United States
 Environmental Protection
 Agency
 Health Effects Research
 Laboratory                   „
 Research Triangle Park NC 27711   ''x
 Research and Development
 EPA-600/S2-82-010  August 1982
 Project Summary
Comparison of Ames
Salmonella typhimurium  Plate
Incorporation Test  Protocols
Stephanie Toney and Larry D. Claxton
  This  document is a companion
volume to the Compilation of Ames
Salmonella typhimurium Plate Incor-
poration Test Protocols. Its purpose is
to tabulate the differences between
the submitted protocols and to note the
modifications from the 1975 Ames
reference. The tables show the differ-
ences obtained between laboratories
in bacterial strain maintenance, meta-
bolic activation systems, chemical
controls, preparation of  media and
solutions, and of the assay procedure
itself. The  recommendations of de
Serres and  Shelby and any revisions
by Ames are also included.
  No attempt is made to evaluate any
laboratory  or indicate a preferable
method for the test. Some laboratories
may have Standard Operating Proce-
dures (SOPs) that are more detailed
than the submitted protocols. Changes
or revisions that have taken place in a
protocol since  submission  are not
noted in this document. In addition,
laboratories that use Ames' reference
(1975)  as their main protocol may
have only sent their modifications.
  This Project Summary  was devel-
oped by EPA's Health Effects Research
Laboratory, Research Triangle Park,
NC, to  announce key findings of the
research project that is fully docu-
ed in a separate report of the same title
(see Project Report ordering informa-
tion at back).

Introduction
  In 1975,  Ames et  al.,  published a
detailed protocol that  incorporated the
 use  of a mammalian metabolizing
 system, thereby establishing the Ames
 test as a routine screening system for
 mutagenicity and potential carcinogeni-
 city. Since then, many laboratories have
 introduced a variety of changes and/or
 additions.
  The U.S. Environmental Protection
 Agency  (EPA) therefore decided to
 conduct an informal survey of laboratories
 that  utilize the Ames test. A list of
 laboratories routinely  performing the
 test was obtained from  Dr. Mike Shelby
 at the National Institute of Environmental
 Health Sciences,  Research  Triangle
 Park, NC. An initial letter was sent to the
 46 laboratories, 33 of which responded.
 These included six laboratories that no
 longer performed the Ames test,  one
 laboratory that had closed and 25
 laboratories that submitted protocols.
 The other responding laboratory elected
 to restrict usage of their protocol. A list
 of names and addresses of participating
 laboratories is  found in Table 1. This
 publication is a tabulated qualitative
 summary and comparison of the submit-
 ted protocols.

 Bacterial Strains

Bacterial Strains Routinely
 Used
  The Ames reference (1975) suggested
using three standard strains for routine
testing (TA1535, TA1537, and TA1538)
to be used in  combination with the
newer derivative strains (TA98.TA100).
  The majority of the participating labor-
atories use  all five tester strains

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Table 1.    Names and Addresses of Participating Laboratories
Dr. Andrew Sivak
Arthur D. Little. Inc.
25 Acorn Park
Cambridge, MA 02140
Mr. James P. Crow/ey
Battelle Columbus Laboratories
505 King Avenue
Columbus, OH 43201
Dr. Douglas M. Hanson
Bioassay Systems Corporation
100 Inman Street
Cambridge, MA 02139
Mr. Clyde R. Goodheart
Biolabs, Inc.
2910 MacArthur Blvd.
Northbrook, IL 60062
Dr. Rae E. Drazin
Bio- Technics Laboratories, Inc.
1133 Crenshaw Boulevard
Los Angeles, CA 90019

Dr. William T. Speck
Case Western Reserve University
Department of Pediatrics
2103 Adalbert Road
Cleveland, OH 44106

Dr. Steve Ha worth
EG&G  Mason Research Institute
1530 E. Jefferson Street
Rockville, MD 20852

Dr. Larry Claxton
Genetic Toxicology Division
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711

Dr. Vincent F. Simmon
Genex  Corporation
6110 Executive Blvd.
Suite 1090
Rockville, MD 20852

Ms. Nancy E. McCarroll
Hazleton Laboratories America, Inc.
9200 Leesburg Turnpike
Vienna. VA 22ISO

Dr. George C. Lavelle
Hill Top Research, Inc.
Department of Toxicology
Miamiville, OH 45147

Mr. Peter W. Barbara
IIT Research Institute
Life Sciences Division
10 West 35th Street
Chicago, IL 60616

Ms. Shirley Louie
Jefferson Professional Services
P.O.  Box 3397
Little Rock, AR 72203
Dr. Andrew M. Tometsko
Litron Laboratories. Ltd.
1351 Mt. Hope Avenue
Rochester, NY 14620

Dr. David Brusick
Litton Bionetics, Inc.
5516 Nicholson Lane
Kensington, MD 20795

Dr. Carol Richardson
Meloy Laboratories, Inc.
6715 Electronic Drive
Springfield, VA 22151

Mr. Andrew M. Losinkoff
Microbiological Associates
5221 River Road
Bethesda, MD 20016

Ms. JoAnne Gridley
Monsanto Research Corp.
1515 Nicholas Road
Dayton Laboratory
Dayton. OH 45407

Dr. John E. Preston
USEPA-NEIC
Bldg. 53
Box 25227
Denver, CO 80225

Dr. Bruce C. Casto
Northrop Services, Inc.
P.O. Box 12313
Research Triangle Park, NC 27709

Dr. Robert A.  Finch
Raltech Scientific Services
A Division of Ralston Purina Co.
P.O. Box 7545
Madison, Wl 53707

Mr. Thomas J. Hughes
Research Triangle Institute
Box 12194
Research Triangle Park, NC 27709

Dr. Nathan Greene
Southwest Foundation for Res. & Ed.
P.O. Box 23147
San Antonio. TX 78284

Dr. David C.L Jones
SRI International
333 Ravenswood Avenue
/We/7/o Park, CA 94025

Ms. Melanie Baltezore
UNILAB Research
2800 7th Street
Berkeley, CA 94710
routinely. Two of the laboratories do n<
use  TA1538 routinely. One uses  onl
three strains: TA98, TA100, and TA153
Another does not say what strains
uses. One laboratory appears to subst
tute TA1575 for TA1535.
Storage of Strains
  Ames is now employing master plate
for the temporary storage of strains. Hi
laboratory stores master plates in a coli
room, where all culturing is performed
The master plates are kept for one to twi
months. Their preparation involve!
making  minimal  glucose  agar  anc
spreading histidine and biotin. Ampicillir
is also spread on plates used for strain:
TA98 and TA100.  The plates sit for one
or two days to allow the compounds tc
diffuse into the media. The  six labora
tories that list a procedure report usinj
the same procedure as Ames. Perma-
nent storage is in a 2 ml sterile glass via
with rubber-lined screw  tops.  The
culture  is stored at a concentration ol
0.8 ml of a 16-h nutrient broth culture tc
0.07 ml DMSO. It is kept at -80°C in a
Revco freezer. The laboratories that list
a  procedure agree with the Ames
permanent test and revised temporary
storage  procedures.

Histidine Requirement Test
  Ames' recommendations for  the
histidine requirement test specify
minimal media petri plates. The Salmo-
nella  is  streaked  onto the  plate, an
aliquot of 0.1 ml of a 0.1 M solution of L-
histidine is then spread. Biotin is  also
used with strains that have the uvrB
deletion. An aliquot of 0.1 ml of a 0.5
mM solution is spread onto the plates.
Plates without histidine are used as a
negative control.  Nine  laboratories do
not mention the methods they employ to
monitor this requirement. Of the ones
who mentioned  a procedure,  five
laboratories  say that they check  this
requirement but  give no description.
Nine  laboratories repeat the Ames
procedure in their protocol. Two others
use an  overlay rather than  streak the
bacteria on the plate.
Determination of rfa
Character
  Ames uses nutrient agar plates and a
16-h incubation of 10s concentration
Salmonella in nutrient broth culture. A
total of  0.1  ml  of the tester strain is
added to an agar overlay and poured
on the nutrient agar plate. Ames gives
two possibilities for a  sensitivity  test
compound: an aliquot of 10/ulofa 1 mg/
ml solution  of crystal violet or 2 mg

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sodium deoxycholate. The  test com-
pound is applied to a sterile filter paper
disc which is then placed on the petri
plate. The plate is incubated for 12 h at
37°C  and then  interpreted. If the
mutation is still present there will be a
zone of inhibition around the disc. The
size of the zone is approximately 14 mm
for  crystal violet  and  13 mm  for
deoxycholate. Six laboratories do not list
a  method of determination,  and four
mention that they do the procedure. Of
the remaining laboratories, nine repeat
Ames' procedure, and two use minimal
agar  rather than nutrient agar. One
laboratory mentions the compound and
adds that it checks for this requirement.
One laboratory streaks the Salmonella
rather  than  using  an  overlay.  Two
others  use Mueller-Hinton plates in
combination  with a swab-streak  of
Salmonella.

Ampicillin Resistance
  Ames (1975) recommends using nu-
trient  agar plates for  the ampicillin
resistance test. A total of 10 /ul of an  8
mg/ml ampicillin solution in 0.02  N
NaOH  is  streaked on  the  plate and
cross-streaked with  Salmonella. After
12-24 h of incubation  at 37°C, the
plates  are evaluated. If the mutation  is
present (TA98, TA100) there should be
no zone of inhibition around the streak.
De Serres and Shelby recommended
that the ampicillin be put on the plate in
a disc form and used in combination
with a top-agar overlay. Six laboratories
do not list a procedure. Six others say
they perform this test but give no in-
structions. Three follow the procedure
given in Ames, 1975. Four laboratories
follow the recommendation of de Serres
and Shelby. Two use a Mueller-Hinton
plate with  an Ampicillin disc and  a
swab-streak of Salmonella. Three
others spread  the ampicillin over the
entire plate and score the mutation as
present with growth on the plate. One
laboratory does not check for this muta-
tion.

uvrB Deletion
  Ames uses nutrient broth agar with  a
streak of Salmonella for this test. Half
the plate is irradiated with a UV light for
6 seconds (8 seconds for TA98, TA100)
at a distance of 33 cm (i.e., plate to lamp
distance). The  plate is then incubated
for 12-24 h at 37°C and scored. If the
mutation is  present, no  growth will
occur  on the  exposed side. Eight
laboratories perform this test as de-
scribed. Eight do not list a procedure.
and four say they perform the test. One
differs from Ames only  in the use of
Mueller-Hinton plates. Two laboratories
use an overlay rather than a streak for
the Salmonella and also employ different
time intervals. One laboratory irradiates
sections of the plate from 10 sec to one
minute, and incubates for 48  h. One
laboratory does not list a  procedure but
says it uses Ames' identically.

Compound Sensitivity
Verification
  Ames recommends comparing TA98
and  TA100 to  its parent strains in a
standard assay with  Aflatoxin  61  and
methyl methanesulfonate  to show
increased  mutagenesis by  TA98 or
TA100. Only one laboratory  mentions
this procedure.

Spontaneous Reversion Rate
  Ames suggests that the spontaneous
reversion rate be checked in a standard
assay; an acceptable interpretation is
that plate counts fall within the standard
individual labortory's limits. Five labora-
tories check the reversion rate but give
no details. Eleven others follow  the
Ames  suggestion, and  nine  do  not
mention the procedure.

Metabolic Activation System

Preparation of S-9 Fraction:
I. Induction of Animal
  Ames uses the  PCB mixture  Aroclor
1254 for inducing male  rats  weighing
approximately  200 g, and suggested
using the Spraque-Dawley/Biol strain.
The  method of induction  is a single
intraperitoneal injection five days
before  sacrificing the  animal. The
dosage is 500 mg of  Aroclor per kg of
body weight, and  the concentration is
200 mg/ml suspended in corn oil. Food
and water are given adlibitrium  until 12
h before sacrifice, at which  time  the
food is removed. Three laboratories do
not describe their induction method.
Five  laboratories restrict their  discus-
sion  to the strain of rat and/or  the
induction chemical used. Nine others
use  essentially the same procedure
described by Ames. One laboratory
differs from Ames only in the strain of
rat used. Five  laboratories differ from
Ames in the time rats are deprived of
food — 24 h rather than 12. One labora-
tory sacrifices the rats by gassing COz.
One  laboratory uses Aroclor 1242
rather 1254 as an alternative to corn oil;
sesame oil is mentioned by one  labora-
tory.
Preparation of S-9 Fraction:
II. Preparation of Fraction
  Ames gives a detailed procedure for
the fraction preparation after sacrifice
of the rat. All work is done between 0
and  4°C using sterile materials and
solutions. The liver is  removed and
washed twice with cold 0.15 M KCI. It is
then minced with sterile scissors and
homogenized using a Potter-Elvehjen
homogenizer with a Teflon pestle. After
homogenizing, a Sorvall RC2-B centri-
fuge with a SS-34 head is used for  10
min  at  8700  rev/min (9000xg). The
decanted supernatant fraction is stored
in a 2 ml plastic liquid nitrogen storage
tube.  It  is quick-frozen on dry ice and
stored in a Revco freezer at -80°C. Five
laboratories  make  no mention of the
procedure. Five others list only the
centrifuge  speed  or organ used  or
storage temperature. Eight laboratories
give essentially the same procedure as
the one described  by  Ames.  Three
laboratories differ only in the amount of
fraction in a  storage container. One
expands the Ames protocol to include a
detailed homogenizing procedure. One
laboratory used a Polytron J21C centri-
fuge instead  of a Sorvall. Two use a
sucrose wash  in combination with two
KCI washes. One laboratory that uses a
sucrose wash also  centrifuges for  25
min rather than 10.

Preparation of S-9 Mix
   Ames lists the following ingredients
and amounts for the S-9 mix:

              S-9  -  0.04-0.1 ml/ml mix
              MgCb -  8 ^mole/ml mix
              KCI  - 33 //mole/ml mix
              G-6-P -  5 ^mole/ml mix
              NADP-  4//mole/ml mix
sodium phosphate buffer - 100 ^mole/ml mix

He recommends keeping the mix on  ice
for the  assay procedure and only
retaining it for several hours. Most
laboratories  use the quantities listed
above.  One laboratory does not list
quantities. The only significant differ-
ence is that one laboratory I isted the use
of 100 //mole  G-6-P/ml mix, 5 /umule
NADP/ml mix, and  4 jumole sodium
phosphate buffer/ml mix. One laboratory
omits KCI as a component in the mix.


Stock Solutions

Sodium Phosphate Buffer
  Ames  recommends using a  0.2  M
sodium phosphate buffer in the S-9 mix.

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 The pH  of the buffer  is 7.4 and the
 amount used per ml of mix is 100/umole.
 One laboratory does not say what buffer
 it  uses,  and two list the pH.  Five
 laboratories list the pH and amount of
 buffer used. Two others list the pH and
 the molarity  as described by Ames.
 Eight laboratories  give essentially the
 same  description  as Ames, and four
 use different  buffer molarities (0.125,
 0.4, 0.1 or 1 M). The laboratory using 1
 M  buffer uses 0.1 ml  buffer/ml mix.
 One other uses an NADPH generating
 system. One laboratory uses a mixture
 of  monobasic and dibasic sodium
 phosphate.

 Microsomal Salt Solution
  Ames  says  that  the microsomal salt
 solution  should consist of 0.4 M MgCI2
 and 1.65 M KCI. The quantities per ml of
 mix are  8 //mole MgClz and 33 //mole
 KCI.
  Twenty laboratories list the same
 quantities and/or  molarity as Ames.
 One laboratory does not give  any
• information  for the microsomal  salt
 solution. One laboratory gives the
 molarity as  0.4 M for both MgCI2 and
 KCI.  One laboratory reports 0.65 M
 concentration for KCI. Another reports
 standard molarities but  gives gram
 weights  10x higher than expected. One
 laboratory uses an NADPH generating
 system.

 Glucose Stock Solution
  Ames  lists no  directions for the
 preparation of a glucose stock solution.
 Five of  the  laboratories  make  no
 mention  of a glucose  stock solution.
 Sixteen laboratories say they use a 2%
 solution.  One laboratory  uses a  0.8%
 solution  and two use a 1% solution. One
 uses a stock solution of 20% but does
 not give the quantity of this solution that
 is used in the agar.

 Histidine/Biotin Stock
 Solution
  Ames reports a molarity of 0.5 mM for
 both the histidine and the biotin in the
 His/Bio  stock solution  or quantities of
 8.7136 mg/l histidine and 11.1045 g/l
 biotin. He recommended using 10 ml of
 the solution  per  100 ml top agar.
 Fourteen of the laboratories use these
 amounts. Two do not give instructions
 for this solution. One laboratory reports
 using trace amounts of His/Bio. Four
 use 0.05 mM  solutions. One laboratory
 uses 39 mg/l of histidine. One laboratory
 uses  10 /ug/ml of histidine and  12
 //g/ml of biotin in  their stock solution.
 One laboratory uses 0.0976 g biotin/l
 and 0.0525 g histidine/l in the solution.
 Another  uses  61.0  mg biotin/500 ml
 and 48.0 mg histidine/500 ml and 100
 ml of the stock solution per liter of top
 agar.

 VBME Salt Solution
   Ames does not give instructions for
 the preparation of the VBME solution.
   Vogel's reference gives the following
 gram amounts per liter of solution:

     MgS04-7H20     - 10g
     Citric Acid • HaO    - 100g
     KZHP04-Anhydrous -500g
     NaNH4-HP04-4H20 -175g
     H20               -670ml

 The pH is 7.0 and the solution is a 50x
 concentration. Fourteen  of the  labora-
 tories use these same instructions and
 10 give none. One laboratory gives the
 same  gram amounts but lists the
 concentration of the solutions at 25x.

Media

Top Agar  Overlays
  Ames recommends a solution of 0.6%
Difco agar and 0.5% NaCI for top agar.
Before using, the top agar is melted in a
steam  bath  and 10 ml  of a His/Bio
solution is added to 100 ml of top agar.
The His/Bio solution consists of a 0.5
mM concentration of histidine and a 0.5
mM concentration of biotin. Aliquots of
2 ml are pipetted into culture tubes and
kept warm until use. Nine laboratories
prepare overlays by this procedure. Nine
others give the quantities  of the
ingredients or the His/Bio concentration
but do not  elaborate  further. One
laboratory does not list information on
the overlays. Three use media other
than Difco, and three use concentrations
different from those recommended by
Ames.

Petri Plate Agar
  Ames specifies Falcon plastic 100 x
15 mm petri  plates, and 30 ml of a 1.5%
Bacto-Difco agar with 2% glucose and
VBME salt solution for the bottom agar.
Two laboratories do not discuss their
petri plate agar. For most, the amount of
agar in a plate ranges from 20 to 30 ml.
Three  laboratories prefer nonethylene
oxide sterilized plates. Two laboratories
do not use Difco agar. Thirteen labora-
tories follow the recommendations of
Ames. One  laboratory uses 16 g/l of
agar.  Four laboratories do not indicate
the agar concentration.
Nutrient Broth
  Ames originally used Difco Nutrien
Broth  but has  since  recommendei
Oxoid #2 broth. Seven laboratories sa
they use Oxoid #2. Five laboratories usi
Difco;  one uses Columbia Broth,  am
one recommends Lab-Lemcopowder an<
peptone. The 11 remaining laboratories
do not indicate the type of broth used ii
this laboratory.

Chemical Controls

Control Mutagens/
Carcinogens Routinely  Used
  For activation  assays Ames recom-
mends using 2-aminoflourene, aflatoxin
Bi, and benzo(a)pyrene. De Serres and
Shelby recommend using 2-aminoan-
thracene solely.  Fourteen laboratories
use  2-aminoanthracene  exclusively.
Two laboratories use 2-aminofluorene
exclusively. Two others use  2-amino-
anthracene and  benzo(a)pyrene.  One
laboratory   uses  2-aminoflourene and
aflatoxin 61, and another uses benzo(a)-
pyrene, 2-aminoanthracene,  and pro-
flavine. Five laboratories do not indicate
what chemical they use.
  For nonactivation assays using strain
TA1535 Ames recommends N-methyl-
N-nitrosoguanidine (MNNG) and de
Serres and Shelby recommend methyl
methanesulfonate (MMS).  Six labora-
tories  use MNNG exclusively. Nine
laboratories use sodium azide solely.
Another uses 1,3-propanesultone. One
laboratory uses MNNG,  MMS, and
sodium azide. Another uses sodium
azide and 4-fluoro-3-nitrophenyl azide.
Still another uses  sodium nitrite, N-
hexyl-N-nitro-N-nitrosoguanidine.  One
laboratory  uses MNNG, MMS,  and 4-
Nitroquinoline-N-oxide, and five do not
say what chemical they use.
  When using TA1537 Ames and de
Serres both recommend using  9-
aminoacridine. Eighteen  laboratories
follow this recommendation. Five labor-
atories do not say what chemical they
use. One  laboratory  uses 4-fluoro-3-
nitrophenyl azide, and another uses
MNNG and 9-aminoacridine.
  For TA1538 Ames suggests 2-amino-
fluorene and de Serres recommends 4-
nitro-0-phenylene diamine, 2-nitro-
fluorene, and hycanthone  methanesul-
fonate. Thirteen laboratories  use 2-
nitrofluorene only. Seven do not list the
chemical they use. One laboratory uses
Daunomycin exclusively,  and another
uses 2-aminofluorene exclusively. One
laboratory uses 2-nitrofluorene and 4-
nitro-0-phenylene diamine while  one

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 uses 2-nitrofluorene and 4-fluoro-3-
 nitrophenyl azide. One laboratory uses
 MNNG and 4-nitroquinoline-N-oxide.
   When using TA98 Ames recommends
 4-nitroquinoline-N-oxide, Oaunomycin,
 2-aminofluorene, and aflatoxin Bi. De
 Serres recommends using 4-nitro-O-
 phenylene diamine, 2-nitrofluorene,
 and hycanthone methanesulfonate.
 Fourteen  laboratories use 2-ntirofluor-
 ene only. Six laboratories do not list a
 chemical. One laboratory uses Dauno-
 mycin only and one uses 4-nitroquino-
 line-N-oxide only. One laboratory uses
 2-nitrofhJorene and hycanthone meth-
 anesulfonate. Another uses 2-nitro-
 fluorene and 4-fluoro-3-nitrophenyl
 azide. Still another uses Daunomycin,'
 MMS, and 4-nitroquinoline-N-oxide.
   For strain TA100 Ames suggests
 MMS, MNNG, 2-aminofluorene, afla-
 toxin Bi, and 4-nitroquinoline-N-oxide.
 De Serres' recommendations are sodium
 azide, MMS, and  nitrofurantoin. Nine
 laboratories use sodium azide only, and
 three use MNNG only. One laboratory
 uses 1,3-propane sultone, and one uses
 MMS;  another  uses  benzo(a)pyrene
 only. Five laboratories do not list  the
 chemical they use. One laboratory uses
 MMS and MNNG.  One laboratory uses
 MNNG, MMS, sodium azide, and nitro-
 furantoin. One laboratory uses sodium
 azide, 4-fluoro-3-nitrophenyl azide.
 Another uses MMS and 2-nitrofluorene.
 Still another uses MNNG, MMS, and 4-
 nitroquinoline-N-oxide.
Preparation of Control
Mutagens/Carcinogens

  Ames recommends the disposable
sterile polystyrene screw cap tube as the
container of use for carcinogens and
lists four possible solvents: H20, DMSO,
ethanol, or p-dioxane. Fourteen labora-
tories do not discuss their method of
preparation. Two  laboratories  follow
Ames' procedure. Five  others list only
the solvent used. Four laboratories list
either their storage container or proce-
dure.
Assay Procedure

  Ames recommends the following
procedure for the assay. An aliquot of
0.1 ml from a 108 culture of Salmonella
is added  to  a  tube containing  2 ml
molten top agar at 45°C, followed by the
sample to be tested and 0.5 ml of S-9
mix. The tube is rotated between the
palms and, within 20 sec, poured onto a
petri plate. The plates are left to harden
for one hour and then incubated in the
dark for two days at 37°C. De Serres and
Shelby recommended a culture of 1 or 2
x 109 concentration of Salmonella and
an  extension of the incubation  time
from 48 h to 48-72 h. They suggested
duplicate plating as the minimum with
triplicate plating preferred, and used ali-
quots of 0.2 fjg to 5 mg of sample. They
recommended both that sterility con-
trols include the solvent and S-9 mix,
and that spot checked phenotype moni-
toring be performed.
  The most variation among the labora-
tories comes in the order  in which
constituents are added. Half the labora-
tories indicate a preference to the order
of addition: Salmonella, sample, and S-
9. The other laboratories use different
permutations or do not list an order.
Temperatures for top agar vary from 43
to 56°C. Incubation times range from 36
to 72 h. Duplicate or triplicate plating is
recommended. Five laboratories substi-
tute the volume taken up by S-9 by using
KCI, saline, or buffer in a nonactivation
assay. Three laboratories place  their
plates in sealed bags for the incubation
time.
  Ames has revised his mixing tech-
nique: he now uses a vortex at low
speed. Eight laboratories mention using
a vortex in their protocols.
  Three laboratories indicate use of
only a preincubation technique with the
Salmonella and sample.
Discussion

  As a first step in establishing Quality
Assurance/Quality Control  (QA/QC)
procedures for in vitro bioassays, the
Ames Salmonella  plate incorporation
bioassay protocols from 25 laboratories
were compared. At  this stage, no
attempt was made to evaluate a protocol
or to designate a preferred method.
  In general, most laboratories follow
most of the procedures as outlined by
Ames; however, it appears that each
laboratory deviates from this standard
protocol in some manner. There was
strong concordance with Ames on the
selection of tester strains, the prepara-
tion of the S-9 mix, and the preparation
of the microsomal salt solution.
  Most  laboratories differ from  the
Ames, et al., 1975 protocol in  the
selection  of some control compound
and in  the actual assay  exposure
procedure. Only one  laboratory pre-
scribed the  routine  verification of
compound sensitivity for strains TA98
and TA100. Most procedures and media
preparation instructions were left out of
one or  more  protocols; however,  a
laboratory SOP may have  included
these instructions.
  Comparison of current protocols may
improve both individual experimental
procedures and the  consistency of
results from different laboratories In
addition, this study may  help identify
monitorable parameters within the test
procedures so that adequate QA/QC
procedures can be established.
   Stephanie Toney is with Northrop Services, Inc., Research Triangle Park, NC
    27709; the EPA author Larry D. Claxton (also the EPA Project Officer, see
    below) is with the Health Effects Research Laboratory, Research Triangle
    Park, NC 27711.
   The complete report, entitled "Comparison of Ames Salmonella typhimurium
    Plate Incorporation Test Protocols," (Order No. PB 82-234 253; Cost: $10. SO,
    subject to change) will be available only from:
          National Technical Information Service
          5285 Port Royal Road
          Springfield, VA 22161
          Telephone: 703-487-4650
   The EPA Project Officer can be contacted at:
          Health Effects Research Laboratory
          U.S. Environmental Protection Agency
          Research Triangle Park, NC 27711
                                                                                                  •US OPO:1M2-599-
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United States
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