&EPA
         United States
         Environmental Protection
         Agency
          Office of Chemical Safety and
          Pollution Prevention
          (751 OP)
EPA712-C-07-074
September 4,2012
Product Performance
Test Guidelines
OCSPP 810.2200:
Disinfectants for Use on
Hard Surfaces—Efficacy
Data Recommendations

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                                  NOTICE

This guideline is one of a series of test guidelines established by the Office of
Chemical Safety and Pollution Prevention (OCSPP) (formerly the Office of
Prevention, Pesticides and Toxic Substances (OPPTS) prior to April 22, 2010),
United States Environmental Protection Agency for use in testing pesticides and
chemical substances to develop data for submission to the Agency under the Toxic
Substances Control Act (TSCA) (15 U.S.C. 2601, et seq.), the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.), and section 408 of
the Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C. 346a), referred to
hereinafter as the harmonized test guidelines.

     The harmonized test guidelines serve as a compendium of accepted scientific
methodologies and protocols that are intended to provide data to inform regulatory
decisions under TSCA, FIFRA, and/or FFDCA.  This document provides guidance
for conducting appropriate tests, and is also used by EPA, the public, and the
companies that are subject to data submission requirements under TSCA, FIFRA
and/or the FFDCA. At places in this guidance, the Agency uses the word "should."
In this guidance, use of "should" with regard to an action means that the action is
recommended rather than mandatory.  As a guidance document, these guidelines are
not binding on either EPA or any outside parties, and the EPA may depart from the
guidelines where circumstances warrant and without prior notice.  The methods
contained in this guideline are strongly recommended for generating the data that are
the subject of the guideline, but EPA recognizes that departures may be appropriate in
specific situations. You may propose alternatives to the methods recommended in
these guidelines, with your supporting rationale.  The Agency will assess such
proposals on a case-by-case basis.

     For additional information about OCSPP harmonized test guidelines and to
access the guidelines electronically, please go to  http://www.epa.gov/ocspp and select
"Test Methods & Guidelines" on the left side navigation menu. You may also access
the guidelines in http://www.regulations.gov grouped by Series under Docket ID #s:
EPA-HQ-OPPT-2009-0150 through EPA-HQ-OPPT-2009-0159, and EPA-HQ-
OPPT-2009-0576.

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OCSPP  810.2200:  Disinfectants for  use  on  hard  surfaces  -  efficacy  data
recommendations

       (a) Scope

       (1) Applicability. This guideline describes test methods that EPA believes will generally
satisfy  testing  requirements of  the  Federal  Insecticide,  Fungicide,  and  Rodenticide Act
(FIFRA)(7U.S.C.  136, et seq.) and the Federal Food, Drug, and  Cosmetic Act (FFDCA) (21
U.S.C. 346a). It addresses testing to demonstrate the  effectiveness of antimicrobial pesticides
bearing claims as disinfectants, fungicides, virucides, and tuberculocides.

       (2) Background. The source materials used in developing this OCSPP test guideline are
OPP  guidelines 91-2: Products for use on hard surfaces  and  91-30: Acceptable  methods
(Pesticide Assessment Guidelines, Subdivision G, Product Performance. EPA report 540/9-82-
026, October 1982).

       (b)  Purpose.  This  guideline  addresses  efficacy testing  for antimicrobial  pesticides
intended to be used on  hard  surfaces,  namely disinfectants,  fungicides,  virucides, and
tuberculocides in a variety of product types (water-soluble powders,  liquids, sprays, towelettes,
etc.).

       (c) General considerations

       (1)  This guideline recommends methods  for use in tests to be conducted to address the
data requirements  for pesticide  registration. Good Laboratory Practice  Standards  (GLP)  as
defined in 40 CFR Part 160 apply to studies to support disinfection on hard, non-porous surfaces.
According to 40 CFR §160.17: "EPA may refuse to consider reliable  for purposes of supporting
an application for a research or marketing permit any data from a study which was not conducted
in accordance with this part." 40 CFR §160.12 (b) requires with any submitted research data "[a]
A statement that the  study  was conducted in  accordance  with this  part; [b] A statement
describing in detail all differences between the practices used  in the study and those required by
this part; or [c]  A statement that the person was not a sponsor of the study, did not conduct the
study, and does not know whether the  study was  conducted in accordance with this part." Note:
The Association of Official Analytical Chemicals (AOAC) recommended tests are designed to
be conducted as written. For deviations (e.g., cultures grown with shaking instead of  static,
dilution of culture prior to drying on carriers) proposed to be  used  in the conduct of these tests,
obtain written approval from the Agency  and document such deviations in the study reports
submitted to the Agency.   The Agency  may  consult with the AOAC  prior  to  accepting
modifications to their standardized methods. Refer to OCSPP Test Guideline 810.2000  for
general testing recommendations prior to initiating tests.

       (2)   Confirmatory  testing.  In  certain  situations an applicant may rely on previously
submitted efficacy data to support an application or amendment for registration of a product and
submit only confirmatory efficacy data on his own product to demonstrate his ability to produce
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an effective formulation. These situations are as listed in paragraphs (C)(3)(i) through (C)(3)(iii)
of this guideline:
       (i)  Duplicated Product  Formulations. In this situation, the applicant manufactures a
formulation which  duplicates a product that is  already  registered  with complete supporting
efficacy data. The chemical composition, manufacturing procedure, label claims, and directions
for use are identical in substance  to those of the original registration,  and specific references
(Master Record ID Numbers [MRTD]) to the  supporting data developed  for the original product
are cited by the applicant.

       (ii) Minor Formulation Change in a Registered Product. In this  situation, the change in
the formulation is relatively minor, e.g.,  a change of an inert ingredient. The label claims and
directions for use are unchanged from those accepted for the registered formulation, and specific
references (MRID) to the supporting data developed for the original formulation are cited by the
applicant.  If the  only  change in the  formulation is  the addition of a fragrance or dye,
confirmatory data do  not  need to be submitted. However, when the product is an  aerosol
formulation, confirmatory data should be submitted for all formulation changes, including  the
addition of fragrances and dyes.

       (iii) The confirmatory data  are to be developed from testing the applicant's own finished
product. When the  test methodology utilized in deriving the original supporting efficacy data
were modified to include additional elements  not specified in the recommended method,  such as
organic soil, hard water, longer or shorter contact time, etc., the  confirmatory data should be
produced under similarly modified  conditions.

       (4) Efficacy claims. Table 1 provides a quick reference guide to testing for basic claims
described in this guideline. Consult the text for detailed testing descriptions.

                      Table 1. Testing for basic efficacy claims
Level of
Efficacy
Limited spectrum
disinfectant/hard
non-porous
surfaces.
Broad-spectrum
disinfectant/hard
Test Methods
Water soluble
powders/liquids
Spray products
Towelettes
Water soluble
powders/liquids
AOAC Use-
Dilution
Method or
AOAC Hard
Surface
Carrier Test
(distilled
water only)
AOAC
Germicidal
Spray
Products Test
Modified
AOAC
Germicidal
Spray
Products Test
AOAC Use-
Dilution
Test
Organisms
Staphylococcus
aureus (ATCC
6538) or Salmonella
enterica (ATCC
10708)
Staphylococcus
aureus (ATCC
No. of
Batches/Carriers
Three batches, one at least
60 days old. 60 carriers
against either organism
claimed (180 carriers).
Three batches, one at least
60 days old. 60 carriers
Evaluation
of Success
59/60 carriers are
negative for each
batch tested for all
methods except
AOAC Hard
Surface Carrier
Test, which is
58/60 carriers are
negative for each
batch.
59/60 carriers are
negative for each

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Level of
Efficacy
non-porous
surfaces.
Hospital or
healthcare
disinfectant/hard
non-porous
surfaces.
Fungicidal
disinfectant/hard
non-porous
surfaces.
Virucidal
disinfectant/hard
non-porous
surfaces.
Tuberculocidal
disinfectant/hard
non-porous
Test Methods

Spray products
Towelettes
Water soluble
powders/liquids
Spray products
Towelettes
Water soluble
powders/liquids
Spray products
Towelettes
Water soluble
powders/liquids
Spray products
Towelettes
Water soluble
powders/liquids
Method or
AOAC Hard
Surface
Carrier Test
(distilled water
only)
AOAC
Germicidal
Spray
Products Test
Modified
Germicidal
Spray Test
AOAC Use-
Dilution
Method or
AOAC Hard
Surface
Carrier Test
(distilled water
only)
AOAC
Germicidal
Spray
Products Test
Modified
Germicidal
Spray Test
AOAC Use-
Dilution Test
modified for
fungi or
AOAC
Fungicidal
Test
AOAC
Germicidal
Spray
Products Test
modified for
fungi
Modified
Germicidal
Spray Test
AOAC Use-
Dilution Test
modified for
viruses or
ASTM E1053-
AOAC
Germicidal
Spray
Products Test
modified for
viruses or
ASTM E1053-
Modified
Germicidal
Spray Test
AOAC
Tuberculocidal
Activity of
Test
Organisms
6538)and
Salmonella enterica
(ATCC 10708)
Staphylococcus
aureus (ATCC
6538)and
Pseudomonas
aeruginosa (ATCC
15442)
Trichophyton
merrfagrophytes
(ATCC 9533)
Virus claimed on
the label or
approved surrogate.

No. of
Batches/Carriers
against each organism (360
carriers).
Three batches, one at least
60 days old. 60 carriers
against each organism (360
carriers).
Two batches, ten carriers
per batch for the modified
AOAC Use Dilution Test,
the modified AOAC
Germicidal Spray Products
Test, and the EPA
Towelette Test. Two
batches for the AOAC
Fungicidal Test.
Two batches. One surface
per batch.
Two batches, ten carriers
per batch.
Evaluation
of Success
batch tested for all
methods except
AOAC Hard
Surface Carrier
Test, which is
58/60 carriers are
negative for each
batch.
59/60 carriers are
negative for each
batch tested for all
methods except
AOAC Hard
Surface Carrier
Test, which is
58/60 carriers are
negative against
Staphylococcus
aureus for each
batch, and 57/60
carriers are
negative against
Pseudomonas
aeruginosa.
All fungal spores
on all carriers
should be killed.
For the AOAC
Fungicidal Test,
all fungal spores
should be killed at
10 and 15 minutes
to support a 10
minute label
claim.
Complete
inactivation of the
virus. Where
cytotoxicity is
present,
demonstrate a 3
Iog10 reduction.
10/10 carriers are
negative for
growth and there

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Level of
Efficacy
surfaces.
Additional
bacteria/hard non-
porous surfaces.
Test Methods

Spray products
Towelettes
Water soluble
powders/liquids
Spray products
Disinfectants,
Quantitative
Tuberculocidal
Activity Test
AOAC
Germicidal
Spray
Products Test
modified for
tuberculocidal
activity
Modified
Germicidal
Spray Test
AOAC Use-
Dilution Test
or
AOAC Hard
Surface
Carrier Test
(distilled water
only)
AOAC
Germicidal
Spray
Products Test
Test
Organisms
Mycobacterium
bovis BCG
Bacteria claimed on
the label in addition
to the base broad-
spectrum claim.
No. of
Batches/Carriers
Two batches, 4 replicates
per batch.
Two batches, ten carriers
per batch.
Two batches, ten carriers
per batch.
Two batches, ten carriers
for each batch.
Evaluation
of Success
is no growth in the
additional test
media.
Survival Curve
constructed from
4 separate
replicates at the
95% confidence
level to show
probability of one
survivor.
10/10 carriers are
negative for
growth and there
is no growth in the
additional test
media.
10/10 carriers are
negative for
growth and there
is no growth in the
additional test
media.
10/10 carriers are
negative for
growth of the test
organism.
       (d)  Disinfectants

       (1) Limited spectrum products. This section addresses efficacy testing for disinfectant
products with limited efficacy (effective against Gram-negative or Gram-positive  bacteria, but
not both).

       (i) Water-soluble powders and non-volatile liquid products test procedure.  The Agency
recommends the use of the AOAC International Use-Dilution Methods (Ref.  1) or the AOAC
International Hard Surface Carrier Test Methods (distilled water only)(Ref. 2).  Sixty carriers for
each of three samples, representing three different batches, one of which should be >60 days old,
should be tested  against Salmonella enterica (S.  enterica)(former\y designated as Salmonella
choleraesuis)(Amencan Type Culture Collect!on)(ATCC 10708) for effectiveness against Gram-
negative bacteria, or Staphylococcus aureus (S. aureus)(ATCC 6538) for effectiveness against
Gram-positive bacteria. If the product is intended to be represented as bactericidal in the
presence of organic soil (one-step), an  appropriate organic soil, such as 5 percent blood serum,
should be included with the bacterial inoculum.

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       (ii) Germicidal  spray  products (aerosol  or pump) and  volatile liquid  products  test
procedure. The Agency recommends use of the AOAC International Germicidal Spray Products
as Disinfectants test (Ref. 3). Sixty carriers for each of three samples, representing three different
batches,  one of which  should be >60 days  old, should be tested against S.  enterica (ATCC
10708)  for  effectiveness against Gram-negative bacteria, or S. aureus  (ATCC  6538) for
effectiveness against  Gram-positive bacteria. If the product is intended to be represented as
bactericidal  in  the presence of organic soil (one-step), an appropriate organic soil, such as 5
percent blood serum, should be included with  the bacterial inoculum.

       (iii) Single-use towelettes test procedure. The Agency recommends the use of a modified
AOAC Germicidal Spray Products as Disinfectants test (Ref. 3) or ASTM E2362  (Ref 4). Sixty
carriers for each of three samples, representing three different batches, one of which should be
>60 days old, should be tested against S. enterica (ATCC 10708) for effectiveness against Gram-
negative bacteria, or S. aureus (ATCC 6538)  for effectiveness against Gram-positive bacteria. If
the product  is intended to be represented as  bactericidal in the presence of organic soil (one-
step), an appropriate organic soil, such as  5  percent blood serum, should be included with the
bacterial inoculum. Instead of spraying the  inoculated surface of the carriers, the product should
be tested by wiping the surface of the carriers with the saturated towelette, and then subculturing
the carriers after the specified holding time. The towelette should be removed from its container
and handled with sterile gloves.  One  towelette should be used to  wipe  a  minimum  of 10
inoculated carriers for a total of 6 towelettes for all 60  carriers. Alternatively, one carrier with a
surface area equivalent to ten 1 x  1 inch carriers can be wiped using one towelette  per carrier set
per batch. The area  of the towelette  used  for wiping should be  rotated  so as to expose a
maximum amount of its surface  in the course of wiping  a set  of carriers.  Note: A detailed
description of the wiping procedure, including the towelette folding and rotation process should
be included in the test protocol and documented in the raw data and final report.

       (iv) Evaluation of limited disinfectant  success. For the AOAC International Use-Dilution
Methods, the Germicidal Spray Products  as Disinfectants test,  and single-use towelettes, the
product should kill the  test microorganisms on 59 out of each set of 60 carriers/slides in< ten
minutes.  In addition,  per the 2009 AOAC  revisions  for the Use-Dilution Method, the mean log
density for S. aureus  is to be at least 6.0 (corresponding to a geometric  mean density of 1.0 x
106);  a mean log density <6.0 invalidates  the test.  For the AOAC International  Hard Surface
Carrier Test Methods, the product should kill the test microorganisms on 58 out of each set of 60
carriers for S. enterica or S. aureus in 
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against either S. aureus (ATCC 6538) or S. enterica (ATCC 10708)(depending on whether the
product is claimed to be effective against Gram-positive  or Gram-negative bacteria).  If the
product is intended to be represented as bactericidal in the presence of organic soil (one-step), an
appropriate organic soil, such as  5  percent blood serum, should be included with the bacterial
inoculum.

       (ii) Germicidal  spray products (aerosol  or  pump) and  volatile liquid  products test
procedure. The  Agency recommends the AOAC International Germicidal  Spray Products as
Disinfectants test  (Ref. 3).  Ten  carriers for each of two product samples, representing two
different batches of the product,  should be tested against either S.  aureus (ATCC 6538) or S.
enterica  (ATCC 10708)(depending on whether the product is claimed to be effective  against
Gram-positive  or  Gram-negative bacteria). If the product is intended to  be represented as
bactericidal in the presence of organic soil (one-step), an appropriate organic soil, such as 5
percent  blood serum, should be  included with the bacterial inoculum.  For pressurized  spray
products,  certification should be furnished  specifying that all  parts  and  materials  used in
manufacturing the  container for pressurized spray disinfectants are identical to those specified by
the basic manufacturer.

       (iii) Single-use towelettes test procedure. The Agency recommends the use of a modified
AOAC Germicidal Spray Products  as Disinfectants test (Ref. 3) or ASTM E2362 (Ref 4). Ten
carriers for each of two samples,  representing two different batches, should be tested against S.
enterica (ATCC 10708) for effectiveness against Gram-negative bacteria, or S. aureus (ATCC
6538) for effectiveness against  Gram-positive  bacteria.  If the product  is intended  to be
represented as bactericidal in the presence of organic soil (one-step), an appropriate organic soil,
such as 5 percent blood  serum,  should be included with  the bacterial inoculum. Instead of
spraying the inoculated surface of the carriers, the product should be tested by wiping the surface
of the carriers with the saturated towelette,  and then subculturing the carriers after the specified
holding time.  The towelette should be removed  from its container  and handled with  sterile
gloves. One towelette should be used to wipe a minimum of 10 inoculated carriers for a total of 1
towelette for all 10 carriers. Alternatively, one carrier with a surface area equivalent to ten 1 x 1
inch carriers can be wiped using one towelette per carrier set per batch. The area of the towelette
used for wiping should be rotated so as to expose a maximum amount of its surface in the course
of wiping a set of  carriers.  Note: A detailed description of the wiping procedure, including the
towelette folding and  rotation process  should be included in the test protocol  and documented in
the raw data and final  report.

       (iv) Evaluation of confirmatory limited  disinfectant success. The  product should kill all
the test microorganisms on  all carriers in 
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labeling as having efficacy against both Gram-negative and Gram-positive bacteria, the product
is considered a general or broad spectrum disinfectant.

       (i) Water-soluble powders and non-volatile liquid products test procedure.  The Agency
recommends the use of the AOAC International Use-Dilution Methods (Ref.  1) or the  AOAC
International Hard Surface Carrier Test Methods (distilled water only)(Ref. 2).  Sixty carriers for
each of three samples, representing three different batches, one of which should be >60 days old,
should be tested against both S.  enterica (ATCC  10708) and S.  aureus (ATCC 6538). If the
product is intended to be represented as bactericidal in the presence of organic soil (one-step), an
appropriate  organic soil, such as  5  percent blood serum, should be included with  the bacterial
inoculum.

       (ii) Germicidal  spray products  (aerosol or  pump) and  volatile liquid products  test
procedure. The Agency  recommends the AOAC International Germicidal  Spray Products as
Disinfectants test (Ref. 3).  Sixty  carriers for each of three samples, representing three different
batches, one of which should be >60 days old, should be tested against both S. enterica (ATCC
10708) and S. aureus (ATCC  6538). If the product is intended to be represented as bactericidal in
the presence of organic  soil  (one-step),  an appropriate organic soil, such as 5 percent blood
serum, should be included with the bacterial inoculum.

       (iii) Single-use towelettes test procedure. The  Agency recommends the use of a modified
AOAC Germicidal Spray Products as Disinfectants test (Ref. 3) or ASTM E2362 (Ref 4). Sixty
carriers for each of three samples, representing three different batches, one of which should be
>60 days old, should be tested against S. enterica (ATCC 10708) for effectiveness against Gram-
negative bacteria, and S. aureus (ATCC 6538) for effectiveness against Gram-positive bacteria.
If the product is intended to be represented as bactericidal in the presence of organic soil (one-
step), an appropriate organic soil, such as 5 percent blood serum, should be included with the
bacterial inoculum. Instead of spraying the inoculated surface of the carriers, the product should
be tested by wiping the surface of the carriers with the saturated towelette, and then subculturing
the carriers after the specified holding time. The towelette should be removed from its container
and handled with sterile gloves. One towelette should be used to wipe  a  minimum of 10
inoculated carriers for a total  of 6 towelettes for all 60 carriers. Alternatively, one carrier with a
surface area equivalent to ten 1x1 inch carriers can be wiped using one towelette per carrier set
per batch. The area  of the  towelette  used for wiping should be rotated  so  as  to expose a
maximum amount of its surface  in the course of wiping a set of carriers.  Note: A detailed
description of the wiping procedure, including the towelette folding and rotation process should
be included in the test protocol and documented in the raw data and final report.

       (iv)  Evaluation  of general  or  broad  spectrum disinfectant success.  For the  AOAC
International Use-Dilution  Methods, the Germicidal Spray Products as Disinfectants test,  and
single-use towelettes,  the product  should kill the test microorganisms on 59 out of each set of 60
carriers/slides in 
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International Hard Surface Carrier Test Methods, the product should kill the test microorganisms
on 58 out of each set of 60 carriers in 
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2009 AOAC revisions for the Use-Dilution Method, the mean log density for S. aureus is to be at
least 6.0 (corresponding to a geometric mean density of 1.0 x  106); a mean log density <6.0
invalidates the test. For the Hard Surface Carrier Test, the dried carrier counts should be 0.5 -
2.0 x 106 for Salmonella enterica and 1 - 5 x 106 for Staphylococcus aureus.

       (5) Hospital or healthcare disinfectants. This  section addresses efficacy testing for
products recommended for use in hospitals, clinics, dental offices, nursing homes, sickrooms, or
any other healthcare-related facility.

       (i) Water-soluble powders and non-volatile liquid product test procedure. The Agency
recommends the use of the AOAC International Use-Dilution Methods (Ref. 1) or the AOAC
International Hard Surface Carrier Test Methods (distilled water only)(Ref. 2). Sixty carriers for
each of three samples, representing three different batches, one of which should be >60 days old,
should  be  tested  against  S.  aureus  (ATCC  6538),  and  Pseudomonas  aeruginosa  (P.
aeruginosa)(ATCC 15442).  If the product is intended to be  represented as bactericidal in the
presence of organic soil (one-step), an appropriate organic soil, such as 5 percent blood serum,
should be included with the bacterial inoculum.

       (ii) Germicidal  spray products  (aerosol  or  pump)  and volatile  liquid products test
procedure. The Agency recommends the  use  of the AOAC International Germicidal  Spray
Products as Disinfectants test (Ref. 3). Sixty carriers for each of three samples, representing three
different batches, one  of which should be >60 days old, should be tested against: S.  aureus
(ATCC 6538), and P. aeruginosa (ATCC 15442). If the product is intended to be represented as
bactericidal in the presence of organic  soil (one-step), an appropriate organic  soil, such as 5
percent blood serum, should be included with the bacterial inoculum.

       (iii) Single-use towelettes test procedure. The Agency recommends the use of a modified
AOAC Germicidal Spray Products as Disinfectants test (Ref. 3) or ASTM E2362 (Ref. 4). Sixty
carriers for each of three samples, representing three different batches, one of which should be
>60 days old, should be tested against S. aureus (ATCC 6538), and P.  aeruginosa (ATCC
15442). If the product is intended to be represented as bactericidal in the presence of organic soil
(one-step), an appropriate organic soil, such as 5 percent blood serum, should be included with
the bacterial inoculum.  Instead of spraying the  inoculated surface of the carriers, the product
should be tested  by wiping the surface of the carriers with  the saturated towelette,  and then
subculturing the carriers after the  specified holding time. The towelette should be removed from
its container and handled with sterile gloves. One towelette should be used to wipe a minimum
of 10 inoculated carriers for a total of 6 towelettes for all 60  carriers. Alternatively, one carrier
with a surface area equivalent to ten  1 x 1 inch carriers can  be wiped using one towelette per
carrier set per batch. The area of the towelette used for wiping  should be rotated so as to expose a
maximum  amount of its surface  in the course of wiping a  set of carriers.  Note: A detailed
description of the wiping procedure, including the towelette folding and rotation  process should
be included in the test protocol and documented in the raw data and final report.

       (iv) Evaluation of hospital or healthcare disinfectant success. For the AOAC International

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Use-Dilution Methods,  the Germicidal Spray  Products as Disinfectants test, and  single-use
towelettes, the product should kill the test microorganisms on 59 out of each set of 60 carriers in

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procedure, including the towelette folding and rotation process should be included in the test
protocol and documented in the raw data and final report.

       (iv) Evaluation of confirmatory hospital or healthcare disinfectant success. The product
should kill all the test microorganisms on all carriers in 60  days old).
Instead  of spraying the inoculated surface of the carrier, the product should be tested by wiping
the surface of the carrier with the saturated towelette, and then subculturing the carriers after the
specified  holding time. One towelette should be used  to treat 10 carriers.  Alternatively, one
carrier with a surface area equivalent to ten 1x1  inch carriers  can be wiped using one towelette
per carrier set per batch.

       (B)  Evaluation of bactericidal  towelette  success. The product should  kill  the test

                                           11

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organism on 59 out of 60 carriers. This testing is intended to support bridging of all vegetative
bacteria listed on the EPA registered liquid disinfectant used to saturate the towelette to the EPA
registered towelette product.

       (8) Disinfectants for Internal Toilet and Urinal Bowl Surfaces Above and Below the
Water Line.  This section addresses efficacy  testing  for  products bearing label claims as
disinfectants (limited, broad-spectrum, or hospital) for internal toilet and urinal bowl  surfaces.
Regarding water-soluble powders and non-volatile liquid products test procedure, the Agency
recommends  the use  of the AOAC  International Use-Dilution Methods (Ref. 1)  modified to
include a 5% organic soil challenge added to the bacterial inoculum. Sixty carriers for each of
three  samples, representing three different batches, one of which is >60 days old, should be
tested against  Salmonella enterica (ATCC  10708) or Staphylococcus aureus (ATCC 6538), for
limited disinfectant products; S. enterica and S. aureus, for broad-spectrum disinfectant products;
and S.  aureus and  Pseudomonas aeruginosa (ATCC 15442), for hospital disinfectant products.
The contained bowl water (-96 fl oz, which represents traditional high volume toilets) should be
used to calculate the appropriate use  dilution for testing. The contained bowl  water for low
volume toilets should be measured and used to calculate the appropriate use dilution for testing.

       (i) Evaluation of disinfectant success for internal toilet bowl and urinal bowl  surfaces.
For the AOAC  International  Use-Dilution Methods and the Germicidal  Spray  Products as
Disinfectants test,  the product should kill the test microorganisms on 59 out of each set of 60
carriers/slides within ten minutes or less. In addition, per the 2009 AOAC revisions for the Use-
Dilution Method, the mean log  density for S. aureus and P. aeruginosa is to be at  least 6.0
(corresponding to a geometric mean density of 1.0 x 106); a mean log density <6.0 invalidates the
test.

       (9) Additional microorganisms. This  section addresses efficacy  testing  for  limited,
broad-spectrum or hospital disinfectants which bear label claims against  bacteria other than
Salmonella enterica (ATCC  10708), Staphylococcus aureus (ATCC 6538) or Pseudomonas
aeruginosa (ATCC 15442).

       (i) Water-soluble powders and non-volatile liquid products test procedure. The Agency
recommends the use of the AOAC International Use-Dilution Methods  (Ref.  1) or the AOAC
International  Hard Surface  Carrier Test  Methods (distilled water only)(Ref. 2). Ten carriers
should be tested  against each specific bacterium for each  of two samples representing two
different batches. If the product is intended to be represented as bactericidal in the presence of
organic soil (one-step), an appropriate organic  soil, such as 5 percent blood serum, should be
included with the bacterial inoculum.

       (ii)  Germicidal  spray  products (aerosol  or  pump)  and  volatile liquid products  test
procedure.  The Agency recommends the use  of the AOAC International Germicidal  Spray
Products as Disinfectants  test (Ref.  3).  Ten carriers should be tested  against each  specific
bacterium for each of two samples representing  two different batches. If the product is intended
to be represented as bactericidal in the presence of organic soil (one-step), an appropriate organic

                                           12

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soil, such as 5 percent blood serum, should be included with the bacterial inoculum.

       (iii) Single-use towelettes test procedure. The Agency recommends the use of a modified
AOAC modified Germicidal Spray Products as Disinfectants test (Ref.3) or ASTM E2362 (Ref
4).  Ten carriers should be tested against  each specific bacterium for each  of two samples
representing two different batches. If the product is intended to be represented as bactericidal in
the presence of organic soil  (one-step), an appropriate organic soil, such  as  5 percent blood
serum, should be included with the bacterial inoculum. Instead of spraying the inoculated surface
of the carrier, the product should be tested by wiping the surface of the carrier with the saturated
towelette,  and then subculturing  the carriers after the specified holding time. The towelette
should be removed from its container and handled with sterile gloves. One towelette should be
used to wipe a minimum of 10 inoculated carriers. Alternatively, one carrier with a surface area
equivalent to ten 1x1 inch carriers can be wiped using one towelette per carrier set per batch.
The area of the towelette used for wiping should be rotated so as to expose a maximum amount
of its surface in the course  of wiping a set of slides. Note: A detailed description of the wiping
procedure,  including the towelette folding  and  rotation process should be included in  the test
protocol and documented in the raw data and final report.

       (iv) Evaluation of disinfectant success for additional microorganisms. The product should
kill all the test microorganisms on all carriers in 5 x 106 conidia/mL. If the product is
intended to be represented as fungicidal in the presence of organic soil (one-step), an appropriate
organic soil, such as 5% blood serum, should be included with the fungal inoculum. The Agency
also recommends the  use of the AOAC International  Use-Dilution Methods (Ref. 1). This test
may be modified to conform to appropriate  elements (e.g., media, growth conditions,  etc.) in the
AOAC International Fungicidal Activity of Disinfectants test.  Ten carriers for  each of two
samples representing  two  different  batches of the  product  should be evaluated  against  T.
mentagrophytes (ATCC 9533).  The inoculum employed should provide a concentration of 1 x
104 - 1 x 105 conidia per carrier. If the product is intended to be represented as fungicidal in the
presence of organic soil (one-step), an appropriate organic soil, such as 5 percent blood serum,
should be included with the fungal inoculum.
                                           13

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       (ii) Evaluation of fungicidal success. For the AOAC International Fungicidal Activity of
Disinfectants test, all fungal spores at 10 and 15 minutes should be killed to support a 10 minute
exposure time. For the AOAC International Use-Dilution Methods, all fungal spores on all 10
carriers should be killed in 
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form, the studies in paragraphs (e)(4)(i) and (e)(4)(ii) of this guideline should be conducted and
submitted to EPA for review:

       (i) Chemical Testing - Comparison of Expressed Liquid from the Towelette(s) to the EPA
Registered Liquid Disinfectant Formulation to which it is being bridged: All active ingredients in
the expressed liquid should be within the  certified limits  of the  Confidential Statement  of
Formula of the  liquid formula being referenced/bridged. The disinfectant towelettes package
should  be  filled according to the  manufacturing  specifications.  Excess  liquid in the bulk
towelette containers cannot be poured off for  use in the chemical testing  for bridging of the
efficacy data.  The liquid used  in the chemical testing should only be that  expressed from the
towelettes.  Two batches should  be tested. Analytical  data for the  active ingredients in the
expressed liquid should be submitted for review.

       (ii)  Efficacy Testing -  Efficacy testing should be  conducted under the same testing
conditions (e.g., soil load,  contact time, temperature) as used for the bulk liquid testing. This
testing allows  bridging of data from the registered bulk liquid used to saturate the towel for each
type of organism  in this paragraph. Note:  A detailed description of the wiping procedure,
including the towelette folding and rotation process should be included in the test protocol and
documented in  the raw data  and  final  report.  For fungicidal  test procedure, the  Agency
recommends the use of the AOAC International  Germicidal Spray Products as Disinfectants
(Ref.  3) modified  for fungicidal towelette testing.  The  test should be modified to conform  to
appropriate  elements (e.g.,  media,  growth conditions)  in the AOAC International Fungicidal
Activity of Disinfectants test. Ten carriers for each of two samples, representing two batches  of
the product should be  evaluated  against T.  mentagrophytes  (ATCC  9533)  for  the  label
recommended contact time.  The inoculum employed should be at a count to achieve 1 x 104 - 1
x 105 conidia  per carrier. Instead of spraying the inoculated surface of the  carrier,  the  product
should  be tested by wiping the surface of the carrier  with the saturated towelette, and then
subculturing the carriers after the specified holding time. One towelette should be used to wipe a
minimum of 10 inoculated carriers. Alternatively,  one carrier with a surface area equivalent  to
ten 1 x  1 inch carriers can be wiped using one towelette per carrier set per batch.

       (A) Evaluation of Fungicidal towelette success. The product should kill the test organism
on all 10 carriers in 
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and Feline Calicivirus, respectively, are currently considered acceptable surrogates for testing.
Additional  guidance   and  protocols  for  surrogate   virus   testing  can  be   found   at
http://www.epa.gov/oppad001/regpolicy.htm. To simulate in-use conditions, the specific virus to
be treated (or surrogate as noted in this paragraph) should be inoculated onto hard  surfaces (e.g.,
Petri dishes, glass carriers, or other appropriate test surface),  allowed to dry, and then treated
with the product according to the directions for use on the product label.

       (1) Water soluble powders and  non-volatile liquid products test procedures. The
Agency recommends the use of either the AOAC International Use-Dilution Methods (Ref 1)
modified for virucidal testing or the ASTM E1053 Test Method for Efficacy of Virucidal Agents
Intended for Inanimate Environmental Surfaces (Ref. 6). One  surface for each of two  samples,
representing two different batches of disinfectant,  should  be tested against a recoverable virus
end point titer of >104 viable viral particles from the test surface for a specified exposure  period
(<10 minutes) at room temperature. If the product is intended to  be represented as virucidal in
the presence  of organic  soil (one-step), an appropriate organic soil, such as  5  percent blood
serum, should be included with the viral  inoculum. When viral  suspensions are grown in  the
presence of at least 5% serum, addition of serum to the inoculum is not expected as part of a
study to support a one-step label claim.

       (2) Germicidal spray  products (aerosol or pump) and  volatile liquid  products test
procedure. The Agency recommends the use of  a  AOAC International Germicidal  Spray
Products  as Disinfectants test (Ref.  3) modified for virucidal testing or  the ASTM  El053
Virucidal Test Method (Ref. 6). One surface for each of two samples, representing two  different
batches of disinfectant, should be tested against a recoverable virus endpoint titer  of at  least  104
viable viral particles from the  test surface for the exposure period specified on the label. If the
product is intended to be represented as virucidal in the presence of organic soil  (one-step), an
appropriate organic  soil,  such as 5 percent blood  serum,  should be included with the viral
inoculum. When viral suspensions are grown in the  presence of at least 5% serum, addition of
serum to the inoculum is not expected as part of a study to support a one-step label  claim.

       (3) Single-use  towelettes test procedure.  The  Agency  recommends the  use  of  the
modified AOAC Germicidal Spray Products as Disinfectants test (Ref. 3) or ASTM El053 (Ref.
6).  One  surface for each of two samples,  representing two different batches of disinfectant,
should be tested against a recoverable virus end point titer  of >104 viable viral particles  from the
test surface for a specified exposure period (<10 minutes)  at room temperature.  If the product is
intended to be represented as virucidal in the presence of organic  soil (one-step), an appropriate
organic soil, such as 5 percent blood  serum, should be included with the viral inoculum. When
viral suspensions are grown in the  presence of at  least  5%  serum, addition  of serum  to  the
inoculum is not expected as part of a study to support a one-step label claim. Instead of spraying
the inoculated surface of the carrier, the product should be tested by wiping the  surface of the
carrier with the saturated towelette, and then subculturing the carriers after the specified holding
time. The towelette should be removed from its container  and  handled with sterile gloves. One
towelette  should be used to wipe a minimum of 10 inoculated carriers. Alternatively, one  carrier
with a surface area equivalent to ten 1x1  inch carriers can be wiped using one towelette  per

                                           16

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carrier set per batch. The area of the towelette used for wiping should be rotated so as to expose a
maximum  amount  of its surface in the course of wiping a  set  of slides.  Note:  A  detailed
description of the wiping procedure, including the towelette folding and rotation process should
be included in the test protocol and documented in the raw data and final report.

       (4)  Evaluation of virucidal success. Following treatment of the test virus with the
disinfectant product, the presence of remaining  viable virus should then  be assayed using an
appropriate  virological technique  (e.g.,  cytopathogenic effect, fluorescent antibody,  plaque
count, or animal response). The protocol for the  viral assay  should provide the information
identified in paragraphs (f)(4)(i)through (f)(4)(ix) of this guideline.

       (i) The virus recovery (titer) should include a minimum  of four determinations per each
dilution in the assay system (e.g., tissue culture, embryonated egg, animal infection, etc.).

       (ii) Cytotoxicity controls.  The  effect of the  disinfectant on the viral assay system should
include a minimum of four determinations per each dilution. For EPA approved protocols for
surrogate virus testing, two determinations per each dilution should be included.

       (iii) The activity of the disinfectant against the test virus should include a minimum of
four determinations per dilution in the assay system.

       (iv) Neutralization controls.  Neutralization controls should be performed (Ref. 7) and
should include a minimum of four determinations per each dilution.  For EPA approved protocols
for surrogate virus testing, two determinations per each dilution should be included.

       (v) Any  special methods which are used to increase the virus titer and to detoxify the
residual disinfectant should be described.

       (vi) The ID50 values calculated for each assay should be provided.

       (vii) The test results should be  reported as the reduction of the virus titer by the activity
of the disinfectant (IDso of the virus control less the IDso of the test system) expressed as the
logarithm to the base  10 and calculated by a statistical method (e.g., Reed and Munch, Most
Probable Number, Spearman-Karber).

       (viii) The product should demonstrate complete  inactivation of the  virus at all dilutions.
If cytotoxicity is present, the virus control titer  should be increased to demonstrate  a >3  logic
reduction in  viral titer beyond the cytotoxic level.  Table 1 provides an example of a typical
laboratory report of a single test with one virus, assayed in a tissue culture system.

       (ix) A laboratory report of a single test with one virus (recovered from a treated surface)
involving a tissue culture assay system should include the details of the methods employed and
the information included in Tables 2-1, 2-2 and 2-3:
                                            17

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                              Table 2-1: Test Results
Dilution of Virus
1C'1
io-2
io-3
1C'4
io-5
io-6
io-7
io-8
Virus - Disinfectant*
T T T T
T T T T
TOGO
0000
0000
0000
0000
0000
Virus - Control*
+ + + +
+ + + +
+ + + +
+ + + +
+ + + +
+ + + 0
+ 000
0000
Cytotoxic - Control
T T T T
T T T T
TOGO
0000
0000
0000
0000
0000
Note: T = toxic; + = virus recovered; 0 = no virus recovered
      Table 2-2: Calculation of the Tissue Culture Infective Dose 50 (TCIDso)
Values
Virus
Dilution
Inoculated
1C'1
ID'2
10'3
1C'4
ID'5
ID'6
ID'7
10'8
No.
Infected /
No.
Inoculated
4/4
4/4
4/4
4/4
4/4
3/4
1/4
0/4
No.
Infected
4
4
4
4
4
3
1
0
No. not
Infected
0
0
0
0
0
1
3
4
Accumulated Values
No.
Infected
24
20
16
12
8
4
1
0
No. not
Infected
0
0
0
0
0
1
4
8
No.
Infected /
No.
Inoculated
24/24
20/20
16/16
12/12
8/8
4/5
1/5
0/8
% Infected
100
100
100
100
100
80
20
0
TCID5n=10'
         6.5
       Table 2-3: Calculations of the Tissue Culture Lethal Dose 50 (TCLD50)
                   Values
Accumulated Values

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Virus
Dilution
Inoculated
1C'1
io-2
10'3
1C'4
io-5
io-6
io-7
io-8
No. Toxic/
No.
Inoculated
4/4
4/4
1/4
0/4
0/4
0/4
0/4
0/4
No. Toxic
4
4
1
0
0
0
0
0
No. not
Toxic
0
0
3
4
4
4
4
4
No. Toxic
9
5
1
0
0
0
0
0
No. not
Toxic
0
0
3
7
11
15
19
23
No. Toxic /
No.
Inoculated
9/9
5/5
1/4
0/7
0/11
0/15
0/19
0/23
% Toxic
100
100
25
0
0
0
0
0
TCLD50 = 1027 Therefore: Virus inactivation = TCID50 - TCLD50 = 1038 log 10

       (5)    Bridging  for disinfectant towelettes.  In some  cases,  disinfectant  towelette
formulations are identical to registered liquid formulations. In order to bridge efficacy data from
the EPA registered bulk  liquid disinfectant used to saturate a towelette or other related product
form, the studies in paragraphs (f)(5)(i)  and (f)(5)(ii) of this guideline should be conducted and
submitted to EPA for review.

       (i)  Chemical Testing—Comparison of Expressed Liquid from the Towelette(s) to the
EPA  Registered Liquid Disinfectant Formulation  to which it  is being  bridged: All  active
ingredients  in the expressed liquid  should be within the  certified limits of the Confidential
Statement of Formula of the liquid formula being referenced/bridged. The disinfectant towelettes
package  should be filled according to the manufacturing specifications. Excess liquid in the bulk
towelette containers  cannot be poured off for use in the chemical testing for bridging of the
efficacy  data.  The liquid used in the chemical testing should only be that expressed from the
towelettes.  Two batches should  be tested. Analytical  data  for  the active ingredients  in the
expressed liquid should be submitted for review.

       (ii)   Efficacy Testing: Efficacy  testing should be conducted  under the same testing
conditions  (e.g.  soil  load, contact time, temperature) as used for the bulk liquid testing. This
testing allows bridging of data from the registered bulk liquid used to saturate the towel for each
type of virus  in paragraphs (f)(5)(u)(A)(l) through  (f)(5)(ii)(A)(%) of this guideline. Note:  A
detailed description of the wiping procedure, including the towelette folding and rotation process
should be included in the test protocol and documented in the raw data and final report.

       (A)  Virucidal  Test Procedure. The Agency  recommends the use of either the AOAC
International  Germicidal Spray  Products as  Disinfectants  (Ref.  3) modified  for  virucidal
towelette testing or the ASTM El053 (Ref. 6) modified for virucidal towelette testing.
                                           19

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       (1)  To support bridging of all viral claims, the most difficult to inactivate small-sized
non-enveloped virus, from the viral strains registered for the bulk liquid,  should be selected for
testing.  Examples  of  small-sized  non-enveloped viral  families  include members  of the
Picornaviridae family  (e.g.,  poliovirus,  enterovirus,  hepatitis A  virus,  rhinovirus), and
Parvoviridae family (e.g., parvovirus).

       (2) To support bridging of viral claims for large-sized non-enveloped and enveloped viral
strains,  the most difficult to inactivate large-sized non-enveloped virus,  from the viral strains
registered for the bulk liquid, should  be selected for testing. Examples  of large-sized non-
enveloped  viral  families  include members of the Adenoviridae  family (e.g., adenovirus),
Reoviridae family (e.g., rotavirus), and Papillomaviridae family (e.g., papillomavirus).

       (3) To support bridging of viral claims for  enveloped viral strains, the most difficult to
inactivate enveloped virus, from the viral strains registered for the bulk liquid, should be selected
for testing. Examples of enveloped viral families include members of the Coronaviridae family
(e.g.,  coronavirus), Flaviviridae  family (e.g.,  hepatitis  C  virus), Herpesviridae family (e.g.,
herpes virus),  Poxviridae family (e.g., vaccinia), Hepadnaviridae family (e.g., hepatitis B virus),
Orthomyxoviridae family  (e.g., Influenza), Paramyxoviridae family (e.g., parainfluenza) and
Retroviridae family (e.g., human immunodeficiency virus).

       (B) Ten carriers for each of two samples, representing two batches of disinfectant, should
be tested against a recoverable dried virus end point titer of >104 viral particles from the test
surface  for a specified exposure period at room temperature. Instead of spraying the inoculated
surface  of the carrier, the  product  should be tested by wiping the surface  of the carrier with the
saturated towelette, and then subculturing the carriers after the specified  holding time.  One
towelette should be used to wipe a minimum of 10 inoculated carriers. Alternatively, one carrier
with a surface area equivalent to ten 1  x 1  inch carriers can be wiped using one towelette per
carrier set per batch.

       The protocol for the viral assay should  provide the information identified in paragraphs
(f)(5)(ii)(B)(7; through (f)(5)(ii)(B)0 of this guideline:

       (1) The virus recovery (titer) should include a minimum of four determinations for each
dilution in the assay system (e.g., cell culture, embryonated egg, animal infection).

       (2)  Cytotoxicity controls.  The effect of the test substance on the viral  assay  system
should include a minimum of four determinations for each dilution. For EPA approved  protocols
for surrogate virus testing, two determinations per each dilution should be included.

       (3) The activity of the test substance against the test virus  should include  a minimum of
four determinations for each dilution in the assay system.

       (4)  Neutralization controls.  Neutralization controls should  be performed (Ref. 7) and
should include a minimum of four determinations per each dilution. For EPA approved  protocols

                                           20

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for surrogate virus testing, two determinations per each dilution should be included.

       (5) Any special  methods which are used to increase the virus titer and to detoxify the
residual test substance should be described.

       (6) The LD50 values calculated for each assay should be provided.

       (7) The test results should be reported as the reduction of the virus titer by the activity of
the test substance (LDso of the virus control less the  LDso of the test system) expressed as the
logarithm to the base 10  and calculated by a statistical  method (e.g., Reed  and Munch, Most
Probable Number, Spearman-Karber).

       (C)  Evaluation  of  virucidal  success.  The  product  should  demonstrate  complete
inactivation of the virus at all dilutions.  If cytotoxicity is present, a >3-log reduction in viral titer
should be demonstrated beyond the cytotoxic level recovered from the carrier surface.
        (g) Disinfectants with tuberculocidal claims This section addresses efficacy testing for
broad-spectrum  or hospital disinfectant  products which bear label  claims of effectiveness  as
tuberculocides. In the Agency's "Data Call-In Notice for Tuberculocidal Effectiveness for All
Antimicrobial Pesticides with Tuberculocidal Claims," dated June 13, 1986 (Ref. 8), applicants
were  given the  option  of choosing from one of three test methods (AOAC  Tuberculocidal
Activity of Disinfectants test, a modified AOAC Tuberculocidal Activity of Disinfectants test, or
the Quantitative Tuberculocidal Activity  Test) for conducting  tuberculocidal  efficacy tests.  In
general, the  Agency  does not believe that the Quantitative Tuberculocidal  Activity Test  (a
suspension test)  is appropriate for disinfectant  formulations used on hard  surfaces. An exception
to this is  for glutaraldehyde-based products,  which have  never been validated in the AOAC
Tuberculocidal Activity of Disinfectants test (a  carrier  based test). Therefore, the Quantitative
Tuberculocidal  Activity Test should  only be  used for glutaraldehyde-based products.  The
Agency  strongly recommends  all  other formulations  to  use  the  carrier-based  AOAC
Tuberculocidal Activity of Disinfectants test.

       (1) Water-soluble powders and non-volatile  liquid products  test  procedures.  The
Agency recommends the  test  procedures in paragraphs  (g)(l)(i)  through  (g)(l)(iv)  of this
guideline.

       (i)  AOAC International  Tuberculocidal  Activity  of Disinfectants test.  The  AOAC
International Tuberculocidal Activity  of Disinfectants test  (Ref. 9) employing a  10 minute
contact time and 20°C temperature.  Ten carriers for  each  of two samples  representing  two
different batches of the  product should be tested against Mycobacterium  bovis (BCG)(M. bovis).
If the product is  intended to be represented as tuberculocidal in the presence of  organic soil (one-
step), an appropriate organic soil, such as 5 percent blood serum, should be included with the
bacterial inoculum.  The log density of M. bovis should be >4.0 (corresponding to a geometric
mean density of >1.0 x 104 CPU/carrier) a mean log density of <4.0 invalidates  the test.

                                            21

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       (ii) AOAC International Tuberculocidal Activity of Disinfectants test with modifications.
The AOAC International Tuberculocidal Activity of Disinfectants test with modifications to the
10 minute contact time and/or 20°C temperature (Ref. 9).  Ten carriers for each of two samples
representing two different batches of the product should be tested against M. bovis (BCG). If the
product is intended to be represented as tuberculocidal in the presence of organic soil (one-step),
an appropriate organic soil, such as 5 percent blood serum, should be included with the bacterial
inoculum. The log  density of M.  bovis  should be >4.0 (corresponding to  a geometric mean
density of >1.0 x 104 CPU/carrier) a mean log density of <4.0 invalidates the test.

       (iii) Evaluation of tuberculocide  success. For the AOAC International Tuberculocidal
Activity of Disinfectants test, all organisms on all carriers should be killed, and there should be
no growth in any of the inoculated subculture media.

       (iv) Validation testing for  Quaternary Ammonium Compounds.   Products  formulated
solely  with quaternary ammonium compounds as the active ingredient(s) should be supported
with validation testing to confirm their tuberculocidal label claim. One additional product sample
should be tested in a different laboratory from the original one, or in the  same laboratory using
different study director, technical staff and quality assurance unit, using the same test procedure
and conditions as used in the first laboratory test.

       (2) Glutaraldehyde formulations

       (i) Test  Procedure.  For glutaraldehyde  formulations, the Agency  recommends the
Quantitative Tuberculocidal Activity Test. This test has been published in the Agency's  "Data
Call-in Notice  for  Tuberculocidal  Effectiveness  for  All   Antimicrobial  Pesticides  with
Tuberculocidal Claims,"  dated June 13, 1986 (Ref. 8). Two samples, representing two different
batches of the product should each be utilized in at least four separate studies (a total of at least
eight studies), against M bovis, so that upper 95 percent confidence limits can be determined for
each point on the survival curve. If the product is intended to be represented as tuberculocidal in
the presence  of organic  soil  (one-step),  an  appropriate organic soil,  such as 5 percent blood
serum, should be included with the bacterial inoculum.

       (ii) Evaluation of tuberculocide  success.  For the Quantitative Tuberculocidal  Activity
Method,  survival curves  should be constructed from the  average of four separate replicates so
that the  upper 95% Confidence Limit  can be  determined for each point  on the curve. The
minimum time claimed  for  efficacy  is  determined by finding the point where the average
survival curve intersects  the probability of one survivor. If the data show a four-log reduction,
but the survivor curve does not intersect the one-survivor line, the minimal time is found  by
extrapolating the  upper  95%  confidence limit  curve such that the value where  it intersects the
one survivor  line is not  50% greater than when the survivor curve intersects the one  survivor
line.

       (3) Germicidal spray products and volatile liquid products—(i) Test procedure. The

                                           22

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Agency recommends the AOAC  International Germicidal Spray Products as Disinfectants test
(Ref. 3), using the media, test culture, and other elements described in the AOAC International
Tuberculocidal Activity of Disinfectants test. Ten carriers for each of two samples representing
two different batches of the product should be tested against M. bovis (BCG). If the product is
intended to be represented as tuberculocidal in the presence of organic soil (one-step), an
appropriate organic soil, such as  5  percent blood serum, should be included  with the bacterial
inoculum. The  log density  of M bovis  should be >4.0 (corresponding to a geometric mean
density of >1.0 x 104 CPU/carrier) a mean log density of <4.0 invalidates the test.

       (ii) Evaluation of tuberculocide success. When using the AOAC International Germicidal
Spray Products as Disinfectants test, all  organisms on all carriers/slides should be killed, and
there should be no growth in any of the inoculated subculture media.

       (4) Single-Use Towelettes

       (i) Test Procedure. The Agency recommends the use of a modified AOAC Germicidal
Spray Products as Disinfectants test (Ref.3) or ASTM 2362 (Ref. 4). Ten carriers for each of two
samples representing two  different batches of the product should be evaluated against M. bovis
(BCG). If the product is intended to be represented as tuberculocidal in the presence of organic
soil (one-step),  an appropriate organic soil, such as 5 percent blood serum, should be included
with the bacterial inoculum. Instead of spraying the inoculated surface of the carrier, the product
should be tested  by wiping the  surface  of the  carrier with the saturated towelette, and then
subculturing the carriers after the  specified holding time. The towelette should be removed from
its container and handled with sterile gloves.  One towelette should be used to wipe a minimum
of 10 inoculated carriers.  Alternatively,  one carrier with  a surface area equivalent to ten 1x1
inch carriers can be wiped using one towelette per carrier set per batch. The area of the towelette
used for wiping should be rotated  so as to expose a maximum amount of its surface in the course
of wiping a set of slides. Note: A  detailed description of the wiping procedure, including the
towelette folding and rotation process should be included  in the test protocol and documented in
the raw data and final report.  The log density of M bovis should be >4.0 (corresponding to a
geometric mean density of >1.0 x 104 CPU/carrier) a mean log density of <4.0 invalidates the
test.

       (ii) Evaluation of tuberculocidal towelette success. All organisms on  all carriers should
be killed, and there should be no growth in any of the inoculated subculture media.

       (5) Bridging  for disinfectant  towelettes.  In  some cases, disinfectant  towelette
formulations are identical to registered liquid formulations. In order to bridge  efficacy data from
the EPA registered bulk liquid disinfectant used to saturate a towelette or other related product
form, the studies in paragraphs (g)(5)(i) and (g)(5)(ii) of this guideline should be conducted and
submitted to EPA for review.

       (i) Chemical Testing - Comparison of Expressed Liquid from the Towelette(s) to the EPA
Registered Liquid Disinfectant Formulation to which it is being bridged: All active ingredients in

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the expressed liquid  should be within the certified limits  of the  Confidential Statement of
Formula of the  liquid formula being referenced/bridged. The disinfectant towelettes package
should  be  filled according to the  manufacturing specifications.  Excess liquid in the bulk
towelette containers cannot be poured off for use in the chemical testing for bridging of the
efficacy data.  The liquid used in the chemical testing should only be that expressed from the
towelettes.  Two batches should  be tested. Analytical  data  for  the  active ingredients  in the
expressed liquid should be submitted for review.

       (ii)  Efficacy Testing:  Efficacy  testing should  be conducted  under the same testing
conditions  (e.g.  soil load, contact time, temperature) as used for the bulk liquid testing. This
testing allows  bridging of data from the registered bulk liquid used to saturate the towel for each
type of organism in paragraph (g)(5)(ii)(A) of this  guideline. Note: A detailed description of the
wiping procedure, including the towelette folding and rotation process should be included in the
test protocol and documented in the raw data and final report.

       (A) Test Procedure. The Agency recommends the use of the modified AOAC Germicidal
Spray Products  as  Disinfectants  test (Ref 3) or ASTM 2362  (Ref 4).  The test should be
modified to conform to appropriate elements (e.g., media, growth conditions, etc) in the AOAC
International Tuberculocidal Activity of Disinfectants test. Ten carriers for each of two samples,
representing two batches of the product,  should be  tested against M. bovis BCG.   Instead of
spraying the inoculated surface of the carrier, the product should be tested by wiping the surface
of the carrier with the saturated towelette, and then subculturing the carriers after the specified
holding time.  One  towelette should be used to wipe  a minimum of 10 inoculated carriers.
Alternatively,  one carrier with a surface area equivalent to ten 1x1 inch carriers can be wiped
using one  towelette per carrier set per batch.  The log  density of M. bovis  should be >4.0
(corresponding to a geometric mean density of >1.0 x 104 CPU/carrier) a mean log density of
<4.0 invalidates the test.

       (B) Evaluation of tuberculocidal towelette  success. All organisms on all carriers should
be killed, and there should be no growth in any of the inoculated subculture media.

       (C) This testing is intended to support bridging of all mycobacteria listed on the EPA
registered liquid disinfectant used to saturate the towelette  to the EPA  registered towelette
product.

       (h)  Data collection  and reporting—(1) General. To assist in the proper  review and
evaluation  of product performance, complete descriptions of the  test employed and the results
obtained should be submitted to  the Agency. All  test reports should include,  at the least, the
following information:

       (i) Study title;

       (ii) Product Identity;
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       (iii) Guideline number/Data Requirement;

       (iv) Identification of the testing laboratory or organization;

       (v) Location where the test was performed;

       (vi) Name(s) of the person(s) responsible for the test;

       (vii) Statement of Confidentiality Claims;

       (viii) Statement of 40 CFR Part 160 Good Laboratory Practice compliance and Quality
Assurance Statement;

       (ix) Purpose of the study;

       (x) Date and time of the start and end of the test;

       (xi)  Test employed and any modifications (e.g., organic soil, hard water,  etc.), when
using standard tests (e.g.,  AOAC,  ASTM,  etc.)  all deviations  to the test methods should be
reported;

       (xii) Test  microorganisms  employed, including  identification of the  specific strain
(ATCC or other);

       (xiii) Description of the test substance, including the percent of active ingredient;

       (xiv) Concentration or dilution of the product tested and how prepared;

       (xv) Number of samples, batches and replicates tested;

       (xvi) Manufacture date of each product batch;

       (xvii) Identification of all material or procedural options employed, where such choice is
provided for or recommended in the test method selected (e.g., growth media, drying time for
inoculated   carriers,   neutralization   confirmation  and/or   subculture  media,   secondary
subculturing);

       (xviii) Test exposure conditions (e.g., contact time, temperature, and relative humidity);

       (xix) Complete reports of results obtained for each replication;

       (xx) Any control data essential to establish the validity of the test.

       (xxi) Carrier counts;

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       (xxii) Statistical treatment of the data;

       (xxiii) Conclusions;

       (xxiv) References;

       (xxv) Appendices, including study protocol and all raw data reports (per 40 CFR Part
160.185) associated with the conduct of the study.

       The applicant is encouraged to use the EPA's standard efficacy report format, which may
be found at http://www.epa.gov/oppad001/efficacvstudvstandards.htm.

       (2) Data for modifications of recommended methods. When recommended methods
are modified to support specific claims and/or use patterns for a product, the protocol, identifying
and describing each modification, should be provided with the study report. The applicant should
submit the proposed modification to the Agency for review and evaluation prior to initiation of
the test.

       (3) Data for other methods. When recommended methods, or modifications thereto, are
not employed to develop  efficacy data (such as actual in-use  or many kinds of simulated-use
testing), complete testing protocols should be submitted with the test reports.  All materials and
procedures employed in testing should be described in a manner consistent with original research
reports published in technical or scientific journals. Where references to published reports or
papers are made, copies or reprints of such references should be provided with  the test reports.
The applicant should submit the proposed testing protocols  for in-use or simulated-use  studies
(with a proposed label to  show the claims  to be supported by the protocol) to  the Agency for
review and evaluation prior to initiation of the test.

       (i) References.   The  references in this paragraph  may  be consulted for  additional
background  information:

       (1) Official Methods of Analysis of the AOAC International, Chapter 6, Disinfectants,
Use-Dilution Methods (955.14, 955.15, & 964.02), Current edition. AOAC International, Suite
500, 481  North Frederick Avenue, Gaithersburg, MD 20877-2417.

       (2) Official Methods of Analysis of the AOAC International, Chapter 6, Disinfectants,
Hard  Surface Carrier Test Methods, Current edition. AOAC  International, Suite 500, 481 North
Frederick Avenue, Gaithersburg, MD 20877-2417.

       (3) Official Methods of Analysis of the AOAC International, Chapter 6, Disinfectants,
Official Method 961.02 Germicidal  Spray Products as Disinfectants, Current  edition.  AOAC
International, Suite 500, 481 North Frederick Avenue, Gaithersburg, MD 20877-2417.
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       (4)  Annual Book of ASTM Standards, Standard Practice for Evaluation of Pre-saturated
or Impregnated Towelettes for Hard Surface Disinfection, Designation E2362. American Society
for Testing  and Materials, 100 Barr Harbor Drive,  West Conshohocken, PA 19428, current
edition.

       (5) Official Methods of Analysis of the AOAC International, Chapter 6, Disinfectants,
Official  Method 955.17   Fungicidal  Activity  of  Disinfectants.  Current  edition.  AOAC
International, Suite 500, 481 North Frederick Avenue,  Gaithersburg, MD 20877-2417.

       (6)  Annual Book of ASTM Standards, Test Method for  Efficacy of Virucidal Agents
Intended for Inanimate Environmental  Surfaces, Designation El053. American  Society for
Testing and Materials, 100 Barr Harbor Drive, West Conshohocken, PA 19428, current edition.

       (7) Annual Book of ASTM Standards, Standard Test Method  for  Neutralization of
Virucidal Agents in Virucidal Efficacy Evaluations, Designation  E1483. American Society for
Testing and Materials, 100 Barr Harbor Drive, West Conshohocken, PA 19428, current edition.

       (8)  Environmental  Protection   Agency,  Data   Call-in   Notice  for  Tuberculocidal
Effectiveness Data for All  Antimicrobial Pesticides with Tuberculocidal Claims (Registration
Division, Office of Pesticide Programs, June 13, 1986).

       (9) Official Methods of Analysis of the AOAC International, Chapter 6, Disinfectants,
Official Method  965.12 Tuberculocidal Activity  of Disinfectants. Current edition. AOAC
International, Suite 500, 481 North Frederick Avenue,  Gaithersburg, MD 20877-2417.
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