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					                 DR .MED . R .      RYLANDER               7237

                 c/o FABRIQUES DE TABAC REUNIES S .A .   FTE/SZA
                                                                SZA11RA1
                 Switzerland




                 S U B R E P O R T M I C R O B I O L O G Y



                 P 0500/3126




                 3-DAY INHALATION STUDY WITH



                 SIDESTREAM SMOKE OF



                 STANDARD REFERENCE CIGARETTE 2R1,



                 NICOTINE, SIDESTREAM SMOKE OF



                 NONTOBACCO CIGARETTE X6D6MW WITHOUT AND WITH



                 ADDED NICOTINE AND WITH FORMALDEHYDE,



                 ACETALDEHYDE, ACROLEIN, AND AMMONIA



                 ON RATS




http://legacy.library.ucsf.edu/tid/nek81f00/pdf
  S




                    INBIFO Institut fiir biologische Forschung • KBIn
                    FORM 51 .KW 86 ERO/MWO RZ50(DIV)B20 (BRA,MWO)


                    SUBREPORT-LAUFZETTEL (a)                                                    P 0500 / 3126 ~

                                                                                            .

                    I TEAM : MB                                                                 BLATT NR
                                                                                                           T
                     TITEL : 3-Day Inhalation Study with Sidestream Smoke of
                             Standard Reference Cigarette 2R1, Nicotine, Sidestream
                             Smoke of Nontobacco Cigarette X6D6MW without and with
                             added Nicotine and with Formaldehyde, Acetaldehyde,
                             Acrolein and Ammonia on Rats (PT)




                     VORGANG                                STELLE        DATUM                                  ZN
                                                            BZW .
                                                            PERSON        EINGANG AUSGANG


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                         1(orrc~~~~_~e~~                                                                              ~
                              ~                                                      (f~          #.,Qp do            ~
                         T t6.~ .~~~c
                                                                          2 4. SEP,198




               N                                            REVIEW DURCBFOHREN (b)
               d
              G
                                                            QA                  x
              r, : (a) Erlauterungen s . Riicks .
              .- (b) von GM eingetragen                     RP-SC

                                                            RP-OP
         61 KW B3


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                                                                                   1-1

                .




                    FORM 46 .KW 86 ERO/MWO RZ50(DIV)B16 (BRA,MWO)




                Erlauterungen zum Subreport-Laufzettel :


                    (1) Der Titel ist vom Projektleiter einzutragen .

                    (2) Jede Weitergabe des Subreports ist durch Ausgangsdatum
                        beim Weitergebenden und Eingangsdatum beim Empfanger
                        mit Datum und Zeichen zu dokumentieren . Der Weiter-
                        gebende ist fur das Eintragen dieser Daten zustandig .

                    (3) Folgende Stationen hat jeder Report mindestens einmal
                        zu durchlaufen und sind demnach fur jeden Report zu
                        dokumentieren :

                       Erstellen der Originale durch RP,
                       Prufung der Originale durch den Autor,
                       Prufung des Subreports durch die auf der Verantwort-
                       lichkeitenseite genannten Personen,
                       Prufung der Numerierung, des Inhaltsverzeichnisses
                       und der Verweise im Text durch RP,
                       Korrekturlesen und Ausfuhren von Korrekturen durch RP,
                       Freigabe durch den Autor, den Team-Manager, den
                       Projektleiter,
                       RP-Meeting,
                       Abgabe bei GM zur Kenntnisnahme, der den weiteren Ablauf
                       bestimmt,
                       QA-Check,
                       Kenntnisnahme letzter Anderungen durch die Personen,
                       die den Report freigaben,
                       Binden des Reports durch RP,
                       Briefbeschaffung, Verpackung und Dokumentation des
                       Reportausgangs durch RP

                    (4) Der Subreport-Laufzettel ist Teil des Project Management
                        Files (PMF), verbleibt bis zum Reportausgang aber beim
                        Report und wird erst danach im PMF eingeordnet .




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                INBIFO Institut fur biologische Forschung • KtSln
                SUBREPORT P 0500/3126 SZA11RA2 7233                     MB PAGE 0-1




                CONTENTS                                                MB PAGE




                ABBREVIATIONS                                           0-3


                1      SUMMARY                                          1-1

                1 .1   Objectives                                       1-1

                1 .2   Experimental Conduct                             1-1

                1 .3   Results                                          1-2

                1 .4   Comment                                          1-2


                2      RESPONSIBILITY                                   2-1


                3      INTRODUCTION                                     3-1


                4      METHOD                                           4-1

                4 .1   Chronology                                       4-1

                4 .2   Groups, Rat No ., and Concentrations             4-1

                4 .3   Microbiological Screening of Rats                4-1

                4 .4   Bacteriological Screening of the Environment
                       within the Animal Quarters                       4-15

                4 .5   Identification of Bacteria According to INBIFO
                       Standard Operating Procedures                    4-18

                TABLE A : CHRONOLOGY OF MICROBIOLOGICAL SCREENING       4-10

                TABLE B : GROUPS, RAT NO ., AND CONCENTRATIONS          4-11

                TABLE C : UNTREATED RATS EXAMINED PATHOLOGICALLY
                           AND MICROBIOLOGICALLY ON ARRIVAL             4-13           N
                                                                                       Q
                TABLE D : SIGNIFICANCE OF ANTIBODY TITERS AGAINST                      N
                           VIRUSES AND MYCOPLASMS                       4-14          (~
                                                                                       ~
                FIGURE A : CHRONOLOGY, EXPERIMENTAL PART                4-2           (~
                                                                                       ~
                                                                                       ~
                                                                                       ~
                                                                                       ~




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                CONTENTS                    (continued)                  MB    PAGE



                 5 RESULTS AND DISCUSSION                                          5-1

                5 .1 Text                                                          5-1
                 5 .1 .1 Laboratory rats                                           5-1
                 5 .1 .2 Environment                                               5-1
                 5 .1 .3 Conclusion                                                5-2

                5 .2 Tables                                                        TABLE

                SEROLOGICAL SCREENING FOR VIRUS AND MYCOPLASM ANTIBODY
                TITER BY EXTERNAL EXPERT                                            1

                BACTERIOLOGICAL SCREENING OF RAT ORGANS                             2

                PARASITOLOGICAL SCREENING OF RAT URINARY BLADDER AND
                INTESTINE FOR ENDOPARASITES                                         3

                PARASITOLOGICAL SCREENING OF RAT SKIN AND HAIR FOR
                ECTOPARASITES                                                       4

                BACTERIOLOGICAL SCREENING OF LABORATORY SURFACE                     5

                BACTERIOLOGICAL SCREENING OF LABORATORY AIR                         6

                BACTERIOLOGICAL SCREENING OF NONAUTOCLAVED DIET FOR
      I         SALMONELLA SP .                                                     7

                BACTERIOLOGICAL SCREENING OF AUTOCLAVED DIET                        8

                BACTERIOLOGICAL SCREENING OF AUTOCLAVED DRINKING WATER              9

                BACTERIOLOGICAL SCREENING OF AUTOCLAVED CAGE BEDDING
                MATERIAL                                                           10

                BACTERIOLOGICAL SCREENING OF LABORATORY STAFF'S
                FINGERTIPS                                                         11

                BACTERIOLOGICAL SCREENING OF LABORATORY STAFF'S FACE                             ~
                MASKS                                                              12            Q
                                                                                                 ~
                                                                                                 ~
                                                                                                 ~
                                                                                                 ~
                                                                                                 ~
                                                                                                 ~
                                                                                                 ~
                                                                                                 N

                Remarks : This subreport, including title page, contains 45 pages .




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                INBIFO Institut fur biologische Forschung • KoIn
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                ABBREVIATIONS (a,b)



                CFU    : colony forming units
                MB     : team Microbiology
                MW     : cigarette type X6D6MW
                RAS    : real time aerosol sensor
                RT     : room temperature
                SOP    : standard operating procedure
                sp .   : species
                SS     : sidestream smoke
                "TPM" : total particulate matter, determined       by RAS




                 (a) in addition to those, which are explained immediately on the
                     same page
                 (b) Units of measure are given in accordance with SI-norms
                     (Systeme International d'Unites) .




                3285

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                 1 SUMMARY



                1 .1 Objectives


                In accordance with the objectives of this study as specified in
                the SUMMARY of the INTEGRATING REPORT, the team Microbiology
                was responsible for
                 (1) the virological, bacteriological, and parasitological screen-
                       ing of the rats and
                 (2) the routine bacteriological surveillance of the environment
                       within the animal quarters .




                1 .2 Experimental Conduct


                In order to determine the hygienic status of the rats on arrival,
                a microbiological screening program was performed . 16 untreated
                rats, 2 of each shipment, were screened microbiologically . Sero-
                logical examinations were performed extramurally to detect anti-
                bodies against rat-related pathogenic viruses and mycoplasms .
                Bacteriological examinations with particular respect to trachea
                and lung and parasitological examinations were performed intra-
                murally .


                A routine surveillance program of the environment within the
                animal quarters was performed to examine periodically the labora-
                tory unit, animal diet, drinking water, cage bedding material as
                well as the laboratory staff for satisfactory hygienic conditions .


                The identification of the bacteria isolated after growth under
                aerobic conditions was carried out according to their growth
                on selective and differential media, their stainability, and their
                biochemical characteristics .




                'hR5


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                 1 .3 Results


                 All 16 untreated rats - 2 of each shipment on arrival - examined
                 for the presence of antibodies to 6 rat-related viruses and to the
                 pneumotropic bacterium Mycoplasma pulmonis were found to be free
                 from those pathogens . The organs heart, kidney, liver, lung,
                 spleen, and trachea as well as the urine of all rats examined
                 for the presence of bacteria were found to be sterile . The intes-
                 tines and the urinary bladder as well as skin and hair of all rats
                 were found to be free from endo and ectoparasites .


                 The laboratory unit was examined prior to the introduction of rats
                 or during the exposure periods and was found to be sufficiently
                 disinfected . The incoming air was sterile and the amount of
                 bacteria detected in the laboratory room air was low . The non-
                 autoclaved diet was free from Salmonella sp . 5 out of 12 samples
                 of the autoclaved diet and 2 out of 8 samples of the autoclaved
                 drinking water were found to be slightly contaminated with non-
                 pathogenic gram-positive bacteria . The cage bedding material was
                 found to be sterile . No pathogenic bacteria were detected on
                 face masks of the laboratory staff . The potential pathogenic
                 gram-positive Staphylococcus aureus observed in 1 room air sample
                 and in 1 fingerprint sample of the laboratory staff was determined
                 as a not human origin strain and may have been derived from the
                 animals .




                 1 .4 Comment


                 All rats examined (i . e . 4 percent of the rats derived) were found
                 to be free from pathogenic viruses, bacteria, and parasites .
                 Aside from some contaminated autoclaved diet and drinking water
                 samples the results of the microbiological examinations of




                II   RS


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                the environment within the animal quarters were in agreement with
                the microbial flora acceptable for the hygienic conditions during
                short-term studies on rats .




                                                               I N B I F O
                                                         Institut fiir biologische
                                                              Forschung GmbH




                'i9AS

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                 2 RESPONSIBILITY

     I




                                                              Dr .rer .nat . F . Tewes
                                                              Biologist (Diplombiologe)




                Quality Assurance :                           . . .  . . . . . . . . . . . . . . . . . . . . . . . . .
                                                              E . Romer
                                                              Biologist (Diplombiologe)




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                3 INTRODUCTION



                Laboratory animals in conventional or barrier-maintained housing
                units are sometimes affected by infectious viruses, bacteria,
                f ungi, protozoa or parasites . Because of the impact on the inter-
                pretation of experimental research, it is important to recognize
                those microorganisms and their effect on the animals .


                In the present inhalation study microbiological checks on infec-
                tious contaminants in the laboratory rats as well as in their
                environment within the animal quarters were performed . The rats
                were screened for pathogenic viruses such as the reovirus type
                3, which is able to cause diseases in the digestive system, for
                the parainfluenza virus type 1 murine, which causes diseases in
                the respiratory system, for the coronavirus, which causes acute
                rhinitis, and for the common endemic and potential covert contam-
                inants such as the H 1 virus, the pneumonia virus of mice, and the
                latent rat virus . The rats were also screened for the presence
                of serological activity to the pathogenic bacterium Mycoplasma
                pulmonis and the presence of endoparasitic protozoa and helminthes
                as well as for ectoparasitic arthropoda .


                In order to detect infectious bacteria as soon as possible, the
                laboratory unit, diet, drinking water, cage bedding material as
                well as the laboratory staff were screened routinely, so that
                preventive steps could be taken to exclude entry of those bacteria
                to the rats . The routine detection of bacteria was limited to
                gram-positive and gram-negative rods and cocci growing under
                aerobic conditions on blood or nutrient agar plates .




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               4 METHOD


               4 .1 Chronology
                          (see FIGURE A and TABLE A)

               4 .2 Groups, Rat No ., and Concentrations
                          (see TABLE B)

               4 .3 Microbiological Screening of Rats

               Serological screening for
               the presence of viruses
               and mycoplasms

                       Sample material and
                       quantity :     approx . 1 .5 ml blood from the retro-
                                           bulbar venous plexus of each of 16 rats
                                           (a), 2 untreated rats of each shipment
                                           (see TABLE C)

                                                           analysis of serum performed by
                                                           CRPS Charles River Professional
                                                           Services, Inc .,
                                                           via Charles River Wiga GmbH,
                                                           D-8741 Sulzfeld 1

                       Time :   1   day     after         arrival       at   INBIFO

                       Results expressed in : species and antibody titer of
                                                   viruses and Mycoplasma pulmonis
                                                    (see TABLE D)


               Bacteriological screening

                       Sample material and
                       quantity : heart,         kidney, liver, lung, spleen,
                                                      trachea, and urinary bladder washout
                                                      of each of 16 rats (a), 2 untreated
                                                      rats of each shipment (see TABLE C)
                                                                                                ~
                       Time :                              1 day after arrival at INBIFO        0
                                                                                                N
                       Results expressed in :              total number of CFU per sample and   ~
                                                           bacteria species                     ~
                                                                                                ~
                                                                                                rA




                (a) identical rats used for all serological, bacteriological, and
                    parasitological screenings



                s2a5

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                                                                       4.              15 .
                                                                       DEC .           DEC .
                                                                       86              86

                                                                       - -             I - -
                 day of study                                         -10               1

                 arrival of rats                                       A

                 identification of rats                                     A

                 screening of rats
                    microbiological                                         A
                    pathological                                       A

                 sham exposure of rats                                                 A

                 test      substance             exposure             of        rats   A    A   A

                 determination for
                 biological monitoring
                    body         weight  A  A  A   A  A   A
                    C02
                    general condition and behavior A A A A

                 determination for monitoring
                 test substance generation
                    CO
                    "T PM"
      I             nicotine
                    ammonia
                    aldehydes                   A                                 A   A
                    temperature of air A                                          A A A
                    relative            humidity A                                A A A

                dissection                                                                      A

                                                                      I - I -               -
                                                                      -10  1




                FIGURE A

                 CHRONOLOGY, EXPERIMENTAL PART

                Remarks : A : groups exposed to acrolein




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                                                                    15 .             26 .
                                                                    JAN .            JAN .
                                                                    87               87

                                                                    - -              I - - - -
                 day of study                                       32               43

                 arrival of rats                                    B

                 identification of rats                                  B

                 screening of rats
                    microbiological                                      B
                    pathological                                    B

                 sham exposure of rats                                               B

                 test     substance             exposure            of       rats    B   B   B

                determination for
                biological monitoring
                   body         weight                      B       B        B   B       B       B
                   C02
                       general condition and behavior B B B B

                determination for monitoring
                test substance generation
                   CO
                   "TPM"
                   nicotine
                   ammonia
                   aldehydes                   B                                 B   B
                   temperature of air B                                          B B B
                   relative            humidity B                                B B B

                dissection                                                                   B

                                                                    I - I - -                -   -
                                                                    32   43




                FIGURE A (continued)

                CHRONOLOGY, EXPERIMENTAL PART

                Remarks : B : groups exposed to acetaldehyde




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                                                                    22 .              2.
                                                                    JAN .             FEB .
                                                                    87                87

                                                                    - -                I - -
                day of study                                         39                50

                arrival of rats                                     C

                identification of rats                                    C

                screening of rats
                   microbiological                                        C
                   pathological                                     C

                sham exposure of rats                                                 C

                test      substance            exposure             of        rats    C     C   C

                determination for
                biological monitoring
                    body              weight                C       C         C   C       C     C
                    C02
                    general        condition           and     behavior           C   C     C   C

                determination for monitoring
                test substance generation
                   CO
                   "TPM"
                   nicotine
                   ammonia
                   aldehydes                   C                                  C   C
                   temperature of air C                                           C C C
                   relative            humidity C                                 C C C

                dissection                                                                      C

                                                                     I -          I - -         -
                                                                     39            50




                FIGURE A (continued)

                CHRONOLOGY, EXPERIMENTAL PART

                Remarks : C : groups exposed to formaldehyde




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                                                                   29 .            9.
                                                                   JAN .           FEB .
                                                                   87              87

                                                                   - -             I - -
                day of study                                       46              57

                arrival of rats                                    D

                identification of rats                                  D

                screening of rats
                   microbiological                                      D
                   pathological                                    D

                sham exposure of rats                                              D

                test        substance          exposure            of       rats   D   D    D

                determination for
                biological monitoring
                   body         weight  D  D  D   D  D                                       D
                   C02
                   general condition and behavior D D D                                     D

                determination for monitoring
                test substance generation
                        Co
                        "TPM"
                        nicotine
                        ammonia                                                            D D
                        aldehydes
                        temperature   of air                                       D D D D
                        relative humidity                                          D D D D

                dissection                                                                       D

                                                                    I -            I - -
                                                                    46         57



                FIGURE A (continued)

                CHRONOLOGY

                Remarks : D : groups exposed to ammonia




                19 HR


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                                                                   12 .     23 .
                                                                   MAR .    MAR .
                                                                   87       87


                 day of study                                      88       99

                 arrival of rats                                   E

                 identification of rats                                 E

                 screening of rats
                    microbiological                                     E
                    pathological                                   E

                 sham exposure of rats                                      E

                 test substance exposure of rats                                    E E

                 determination for
                 biological monitoring
                        body weight                                     E   E E E E E
                        C02                                                 E E E E
                        general condition and behavior                      E E E E

                 determination for monitoring
                 test substance generation
                        CO        E     E      E
                        "TPM"          E   E    E
                        nicotine         E   E   E
                        ammonia         E    E   E
                        aldehydes        E   E   E
                        temperature of air E E E E
                        relative humidity  E E E E

                 dissection                                                         E

                                                                   I - I - -        -     -
                                                                   88   99



                 FIGURE A (continued)

                 CHRONOLOGY, EXPERIMENTAL PART

                 Remarks : E : groups exposed to SS of MW




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                                                                     19 .             30 .
                                                                     MAR .            MAR .
                                                                     87               87

                                                                     - -              I - - -
                 day of study                                        95               106

                 arrival of rats                                     F

                 identification of rats

                 screening of rats
                    microbiological                                       F
                    pathological                                     F

                 sham exposure of rats                                                F

                 test      substance             exposure            of       rats    F   F   F

                 determination for
                 biological monitoring
                        body     weight     F   F  F   F  F   F
                        C02           F      F      F      F
                        general condition and behavior F F F F

                 determination for monitoring
                 test substance generation
                    CO
                    "TPM"
                    nicotine                                         F            F       F
                    ammonia
                        aldehydes
                        temperature  of air                                   F   F   F       F
                        relative  humidity                                    F   F   F       F

                 dissection                                                                   F

                                                                      I - - I - -
                                                                      95   106



                 FIGURE A (continued)

                 CHRONOLOGY, EXPERIMENTAL PART

                 Remarks : F : groups exposed to nicotine




                 3285


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                                                                      26 .           6.
                                                                      MAR .          APR .
                                                                      87             87

                                                                      - -            I - -
                 day of study                                         102            113

                 arrival of rats                                      G

                 identification of rats                                   G

                 screening of rats
                    microbiological                                       G
                    pathological                                      G

                 sham exposure of rats                                               G

                 test      substance            exposure             of       rats   G   G   G

                 determination for
                 biological monitoring
                        body    we   ight    G   G  G  G  G   G
                        C02           G      G      G      G
                        general condition and behavior G G G G

                 determination for monitoring
                 test substance generation
                        CO        G     G      G
                        "TPM"          G   G    G
                        nicotine         G   G   G
                        ammonia         G    G   G
                        aldehydes        G   G   G
                        temperature of air G G G G
                        relative humidity  G G G G

                 dissection                                                                  G

                                                                      I - I - -
                                                                      102  113




                 FIGURE A (continued)

                 CHRONOLOGY, EXPERIMENTAL PART

                 Remarks : G : groups exposed to SS of MW with added nicotine




                 t?RS

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                                                                    2.              13 .
                                                                    APR .           APR .
                                                                    87              87

                                                                     - -            I - - -
                day of study                                         109            120

                arrival of rats                                      H

                 identification of rats                                  H

                screening of rats
                   microbiological                                       H
                   pathological                                      H

                sham exposure of rats                                               H

                test      substance             exposure            of       rats   H   H   H

                determination for
                biological monitoring
                       body     weight      H  H  H   H  H   H
                       C02           H      H      H      H
                       general condition and behavior H H H H

                determination for monitoring
                test substance generation
                       CO        H     H      H
                       "TPM"          H   H    H
                       nicotine         H   H   H
                       ammonia         H    H   H
                       aldehydes        H   H   H
                       temperature of air H H H H
                       relative humidity  H H H H

                dissection                                                                  H

                                                                     I - I - -              -
                                                                     109  120




                FIGURE A (continued)

                CHRONOLOGY, EXPERIMENTAL PART

                Remarks : H : groups exposed to SS of 2R1




                3285

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            YEAR MON'!ii LABORAZORY LABORA7.ORY ANIMAL DIET   DRINKING CAGE IABORATORY STAFF
                         RAT UNIT                             4PTER BEDDIN6
                                                                        NATERIAL
                                           SUR- AIR NONAUIC)- AUi'C}- FINGER- FACE
                                           FACE CLAVED (a) CLAVED PRIU7r MASK


             1986 Dec . +                  +             +    +         +         +    +   +    +
             1987 Jan . +                  +             +    +         +         +    +   +    +
                  Feb . (b) -
                  Mar . +                  +             +    -         +         +    +   +    +
                  Apr . +                  +             +    -         +         +    +   +    +
                                                                                                          7
                                                                                                          a
                                                                                                          ~
            TABLE A

            CHROiOLOG'Y OF M,IC%)BIOIfJGICAL SCREENING




            (a) each batch of diet examined microbiologically immediately on arrival
            (b) due to technical reason not samples taken in Feb .87




              4sst ss szoz

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          SUBREPORT P 0500/3126 SZA11RA21 7233                                                                                   1rB PAC'~E 4-11



         TEST GfmUP RAT IQ) . C70r1CENi1tP.TION
         SUBSTANCE
                                  00 "Tw" NICOTINE FCIRMAIDEIimE ACEPALDEEIYDE ACRlJLEIN AMMCNIA
                                                     (ul/1) (ug/1) (ug/1) (ul/1) (ug/1) (ul/1) (ug/1) (ul/1) (ug/1) (ul/1) (ug/1) (ul/1)

                                                                                                                                                     0
                                                                                                                                                     0
         sham-exposed 1 .0-GR       100   to   109     0      0       0      0         0      0       0      0      0   0           0  0            co
         SS of 2R1 1 .1-GR          110   to   119    33     14 .2    1 .6   0.2       0 .2   0 .2    2      1 .1   0 .2 0 .1       4  5 .7          ~
                                                                                                                                                    C)
                       1 .2-GR      120   to   129   100     42 .7    4 .7   0 .7      0 .6   0 .5    6      3 .3   0 .7 0 .3      12 17 .1         =r
                                                                                                                          0 .9                      cu
                       1 .3-GR      130   to   139   300    128      14      2 .1      1 .8   1 .5   18      9 .9   2              36 51 .2
                                                                                                                                                    0
         sham-exposed 2 .0-GR       200 to 209         0        0     0      0         0      0          0   0             0           0        0    ~
                                                                                                                                                     n
         SS of MW 2 .1 -GR          210 to 219        13    -         0      0         -      -      -       -                                       ~
                                                                                                                                                     c
                      2 .2-GR       220 to 229        50    -         0      0         -      -      -       -                                       ~
                      2 .3-GR                                                          -      -      -       -                                      ca
                                    230 to 239       200    -         0      0

         sham-exposeo 3 .0-GR       300   to   309     0        0     0 0              0      0          0   0      0    0             0        0   ~
                                                                                                                                                    a
         nicotine 3 .1-GR           310   to   319     0        0     1 .8 0 .3        0      0          0   0      0    0             0        0   5
                      3 .2-GR       320   to   329     0        0     7 1 .0           0      0          0   0      0    0             0        0
                      3 .3-GR       330   to   339     0        0    28 (a) 4 .2 (a)   0      0          0   0      0    0             0        0

         sham-exposed 4 .0-GR       400   to   409     0        0     0 0              0      0          0   0      0    0             0        0
         SS of lriw' with 4 .1-GR   410   to   419    13    -         1 .8 0 .3        -      -      -       -      -    -         -        -
         added nicotine 4 .2-GR     420   to   429    50    -         7 1 .0           -      -      -       -      -    -         -        -
                          4 .3-GR   430   to   439   200    -        28 (a) 4 .2 (a)   -      -      -       -      -    -         -        -



         TABLE B

         GROLJPS, RAT NO ., AND CONCENTRATIOI3S

         Remarks : In ac9dition, 40 untreated rats will be used for microbiological and pathological examinations on arrival .



          (a) concentration 2 times higher as in the high-concentration group of SS of 2R1




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                                                                                                                                                     W
                                                                                                                                                     ~
                                                                                                                                                     O
                                                                                                                                                     5
          TEST            GROUP      PAT N0 .         OONCENTRATION                                                                                  ~
          SUBSTANCE                                                                                                                                  ~
                                                                                                                                                     c
                                                      00         "TPM"   NIOOTINE   FORMAIDEHYDE ACETAIDEHYDE   ACRULEIN         AMMCNIA             ~
                                                                                                                (ug/1) (ul/1) (ug/1) (ul/1)
                                                      (ul/1) (ug/1) (ug/1) (ul/1) (ug/1) (ul/1) (ug/1) (ul/1)
                                                                                                                                                     Cr
                                                                                                                                                     0
                                                                                                                                                      0
          sham-exposed    5 .0-GR    500   to   509   0          0       0    0     0        0      0    0      0    0            0        0         co.
          formaldehyde    5 .1-GR    510   to   519   0          0       0    0     0 .2 0 .2 0 0               0    0            0        0         A
                                                                                                                                                     ?
                          5 .2-GR    520   to   529   0          0       0    0     0 .9 0 .7 0 0               0    0            0        0         CD
                          5 . 3-GR   530   to   539   0          0       0    0     3 . 6 (a) 2 . 9 (a) 0 0     0    0            0        0
                                                                                                                                                     0
                                                                                                                                                     ~
                                                                                                                                                     ~
          sham-exposed    6 . 0-GR   600   to   609   0          0       0    0     0   0        0  0           0    0            0        0         n
                                                                                                                                                      s
          acetaldehyde    6 .1-GR    610   to   619   0          0       0    0     0   0       2 .3 1 .3       0    0            0        0          c
                                                                                                                                                      ~
                          6 .2-GR    620   to   629   0          0       0    0     0   0        9  4 .9        0    0            0        0         ca
                          6 .3-GR    630   to   639   0          0       0    0     0 0 36      (a) 19 .8 (a)   0    0            0        0
                                                                                                                                                     ~
          sham-exposed    7 .0-GR    700   to   709   0          0       0    0     0     0      0     0        0    0            0        0         a
                                                                                                                                                     ~
          acrolein        7 .1-GR    710   to   719   0          0       0    0     0     0      0     0        0 .3 0 .1         0        0
                          7 .2-GR    720   to   729   0          0       0    0     0     0      0     0        1 0 .4            0        0
                          7 .3-GR    730   to   739   0          0       0    0     0     0      0     0        4 (a) 1 .7 (a)    0        0

          sham-exposed    8 .0-GR    800   to   809   0          0       0    0     0     0      0     0        0    0            0       0
          artmonia        8 .1-GR    810   to   819   0          0       0    0     0     0      0     0        0    0            4 .5    6 .4
                          8 .2-GR    820   to   829   0          0       0    0     0     0      0     0        0    0           18      25 .6
                          8 .3-GR    830   to   839   0          0       0    0     0     0      0     0        0    0           72 (a) 102 .3 (a)



          TABLE B (continued)

          GRCXJPS, RAT NO ., AND CONCQ3TRATIONS

          Remarks : In addition, 40 untreated rats will be used for microbiological and pathological examinations on arrival .



          (a) concentration 2 times higher as in the high-concentration group of SS of 2R1




               s9sVssszoz -

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                 SHIPMENT        GROUP            RAT NO .                 EXAMINATION
                 NO .


                 1               7-GR             740, 741,     742        pathological
                                                  743,   744               microbiological

                 2               6-GR             640,   641,   642        pathological
                                                  643,   644               microbiological

                 3               5-GR             540,   541,   542        pathological
                                                  543,   544               microbiological

                 4               8-GR             840,   841,   842        pathological
                                                  843,   844               microbiological

                 5               2-GR             240,   241,   242        pathological
                                                  243,   244               microbiological

                 6               3-GR             340,   341,   342        pathological
                                                  343,   344               microbiological

                 7               4-GR             440,   441,   442        pathological
                                                  443,   444               microbiological

                 8               1-GR             140,   141,   142        pathological
                                                  143,   144               microbiological



                 TABLE C

                 UNTREATED RATS EXAMINED PATHOLOGICALLY AND
                 MICROBIOLOGICALLY ON ARRIVAL




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                  PATHOGEN                                METHOD     POSITIVE ANTIBODY TITER
                                                          (a)        (RECIPROCAL VALUE)

                                                                     LOW            HIGH


                  coronavirus (SDAV)                      CF         10                80

                  H 1 virus (H1)                          HI         20             640

                  latent rat virus (KRV)                  HI         20             640

                  parainfluenza virus type 1              CF         10             160
                  murine (sendai)

                  pneumonia virus of mice (PVM)           HI         10             320

                  reovirus type 3 (reo3)                  HI         20                80
                 Mycoplasma pulmonis (M . pulm .) ELISA              -             -



                 TABLE D

                 SIGNIFICANCE OF ANTIBODY TITERS AGAINST VIRUSES AND MYCOPLASMS

                 Remarks : from Parker, J .C . : Diagnostic procedures for murine viruses,
                             in : Catalog 1980, M . A . Bioproducts, Walkersville, 1980,
                             p . 164




                 (a) CF : complement fixation assay
                     HI : hemagglutination inhibition assay
                     ELISA : enzyme-linked immunosorbent assay


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     I         Parasitological screening

                       Endoparasites

                         Sample material and
                         quantity :                       urinary bladder and intestines (ileum,
                                                          cecum, colon) of each of 16 rats (a),
                                                          2 untreated rats of each shipment
                                                          (see TABLE C)

                         Time :     1   day   after        arrival        at   INBIFO

                         Results expressed in : presence or absence of endoparasites,
                                                    species of organism detected micro-                 r

                                                    scopically

                       Ectoparasites

                         Sample material and
                         quantity : skin and          hair of each of 16 rats (a)
                                                        during deep ether narcosis, 2 untreated
                                                        rats of each shipment (see TABLE C)

                         Time :     1   day   after       arrival         at   INBIFO

                         Results expressed in : presence or absence of ectoparasites,
                                                    species of organism detected micro-
                                                    scopically


               Scientific version : SOP MB 4/3, MB 5/5, MB 11/3, MB 12/2,
                                             MB 69/3
               Text version :         18 .Aug .87




               4 .4 Bacteriological Screening of the Environment within the
                     Animal Quarters

               Surfaces of laboratory unit

                       Sample material and                                                         ~
                       quantity :                         impression plates from surfaces of       N
                                                          (1) floor
                                                          (2) floor, wall, rack, worktable, and    ~
                                                              door handle                          ~
                                                          2 samples each/room
                                                                                                   rp
                       Time :   (1)     after      disinfection with "Indulfan"                    ~
                                                      (2) after disinfection with formalin
                                                                                                   ~

                (a) identical rats used for all serological, bacteriological, and
                    parasitological screenings


                39AF


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                       Results expressed in : bacterial species and number of
                                                   CFU/sample


                 Air conditioning system

                       Sample material and
                       quantity : incoming              air and room          air,
                                                          500 1/sample each

                       Time :   1   time/month               (a),   unannounced

                       Results expressed in : bacterial species and number of
                                                   CFU/m3


                 Animal diet

                       Nonautoclaved

                         Sample material and
                         quantity : nonautoclaved diet of each batch,
                                               1 sample of approx . 10 g/batch

                         Time :     before               feeding

                         Results expressed in : absence or presence of Salmonella sp .


                       Autoclaved

                         Sample material and
                         quantity : autoclaved             diet, 2      samples   of   approx .
                                                           10 g/batch

                         Time :   within        9   days after sterilization,
                                                        1 time/month (a), unannounced

                         Results expressed in : absence or presence of bacteria


                 Drinking water

                       Sample material and
                       quantity :   autoclaved             drinking water from
                                                           drinking bottles with sipper tubes,
                                                           approx . 250 ml, 2 samples

                       Time ;     after         sterilization,
                                                    1 time/month (a), unannounced

                       Results expressed in : bacterial species and number of CFU/1



                 (a) with the exception of Feb .87



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                Cage bedding material

                        Sample material and
                        quantity :                     autoclaved bedding material, 2 samples
                                                       of approx . 0 .5 g each

                        Time :                         after sterilization,
                                                       1 time/month (a), unannounced

                        Results expressed in :         absence or presence of bacteria


                Laboratory staff

                        Fingertips

                          Sample material and
                          quantity :                   5 fingertips of each person working
                                                       within the laboratory unit

                          Time :                        1 time/month (a), unannounced

                          Results expressed in :       bacterial species and number of
                                                       CFU/5 fingers

                        Face masks

                          Sample material and
                          quantity :                   outer side of face mask used for
                                                       approx . 1 h, 1 f ace mask of each person
                                                       working within the laboratory unit

                          Time :                        1 time/month (a), unannounced

                          Results :                    bacterial species and number of
                                                       CFU/25 cm2


                Scientific version :                   SOP MB 13/3, MB 14/6, MB 16/5, MB 17/1,
                                                       MB 18/3, MB 19/5, MB 22/2, MB 68/2
                Text version :                         18 .Aug .87




                 (a) with the exception of Feb .87



                l'+F5

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                4 .5 Identification of Bacteria According to INBIFO Standard Operating
                      Procedures

                Aerobic and facultative
                anaerobic rods and cocci : identification of bacteria by micro-
                                                scopical determination, stainability,
                                                biochemical reactions, growth behavior
                                                on selective and differential media
                                                as well as susceptibility towards
                                                antibiotics


                Standard operating procedures : see attached microfiche no . E580




      I




                                                                                                  N
                                                                                                  C
                Scientific version :                      SOP MB 25/6 11 MB 26/1, MB 27/1, MB 28/3, N
                                                          MB 29/1, MB 30/3, MB 31/1, Mb 35/2,
                                                          MB 36/2, MB 37/1, MB 38/1, MB 39/1, ~
                                                          MB 40/3, MB 41/2                          ~
                Text version :                            20 .Jul .87                               ~
                                                                                                    ~
                                                                                                    ~
                                                                                                    ~




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                 5 RESULTS AND DISCUSSION



                 5 .1 Text


                 5 .1 .1 Laboratory_rats



                 All 16 untreated rats - 2 of each shipment on arrival - were found
                 to be free from antibodies to viruses such as corona-, H 1, latent
                 rat, sendai, pneumonia, and reovirus (see TABLE 1) . All rats
                 examined also for the presence of serological activity to the
                 pneumotropic bacterium Mycoplasma pulmonis were found to be free
                 from this pathogen .


                 The organs heart, kidney, liver, lung, spleen, and trachea and the
                 urine of all 16 rats examined for the presence of bacteria were
                 found to be sterile (see TABLE 2) . The intestine and the urinary
                 bladder of all 16 rats were found to be free from endoparasites
                 (see TABLE 3) . The skin and hair of all 16 rats were found to be
                 free from ectoparasites (see TABLE 4) .




                 5 .1 .2 Environment



                 The laboratory unit was examined prior to the introduction of rats
                 or during the exposure periods and was found to be sufficiently
                 disinfected (see TABLE 5) . The incoming air was found to be
                 sterile (see TABLE 6) . The amount of bacteria detected in the
                 laboratory room air was low (see TABLE 6) . In 1 sample of room air
                 the potential pathogenic gram-positive bacterium Staphylococcus
                 aureus was detected .


                 The nonautoclaved diet was free from Salmonella sp . (see TABLE 7) .
                 5 out of 12 samples of the autoclaved diet stored for maximally
                 9 days at RT and 2 out of 8 samples of the autoclaved drinking




                37R5

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                 water were found to be contaminated with nonpathogenic gram-
                 positive rods       and cocci       (see TABLES     8 and   9) .   Samples of   the
                 autoclaved cage        bedding    material were     found   to     be sterile   (see
                 TABLE 10) .


                 In 1 sample of the fingerprints from the laboratory staff Staphy-
                 lococcus aureus was observed (see TABLE 11) .


                 The face masks of the staff were found to be free from pathogenic
                 bacteria (see TABLE 12) .


                 The Staphylococcus aureus observed in 1 room air sample and
                 1 fingerprint sample of the staff was determined as a not human
                 origin strain and may have been derived from the rats .




                 5 .1 .3 Conclusion


                 All rats examined (i . e . 4 percent of the rats derived) were found
                 to be free from pathogenic viruses, bacteria, and parasites . Aside
                 from the autoclaved diet and drinking water samples contaminated
                 with bacteria, the results of the microbiological examinations of
                 the environment within the animal quarters were in agreement with
                 the microbial flora acceptable for the hygienic conditions during
                 short-term studies on rats .




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                5 .2 Tables



                DATE OF SERUM                RAT                ANTIBODY TITER DETECTED
                SAMPLING                     NO .



                1986, Dec .      5           743                no
                                             744                "

                1987, Jan .     16           643                go
                                             644                g

                                23           543                m
                                             544                m

                                                                n
                                30           843
                                             844                I

                       Mar .                 243                11
                                13
                                                                m
                                             244
                                                                11
                                20           343
                                                                    f
                                             344
                                                                IU
                                27           443
                                                                t
                                             444
                                                                n
                        Apr .    3           143
                                             144



                TABLE 1

                SEROLOGICAL SCREENING FOR VIRUS AND MYCOPLASM ANTIBODY TITER BY
                EXTERNAL EXPERT




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                DATE              RAT         SAMPLE       OFiOANISN( ID E .vTIFIED
                                  NO .
                                                           COUNT         NAME
                                                           (CFU/sample)


                1986, Dec .   5   743         heart        0
                                              kidney       0
                                              liver        0
                                              lung         0
                                              spleen       0
                                              trachea      0
                                              urinary      0
                                              bladder

                                  744         heart        0
                                              kidney       0
                                              liver        0
                                              lung         0
                                              spleen       0
                                              trachea      0
                                              urinary      0
                                              bladder


                1987, Jan . 16    643         heart        0
                                              kidney       0
                                              liver        0
                                              lung         0
                                              spleen       0
                                              trachea      0
                                              urinary      0
                                              bladder

                                  644         heart        0
                                              kidney       0
                                              liver        0
                                              lung         0
                                              spleen       0
                                              trachea      0
                                              urinary      0
                                              bladder



                TABLE 2

                BACTERIOLOGICAL SCREENING OF RAT ORGANS




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     (   DATE      RAT    SAMPLE        (Y2GANISM            IDENTIFIED
                              NO .
                                                            OGUNT        NAME
                                                             (CFU/sanmple)



                1987, Jan . 23   543           heart       0
                                               kidney      0
                                               liver       0
                                               lung        0
                                               spleen      0
                                               trachea     0
                                               urinary     0
                                               bladder

                                    4          heart       0
                                               kidney      0
                                               liver       0
                                               lung        0
                                               spleen      0
                                               trachea     0
                                               urinary     0
                                               bladder


                             0      3          heart       0
                                               kidney      0
                                               liver       0
                                               lung        0
                                               spleen      0
                                               trachea     0
                                               urinary     0
                                               bladder

                                    4          heart       0
                                               kidney      0
                                               liver       0
                                               lung        0
                                               spleen      0
                                               trachea     0
                                               urinary     0
                                               bladder




                TABLE 2 (continued)

                BACTERIOLOGICAL SCREENING OF RAT OEaGANS




                19PF


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                 DATE     RAT     SAMPLE      ORGANISM             IDENTIFIED
                                  NO .
                                                               OOUNT      NAME

                                                               (CFU/sample)



                 1987, Mar . 13   243           heart          0
                                                kidney         0
                                                liver          0
                                                lung           0
                                                spleen         0
                                                trachea        0
                                                urinary        0
                                                bladder

                                    4           heart          0
                                                kidney         0
                                                liver          0
                                                lung           0
                                                spleen         0
                                                trachea        0
                                                urinary        0
                                                bl adder


                              0     3           heart          0
                                                kidney         0
                                                liver          0
                                                lung           0
                                                spleen         0
                                                trachea        0
                                                urinary        0
                                                bladder

                                    4           heart          0
                                                kidney         0
                                                liver          0
                                                lung           0
                                                spleen         0
                                                trachea        0
                                                urinary        0
                                                bladder



                TABLE 2 (oontinued)

                 BACTERIOIAGICAL SCREENING OF' RAT OI~'~AD]S




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                DATE     RAT      SAMPLE       ORGANISM          IDENTIFIED
                                   NO .
                                                              OOUDPP         NAME
                                                              (CFV/sample)



                1987, Mar . 2 7   443           heart       0
                                                kidney      0
                                                liver       0
                                                lung        0
                                                spleen      0
                                                trachea     0
                                                urinary     0
                                                bladder

                                    4           heart       0
                                                kidney      0
                                                liver       0
                                                lung        0
                                                spleen      0
                                                trachea     0
                                                urinary     0
                                                bladder


                         r.   3     3           heart       0
                                                kidney      0
                                                liver       0
                                                lung        0
                                                spleen      0
                                                trachea     0
                                                urinary     0
                                                bladder

                                     4          heart        0
                                                kidney       0
                                                liver        0
                                                lung         0
                                                spl een      0
                                                trachea      0
                                         ,      urinary      0
                                                bladder



                TABLE 2 (continued)

                 HACTERIOLOGICAL SCREENING OF RAT ORGAt1S




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                 DATE             RAT          SAMPLE (a)           OFCiANISM IDF1V'I'IFIED
                                  ND .


                 1986, Dec . 5    743          urinary bladde r     n
                                               ileum                      o
                                               cecum
                                               colon

                                  744          urinary bladde r     01
                                               ileum                it
                                               cecum                 go
                                               colon


                                                                     ,
                 1987, Jan . 16   643          urinary bladde r
                                               ileum
                                               cecum                ~
                                               colon

                                  644          urinary bladde r      ~
                                               ileum
                                               cecum                 ~
                                               colon                 m


                             23   543          urinary bladde r      ~
                                               ileum
                                               cecum                 ~
                                               colon

                                  544          urinary bladder       g
                                                                     u
                                               ileum
                                               cecum                 is
                                               colon                 of

                                               urinary bladde r      g
                             30   843
                                               ileum                 of
                                                                     s
                                               cecum
                                                                     n
                                               colon
                                  844          urinary bladder       go
                                               ileum                 ~
                                               cecum
                                               colon



                 TABLE 3

                 PARA.SITOTAGICAL SCREENING OF RAT URINARY BLADDER AND INTESTINE FOR
                 ENDOPARASITES


                 (a) mucus and content


                3285

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                DATE               RAT        SAMPLE (a)            ORGANISM IDENTIFIED
                                   NO .


                1987, Mar . 13     243        urinary bladder       no
                                              ileum                 "
                                              cecum                 "
                                              colon                 "

                                   244        urinary bladder       m
                                                                    I
                                              ileum
                                                                    m
                                              cecum
                                              colon                 m



                               0    43        urinary bladder       It
                                                                    n
                                              ileum
                                              cecum
                                              colon                 oof

                                    44        urinary bladder        N
                                              ileum                 to
                                              cecum
                                              colon                 Iit


                                              urinary bladder       ~
                               7    43
                                              ileum
                                              cecum
                                              colon

                                    44        urinary bladder       I
                                              ileum                  11
                                              cecum                  Is
                                              colon                 11


                       Apr .   3   143        urinary bladder
                                              ileum
                                              cecum                 ~
                                              colon                 ~

                                   144        urinary bladder       I
                                              ileum                 to
                                              cecum
                                              colon                 i10




                TABLE 3 (continued)

                PARA .SITOIOGICAL SCREENING OF RAT URINARY BIADDER Atm INTESTINE FOR
                ENDOPARASITES

                (a) mucus and content

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                DATE                 RAT           SAMPLE           ORGANISM IDENTIFIED
                                     NO .


                 1986, Dec .     5   743           skin, hair       no
                                     744           "                "

                                                   n                n
                 1987, Jan .    16   643
                                                   n                n
                                     644
                                                   u                n
                                23   543
                                                   u                n
                                     544

                                30   843           11               11
                                                   u                u
                                     844
                                                   n                n
                        Mar .   13   243
                                                   n                u
                                     244

                                20   343           11               is
                                     344                            i




                                                   It               11
                                27   443
                                                   w                u
                                     444
                                                   U                II
                        Apr .    3   143
                                                   n                go
                                     144



                TABLE 4

                PARASITOLOGICAL SCREENING OF RAT SKIN AND HAIR FOR
                ECTOPARASITES




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                DATE               ROCriI       SAMPLE        ORGANISM IDENTIFIED
                                   NO.
                                                              COUNIP         NAME

                                                              (CFU/sample)



                1986, Dec . 1 6    R513         floor          0
                                                               0

                1987, Jan . 1 2    R513 (a)     floor          0
                                                               0
                                                wall           0
                                                               0
                                                rack           0
                                                               0
                                                wurktable      0
                                                               0
                                                door handle    0
                                                               0


                       Mar .   9   R512         floor          0
                                                               3
                                   R513         "              0
                                                               0
                                   R5 14        "              4
                                                               1


                       Apr . 10    R513         floor          2
                                                              20
                                   R513         "             64 (b)
                                                               9 (b)
                                   R514         "              3
                                                               3



                TABLE 5

                BACTERIOIAGICAL SCREFNING OF LABORATORY SURFACE

                Remarks : sample size 25 cm2




                (a) prior to introductiion of rats
                (b) animals present in that roan



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                DATE                 F0OM      AIR          ORGAt`iISM IDENTIFIED
                                     NO .
                                                            CC(RNT          NAME
                                                            (CFU/m3)


                 1986, Dec . 1 1     R513      room         6               Aerococcus viridans
                                                            6               Staphylococcus epidermidis
                                                            2               gram-positive rods

                                16   R513      incoming     0

                 1987, Jan . 2 0     R513      room         6

                        Mar .    9   R513      incoming     0
                                               room         4

                        Apr .    8   R513      incoming     0               -
                                               room         2               gram-positive rods
                                                            2               Staphylococcus aureus (a)



                TABLE 6

                BACTERIOLOGICAL SCREENING OF I,ABORATOkY AIR

                Remarks : sample size 500 1




                 (a) identified as not human origin strain according to
                     WildfUhr, G ., Wildfuhr, W . (Eds .) : Medizinische Mikrobiologie Imnunologie
                     und Epidemiologie, Leipzig : VEB Georg Thieme, 1982, pp . 138 and 142



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                DATE                SAMPLE         SAMPLE     SALMONELLA   IDENTIFIED
                                    NO .           SIZE

                                                   (g)
     I


                1986, Aug . 26      7934           12           no

                       Dec . 3      8497           12                "

                1987, Jan . 26      8785           12                "



                TABLE 7

                BACTERIOLOGICAL SCREENING OF NONAUTOCLAVED DIET FOR SALMONELLA SP .

                Remarks : batch no . : 3451, 4912, 441
                           date of supply : 25 .Aug .86, 2 .Dec .86, 23 .Jan .87




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                 DATE               SAMPLE     STOWE      SAMPLE     ORG111dISM IDEN'I'IFIED
                                    NO .       TIME       SIZE
                                               (d)        (g)


                 1986, Dec . 1 1    8590       9           8         no
                                    8591       "          10         "

                 1987, Jan . 20     8724       7          11         g
                                    8725       O
                                                          11          I

                        Mar . 1 7   9045       is
                                               6          12         Staphylococcus epidermidis
                                    9046                  10         gram-positive rods
                                    9047 (a)   41         10         no
                                                          10         gram-positive rods

                        Apr .   8   9211       8          10         no
                                    9212       "          10         Staphylococcus saprophyticus
                                    9213 (a)   "          10         no
                                                           9         Staphylococcus epidermidis



                 TABIE 8

                 BACTERIOLOGICAL SCREENING OF AUIiOCLAVID DIET

                 Remarks : batch no . : 3451, 4912, 441
                            stored after autoclaving at RT




                 (a) reserve samples


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                DATE               SAMPLE        OFGANISM IDENTIFIED
                                   NO .
                                                 COUNT               NAME
                                                 (CFU/1)



                 1986, Dec . 11    8600            0
                                   8601            0

                 1987, Jan . 20    8730            0
                 (a)               8731          220

                       Mar . 18    9055            0
                                   9056            0

                       Apr . 9     9226            0                 -
                                   9227            4                 Staphylococcus epidermidis



                 TABLE 9

                 BAGTERIOLAGICAL SCREENING OF AUTOCLAVED DRINKING WATE:R

                 Remarks : sample size 250 ml




                 (a) sample size 200 ml



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                DATE                  SAMPLE          SAMPLE         ORGANISM IDENTIFIED
                                      NO .            SIZE

                                                       (g)


                 1986, Dec . 11       8593            0 .4           no
                                      8594            0 .4           "

                 1987, Jan . 20       8727            0 .4           "
                                      8728            0 .4           "

                        Mar . 17      9048            0 .5           "
                                      9049            0 .5           "

                        Apr . 8       9214            0 .5           IN
                                      9215            0 .6           IN




                TABLE 10

                BACTERIOLOGICAL SCREENING OF AUTOCLAVED CAGE BEDDING MATERIAL




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                DATE                 SAMPLE       ORGANISM IDENTIFIED
                                     NO .
                                                  COUNT             NAME
                                                   (CFU/sample)



                1986, Dec .     11   8598         38                Staphylococcus epidermidis

                1987, Jan . 20       8732          12

                        Mar .   17   9051         37                Staphylococcus epidermidis
                                                    1               gram-positive rods
                                     9052         45                Staphylococcus epidermidis

                        Apr .    8   9223          55               Staphylococcus epidermidis
                                                    4               Staphylococcus aureus (a)
                                                    1               gram-positive rods



                TABLE 11

                BACTERIOLOGICAL SCREENING OF LABORATORY STAFF'S FINGERTIPS

                Remarks : sample size : impression from 5 fingertips




                (a) identified as not human origin strain according to
                       Wildfiihr, G ., WildfUhr, W . (Eds .) : Medizinische Mikrobiologie
                       Immunologie und Epidemiologie, Leipzig : VEB Georg Thieme, 1982,
                       pp . 138 and 142


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                DATE                SAMPLE        ORGANISM IDENTIFIED
                                    NO .
                                                  COUNT             NAME
                                                  (CFU/sample)



                1986, Dec .    11   8599           3                Staphylococcus epidermidis

                1987, Jan . 20      8733           0                -

                       Mar .   17   9053          27                Staphylococcus epidermidis
                                    9054           6                Staphylococcus epidermidis

                       Apr .    8   9224           5                Staphylococcus saprophyticus
                                                   4                Streptococcus sp . group D
                                                                    without hemolysis



                TABLE 12

                BACTERIOLOGICAL SCREENING OF LABORATORY STAFF'S FACE MASKS

                Remarks : sample size 25 cm2


                                             END OF SUBREPORT MB




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