chlorhexidine, Chlorhexidine diacetate Methylisothiazolinone

Chloroacetamide o-Cymen-5-ol Chlorophene Parabens

Chloroxylenol p-Chloro-m-CresolChlorphenesin (0.3%) Phenoxyethanol (1.0%)

Dehydroacetic acid, Na dehydroacetate (0.6%)

Phenoxyisopropanol [Rinse-off only]

Diazolidine urea Polyaminopropyl biguanideDichlorobenzyl Alcohol (0.15%) Quaternium-15

DMDM Hydantoin Silver chlorideGlutaral Sodium Hydroxymethylglycinate

Imidazolidinyl ureaSorbic acid and sorbates (0.6% as acid)Undecylenic acid & salts (0.2% as acid)

Annex V Very Very Simplified

COSMOS permitted preservatives

Benzoic acid & its salts

pH & solubility problems

Benzyl alcohol

Known allergen

Salicylic acid & its salts

pH & solubility problems

Sorbic acid & its salts

pH & solubility problems

Dehydroacetic acid & its salts

pH problems

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Frequency of Use: List prepared by David Steinberg showing numbers of products containing preservatives as shown

US 2007 US 2010 Canada

2008

Canada

2010

Methylparaben 25.38% 22.53% 25.71% 25.39%

Propylparaben 20.40% 17.48% 22.27% 15.83%

Phenoxyethanol 11.22% 14.89% 12.71% 15.83%

Butylparaben 9.72% 8.87% 9.06% 9.50%

Ethylparaben 8.28% 8.17% 8.02% 8.60%

Isobutylparaben 3.68% 4.52% 4.23% 0.25%

MI 3.08% 4.04% 2.24% 4.21%

MCI/MI mix 3.04% 3.75% 1.52% 3.92%

DMDM Hydantoin 3.64% 3.41% 3.22% 3.45%

Imidazolidinyl urea 4.95% 3.37% 4.45% 3.72%

Benzyl Alcohol 2.46% 3.34% 1.98% 2.95%

Caprylyl Glycol 1.29% 2.87% 0.62% 2.07%

Diazolidinyl urea 2.84% 2.76% 3.96% 4.28%

Preservatives in common use in USA & Canada

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Parabens 67.47% 61.57% 69.29% 59.57%

Formaldehyde Donors 11.43% 9.54% 11.64% 11.45%

Phenoxyethanol 11.22% 14.89% 12.71% 15.83%

MCI + MCI/MI mix 6.12% 7.79% 3.76% 8.13%

Benzyl Alcohol 2.46% 3.34% 1.98% 2.95%

Caprylyl Glycol 1.29% 2.87% 0.62% 2.07%

Frequency of Use: List prepared by David Steinberg showing numbers of products containing preservatives as shown US 2007 US 2010

Can

2008

Cana

2010

Simplified by preservative types

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0.00%

2.00%

4.00%

6.00%

8.00%

10.00%

12.00%

14.00%

16.00%

1 2

Trends in preservative use: USA 2007 - 2010

Phenoxyethanol

Formaldehyde donors

MCI + MI + MCI

Benzyl alcohol

Caprylyl glycol

Trends in preservative use in EU

European skin care

2009 2010 2011 2012 2013 2014

Benzoates 6.89% 5.77% 13.00% 13.34% 13.67% 13.59%

Isothiazolines 0.00% 0.01% 0.07% 0.29% 0.26% 0.29%

Parabens 63.15% 63.37% 61.43% 61.39% 61.32% 61.35%

Phenoxyethanol 29.96% 30.85% 25.50% 24.98% 24.75% 24.78%

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0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

35.00%

1 2 3 4 5 6

Trends in European preservative use

Benzoates Isothiazolines Phenoxyethanol

Phenoxyethanol

Benzoic acid/Benzoates

Isothiazolines

Parabens make up the difference @ ~ 61%

Permitted preservatives: improve effect

• Activity of parabens increases with the increase in alkyl chain length, however their

solubility in water is inversely proportional to the length of alkyl chain

• Methylparaben is only soluble at 0.25% in water –

• If oils are present its partition coefficient will favour migration into the oil phase but

adding 0.02% propylparaben to the emulsion keeps methylparaben in the aqueous

phase

• 2% propylene glycol allows the minimum inhibitory concentration of methylparaben to

be reduced from 0.18% to 0.1% when combined with 0.02% propylparaben

• Prickett PS, Murray HL, Mercer NH. Potentiation of preservatives (parabens) in pharmaceutical formulations by low concentrations of propylene glycol. J Pharm Sci 1961; 50: 316–320

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Permitted preservatives: improve effect

• Phenoxyethanol is a favoured solvent for parabens

• Other materials that enhance activity by promoting solubility are

• benzyl alcohol

• Ethylhexylglycerin

• Ethanol

• 1,2 Hexanediol is a solvent that enhances the preservative potency of known mild

preservatives

• these materials plus propylene glycol frequently appear in preservative systems

offered as alternatives to parabens because of their antimicrobial activity and

solvent properties

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Improving the effect: Phenoxyethanol

Phenoxyethanol is permitted to a maximum level of 1% and has bactericidal

activity across the total pH range likely to be found in cosmetics

Best against Gram –ve bacteria; weak activity against other microbial

contaminants so it is usually found in combination with other preservatives;

traditionally parabens but other mixtures are now widely available

Its solubility in water is about 2.4%

It is compatible with cationic and anionic surfactants but it may be

inactivated by ethoxylated surfactants

Increasingly popular but does not have COSMOS or Ecocert approval

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Improving the effect: Benzyl alcohol

Benzyl alcohol is approved as a preservative in EU at a maximum level of 1%

Water soluble up to about 3g/L and is bactericidal at between 1% and 2%

OK against Gram +ve; some activity against Gram –ve & yeast; poor against mould

Optimum pH <5; little effect above pH 7. Inactivated by non-ionics

Good as solvent for parabens

It is often used in perfumery as a solvent but because it is a potential irritant its presence must be indicated on the label when its concentration exceeds 0.001 % in leave-on products and 0.01 % in rinse-off products

The anomaly is that despite these concerns it can be used above 1% for purposes other than inhibiting the development of microorganisms but this purpose has to be apparent from the presentation of the product

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Improving the effect: Ethylhexylglycerin

Ethylhexylglycerin has no restrictions under current EU legislation

It is a weak preservative in its own right. It works by reducing interfacial tension on the

cellular walls of micro-organisms, enhancing the effect of other preservatives by

increasing their penetration through the cell membrane

Its HLB is approximately 7.5 and this can upset some emulsifier systems

Its water solubility is about 1.8g/L but it is soluble to about 30% in propylene glycol

Interestingly it has demonstrable emollient properties and is increasingly used as a

multifunctional component in preservative mixtures

It shows minimal dermal penetration

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Use organic acids

• .

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Table by Courtesy of Inolex: CHA is caprylhydroxamic acid

CHA is the only organic acid with significant antimicrobial activity at pH 7. CHA is also a powerful chelating agent for iron

Organic acids

Generally the activity of organic acids is not wide spectrum and their efficacy is very pH dependent

Benzoic acid is effective at a concentration of 0.1% to 0.3%, which is the limit of its solubility in water. Its pKa = 4.19 and it is ineffective in solutions with a pH above 5

Because of its insolubility in water it is often used as the very soluble sodium salt but its effectiveness may be reduced by non-ionic surfactants such as the polysorbates

Widely available in mixtures with other organic acids and phenoxyethanol and/or ethylhexylglycerin and/or benzyl alcohol

Sorbic acid - effective concentration of 0.05% to 0.2% that is very close to its limit of

solubility so potassium sorbate is often used

Sorbic acid may be used at a higher pH than benzoic acid but is said to have little antimicrobial

activity above pH 6

Commonly used in mixtures

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Organic acids

Dehydroacetic acid is permitted to 0.60% but is almost insoluble in water (≥0.1%) however it remains effective to pH 6

Salicylic acid is permitted to 0.50% and may be used at higher levels if its primary purpose is not as a preservative e.g. Anti-acne and exfoliating products*

• Effective antifungal and better antimicrobial properties than benzoic acid

• It is soluble in water to about 0.2% effectiveness declines rapidly above pH 2

• Mostly found in mixtures:

*It is the opinion of the SCCNFP that those substances in Annex V, that when incorporated into cosmetic formulations for non-preservative functions, should be subjected to the same restrictions in usage levels and warnings as when used for preservative effect

This opinion is widely ignored

*Scientific Committee on Cosmetic Products and Non-food Products

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Plugging the anti-fungal gap

Iodopropynylbutyl carbamate (IPBC) is a highly effective fungicide at low usage levels from as little

as 15ppm. Annex V: Rinse-off products 0.02%; Leave-on products 0.01%; APDs/DEOs 0.0075% and

not to be used in body lotions and body creams or for children under 3 years of age

Dichlorobenzyl alcohol is described as a broad spectrum antifungal preservative with good

bacteriostatic properties over a pH-range of 3 – 10 and is permitted in the EU to 0.15%

Dehydroacetic acid and the water soluble sodium dehydroacetate are said to have high

antifungal activity <pH7

Salicylic acid at pH 2 – 4

Caprylhydroxamic acid is said to have antifungal activity

Chlorphenesin

Undecylenic acid

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Unlisted preservativesi.e. materials that are not classified as preservatives yet have antimicrobial activity

Glyceryl monoesters are a good example and are to be found in many of the alternative

systems

Glyceryl caprylate; glyceryl laurate; glyceryl undecylenate

Sorbitan caprylate

Higher diols like pentylene glycol, 1,3-propanediol, methylpropanediol, 1,2-hexanadiol and

caprylyl glycol

Caprylyl Glycol provides biological synergism with moisturizing and wetting capabilities

The one that got it wrong - Aqua/water, phenoxyethanol, methylparaben, sorbic acid, butylparaben, ethylparaben, propylparaben, isobutylparaben, methylchloroisothiazolinone, methylisothiazolinone

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Essential oils

A company in India produces mixtures of naturally occurring essential oils with

preservative activity

• Mix 1- based on curry leaf and cinnamon leaf oils

• Mix 2 - based on orange, lemon grass and sesame oils

• Mix 3 - based on basil extract with clove bud, lemon grass and sesame oils

• Mix 4 - based on turmeric oil with clove bud, lemon grass and sesame oils

All have applications other than for preservative use and have Ecocert approval

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Biocidal botanical extracts

A company in the USA produces multiple component mixtures claimed to have antimicrobial activity

• Mix 1: INCI: Origanum vulgare leaf extract, thymus vulgaris (thyme) extract, cinnamomum

zeylancum bark extract, olea europaea (olive) leaf extract, rosmarinus officinalis (rosemary)

leaf extract, mentha piperita leaf extract, lavandula angustifolia (lavender) flower extract,

hydrastis canadensis (golden seal) root extract

• Mix 2: INCI: Origanum vulgare leaf extract, thymus vulgaris (thyme) extract, olea europaea(olive) leaf extract, rosmarinus officinalis (rosemary) leaf extract, lavandula angustifolia (lavender) flower extract, hydrastis canadensis (golden seal) root extract

• Mix 3: INCI: Origanum vulgare leaf extract, thymus vulgaris (thyme) extract, cinnamomumzeylancum bark extract, rosmarinus officinalis (rosemary) leaf extract, lavandula angustifolia (lavender) flower extract, hydrastis canadensis (golden seal) root extract

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Natural alternatives

p-Anisic acid is found naturally in anise and has a strong action against yeast and

mould below pH 5.5

Magnolia officinalis bark extract is not pH dependent and is effective against

yeast and mould.

Melaleuca alternifolia (Tea tree) leaf oil

Rose oil – (phenylethanol) has a mild rose-like odour

Usnic aid from tree lichen (Usnea barbata)

Honeysuckle (Lonicera japonica)

Wasabi (Wasabia japonica) – Japanese Horseradish

Asparagopsis armata is a red seaweed gathered off the coast of Brittany that

provides natural antimicrobial properties

Expert on all things natural is Tony Dweck - www.dweckdata.com37

New? Ethyl Lauroyl Arginate HCl

Claimed to be a natural preservative made from lauric acid and L-arginine it is

cationic in nature

EU approved (V/58)

Permitted to 0.4% but not to used for lip, oral and spray products

Can be used to 0.8% in soap, anti-dandruff shampoos and non-spray DEOs

It is available as 20% active solution and recommended use levels in skin care,

hair care and wet wipes 0.5 – 2%

Said to be broad spectrum it is water-soluble and stable at pH 3 - 7

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Chelating agents

Chelating agents are not preservatives but may provide a synergistic effect for the

overall preservative system. They contribute to the partial solubilising of the cell

membrane, which allows preservatives a pathway into the cell.

• EDTA and its sodium salts

• Citric acid, sodium citrate

• Etridonic acid

• Pentasodium triphosphate

• Natural chelates: Phytic acid, sodium gluconate, gluconolactone, zinc gluconate

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Thank you for listeningJohn Woodruff

www.creative-developments.co.uk

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