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Meeting Summary 

EPA/U.S. Silver Task Force/Zeolite Registrants Meeting 

October 5, 2010, 10:00 AM to 11:30 AM 

Room S-8100, 2777 S. Crystal Drive, Arlington, VA 22202 

Participants

U.S. Silver Task Force/Zeolite Registrants: Joe Hayes, Gary Burin, Erik R. Janus, Erin 

Tesch, Paul Ford, Javier Takahashi 

EPA: A. Najm Shamim, Nader Elkassabany, Tim Leighton, Mark Hartman, Seiichi 

Murasaki, Talia Lindheimer, Abigail Downs, Rebecca von dem Hagen, William Hazel, 

Tim McMahon, Jonathan Chen, Earl Goad, Jenny Tao, Steven Malish, Jim Breithaupt, 

Lance Wormell 

Summary

On Tuesday, October 5, 2010, members of AD’s silver registration review team and the 

silver zeolite work group hosted a meeting with the US Silver Task Force (STF) zeolite 

antimicrobial registrants (AgION Technologies, Sinanen Inc., BASF Corporation, and 

Fuji Chemical). The STF/zeolite antimicrobial registrants requested this meeting to 

discuss the possibility of bridging available data between the antimicrobial zeolites 

including silver, zinc, silver zinc and silver copper zeolites, all of which are manufactured 

from zeolite A, a material widely used in household detergents. During the meeting, the 

STF/zeolite registrants presented an overview of zeolite A and highlights of a previously 

submitted white paper on available chemistry and toxicology data for zeolites and zeolitebased antimicrobial products. 

Next Steps

Prior to issuing the data call-ins associated with the silver registration review case, EPA 

will make a determination on whether or not to bridge available data between the 

antimicrobial zeolites. 
Zeolite-Based Antimicrobials

Chemistry, Toxicology, Exposure

Registrants of Zeolite-Based Products 

on the U.S. Silver Task Force

Environmental Protection Agency Meeting

October 5, 2010

Washington, DC
Items for Discussion

Zeolite

• Zeolite structure & 

chemistry

• Zeolite A 

Antimicrobials

• Silver zeolites & 

silver salts

• Elution of metals

Toxicity

• Zeolite A

• Silver,copper,zinc

• Zeolite-based 

antimicrobials

Exposure

Summary
Al3+

Tetrahedrons

Oxygen

Aluminum

Silicon

Symbol Element

Si4+

Central (metal) atoms referred to as “T” atoms; structure sometimes called “TO4.”

Rules:

One external cation 

needed for each Al

Two Al may not share 

an O (Loewenstein)

Therefore Al ≤ Si
Aluminosilicates

Form Type CAS # Structure (example)

Phylloaluminosilicates

Layered Clays

1302-78-9,

1318-93-0,

etc.

Tectoaluminosilicates

Cage-like: 

All oxygens 

link two 

metals

Zeolites 1318-02-1

1344-00-9

Amorphous

aluminosilicatesAmorphous

Silicic acid, 

sodium aluminum 

salt;

Aluminum 

sodium dioxido 

(oxo) silane; etc.

Amorphous; anti-caking agents, 

etc.
• Over 40 natural minerals

• Numerous synthetic zeolites

• Over 190 possible frameworks

Natrolite Heulandite Stilbite

Many Zeolites Exist
Structure of Sodalite Cell

(basic structure of Zeolite A)

Generalized model. Green: aluminum or silicon; yellow: oxygen. Tetrahedrons shown 

on left, omitted on right. Adsorbed cations and water omitted. 
β-cage (SOD cell)

Link Oxygen)

16

+

16/2

Oxygen

Aluminum 12

Silicon 12

Symbol Element #
Structure of Zeolite A

a

b

c

d

Structure of Zeolite A (LTA). Oxygen, adsorbed water, and cations omitted. (a) SOD sub-structure, 

with 24 “T” atoms. (b), (c), and (d): increasingly consolidated structures. Dashed red lines show 

position of one four-T-atom group in each of the sketches. Pore opening (dotted green arrows) 

about 4.2 Å dia., opens into 11.4 Å diameter α cavity.
Largest Application for

Zeolite A

(“sodium aluminosilicate”):

Softens wash water by ion 

exchange (Na+ for Ca++ 

and Mg++)

Replaced phosphates (TPP) in 

powdered detergents

Detergent Builders: 

>>1,000,000 tons/year 

(1990’s)

Antimicrobials: 

~100 tons/year

Tide Coldwater Powder Detergent Ingredients

Ingredients By Prominence

Fresh Scent

Sodium Aluminosilicate

Sodium Carbonate 

Alkyl Sulfate 

Water 

Sodium Sulfate 

Linear Alkylbenzene Sulfonate 

Sodium Percarbonate 

Nonanoyloxybenzenesulfonate 

Sodium Polyacrylate 

Polyethylene Glycol 4000 

Diethylenetriamine Pentaacetate 

(Sodium Salt)

Fragrance 

Palmitic Acid 

Protease 

Disodium Diaminostilbene

Disulfonate 

FD&C Blue 1 

Silicone 

Sodium Aluminosilicate

is an additive which captures 

hardness from the wash water.

Source: http://www.tide.com/en-US/product/tide-coldwater-powder.jspx

Widespread Use in Detergents
History of Zeolite-Based 

Antimicrobials

• Conceived by Zenji Hagiwara (Japan), early 1980’s

– Patent priority 1/21/1983 (Japan)

– US patents 4,775,585; 4,911,898; and 4,911,899

• Development by two Japanese companies, still the 

only manufacturers, both from zeolite A

– Sinanen (makes its own zeolite)

– Kanebo, now Fuji Chemical (contracts manufacture)

• US Registrations from 1990’s

– Kanebo from 7/2/93

– Sinanen from 5/13/99

• Partners for US and European markets:

– Sinanen / AgION

– Kanebo (Fuji) / Ciba (BASF)
Silver Ion Antimicrobials

• Advantages:

– Silver is found in environment and human body.

– Does not elicit resistance.

– Toxic to prokaryotes, generally inactive against 

eukaryotes.

• Problem:

– Incompatible with organic polymers.

• Resolution:

– Use zeolite as an inert, inorganic carrier to put 

silver ions into organic matrices.
Why Zeolite A for Antimicrobials?

• Maximal weight capacity (Al:Si = 1:1)

– One exchange cation for each Al

• Large cavities (α 11.2 Å; β 6.6 Å)

– 12 cations, 27 H2O per unit

• Small window size (4.2 Å)

– Controlled slow rate of elution

• Beveled crystal edges

– Good blending in matrix, low abrasion

• Simple chemistry, stable quality

– Manmade inorganic material

• Benign, ubiquitous, economical

– Widespread use in detergents

α

β
Conversion to Antimicrobials

• Production of antimicrobials from zeolite 

A is a simple soaking process.

• Salts of the selected cations (Ag, Zn, 

Cu, NH4, etc.) are added to an acidified 

slurry of zeolite A in deionized water.

• When ion exchange (replacing sodium) 

is complete the slurry is rinsed, filtered, 

dried, and packaged.
Discoloration

• Problem:

– Sodium (Na+) in zeolite A may exchange with aqueous H+.

– The resulting alkaline surface environment promotes:

Ag+ + OH- => AgOH

AgOH + Ag+ => Ag2O + H+

[AgO2is brown/black, insoluble]

• Techniques to reduce discoloration:

– Low pH during manufacture

– Mask with white pigments

– Using Ag-Cu zeolite for “bluing” [USP 7,645,824 to AgION]

• Zn++ and Cu++ to limit residual sodium:

– Originally expected to increase efficacy

– Antimicrobial effect << Ag+

– Now used primarily to reduce discoloration
Silver Zeolites & Silver Salts

(Agency Position)

• The ADTC concluded that chemically, zeolite-based 

silver active ingredients were not similar to salts of 

silver and hazards would need to be considered 

separately for each silver compound. 

• However, for purposes of hazard characterization 

and endpoint selection for risk assessments involving 

elemental silver and silver salts, the ADTC concluded 

that silver salts can be treated together as a class, 

based on the knowledge that once internalized to the 

body, the compound of interest is ionic silver, which 

is common to the silver salts. Therefore, one 

toxicology dataset can represent the hazard for the 

silver salts. 

[McMahon to Kish/Swindell, 10/20/2004: EPA-HQ-OPP-2009-0011-0009; repeated almost verbatim in Chen & Malish thru 

Petrie/Elkassabany/Cook, 09/15/09: EPA-HQ-OPP-2009-0011-0011]
Silver Zeolites & Silver Salts

(Our View)

• The term “zeolite-based silver active ingredients” is 

incorrect. The active ingredients in zeolite-based 

antimicrobials are silver (and/or other metal) ions in 

an inert zeolite A carrier. 

(See PWP Tables 1 and 6 and product registrations/labels.)

• The term “silver compound” is also incorrect. The 

ions are held to internal zeolite surfaces by 

electrosorption, not bound into compounds.

• Exactly as for silver salts, for zeolite-based silver 

antimicrobials, “once internalized to the body, the 

compound of interest is ionic silver, which is common 

to the silver salts.”
Silver Zeolites AS Silver Salts

(Our argument)

• Such zeolites may be considered as type of 

salt, in which the anion is an essentially 

insoluble crystal.

• Cations enter solution through ion exchange, 

the rate controlled by diffusion (in and out) 

through the anionic crystal structure.

• Zeolites carrying multiple ions may be 

compared to mixtures of ordinary salts.

• The zeolite anion should be regarded as an 

inert carrier; the carried ions are responsible 

for all antimicrobial effects.
Zeolite Antimicrobials as Salts

CAS#

PC code

Wt % (range)

Wt % (typical) Cations*

(typical cell)

Anion

(8 cells 

shown) Ag+ Zn++ Cu++

Zeolite A

(Na-zeolite)

68989-22-0

---

---

---

---

---

---

---

++++++

++++++

Ag

zeolite

130328-18-6

221700

2.5-22

3.5

---

---

--

--

+ +++++

++++++

Ag-Zn

zeolite

130328-20-0

129103

3-5?

3.5

6-15?

6.5

--

--

+ ‡ † ++

++++++

Ag-Cu

zeolite

130238-19-7

129057

3.5

3.5

---

---

6.1

6.1

+ ‡ † ++

++++++

Zn

zeolite

---

---

---

---

14.3

14.3

---

---

‡ ‡ ‡ ‡

++++

* Cations: + Na+, H+, etc.; + Ag+; ‡ Zn++; ‡ Cu++. 

Not shown: 27 water molecules/cell when fully hydrated.
Application: Material Preservative

• Zeolite particles blended into polymer matrix (1~3 wt%)

• Ag+ eluted only from particles exposed on surface

• Typical Ag+ concentration in surface moisture: 5~50 ppb

(Photo is actually soap – sorry about the color.)
Elution of Metals

• Typical Ag content in antimicrobial: 3% or less

• Typical Ag-zeolite in final product: 3% or less

• Elution only from particles at the surface of the 

protected material

• Leaching studies on Ag-Zn and Ag-Cu zeolites found ppb water 

concentrations, well below US drinking water standards 

– Leaching depends on surface-to-volume ratio (greater for fibers than for 

plaques); for fibers silver generally < 20 ppb, Zn difficult to distinguish from 

background, only copper >100 ppb. [MRID 41615818 & 42032807]

• FDA-type migration study on 3% of agent (of which 20% = Ag-Zn 

zeolite) in polyethylene found no detectable silver (<5 ppb) and 

ca. 100 ppb zinc (significant component in inert ingredients).

[EPA-HQ-OPP-2009-0011-0007.2]
FDA and EPA Regulation of 

Zeolites in Pesticides and Food

• Allowed as “4A” inerts in FIFRA 25(b) “reduced risk” pesticides 

[www.epa.gov/opprd001/inerts/section25b_inerts.pdf ]

• Permitted as inerts in non-food-use pesticides 

[www.epa.gov/opprd001/inerts/inert_nonfooduse.pdf]

• Exempt from tolerance as inert agricultural pesticide ingredient 

(diluent, carrier) [40 CFR 180.910]
FDA Food Contact 

Notifications for Zeolites

47 Zeolite A in which silver, zinc and ammonium ions have 

been exchanged for sodium ions. The silver content of 

the modified zeolite shall not exceed 2.5 percent by 

weight.

Sinanen Company, 

Ltd.

6/9/2000

134 Sodium zeolite A (CAS Reg. No. 68989-22-0). PQ Corporation 5/30/2001

193 Silver zinc zeolite, a mixture of silver-magnesium-zinccalcium phosphate sodium alumino silicate, zinc oxide 

(CAS Reg. No. 1314-13-2), and hydrotalcite (CAS Reg. 

No. 12304-65-3).

Kanebo Chemical 

Industries, Ltd.

3/6/2002

270 A silver-zinc-sodium aluminosilicate zeolite containing up 

to 2.9 percent by weight of silver and 19 percent by 

weight of zinc. The finished zeolite will also contain small 

amounts of calcium metaphosphate, zinc oxide and 

silica.

Kanebo Chemical 

Industries, Ltd.

12/18/2002

294 Zinc zeolite A (zinc sodium aluminosilicate). Kanebo Chemical 

Industries, Ltd.

2/13/2003

351 A type of zeolite in which silver, zinc and ammonium ions 

have been exchanged for sodium ions. The silver content 

of the modified zeolite shall not exceed 5 percent by 

weight.

AgIon 

Technologies

10/21/2003

535 A type of zeolite in which silver, copper and ammonium 

ions have been exchanged for sodium ions.

AgIon 

Technologies

11/11/2005

614 Zeolite Na-P REPLACES FCN #548 Ineos Silicas Group 6/14/2006

697 Zeolite A in which silver and zinc ions have been 

exchanged for sodium ions.

Cosmo Advanced 

Material Company, 

Ltd.

4/27/2007

773 Zeolite A (CAS Reg. No. 68989-22-0) in which silver and 

ammonium ions have been exchanged for sodium ions.

Sinanen Zeomic 

Company, Ltd.

1/22/2008
Questions on Zeolite A?
CEDI/ADI Comparison for 

Zeolite Na-A as a Food Contact 

Substance

ZEOLITE Na-A

CAS RN or Other ID Code: 068989220 

Acceptable Daily Intake: 0.2925 mg/kg/day

Cumulative Dietary Concentration: 550 ppb 

Cumulative Estimated Daily Intake: 0.028 mg/kg/day

REGNUM: 176.170 (21 CFR)

TOX Study Date: 10/26/1982 

http://www.fda.gov/Food/FoodIngredientsPackaging/FoodContactSubstancesFCS/CEDIADIDatabase/default.htm
Toxicity of Zeolite A

(Gloxhuber)

Gloxhuber, Ch., et al., Zeolithe A – A Phosphate Substitute for Detergents:

Toxicological Investigation, Fd Chem. Toxic, Vol. 21, No. 2, pp 209-220, 1983.

Table 1: Toxicity of studies of zeolite A (Gloxhuber et al., 1983)

Study Type Species Results

Acute oral rat No toxicity at 10 g/kg

Dermal irritation (21 days) rabbit No reaction

Acute eye rabbit Foreign body reaction, 

resolved within 48 hours

Subchronic oral rat Urinary calculi at 10,000 ppm, 

NOAEL is 5,000 ppm 

(equivalent to 500 mg/kg)

Chronic oral rat Not carcinogenic, no 

treatment-related effects and 

the NOAEL appeared to be 

1,000 ppm (HDT) (equivalent 

to 50 mg/kg)

Subchronic inhalation rat No toxicity at mean 

concentration of 0.89 mg/m3 

(HDT)

Absorption (oral) rat Less than 1% of silicon was 

absorbed and eliminated via 

the kidneys
Metals Used in Zeolite 

Antimicrobials

• Zeolite serves as a convenient carrier 

for the cations and has no antimicrobial 

properties

• Copper, zinc and silver are cations used 

in zeolite antimicrobials

• Zeolite antimicrobials are typically 

incorporated into polymers or other 

hydrophobic organic materials
Zeolite Antimicrobial 

Toxicity

• The toxicity of zeolite-based 

antimicrobials is due to the toxicity of 

the metal ions (silver, zinc or copper) 

carried by the zeolite

• This can be shown by examining the 

toxicity profiles of silver, zinc and 

copper and comparing those profiles 

with available data for zeolite 

antimicrobials
Zinc Toxicity

• Zinc is an essential element with an 

RDA of 2-14 mg/person

• This compares with the EPA IRIS RfD 

of 0.3 mg/kg/day (18 mg/person).

• Daily intake in US ranges from 5.2 to 

16.2 mg/person

• Excess zinc intake results in 

hematological and GI effects
Copper Toxicity

• US population is exposed to copper 

from air, water, diet, and contact with 

soil and consumer products e.g., 

doorknobs

• RDA for copper is 0.9 mg/person

• RfD not established

• EPA- quantitative assessment not 

necessary for copper
Silver Toxicity

• EPA- no adverse systemic effects after 

oral or dermal exposure to silver

• Laboratory animal studies not relevant 

for pesticidal risk assessment because 

EPA risk assessment will be on the 

basis of argyria seen in human study 

• 28-day rat inhalation study to be 

required by EPA (FWP)
Zeolite-based Antimicrobial 

Toxicity

• Acute studies available for zeolite 

antimicrobials generally show no toxicity 

except for irritation

• Other available data include subchronic 

oral rat and dog, and subchronic dermal 

rat, multigeneration reproduction, rat 

teratology, genotoxicity 

• Subchronic rat and reproduction studies 

not acknowledged by FWP
Subchronic Oral Toxicity - Rat 

• Dose levels of 1000, 6250 and 12500 ppm 

(equivalent to 13, 81.25 and 156 mg/kg/day 

of zinc) of silver zinc zeolite were given to rats 

in the diet for 90-days

• Hematological effects indicative of microcytic 

anemia were seen at mid-dose and high 

dose levels in this study

• NOAEL in rat for hematological effects of zinc 

is 53 mg/kg/day (EPA/635R-5/002).

• Toxicity observed is clearly zinc-related 
Development 

Toxicityrodent

Reproductive 

Toxicity

SubchronicrodentSubchronicnonrodent

Subchronic 

dermalrodent

Silver zeolite Read across 

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Zinc zeolite Read across 

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Silver copper 

zeolite Study available Read across and/or down

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Study 

Available

Silver zinc 

zeolite

Read across 

and/or down Study available Study available

Study 

available

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and/or down

Available Toxicity Studies 

for Antimicrobial Zeolites
Exposure to Zeolite 

Antimicrobials

• The use of zeolite antimicrobials as material 

preservatives poses low exposure potential

– Both indoor and outdoor uses designed to 

remain in material for its lifetime to the 

greatest extent possible

– Migration studies done to support FDA Food 

Contact Notifications show zeolite itself is not 

released

• Extremely low levels of Al, Ag and Zn released, if 

detected (see FCN 351 for silver zinc zeolite)
Worker Exposure to Zeolite 

Antimicrobials

• Dermal exposure to workers prior to 

incorporating the antimicrobial is possible; 

HOWEVER,

– Zeolites would not be absorbed intact

– Metal ions would be poorly absorbed in 

absence of PPE

• Risk to workers or general population 

should be assessed by comparison of 

exposure to relevant metal reference dose 

(as the zeolite is inert)
Summary

• Zeolite-based antimicrobials consist of Ag+ (and/or 

other metal) ions (cations) in an inert zeolite carrier 

framework.

• All biological effects are attributable solely to the 

metal ions (since zeolite is toxicologically inert).

• Zeolite-based silver antimicrobials are similar to silver 

salts, in that they can be “treated together [with the 

salts] as a class, based on the knowledge that once 

internalized to the body, the compound of interest is 

ionic silver.”

– (This applies to zeolite-based antimicrobials with copper and 

zinc as well.)