Mic reduction with lithium ions

Abstract

The invention relates to a process for reducing the minimum inhibitory concentration (MIC) of a biocide against at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould in an aqueous preparation. The invention further relates to the use of a water soluble source of lithium ions for reducing the minimum inhibitory concentration (MIC) of a biocide against at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould in an aqueous preparation.

Claims

1. An aqueous preparation comprising (i) from 15.0 to 800.0 mMol/L, calculated relative to the weight of water in the aqueous preparation, of lithium ions in the water phase of the aqueous preparation, and (ii) at least one biocide, wherein said biocide is selected from phenols, halogenated phenols, isothiazolinones, guanidines, sulfones, thiocyanates, pyrithiones, antibiotics β-lactam antibiotics, quaternary ammonium salts, peroxides, perchlorates, amides, amines, heavy metals, biocidal enzymes, biocidal polypeptides, azoles, carbamates, glyphosates, sulphonamides, 2-bromo-2-nitro-1,3-propanediol, 5-bromo-5-nitro-1,3-dioxane, 2,2-dibrom-3-nitrilpropionamid (DBNPA), 1,2-dibromo-2,4-dicyanobutane, monochloroamine, ammonium bromide, calcium hypochlorite, iodine, tri-iodide, potassium iodate, and any mixture thereof; and said biocide being effective against at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould, wherein the lithium ions are present in a greater than stoichiometric ratio in relation to the biocide, (iii) at least one inorganic particulate material, and (iv) optionally at least one organic material selected from carbohydrates, glycerol, hydrocarbons and mixtures thereof; and wherein the aqueous preparation comprises the at least one biocide in an amount such that the minimum inhibitory concentration (MIC) of the at least one biocide against the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould fulfils the equation (I)
MIC.sub.withoutLi/MIC.sub.Li≥1.1  (I) wherein MIC.sub.withoutLi is the minimum inhibitory concentration (MIC) of the at least one biocide against the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould without the water soluble lithium ions in ppm, calculated relative to the weight of water in the aqueous preparation, MIC.sub.Li is the minimum inhibitory concentration (MIC) of the at least one biocide against the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould with the water soluble lithium ions in ppm, calculated relative to the weight of water in the aqueous preparation; and wherein the at least one biocide is free of aldehyde-releasing and/or aldehyde-based biocides.

2. The aqueous preparation according to claim 1, wherein the aqueous preparation comprises the at least one biocide in an amount such that the minimum inhibitory concentration (MIC) of the at least one biocide against the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould meets equation (Ia), or equation (Ib), or equation (Ic):
MIC.sub.withoutLi/MIC.sub.Li≥1.5  (Ia)
MIC.sub.withoutLi/MIC.sub.Li≥2.0  (Ib)
MIC.sub.withoutLi/MIC.sub.Li≥4.0  (Ic) wherein MIC.sub.withoutLi is the minimum inhibitory concentration (MIC) of the at least one biocide against the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould without the water soluble lithium ions in ppm, calculated relative to the weight of water in the aqueous preparation, MIC.sub.Li is the minimum inhibitory concentration (MIC) of the at least one biocide against the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould with the water soluble lithium ions in ppm, calculated relative to the weight of water in the aqueous preparation.

3. The aqueous preparation according to claim 1, wherein the aqueous preparation further comprises at least one organic material selected from carbohydrates, glycerol, hydrocarbons and mixtures thereof.

4. The aqueous preparation according to claim 1, wherein the aqueous preparation has a solids content of up to 85.0 wt.-%, based on the total weight of the aqueous preparation.

5. The aqueous preparation according to claim 1, wherein the at least one strain of bacteria is selected from the group consisting of gram-negative bacteria, gram-positive bacteria and mixtures thereof.

6. The aqueous preparation according to claim 1, wherein (i) the at least one strain of bacteria is selected from the group comprising Methylobacterium sp., Salmonella sp., Escherichia sp. Shigella sp., Enterobacter sp., Pseudomonas sp. Bdellovibrio sp., Agrobacterium sp., Alcaligenes sp., Flavobacterium sp., Rhizobium sp., Sphingobacterium sp., Aeromonas sp., Chromobacterium sp., Vibrio sp., Hyphomicrobium sp., Leptothrix sp., Micrococcus sp., Staphylococcus sp. Agromyces sp., Acidovorax sp., and mixtures thereof, and/or (ii) the at least one strain of yeast is selected from the group comprising Saccharomycotina, Taphrinomycotina, Schizosaccharomycetes, Basidiomycota, Agaricomycotina, Tremellomycetes, Pucciniomycotina, Microbotryomycetes, Candida sp., Yarrowia sp., Cryptococcus sp., Zygosaccharomyces sp., Rhodotorula sp., and mixtures thereof, and/or (iii) the at least one strain of mould is selected from the group comprising of Acremonium sp., Alternaria sp., Aspergillus sp., Cladosporium sp., Fusarium sp., Mucor sp., Penicillium sp., Rhizopus sp., Stachybotrys sp., Trichoderma sp., Dematiaceae sp., Phoma sp., Eurotium sp., Scopulariopsis sp., Aureobasidium sp., Monilia sp., Botrytis sp., Stemphylium sp., Chaetomium sp., Mycelia sp., Neurospora sp., Ulocladium sp., Paecilomyces sp., Wallemia sp., Curvularia sp., and mixtures thereof.

7. The aqueous preparation according to claim 1, wherein the at least one biocide is selected to be: (i) in an amount of at least 9%, below the minimum inhibitory concentration (MIC) of the at least one biocide for the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould, and/or (ii) in an amount of from 0.5 ppm to 6000 ppm, calculated relative to the weight of water in the aqueous preparation.

8. The aqueous preparation according to claim 1, wherein the at least one biocide is selected to be in an amount of at least 33%, below the minimum inhibitory concentration (MIC) of the at least one biocide for the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould.

9. The aqueous preparation according to claim 1, wherein the at least one biocide is selected to be in an amount of at least 50%, below the minimum inhibitory concentration (MIC) of the at least one biocide for the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould.

10. The aqueous preparation according to claim 1, wherein the at least one biocide is selected to be in an amount of at least 75%, below the minimum inhibitory concentration (MIC) of the at least one biocide for the at least one strain of bacteria and/or at least one strain of yeast and/or at least one strain of mould.

11. The aqueous preparation according to claim 1, wherein the at least one inorganic particulate material is selected from natural ground calcium carbonate, natural and/or synthetic precipitated calcium carbonate, dolomite, kaolin, talcum, aluminium hydroxide, aluminium silicate, titanium dioxide and mixtures thereof.

12. The aqueous preparation according to claim 11, wherein the at least one inorganic particulate material comprises natural ground calcium carbonate and/or synthetic precipitated calcium carbonate.

13. The aqueous preparation according to claim 1, wherein the aqueous preparation has (i) a pH value of from 6 to 12, and/or (ii) a solids content of from 10.0 to 82.0 wt.-%, based on the total weight of the aqueous preparation.

14. The aqueous preparation according to claim 1, wherein the aqueous preparation has (i) a pH value of from 7 to 10.5; and/or (ii) a solids content of from 20.0 to 80.0 wt.-%, based on the total weight of the aqueous preparation.

15. The aqueous preparation according to claim 1, wherein the aqueous preparation has (i) a pH value of from 2 to 12; and/or (ii) a solids content of from 20.0 to 80.0 wt.-%, based on the total weight of the aqueous preparation.

16. The aqueous preparation according to claim 1, wherein the aqueous preparation has (i) a pH value of from 7 to 10.5; and/or (ii) a solids content of from 10.0 to 82.0 wt.-%, based on the total weight of the aqueous preparation.

17. The aqueous preparation according to claim 1, wherein the aqueous preparation has (i) a pH value of from 6 to 12; and/or (ii) a solids content from 20.0 to 80.0 wt.-%, based on the total weight of the aqueous preparation.

18. The aqueous preparation according to claim 1, wherein the total amount of lithium ions is selected from 15.0 to 700.0 mMol/L, calculated relative to the weight of water in the preparation.

19. The aqueous preparation according to claim 1, wherein the aqueous preparation is a suspension, a slurry, or a dispersion.

Description

EXAMPLES

(1) Measurement Processes

(2) The following measurement processes were used to evaluate the parameters given in the examples and claims.

(3) BET Specific Surface Area of a Material

(4) The BET specific surface area was measured via the BET process according to ISO 9277 using nitrogen.

(5) Particle Size Distribution (Mass % Particles with a Diameter<X) and Weight Median Diameter (d.sub.50) of a Particulate Material

(6) Weight median grain diameter and grain diameter mass distribution of a particulate material were determined via the sedimentation process, i.e. an analysis of sedimentation behaviour in a gravitational field. The measurement was made with a Sedigraph™ 5100 of Micromeritics Instrument Corporation.

(7) The method and the instrument are known to the skilled person and are commonly used to determine grain size of fillers and pigments. The measurement is carried out in an aqueous solution of 0.1 wt % Na.sub.4P.sub.2O.sub.7. The samples are dispersed using a high speed stirrer and supersonics.

(8) pH Measurement

(9) The pH of the water samples is measured by using a standard pH-meter at approximately 25° C.

(10) Brookfield-Viscosity

(11) All Brookfield-viscosities are measured with a Brookfield DV-II Viscometer equipped with a LV-3 spindle at a speed of 100 rpm and room temperature

(12) (20±3° C.).

(13) Amounts of Biocide and Lithium

(14) All biocide and lithium amounts quoted in ppm represent mg values per kilogram of water in the aqueous preparation. Lithium ion concentrations are further quoted in mMol/L (millimol per litre) or mM (millimolar) according to the International System of Units in the water of the aqueous preparation.

(15) Bacterial Count

(16) When not otherwise indicated, the quoted bacterial counts (values are in cfu/plate) in the Tables here below are determined after 2 days following plate-out and incubation at 30° C. The counting method was as follows. The aqueous preparations were stirred well with a cotton swap (e.g. Applimed SA, No. 1102245); the excess aqueous preparation was removed by dipping it gently to the side of the aqueous preparation container, leaving approximately 200 mg of aqueous preparation on the swap. Then three even streaks were made on a tryptic soy agar plate (TSA, prepared using BD 236950) from right to left and three more from top to bottom. TSA plates were then incubated for 48 h at 30° C. Colony forming units (cfu) were then counted and reported as cfu/plate. Counts from 100 to 999 cfu per plate are reported as ≥100 cfu/plate. Counts of 1000 cfu and above per plate are reported as ≥1000 cfu/plate. Yeast and moulds were counted as described for bacteria with the following exceptions, a) Sabouraud Dextrose Agar (SDA) containing Chloramphenicol (e.g. heipha Dr. Miller GmbH, No. 1460030020) were used instead of TSA, b) SDA plates were incubated at 25° for 5 days and c) cfu were counted and reported after 48 h and 5 days of incubation. Yeast and moulds counts from 20 to 99 cfu per plate are reported as 220 cfu/plate. Yeast and moulds counts of 100 cfu and above per plate are reported as >100 cfu/plate.

(17) Solids Content

(18) The solids content is measured using a Moisture Analyzer of Mettler-Toledo MJ33. The method and the instrument are known to the skilled person.

(19) Minimum Inhibitory Concentration (MIC)

(20) For determining the MIC, the tested microorganism, i.e. the strain of bacteria and/or strain of yeast and/or strain of mould, were freshly grown until the end of the logarithmic growth phase according to the requirements of the individual species to a density of approximately 10.sup.7-10.sup.9 cells/ml.

(21) For example, fresh bacteria cultures of the bacteria E. coli, e.g. E. coli ATCC 11229, and S. aureus, e.g. S. aureus strains DSMZ 346, were prepared by inoculation of 3 ml liquid growth media (tryptic soy broth, e.g. Fluka Cat. No. 22092) from a stock culture and incubation for 16 to 20 h at 30° C. with agitation at 150 rotations per minutes (rpm) leading to a cell density of approximately 2×10.sup.8 cells/ml. Fresh cultures of resistant bacteria, adapted to the conditions in biocide containing CaCO.sub.3 slurries, were prepared by inoculation of 50 g 75 wt.-% solid content CaCO.sub.3 slurry from a stock culture and incubated for 14 to 28 days at 30° C. without agitation. The slurry contained the corresponding biocides to which the strains are resistant at the concentrations described herebelow. rOmyAK, is a Pseudomonas mendocina strain resistant to a biocide mixture of 750 ppm 1,6-Dihydroxy-2,5-dioxane (CAS NO. 3586-55-8) and 19 ppm CMIT/MIT (CAS NO. 55965-84-9). rOPP, is a Pseudomonas mendocina strain resistant to 660 ppm 2-phenylphenol (OPP) (CAS NO 90-43-7). rGDA/IT, is a Pseudomonas mendocina strain resistant to a biocide mixture of 340 ppm glutaraldehyde (CAS NO. 111-30-8) and 20 ppm CMIT/MIT (CAS NO. 55965-84-9).

(22) Lithium ions were added to the aqueous preparation (e.g. CaCO.sub.3 slurry) by the addition of a water soluble lithium salt. For example to 50 g CaCO.sub.3 slurry with a solid content of 75% (w/w) 1.177 ml of a 74 g/Li.sub.2CO.sub.3 suspension was added and mixed well leading to a lithium ion concentration of 172 mM or 1205 ppm in the water phase. As another example to 50 g CaCO.sub.3 slurry with a solid content of 75 wt.-% (w/w) 0.04 ml of a 292 g/L Li.sub.3Citrate (2M) solution was added and mixed well leading to a lithium ion concentration of 19 mM or 135 ppm in the water phase.

(23) The biocide to be tested was added to the aqueous preparation (e.g. CaCO.sub.3 slurry with or without lithium ions) in increasing concentrations starting from 0 ppm (without biocide). The concentrations ranged from concentrations higher than recommended by the supplier, to very low amounts (as low as 1 ppm or lower). Of each biocide concentration a 3 ml sample of aqueous preparation was combined with 20 μl fresh bacterial culture.

(24) If a curative MIC was tested, the bacteria were added to the aqueous preparation before the biocide and the lithium was added, using 20 μl of a fresh bacterial culture per 3 ml of aqueous preparation or 0.1 ml of a fresh culture of resistant bacteria from a slurry per 3 ml of aqueous preparation.

(25) All samples were incubated at 30° C. for 24 h. After incubation colony forming units (cfu) per plate (cfu/plate) were determined as described above under bacterial count.

(26) The MIC for bacteria is defined as the lowest concentration of biocide in the presence or absence of lithium ion amongst all samples tested, where the bacterial concentration dropped below 100 cfu/plate. The MIC for yeast and mould is defined as the lowest concentration of biocide in the presence or absence of lithium ion amongst all samples tested, where the microbial concentration dropped below 20 cfu/plate. The test was valid only, if the sample without biocide showed more than 100 cfu/plate for bacteria and more than 20 cfu/plate for yeast and mould. If none of the samples containing the respective biocide dropped below 100 cfu/plate for bacteria and below 20 cfu/plate for yeast and mould the MIC was reported as >highest biocide concentration tested (e.g. >1000 ppm).

Example 1: Preparation of Calcium Carbonate Slurries

(27) An aqueous slurry of calcium carbonate (Italian marble; d.sub.50=10 μm; 21 wt.-%<2 μm) was prepared at 75 wt.-% solid content. The slurry was wet ground at 95° C. using 0.6 wt.-% in respect to dry solids material of a sodium/calcium neutralized polyacrylate grinding agent (Mw 6 000) in a 2001 vertical ball mill to a final particle size distribution of d.sub.50=0.7 μm; 90 wt.-%<2 μm.

Example 2: MIC Determination and Reduction

(28) The determination of the minimum inhibitory concentration (MIC) for various biocides in the absence of lithium ions and the corresponding MIC reduction of the respective biocide in the presence of lithium ions against strains of various bacterial species are summarized in Tables 1 to 4 here below. The tests were carried out with differing biocide concentrations at constant lithium ion concentration. Numbers indicate cfu/plate.

(29) TABLE-US-00001 TABLE 1 Testing the MIC of MIT (CAS NO 2682-20-4) in the presence and absence of lithium ions against the bacterial strain rOmy AK no 18 ppm 35 ppm 106 ppm rOmy AK MIT MIT MIT MIT 329 mM Li.sup.+ ≥1000 ≥100  68 0 no Li.sup.+ ≥1000 ≥1000 ≥100 0

(30) The MIC for bacteria was defined as the lowest concentration of biocide in the presence or absence of lithium ions amongst all samples tested, where the bacterial concentration dropped below 100 cfu/plate. As can be gathered from Table 1, the minimum inhibitory concentration (MIC) of MIT against the rOmy AK strain is clearly above 35 ppm MIT when the biocide is implemented alone at the listed amount, i.e. in the absence of lithium ions, the MIC.sub.withoutLi is 106 ppm. The results also show that when lithium ions are provided alone via the addition of Li.sub.2CO.sub.3, they have no antimicrobial effect on the rOmy AK strain. However, if the biocide is implemented in combination with lithium ions, the MIC.sub.Li of MIT against the rOmy AK strain is reduced to 35 ppm MIT.

(31) TABLE-US-00002 TABLE 2 Testing the MIC of 4-chloro-3-methylphenol (CAS NO 59-50-7) in the presence and absence of lithium ions against the bacterial E. coli strain ATCC11229 no 88.5 ppm 177 ppm 354 ppm E. coli 4-chloro-3- 4-chloro-3- 4-chloro-3- 4-ch1oro-3- A.TCC11229 methylphenol methylphenol methylphenol methylphenol 197 mM/Li.sup.+ ≥100 ≥100  23 0 no Li.sup.+ ≥1000 ≥1000 ≥100 0

(32) As can be gathered from Table 2, the minimum inhibitory concentration (MIC) of 4-chloro-3-methylphenol against the E. coli strain is clearly above 177 ppm 4-chloro-3-methylphenol when the biocide is implemented alone at the listed amount, i.e. in the absence of lithium ions, the MIC.sub.withoutLi is 354 ppm. The results also show that when lithium ions are provided alone via the addition of Li.sub.2CO.sub.3, they have no antimicrobial effect on the E. coli strain. However, if the biocide is implemented in combination with lithium ions, the MIC.sub.Li of 4-chloro-3-methylphenol against the E. coli strain is reduced to 177 ppm 4-chloro-3-methylphenol.

(33) TABLE-US-00003 TABLE 3 Testing the MIC of a CMIT/MIT (CAS NO. 55965-84-9) mixture (weight ratio: 3:1) in the presence and absence of lithium ions against the bacterial S. aureus strain DSMZ 346 S. aureus no 7 ppm 14 ppm 28 ppm DSMZ 346 CMIT/MIT CMIT/MIT CMIT/MIT CMIT/MIT 197 mM Li.sup.+ ≥1000 30 0 0 no Li.sup.+ ≥1000 ≥100 ≥100 87

(34) As can be gathered from Table 3, the minimum inhibitory concentration (MIC) of CMIT/MIT against the S. aureus strain is clearly above 14 ppm CMIT/MIT when the biocide is implemented alone at the listed amount, i.e. in the absence of lithium ions, the MIC.sub.withoutLi is 28 ppm. The results also show that when lithium ions are provided alone via the addition of Li.sub.2CO.sub.3, they have no antimicrobial effect on the S. aureus strain. However, if the biocide is implemented in combination with lithium ions, the MIC of CMIT/MIT against the S. aureus strain is reduced to 7 ppm CMIT/MIT.

(35) TABLE-US-00004 TABLE 4 Testing the MIC of a Sodium pyrithione (CAS NO 3811-73-2) in the presence and absence of lithium ions against the bacterial S. aureus strain DSMZ 346 S. aureus Sodium pyrithione DSMZ 75 150 300 600 900 346 no ppm ppm ppm ppm ppm 96 mM ≥1000 ≥100 93 12 0 0 no Li.sup.+ ≥1000 ≥1000 ≥100 ≥100 ≥100 ≥100

(36) As can be gathered from Table 4, the minimum inhibitory concentration (MIC) of sodium pyrithione against the S. aureus strain is clearly above 900 ppm sodium pyrithione when the biocide is implemented alone at the listed amount, i.e. in the absence of lithium ions, the MIC.sub.withoutLi is >900 ppm. The results also show that when lithium ions are provided alone via the addition of lithium citrate, they have no antimicrobial effect on the S. aureus strain. However, if the biocide is implemented in combination with these lithium ions, the MIC.sub.Li of sodium pyrithione against the S. aureus strain is reduced to 150 ppm sodium pyrithione.

Example 3: MIC Reduction for Various Biocides

(37) The MIC reduction of the tested biocides in the presence of lithium ions against strains of various bacterial species are summarized in Table 5 here below. The tests were carried out with differing biocide concentrations, differing lithium ion concentrations and differing sources of lithium ions as described in the Table 5.

(38) It is shown in Table 5 that the presence of lithium ions reduces the MIC of the tested biocides. In particular, the MIC reduction is expressed by a MIC ratio (MIC.sub.without Li/MIC.sub.Li) of ≥1.1.

(39) TABLE-US-00005 TABLE 5 Analysis of the MIC reduction for various biocides Li.sup.+ conc./aequeous MIC active/aequeous MIC Li.sup.+ Biocide/Active Strain mM ppm mM ppm ratio * source/remark 1,6-Dihydroxy-2,5-dioxane rOmyAK no Li.sup.+ no Li.sup.+ 3.1 >1593 — Li.sub.2CO.sub.3 (CAS NO. 3586-55-8) Li.sup.+ 197 Li.sup.+ 1380 8.7 1062 >1.5 Li.sup.+ 423 Li.sup.+ 2964 5.8 708 >2.25 Ampicilin E. coli no Li.sup.+ no Li.sup.+ 0.016 5.7 — Li.sub.2CO.sub.3 (CAS NO 69-53-4) Li.sup.+ 423 Li.sup.+ 2964 0.001 0.4 16 Benzisothiazolinone (BIT) S. aureus no Li.sup.+ no Li.sup.+ >4.7 >708 — Li.sub.2CO.sub.3 (CAS NO 2634-33-5) Li.sup.+ 423 Li.sup.+ 2964 2.3 354 >2 S. aureus no Li.sup.+ no Li.sup.+ 7.94 1200 — Li.sub.2CO.sub.3/Curative treatment Li.sup.+ 329 Li.sup.+ 2305 3.97 600 2 Bronopol E. coli no Li.sup.+ no Li.sup.+ 0.53 106.2 — Li.sub.2CO3 (CAS NO 52-51-7) Li.sup.+ 197 Li.sup.+ 1380 0.18 35.4 3 E. coli no Li.sup.+ no Li.sup.+ >0.45 >90 — Li.sub.2CO.sub.3 Li.sup.+ 172 Li.sup.+ 1205 0.12 24 >3.75 S. aureus no Li.sup.+ no Li.sup.+ 0.90 180 — Li.sub.2CO.sub.3 Li.sup.+ 197 Li.sup.+ 1380 0.45 90 2 Li.sup.+ 329 Li.sup.+ 2305 0.15 30 6 Li.sup.+ 423 Li.sup.+ 2964 0.05 9 20 S. aureus no Li.sup.+ no Li.sup.+ 0.90 180 — Li.sub.2CO.sub.3 Li.sup.+ 172 Li.sup.+ 1205 0.15 30 6 4-Chloro-3-methylphenol E. coli no Li.sup.+ no Li.sup.+ 2.48 354 — Li.sub.2CO.sub.3 (CAS NO 59-50-7) Li.sup.+ 197 Li.sup.+ 1380 1.24 177 2 Li.sup.+ 329 Li.sup.+ 2305 0.62 88.5 4 S. aureus no Li.sup.+ no Li.sup.+ 3.72 531 — Li.sub.2CO.sub.3 Li.sup.+ 423 Li.sup.+ 2964 2.48 354 1.5 CMIT/MIT (weight ratio 3:1) S. aureus no Li.sup.+ no Li.sup.+ 0.11 28.32 — Li.sub.2CO.sub.3 (CAS NO 55965-84-9) Li.sup.+ 197 Li.sup.+ 1380 0.03 7.08 4 Li.sup.+ 329 Li.sup.+ 2305 <0.03 <7.08 >4 S. aureus no Li.sup.+ no Li.sup.+ >0.23 >60 — Li.sub.2CO.sub.3/Curative treatment Li.sup.+ 423 Li.sup.+ 2964 0.11 30 >2 3.5-Dimethyltetrahydro-1,3,5- E. coli no Li.sup.+ no Li.sup.+ 1.09 177 — Li.sub.2C.sub.3O thiadiazine-2- Li.sup.+ 329 Li.sup.+ 2305 0.87 141.6 1.25 (CAS NO 533-74-4) S. aureus no Li.sup.+ no Li.sup.+ >1.09 >177.4 — Li.sub.2CO.sub.3 Li.sup.+ 423 Li.sup.+ 2964 0.44 70.8 >2.5 Formaldehyde rOmyAK no Li.sup.+ no Li.sup.+ >35.4 >1062 — Li.sub.2CO.sub.3 (CAS NO 50-00-0) Li.sup.+ 197 Li.sup.+ 1380 11.8 354 >3 E. coli no Li.sup.+ no Li.sup.+ >1.18 >35.4 — Li.sub.2CO.sub.3 Li.sup.+ 197 Li.sup.+ 1380 0.59 17.7 >2 S. aureus no Li.sup.+ no Li.sup.+ >1.18 >35.4 — Li.sub.2CO.sub.3 Li.sup.+ 197 Li.sup.+ 1380 0.118 3.54 >10 Glutaraldehyde S. aureus no Li.sup.+ no Li.sup.+ >0.35 >35.4 — Li.sub.2CO.sub.3 (CAS NO. 111-30-8) Li.sup.+ 197 Li.sup.+ 1380 0.04 3.54 >10 Guanidinedodecyl monochloride E. coli no Li.sup.+ no Li.sup.+ >0.13 >35.4 — Li.sub.2CO.sub.3 (CAS NO 13590-97-1) Li.sup.+ 197 Li.sup.+ 1380 0.05 14.16 >2.4 Hexachlorodimethyl sulfone E. coli no Li.sup.+ no Li.sup.+ 0.12 35.4 — Li.sub.2CO.sub.3 (CAS NO 3064-70-8) Li.sup.+ 197 Li.sup.+ 1380 0.07 21.24 1.67 S. aureus no Li.sup.+ no Li.sup.+ 0.09 28.32 — Li.sub.2CO.sub.3 Li.sup.+ 329 Li.sup.+ 2305 0.07 21.24 1.33 Methylene bis(thiocyanate) S. aureus no Li.sup.+ no Li.sup.+ 2.18 283.2 — Li.sub.2CO.sub.3 (CAS NO 6317-18-6) Li.sup.+ 329 Li.sup.+ 2305 0.54 70.8 4.04 2-Methyl-2H-isothiazolin-3-one rGDA-IT no Li.sup.+ no Li.sup.+ 1.54 177 — Li.sub.2CO.sub.3 (MIT) Li.sup.+ 197 Li.sup.+ 1380 0.92 106.2 1.67 (CAS NO 2682-20-4) rOmyAK no Li.sup.+ no Li.sup.+ 0.92 106.2 — Li.sub.2CO.sub.3 Li.sup.+ 197 Li.sup.+ 1380 0.92 106.2 1 Li.sup.+ 329 Li.sup.+ 2305 0.31 35.4 3 Li.sup.+ 423 Li.sup.+ 2964 0.15 17.7 6 E. coli no Li.sup.+ no Li.sup.+ >1.54 >177 — Li.sub.2CO.sub.3 Li.sup.+ 197 Li.sup.+ 1380 0.61 70.8 >2.5 S. aureus no Li.sup.+ no Li.sup.+ >1.54 >177 — Li.sub.2CO.sub.3 Li.sup.+ 329 Li.sup.+ 2305 <0.31 <35.4 >5 Sodium pyrithione E. coli no Li.sup.+ no Li.sup.+ 3.56 531 — Li.sub.2CO.sub.3 (CAS NO 3811-73-2) Li.sup.+ 197 Li.sup.+ 1380 1.19 177 3 S. aureus no Li.sup.+ no Li.sup.+ >4.75 >7.8 — Li.sub.2CO.sub.3 Li.sup.+ 423 Li.sup.+ 2964 2.37 354 >2 S. aureus no Li.sup.+ no Li.sup.+ >6.04 >900 — Li3Citrate Li.sup.+ 19 Li.sup.+ 135 2.01 300 >3 Li.sup.+ 96 Li.sup.+ 670 1.01 150 >6 2-Phenylphenol (OPP) rOPP no Li.sup.+ no Li.sup.+ >9.36 >1539 — Li.sub.2CO.sub.3 (CAS NO 90-43-7) Li.sup.+ 197 Li.sup.+ 1380 2.08 354 >4.5 Li.sup.+ 329 Li.sup.+ 2305 1.04 177 >9 rOPP no Li.sup.+ no Li.sup.+ 0.53 90 — Li.CO.sub.3 Li.sup.+ 172 Li.sup.+ 1205 0.26 45 2 E. coli no Li.sup.+ no Li.sup.+ 3.12 531 — Li.sub.2CO.sub.3 Li.sup.+ 197 Li.sup.+ 1380 2.08 354 1.5 S. aureus no Li.sup.+ no Li.sup.+ 1.76 300 — Li.sub.2CO.sub.3 Li.sup.+ 53 Li.sup.+ 370 0.88 150 2 S. aureus no Li.sup.+ no Li.sup.+ 1.76 300 — LiOH Li.sup.+ 67 Li.sup.+ 470 0.18 30 10 Biocide mixture (25% (w/w) rGDA-IT no Li.sup.+ no Li.sup.+ N/A >1593 — Li.sub.2CO.sub.3 glutaraldehyde (CAS NO. 111-30- Li.sup.+ 197 Li.sup.+ 1380 N/A 1239 >1.29 8) and 1.5% (w/w) CMIT/MIT Li.sup.+ 329 Li.sup.+ 2305 N/A <177 >9 (weight ratio CMIT/MIT 3:1) E. coli no Li.sup.+ no Li.sup.+ N/A 177 — Li.sub.2CO.sub.3 (CAS NO. 55965-84-9) Li.sup.+ 197 Li.sup.+ 1380 N/A 70.8 2.5 Li.sup.+ 329 Li.sup.+ 2305 N/A 17.7 10 S. aureus no Li.sup.+ no Li.sup.+ N/A 354 — Li.sub.2CO.sub.3 Li.sup.+ 197 Li.sup.+ 1380 N/A 35.4 10 Polyethoxyethoxyethylguanidinium E. coli no Li.sup.+ no Li.sup.+ >0.71 >708 — Li.sub.2CO.sub.3 hexachloride Li.sup.+ 197 Li.sup.+ 1380 0.53 531 >1.33 (CAS NO 374572-91-5) Li.sup.+ 423 Li.sup.+ 2964 0.09 88.5 >8 * MIC.sub.without Li/MIC.sub.Li