Integra® 44 - A Biocide for Industry

The safety and integrity of your products are of paramount importance. Integra® 44 from ISP can help ensure your success. For over thirty years the personal care industry has relied on preservatives from Sutton Laboratories, a division of the ISP Group of companies, to prevent microbiological contamination in products such as shampoos, eye creams and skin creams. Now all that experience and expertise is available for a wide range of industrial applications with ISP's new Integra 44. This highly convenient liquid biocide provides broad spectrum antimicrobial activity. Integra 44 is unusual in that it remains active at alkaline pH. Integra 44 is active between pH 3.5 to 12, providing very wide flexibility for the formulator. Integra 44 is ideal for water-based applications. ISP International Specialty Products is a specialty chemicals company that strives to go above and beyond our customers' expectations by providing innovative technology, performance-enhancing products, and exceptional service. Vital to the current success of our above and beyond efforts is ISP's exceptional technical service organization, which works directly with formulation and application scientists. We keep abreast of market trends to provide for our customers' future needs - and Integra44 has been introduced to provide the customer with a versatile, convenient, and cost-effective biocide. Integra 44 is the first ISP industrial biocide to receive approval from the U.S. Environmental Protection Agency. It complements an existing product line with over 325 specialty chemicals that are used in all types of industrial applications. Sample formulations for industrial applications have been included. Call ISP Technical Service at (201) 701-7249 for additional applications assistance. For further information and your sample requirements, contact your nearest ISP office. Integra® 44 HIGHLIGHTS Aqueous solution of Sodium hydroxymethylglycinate. Derived from Glycine - a naturally occurring amino acid. Broad spectrum antimicrobial activity. Effective against bacteria and fungi. Active from pH 3.5 to pH 12. Easy to use and safe to handle. Excellent for water based applications such as adhesives, coatings, liquid detergents and dishwashing liquids, cleaning products, inks, emulsions and lubricants. APPLICATIONS Integra 44 is being used increasingly in a number of important applications. A summary of applications and potentials is given below. HOUSEHOLD, INDUSTRIAL & INSTITUTIONAL Many applications in this area including hand cleaners, fabric softeners, dishwashing detergents, industrial cleaners, laundry detergents, liquid soaps, and hard surface cleaners. Integra 44 when used between 0.2 and 1.0% as supplied provides adequate protection . COATINGS Integra 44 has been shown to be effective in latex paint systems, and has excellent performance as an in-can preservative. Typical use levels vary from 0.2 to 1.0% as supplied. ADHESIVES Adhesives based on starches, latexes and natural or synthetic gums can be preserved with Integra 44 at levels up to 1.0% as supplied. Integra 44 is particularly effective in starch based adhesives, which are normally alkaline pH. OTHERS Includes: water-based inks, polishes, textiles, pulp and paper, airfresheners, car care products, lubricants. It is important that each formulation is challenge tested to assure preservative efficacy. BROAD SPECTRUM ACTIVITY Integra® 44 is very active against Gram-negative and Gram-positive bacteria, but is also effective against fungi. Integra 44 is particularly effective against Pseudomonas aeruginosa, a common spoilage organism. REMAINS ACTIVE AT ALKALINE pH Most microorganisms require an environment with a pH between 5 and 9. Sometimes a species will survive up to pH 12. Integra 44 remains active from pH 3.5 to pH 12 giving the formulator very wide pH flexibility. COMPATIBILITY Integra 44 is not inactivated by surfactant systems and most common formulations. Color changes have been observed, however, with fragrances containing citral, although the antimicrobial properties are not affected. EFFECTIVE AT LOW CONCENTRATIONS Typical formulations use Integra 44 at low concentrations, usually 0.2 - 1.0% as supplied, thereby providing cost effective preservation. EASE OF HANDLING Integra 44 is supplied as a 50% aqueous solution allowing for easier handling in manufacturing when compared to powdered preservatives. Integra 44 also shows excellent water solubility and low oil solubility, so it will remain in the water phase where it acts against microorganisms. LOW ORDER OF TOXICITY The information provided below are typical properties of Integra 44 and are not necessarily specifications. Integra® 44 Sodium hydroxymethylglycinate

Active Ingredient Sodium hydroxymethylglycinate 48.0 - 52.0% Appearance Colorless to yellow Color (APHA) 500 max Odor Characteristic amine pH 9.5- 12.0 Specific Gravity (@25°C) 1.27 - 1.30 CAS Registry Formula 70161-44-3 EPA Reg. No. 57978-4 Molecular Formula C3H6NO3Na Molecular Weight 127.10

SOLUBILITY Integra® 44 shows ideal solubility characteristics for water-based systems. It is highly water soluble and has a very low solubility in non-aqueous solvents, as shown in the following table:

Solvent Solubility (in grams/100g of solvent) Water miscible Propylene Glycol 112g Glycerin 119g Butylene Glycol <0.10g Mineral Oil <0.10g Ethanol 3-A Anhydrous <0.10g

Integra® 44 MINIMUM INHIBITORY CONCENTRATION (MIC)

BACTERIA ATCC No. Active Ingredient (ppm) Gram-Positive     Bacillus subtilis 6633 300 Staphylococcus aureus 6538 600 Gram-Negative     Enterobacter aerogenes 13048 600 Enterobacter cloacae 33457 300 Escherichia coli 8739 600 Proteus vulgaris 9920 300 Pseudomonas aeruginosa 9027 600 Burkholderia cepacia 25416 450 Pseudomonas fluorescens 13525 300 FUNGI     Aspergillus niger 16404 1200 Candida albicans 10231 2500

Minimum Inhibitory Concentrations are a useful screening procedure for antimicrobial activity, however, they do not necessarily represent antimicrobial activity in finished products. Adequate preservative efficacy can only be assured by running appropriate challenge studies. HANDLING Material may darken with prolonged exposure to elevated temperatures. Do not store above 30°C. Increased color does not diminish the antimicrobial activity. Care should be taken when using fragrances. Citral, for instance, can cause color changes, although the antimicrobial activity is not affected. TOXICOLOGY AND SAFETY Integra® 44 has an extensive safety database available from a large number of studies which overall demonstrated a low level of product toxicity to humans and the environment. Integra 44 was shown to be neither teratogenic, nor mutagenic, and failed to produce evidence of cumulative skin irritation nor allergic contact dermatitis when tested in a human repeated insult patch test panel. Further ecological testing show Integra 44 to be practically non-toxic in standard avian and fresh-water fish and invertebrate species. Integra® 44 Toxicology Summary (Data presented is for 50% active product unless otherwise specified) Acute Oral LD50 in Rats (both sexes) = 2100 mg/kg Acute Dermal LD50 in Rabbits > 2000 mg/kg Primary Eye Irritation in Rabbits: Mildly irritating without washout, non-irritating with washout (5% aqueous solution) Primary Skin Irritation in Rabbits: Non-irritating Dermal Sensitization in Humans: Not a sensitizer (0.5% aqueous solution) Mutagenicity: Non-mutagenic in Salmonella Reverse Mutation Assay (Ames), Chromosomal Aberration Assay, Rat Hepatocyte, Primary Culture / DNA Repair Test. Developmental Toxicity in Rats: Not teratogenic Overall these data show Integra 44 may be safely used as a broad spectrum preservative and biocide for industrial applications.

LIQUID HAND SOAP CHALLENGE TEST

INTEGRA® 44 - CHALLENGE STUDIES 28 DAY CHALLENGE TEST LIQUID HAND SOAP A 28 day challenge study was run to determine the antimicrobial activity of Integra® 44 at levels of 0.2% and 0.4% in a liquid hand soap. Separate samples of the liquid hand soap were tested using selected industrial challenge organisms. Integra 44 at levels of 0.2% and 0.4% showed complete kill of all microorganisms tested in 48 hours and 28 days. The control which did not contain preservative failed the challenge test with bacteria, yeast and mold. LIQUID HAND SOAP FORMULATION

INGREDIENT WEIGHT % Water, deionized 48.8 Sodium lauryl ether sulphate (28%) 40.0 Alkateric® CAB-O (Rhone-Poulenc) 10.0 Surfadone®LP-300 (ISP) 1.0 Integra 44 0.2

Manufacturing Procedure: Mix all ingredients into water until a clear gel forms. Warm as necessary to dissolve ingredients. CHALLENGE ORGANISMS Method MLM 100-9 was followed for this study. The organisms were cultured and the inoculum was prepared and standardized according to procedures MLM 100-3, 4 & f. The inoculum and reinoculum (second value) concentrations were:

S. aureus 6538 7.1x104 CFU/g of product; 4.4x105 CFU/g P. fluorescens 13625 2.7x105 CFU/g of product; 1.5x106 CFU/g P. putida 31800 6.9x106 CFU/g of product; 2.3x106 CFU/g P. vulgaris 9920 9.9x103 CFU/g of product; 5.1x104 CFU/g C. albicans 10231 8.7x104 CFU/g of product; 4.8x104 CFU/g A. niger 16404 3.8x103 CFU/g of product; 2.l x104 CFU/g

CHALLENGE STUDY ON LIQUID HAND SOAP

PRESERVATIVE ASSAY (CFU/g) 48 HOURS 7 DAYS 14 DAYS 21 DAYS 28 DAYS Integra 44 0.20% A. niger 16404 <10 <10 <10 <10 <10 C. albicans 10231 <10 <10 <10 <10 <10 P. fluorescens 13625 <10 <10 <10 <10 <10 P. putida 31800 <10 <10 <10 <10 <10 P. vulgaris 9920 <10 <10 <10 <10 <10 S. aureus 6538 <10 <10 <10 <10 <10

RESULTS All formulations preserved with Integra 44 passed the challenge test as adequately preserved at a low level of 0.20% as supplied.

LIQUID FABRIC SOFTENER CHALLENGE TEST

INTEGRA® 44 - CHALLENGE STUDIES 28 DAY CHALLENGE TEST LIQUID FABRIC SOFTENER A 28 day challenge study was run to determine the antimicrobial activity of Integra® 44 at the level of 0.2% and 0.4% in a liquid fabric softener. Separate samples of the fabric softener were tested using selected industrial challenge organisms. Integra 44 at a level of 0.4% showed complete kill of all microorganisms tested in 7 and 28 days. The control, which did not contain preservative, failed the challenge test with bacteria and mold. LIQUID FABRIC SOFTENER FORMULATION

INGREDIENT WEIGHT % Water, deionized 93.35 Miranol DM (Miranol) 3.00 Arquad 2HT 75 (AKZO) 2.00 Surfadone LP-300 (ISP) 1.00 Fragrance 0.25 Integra 44 0.40

Procedure: Mix all ingredients until uniform. CHALLENGE ORGANISMS The following organisms were cultured, prepared and standardized according to methods MLM 100-3, 4 & 5. The inoculum concentrations are listed as the original inoculum and reinoculum counts.

S. aureus 6538 1.7 x 106 CFU/g of product; 4.4 x 106 CFU/g E. aerogenes 13048 3.9 x 106 CFU/g of product; 3.8 x 106 CFU/g P. vulgaris 9920 1.6 x 106 CFU/g of product; 4.2 x 105 CFU/g P. putida 31800 1.3 x 106 CFU/g of product; 6.5 x 105 CFU/g P. fluorescens 13825 2.2 x 106 CFU/g of product; 2.0 x 106 CFU/g C. albicans 10231 6.3 x 105 CFU/g of product; 2.9 x 106 CFU/g A. niger 16404 2.6 x 104 CFU/g of product; 1.0 x 1010 CFU/g

CHALLENGE STUDY ON LIQUID FABRIC SOFTENER

PRESERVATIVE ASSAY (CFU/g) 48 HOURS 7 DAYS 14 DAYS 21 DAYS 28 DAYS Integra 44 0.20% A. niger 16404 4.0x101 3.0x101 <10 <10 <10 C. albicans 10231 <10 <10 <10 <10 <10 E. aerogenes 13048 <10 <10 <10 <10 <10 P. putida 31800 <10 <10 <10 <10 <10 P. vulgaris 9920 <10 <10 <10 <10 <10 S. aureus 6538 <10 <10 <10 <10 <10 P. fluorescens 13625 <10 <10 <10 <10 <10 Integra 44 0.40% A. niger 16404 1.5x101 <10 <10 <10 <10 C. albicans 10231 <10 <10 <10 <10 <10 E. aerogenes 13048 <10 <10 <10 <10 <10 P. putida 31800 <10 <10 <10 <10 <10 P. vulgaris 9920 <10 <10 <10 <10 <10 S. aureus 6538 <10 <10 <10 <10 <10 P. fluorescens 13625 <10 <10 <10 <10 <10

RESULTS All formulations preserved with Integra 44 passed the challenge test as adequately preserved at a low level of 0.40% as supplied.

LIQUID DISH WASHING DETERGENT CHALLENGE TEST

INTEGRA® 44 - CHALLENGE STUDIES 28 DAY CHALLENGE TEST LIQUID DISH WASHING DETERGENT A 28 day challenge study was run to determine the antimicrobial activity of Integra® 44 at levels of 0.2% and 0.4% in a liquid dish washing detergent. Separate samples of the dish washing detergent were tested using selected industrial challenge organisms. Integra 44 at levels of 0.2% and 0.4% showed complete kill of all microorganisms tested in 48 hours and 28 days. The control which did not contain preservative failed the challenge test with bacteria and mold.

LIQUID DISH WASHING DETERGENT FORMULATION

INGREDIENT WEIGHT % Water, distilled 88.4 Alkylbenzene sulfonic acid 7.3 Alkamide DC 212/S 2.3 NaOH 1.0 NaCI 0.8 Integra 44 0.2

Manufacturing Procedure: To water at room temperature add alkylbenzene sulfonic acid and NaOH with agitation. Mix thoroughly. Add Alkamide DC 212/S. Add NaCI. Adjust pH to 9.2 using 10% NaOH. Add Integra 44. CHALLENGE ORGANISMS The following organisms were cultured, prepared and standardized according to methods MLM 100-3, 4 & 5. The inoculum concentrations are listed as the original inoculum and reinoculum counts.

S. aureus 6538 3.0 x 106 CFU/g of product; 2.2 x 106 CFU/g E. aerogenes 13048 6.1 x 106 CFU/g of product; 5.0 x 106 CFU/g P. vulgaris 9920 2.5 x 106 CFU/g of product; 5.6 x 105 CFU/g P. putida 13625 1.8 x 106 CFU/g of product; 1.1 x 106 CFU/g P. fluorescens 13625 1.1 x 106 CFU/g of product; 7.8 x 106 CFU/g C. albicans 10231 2.5 x 106 CFU/g of product; 1.3 x 106 CFU/g A. niger 16404 1.2 x 105 CFU/g of product; 1.0 x 105 CFU/g

CHALLENGE STUDY ON LIQUID DISH WASHING DETERGENT

PRESERVATIVE ASSAY (CFU/g) 48 HOURS 7 DAYS 14 DAYS 21 DAYS 28 DAYS Integra 44 0.20% A. niger 16404 <10 <10 <10 <10 <10 C. albicans 10231 <10 <10 <10 <10 <10 E. aerogenes 13048 <10 <10 <10 <10 <10 P. putida 31800 <10 <10 <10 <10 <10 P. vulgaris 9920 <10 <10 <10 <10 <10 S. aureus 6538 <10 <10 <10 <10 <10 P. fluorescens 13625 <10 <10 <10 <10 <10

RESULTS All formulations preserved with Integra 44 passed the challenge test as adequately preserved at a low level of 0.20% as supplied.

WATERLESS HAND CLEANER CHALLENGE TEST

INTEGRA® 44 - CHALLENGE STUDIES 28 DAY CHALLENGE TEST WATERLESS HAND CLEANER A 28 day challenge study was run to determine the antimicrobial activity of Integra® 44 at the level of 0.4% in a waterless hand cleaner. Separate samples of the waterless hand cleaner were tested using selected industrial challenge organisms. Integra 44 at the level of 0.4% showed complete kill of all microorganisms tested in seven days. The control which did not contain preservative failed the challenge test with bacteria, yeast and mold. WATERLESS HAND CLEANER FORMULATION

INGREDIENTS WEIGHT % Water, distilled 49.00 Isopar® M (Exxon) 25.00 Sodium hydroxide (10% aqueous) 7.50 Emersol® 233LL (Emery) 7.50 Surfadone® LP-300 (ISP) 3.00 lgepal® CO-730 (Rhone Poulenc) 3.00 Carnation® mineral oil (Carnation) 2.50 Propylene glycol 1.50 Antaron® V-216 (ISP) 0.50 Lanolin, USP 0.10 Integra 44 0.40

Manufacturing Procedure: Phase A Combine water, sodium hydroxide, and propylene glycol and mix until homogeneous. Phase B In a separate vessel gently heat Isopar M, Emersol 233LL, mineral oil, Surfadone LP-300, Antaron V-216, and lanolin to 35-40°C. Use continuous mixing until homogeneous. Add to Phase A and continue mixing. Add Igepal CO-730, Cool to 25-30°C, cover and let stand overnight.

CHALLENGE ORGANISMS

A. niger 16404 2.0x104 CFU/g of product; 8.6x104 CFU/g C. albicans 10231 8.2x105 CFU/g of product; 6.9x104 CFU/g E. aerogenes 13048 3.1x106 CFU/g of product; 1.6x106 CFU/g B. cepacia 25416 3.2x106 CFU/g of product; 4.3x104 CFU/g P. fluorescens 13625 1.4x106 CFU/g of product; 8.8x105 CFU/g S. aureus 6538 2.3x106 CFU/g of product; 1.5x106 CFU/g

CHALLENGE STUDY ON WATERLESS HAND CLEANER

PRESERVATIVE ASSAY (CFU/g) 48 HOURS 7 DAYS 14 DAYS 21 DAYS 28 DAYS Integra 44 0.20% A. niger 16404 <10 <10 <10 <10 <10 C. albicans 10231 <10 <10 <10 <10 <10 E. aerogenes 13048 <10 <10 <10 <10 <10 B. cepacia 25416 <10 <10 <10 <10 <10 P. fluorescens 13625 <10 <10 <10 <10 <10 S. aureus 6538 <10 <10 <10 <10 <10

RESULTS

The formulation preserved with Integra 44 at the level of 0.4% as supplied passed the double challenge test as adequately preserved.

POLYVINLY ACRYLIC LATEX PAINTS CHALLENGE TEST

INTEGRA® 44 - CHALLENGE STUDIES CHALLENGE TEST POLYVINYL ACRYLIC LATEX PAINTS A series of studies were developed to demonstrate the application of Integra® 44 in polyvinyl acrylic latex paints. Both microbiological testing and stability studies were run. The Integra preservative was formulated in a white polyvinyl acrylic interior flat paint based on UCAR Latex 367.

LATEX PAINT FORMULATION

INGREDIENT WEIGHT % Water 13.00 Ethylene Glycol 1.71 Ucar Filmer IBT 0.85 PAG 188 0.34 Cellosize QP-15,000 19.21 AMP-95 0.09 Colloid 111 0.51 Tergitol NP-10 0.26 Ti-Pure R-931 18.78 Satintone No.l 9.39 Snowflake White 10.24 UCAR Latex 367 25.70 Integra 44 0.50

Manufacturing Procedure: Blend half the recommended quantity of water with everything but UCAR Latex 367 and Integra 44. Once materials have been adequately agitated, add the remaining water, UCAR Latex 357 and Integra 44. Disperse at high speed. CHALLENGE ORGANISMS Using ASTM D2574-86, a polyvinyl paint was evaluated using Integra 44 at various concentrations. The material was inoculated with ATCC 10145 culture Pseudomonas aeruginosa. The sample was streaked to tryptone-glucose agar plates, incubated for seven days at 27°C and evaluated. After six weeks the samples were rechallenged with contaminated product, inoculated at 27°C and evaluated after two weeks. RESULTS After one week there were no detectable levels of the test organism in any of the preserved samples. Microbiological growth did persist throughout the study period in the control samples. This indicates that Integra 44, even at the low use level of 0.50% as supplied, is an effective preservative for use in latex paint systems.

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