Irwin Palefsky Cosmetech Laboratories Inc.

Irwin Palefsky Cosmetech Laboratories Inc. Irwin@cosmetech.com www.cosmetech.com The prevention or retardation of product deterioration caused by microorganisms from the time of production until the product is used up by the consumer The prevention of microbial contamination caused by typical consumer use of the product The preservative system is NOT a replacement for good hygiene/cleanliness during manufacturing The preservative system is a NOT intended to replace microbial control of raw materials or water used in the formulation 1

Each batch of a cosmetic which is not self-preserving, must be tested for contamination, before it is released for shipment Each cosmetic must be tested for adequacy of preservation during product development, for preservation against microbial contamination under foreseeable conditions of customer use How will product be used Preservative Free???? Market Regulations NGO requirements(i.e. Natural, NPA, Ecocert) Consumer issues real or perceived (i.e. parabens) Safety of the materials you are considering Cost 2

All preservatives need to be in the water phase of the formulation. ph of the formulation (water phase) The chemistry of the formulation and the preservatives that can be used Susceptibility of the product to microbial growth (i.e. water activity, anhydrous) Consumer potential to contaminate the product Formulation factors that Impact preservative efficacy continued Partition Coefficient of the preservative Temperature of Incorporation Percentage of Active Ingredients/proteins in Formula Type of Surfactant System-i.e. high ethoxylates Presence of particulates i.e.: talc, metallic oxides, clays 3

Combinations that provided predictable preservative efficacy: Imadazolidinyl urea + Parabens Diazolidinyl Urea +Parabens Phenoxyethanol +Parabens Quaternium-15 (+Parabens) Chlorphenesin + Parabens DMDM Hydantoin (Rinse off Products) Isothiazolinones Use of EDTA Cosmetic ingredients Ethylhexylglycerin Caprylyl Glycol Pentylene glycol 1,2 hexanediol + Caprylyl glycol Glyceryl Monolaurate (i.e. Lauricidin) Essential Oil combinations Cinnamon Leaf oil, Curry Leaf oil, Lemon Grass oil, Orange oil Perfumes Botanicals Leuconostoc/Radish Root Ferment Filtrate Leuconostoc/Sorbus aucuparia Botanical blends (oregano,thyme,cinnamon,olive, rosemary, peppermint, lavendar, goldenseal, Lemon Peel) 4

Preservatives for Leave on formulations Methylisothiazolinone Phenoxyethanol Chlorphenesin Polyaminopropyl Biguanide Dehydroacetic acid Benzyl Alcohol Sorbic Acid and Benzoic acid Isopropynyl Butylcarbamate(IPBC) Benzalkonium chloride Parabens Combinations of above preservatives with non preservatives Preservatives used in Rinse Off formulations Methylchloroisothiazolinones(MCIT) + Methylisothiazolinones(MIT) DMDM Hydantoin 5

Methylisothiazolinone Always available as a solution- either in water, Phenoxyethanol, Caprylyl glycol or Ethylhexylglycerin Max level of 100 ppm in leave on products Formulation Considerations Effective over a wide ph range 2-10 Can be added at any temp. up to 70 C Can use help with mold and yeast Inactivity in presence of sulfites Can sometimes cause transient irritation Phenoxyethanol Good activity against bacteria Always used with other preservatives Commonly used as solvent for other preservatives Formulation Considerations Limited water solubility Used at levels up to 1%(generally 0.7%) Can be added to formulation at any temperature Very stable over broad ph range 2-12 Can be used with all types of systems Can effect emulsion stability/viscosity 6

Chlorphenesin Available as a powder or in combination with other preservatives in liquid form Good against bacteria -needs help with mold & yeast Formulation Considerations ph range 3-9 Max allowed concentration in EU & Japan-0.3% Soluble in warm water, alcohol and glycols No significant compatibility issues Add below 60 C in solution Polyaminopropyl Biguanide Usually supplied as a solution Good against bacteria-needs help with mold & yeast %active use level between 0.05-0.3%(Japan has max level of 0.1%) Formulation Considerations ph<7.0 Soluble in water Stable up to 70 C-add at the end Good compatibility with non-ionic and cationic materials. Can be an issue with anionic surfactants 7

Benzalkonium Chloride Very effective broad spectrum preservative Effective use level 0.08-0.13% Use in EU(max 0.1%) must have warning statement about use around the eyes In Japan max use for leave on-0.05%--no max % for rinse off Formulation Parameters Very cationic preservative Surface active Dehydroacetic acid or Sodium Dehydroaceteate (the other DHA) Use level 0.2-0.6%(as DHA) Effective broad spectrum coverage (bacteria, mold and yeast) One of the few Ecocert approved preservatives Formulation Considerations Available in liquid combinations Sodium salt is water soluble Maximum ph 7.0 (preferably below 5) Can cause discoloration 8

Benzyl alcohol Liquid Effective against bacteria-needs help with mold & yeast Ecocert, NPA approved Use level up to 1% Formulation Parameters Broad temperature stability Soluble up to 4% in water Effective over broad ph range 2-12 Can contribute an odor(benzaldehyde) Can affect formulation viscosity Potassium Sorbate and Sodium Benzoate Both materials frequently used together Available as powders or as aqueous solutions Effective against mold and yeast Use levels of 0.3% sodium benzoate and 0.15% potassium sorbate Formulation Considerations Should be used at ph below 5.5 Needs to be used with anti-bacterial preservatives Ecocert, NPA approved Acts as salts 9

Isopropynyl Butylcarbamate(IPBC) Primary activity is against mold & yeast Approved use level in EU at 0.01% max. for leave on**; approval in Japan at 0.02% max., US CIR max 0.1% Formulation Considerations Very insoluble in water. Soluble in alcohol and some glycols Sold as a solution or in combination with other preservatives Should be added at low temperature Recommended ph 3.0-9.0 ** severe limitations on use in EU- no body lotions/creams, no lip products DMDM Hydantoin Classic formaldehyde donor Very effective broad spectrum protection Formulation parameters Should be used primarily in rinse off products Typical use level 0.2-0.3%-recommended up to 0.6% Can be used in ph range of 3.0-10.0 Must be added at the cool down end of the process 10

Methylchloroisothiazolinones + Methylisothiazolinone Rinse off application only Use level max 15 ppm of the actives-generally used at 5-10 ppm Very effective broad spectrum protection Formulation parameters Must be added at low temperatures <50 C Must be used at ph below 8.0 Solution contains magnesium salts Some compatibility issues with sulfites, amines, proteins, zinc pyrithione Alcohol (Ethanol or Isopropanol) FDA approved antimicrobial when use at 62% w/v Can be effective at levels > 20% Broad spectrum Obvious formulation challenges Can be drying to the skin Flammable Consumer resistance 11

Parabens Powders Very effective against Mold & Yeast Methyl & Propyl esters most popular Methyl used at 0.1-0.3%; Propyl used at 0.02-0.1% Up until recently, very ubiquitous Formulation Parabens Not very soluble in water Should be used below ph 8.0 Generally added to water phase and heated to dissolve Can be inactivated by ethoxylated surfactants Caprylyl Glycol Primarily functions as humectant/emollient Effective as a boost or aid to preservation activity when used at 0.5-1.0% primarily effective against mold & yeast (i.e. paraben replacement) Efficacy probably due to the antimicrobial efficacy of high purity short chain(c 8 -C 12 ) fatty alcohols, glycols and esters Solvent for other anti-microbial materials Formulation parameters An oil soluble semi solid material that melts at 30-35 C Must be used with other glycols to optimize partition coefficient Very stable material 12

Ethylhexylglycerin A liquid emollient & humectant Claims to inhibit the growth and multiplication of odor causing bacteria Always used in combination with other preservatives Formulation Parameters Use level 0.3-1.0% Limited solubility in water (0.1%) Very stable temperature, ph etc. Can effect viscosity Surface activity Pentylene Glycol Clear odorless moisturizing liquid Claims to improve preservative efficacy of other antimicrobial materials Formulation parameters Soluble in water Used at concentrations of 1-5% Always used with other antimicrobials or nonpreservatives Can effect viscosity 13

Monolaurin Appears to work primarily against Gram+ bacteria High Mono C 12 Glyceryl Monolaurate Sold as a food additive under the name Lauricidin Formulation parameters ph stable 3.5-8.0 Emulsifier The % used can vary but usually starts at 0.5%for efficacy 1,2 Hexanediol and Caprylyl glycol Good broad spectrum coverage Good stability over wide ph range Good temperature stability Can have solvent effect on formulation-viscosity, emulsion stability Recommended use level 0.4-1.0% 14

Caprylyl glycol and Ethylhexylglycerin Moisturizing and humectant benefits Primarily Recommended as a deodorant material Can be used in combination with other traditional preservatives to reduce their levels Recommended use level range 0.5-2.0% SPF 30 O/W sunscreen emulsion; ph 6.2 Non-ionic emulsifier system Organic sunscreens(no TiO2 or ZnO) Preservative system 0.2% Chlorphenesin 0.8% Ethylhexylglycerin 2.0 Pentylene Glycol Contains 0.1% Disodium EDTA Formulation passed USP micro challenge test 15

O/W night treatment emulsion, ph 6.1 Non-Ionic Emulsifier system Emollients-natural oils, butters, silicones Preservative system 0.2% chlorphenesin 1.0% phenoxyethanol Formula contained 0.10% Disodium EDTA Formulation passed CTFA micro challenge test Cleansing body wash formulation ph 6.7 Anionic/amphoteric surfactants, cationic polymeric conditioner, PE exfoliators Preservative system 0.05% of a 9.5% sol n of Methylchloroisothiazolinone + Methylisothiazolinone Contains 0.1% Disodium EDTA Formulation passed CTFA challenge test 16

Topical anesthetic 4% lidocaine, o/w emulsion, ph 6.2 Cationic emulsion Preservative system 0.8% Caprylyl Glycol 1.0% Ethylhexylglycerin 3.0% Pentylene Glycol Formula contained 0.1% Disodium EDTA Formulation passed USP challenge test PVP aqueous styling gel, ph 5.7 Aqueous gel with Carbomer thickener No Ethanol Preservative system 0.5% of a mixture of 1,2 Hexanediol + Caprylyl Glycol 1.0% of a sol n of Na benzoate + K Sorbate Formula contains 0.03% Disodium EDTA Formulation passed CTFA challenge test 17

Cationic O/W Emulsion ph 5.25 Contains 1% Polysorbate 20 as fragrance solubilizer Preservative system 0.5% 1,2 hexanediol+caprylyl Glycol 1.0% Sol n of Na Benzoate + K Sorbate Formula contains 0.1% Disodium EDTA Formulation passed CTFA Double Challenge 5.0 % Benzoyl Peroxide Carbomer gel- ph 6.6 Preservative system 0.08% of a 9.5% MIT solution No EDTA Formulation passed USP Challenge test 18

O/W emulsion-combination nonionic/cationic emulsifiers and cationic skin conditioners Develop a self preserving formulation Preservative system Ethylhexylglycerin 1.0% Contained 0.1% Disodium EDTA Formulation failed CTFA challenge test Exfoliating facial scrub-aos surfactant, Acrylate thickener, natural exfoliant ph 6.3 Preservative system 0.2% Chlorphenesin 1% mixture of Caprylyl Glycol + Ethylhexylglycerin Formulation contained 0.05% disodium EDTA Formulation failed CTFA challenge test Replaced Preservative system with 0.08% of a 9.5%MIT/MCIT solution-formulation passed CTFA Challenge test 19

Select a more robust preservative system based on the preservative challenge test failure Call Steve Schnitger from Estee Lauder and ask his advice Work with preservative supplier who will screen preservatives in the base formula. 20