Document O1LRN1QM2614jngv6q6gRazv1

905 Sheehy Drive, Bldg. A Horsham, PA 19044 Telephone: (215) 443-8710 Telefax: (215)443-8587 M S- II2 V - ARGUS RESEARCH Charles River Laboratories Discovery and Development Services September 11, 2002 John Butenhoff, Ph.D., DABT, CIH 3M Corporate Toxicology 3M Medical Department 3M Center, Building 220-2E-02 St. Paul, Minnesota 55144-1000 Telephone: (651) 733-1962 Telefax: (651) 733-1773 RE: Protocol 418-020 - Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO) in Rats Sponsor's Study Number: T-6889.6 Dear Dr. Butenhoff: Enclosed are the copies of the estrous cycle evaluation for P and FI generation rats which you requested. If you have any questions, please do not hesitate to contact me. Sincerely, Study Coordinator rCoT3 O --i ! ro Enc. co cn vD 000003 002947a. ESTROUS CYCLE EVALUATION P GENERATION FEMALE RATS 000004 EXACT COPY 0 0 3 ^^7 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 APFO Estrous Cycle Evaluation DOSAGE: GENERATION: ROUTE: SPECIES/STRAIN: 0 (Vehicle) MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE i- io l M O I l-3-ei \M \ tf-ol /-VO1 i -j * t ' -5-01 .iO.O> \w\ (//Jo/ i-iv a N to j 1 2 3 4 5 6 7 8 9 10 11 12 13 14 ac Saline Pre-Check Tech/Time 112,3 a ie oJc oJ?c \\2Xp I6 l a o //33 TS Ilio */ xOiT- li W3 llfl ^\\b 0\A II33 V piA u3i CtPc o J c aJDc_ Saline PostCheck Tech/Time 12,00 (|55 ib Tb l^o6> i K 1 U5*> II 12CO sW piA (Ka p /2 I^ IZC3 \iS ^ I V ^ Smears Taken fct/Wyvc Tech/Time Start "$0 1(31 tic/ put iL tiW a iW Il V f 4uCp^* liZ/S cm-*"10 ll 3^ / m Mift&tftlfrgy. iU(# nil? .-vilHzO* HAiC IDb crH*3uihisud7 Smears Taken Time End an 1157. US'S i \ 5 i l<% 11*11 US! U 5 i<?n to o im iT ilS Smears Read aie oJ>c_ C& jkA W 3 Tech/Time Start IXOt U55 12X UOi. Kf i/*n IZl 115^ 5CI ?p3 Tt % StH pv4 -^>A ric z XlHi, \xf2> Smears Read Time End \m> ILM5 i < 5 31 i3zS 1230 a 3D l^o ( D m i9 \\ Animal Number 13801 13802 b b br WP bb f nn b b b ?s 6b /H D OP 13803 13804 13805 13806 (VA b b p (W NA V PA b < bb P & E p Al p Mb D> Db ? DD ? fr M p p fr jm rvv b 7$ b 0 13807 b 13808 13809 13810 P 13811 b 13812 p Reviewed By: b P b T> b yp E ? P ~D E& M ftl ;__ ? , E 9 e b Pt V) bf A\ b P b p - r n & b J I_ p E on b b O Date: 0Sl:dLQ l^^a- 13-Uia r* A ie 5 |:duA 1 3 * 1 3 - 13 43TC `h iv @/&'l'tloI ^C VI bb Dp bb 0 <1 C 0 D _nJ Q P /4 o O P RT 01.14.00 EC2-04a *-PH . tKPrt y * / - / - 0/ W *,-, OOOOOS u?I, <K&^`l^ v 11rtoIo|i /fcf 002948 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 0 (Vehicle) MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE l-l-bl WxA V*i|oI Il f-o' IVO 1A.01 i-ti.lJI I H>0l m-* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Animal Number 13813 KV\ b P? aA P ? e m D A7 13814 13815 T> T> p b IVA b ?. |Y1 ? f a IT) p e /A D ? p P ** V> T4 o 13816 0b b nrt E' m P OTj o T> 13817 13818 13819 13820 13821 zINA b p IT P & T> _ h _ _ L E D Pb P 9 (V\ V m b b 0 Vb P P i> p V pa D P p bA > p E /A ?F PM P 1 p A6 > b PP p _ b _ b _ 13822 c ?IV \ b> aA P P i> _ _ P D 13823 13824 B (V\ b Gb ) aA P f m P 1 D 9 aA p m b f. n 13825 13826 wb P m &? ? P P? INA T> fci b . ? P f - lb mO D p 13827 13828 13829 13830 B b? P IW \> b b t> b ? c aA P P P 9 A* AA D P g \> p O D P jvL b . D P M o P P S D i> D /I AJcM -o ] il*A o \ Reviewed By: fli-w im a . Date: / RT 01.14.00 EC2-04b 000006 iEXACT COPY I *}} Rlulo> 002949 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: AP FO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 1 MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estais M = Metestois D = Diestrus DATE H-ol (-7 Dl \0-oi 123 i-iol 45 6 l-t-Ol i-9-' |.1-OI IU-I l-iai I-&4I ni-* 7 8 9 10 11 12 13 14 Animal Number 13831 13832 13833 13834 13835 13836 13837 13838 bb B e- b b ff\ D D E /v\ b D b %* pn b D O D D b 9 m O? mb ? eD VP m PP B i> P % - K m b t> XD P b EB b Pf T b b &b D F PP B b T) f F F M b p? B b b > F w b ? fit\ V L P ~b t /A b P P 0 D 13839 13840 b P B Ai D P F o\ P P B OO Pb m b t F P I v> b 13841 13842 13843 13844 G AA D P > ? MP v> &b P0 F P b ? i b>P c P P F. ' 3> D O b ?r L ? B h\ b P aA b b Dc 13845 13846 13847 13848 13849 E Bb b ? PbP9 M bO 9N \ b e b O V F m b TT D O P Eb b > b n? PG Db /A P D b P , t>0 b L m & P O bb P J? f b9 (S X 3 )3 1 > BDO 16|6\ Reviewed By: CT _________M 7V 0} ^ Ml-oi Date: - ( . ! S RT 01.14.00 EC2-04 w fte jm 000007 fl i w * 1 " H m t/7M 002950 PROTOCOL: 418-020 DOSAGE: 1 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE Animal Number 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860 Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: P ROUTE: Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus Mol llo l 12 3 l>6*o| 456 i '*0 <*<=1 l 0 | -i i i l-tt-61 \i}0\ M-o 7 8 9 10 11 12 13 14 b E b T? Pb f . b D b E b f On b b D b G (V\ 'D cT i ) P w b D P G "b "D aa P p Mb OC E b T> s fr P b P Dr*\ \> T> f\A ~D P c Pb P G ISA P M t> P P b b \ D L Mb P 1 b( "b b 04 'T. D P ET r< f n D F, c 1W D b- u,t > b KA b ,V\ D f t> b P b b p 6 /w ,P p F , t) b P L Q & X & H z i 003Tb Reviewed By:______ _____________ Hfl . HflaL - Date: 000008 l-lS'fPI RT 01.14.00 EC2-04b EXACT COPY 002951 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 3MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE A/-0/ i-2o( l i o l 12 3 / Soi AV| KHI l-Y-Oi 1-401 1.1001 / 'M j.<A.o\ l-IS-ol 4 5 6 7 8 9 10 11 12 13 14 Animal Number 13861 13862 13863 13864 Ee M b BE b b^ bfE eb P N\ b D 13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878 PB b P GL B hA > D bb PPc & NA b fc Bb b > c ?F b b P i> P 't B IA b PH D b E b b P ? !> B E b 0 ?B eB bb na. b & IVA b b c 0 Z mb PE b 13879 Q )(g5Bl|5]0' b _b_ b ? E r? b P E r> Q 9 P ? . T> b P e 0 ? E t> t bB f t t> P P t DD et AA b a u bB ? E Ebb pB O _ m/A P /VA P b ? e- D e D (ESl . b il XL /* P b __ m b _ b _ L A E p t P S ... JH T? P C , ?EmD P L D p D D b L b T> X l 1 X L P JP 0 e T> b b O DP E r . P b F c P D p E M W B x_ E P > ? _ i J L b O . 9M P f _ b _ > X __ E - P E F , rn _D__ P f E) X L E /A J D _ P & M jL 1 Reviewed By:_____ ____________ 'f t t . 'n t L - Date:__________ _________________ RT 01.14.00 EC2-04b 000009 exact copy 002952 PROTOCOL: 418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE Animal Number 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890 Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Cri:CD (SD) IGS BR VAF/Plus //d IZ o V V i 12 34 5 |->` i I' .i t -S.I M00I l-ll-Df l.it-Oi H M 6 7 8 9 10 11 12 13 14 ? bb V M t> P T m DP e D b E E iP ID mb DB mb Bw T'A PE yv\ D ? E o n p e E DO C |M O Pb b ? E- P E i > D JD t> i> V . D B F, E f. E E eE <r t> ?. 6 /\A S E e t f . 1 eb fn "b ( b t> &D -r' Dt V pE T7 P ? m ?C O T> -- J c . e B tA b Pb P b b >> P E eb 4$ c b f P fr r> T> b r `Hi&t Reviewed By:___________________ M , / M a ^ _____ Date:________ __________ ;_________ RT 01.14.00 EC2-04 O O O O IO , -F tUuLor 002953 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: 10 MKD APFO GENERATION: P ROUTE: Oral (Gavage) Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Cri:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestms D = Diestrus DATE /-/-cl i-2-ot 1-3*1 H i"?' 1"i-o* 1-9-ti 1-IOOi i-ll-DI l--CV \-fyoi l-W-ai 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Animal Number 13891 13892 V\ b b b e 5 D b e c*-* b b P ? m b P A - V D A] 13893 E INA V P [> b T> E b D O C 13894 13895 b EmD D b b T > -p O 75 E E fn 0 D f m _D_ Emo D 13896 13897 s b b F . b 5 b b > b b D P J2_ H - p b > _ p 13898 *? E IVA b P B b b ? e JU_ b XD i l 13899 13900 D !> P ? e E nn O eyr* f /A ,p b p P E m DO E f i rt--b' 13901 13902 m "b P E (VI f # p f , P b m D D ? E T) D p E m P & nn t) P 13903 ra b 0 n p f . p b p s y D 13904 13905 13906 13907 mb ~D P b eE E. xf. ^ 1 0 p r> r . (P p E m0p n m b D c r b m b )) P T - T T ? m p bp O b r> p . P b D P i> b 13908 13909 ~P e Eb *A b b ? B b > p D _D_ E D b D _ J k _ P P 1 D Reviewed By:_____ _______________ ' M . j k L _ Date: 1 - & 01________________ RT 01.14.00 EC2-04 O O O O ll 4 r\ 002954 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 10 MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE H-oi 12-01 1*3-01 HIox J.&oi H w f-T-oi l--v i-'i-l 1-lfcCl v(y0\ hH-a 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Animal Number 13910 9 eb 13911 13912 13913 es. tvs b D b r\ b p b b Z 13914 13915 13916 13917 13918 13919 13920 bb eb "D b eB Eb rw b b eF b? B ISA b bP Pf bL Db Dt D OP e 1* b pP B0 fV\ p P mb b bL b F bb O r-> b t) D P v> b P X) D bb D D > O t> P 1. G & p F. b P e P (T) > e z -D O b b P f. M P IL P P b b P - O P D t> T> D t m P p, nD Reviewed By:________________ % _______ Date:_______ ( .01______________ RT 01.14.00 EC2-04b 000012 EXACT COPY ^luUi- 002955 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 30 MKD P = Proestrus P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus E = Estrus M = Metestrus D = Diestrus DATE t-i-o1 Moi '3-ol h\ 12345 i-Y-Ol 1-1ot /I6-0I (n-i |./a-oi HV ) 6 7 8 9 10 11 12 13 14 Animal Number 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 "D b B D ~) B X) E V y E T> TD E (VA ? "D B Cri D PE m "P B (NA b P fi D P e PT) e b ~b P D "b P 13933 B 13934 13935 13936 e "b N < E B NA E b 13937 !D 13938 13939 D __ GfW H U I e e Z ' B T? EV bf D PF PF n Df Df Df P E Dp B IA |W h cn Dp Ch bp bf bP f . "D b hb m 1) ? tm Em h t> h (Tl eD bf b pZ b? Eb rp )f E6 HD s* O T> E b T> f EV p A/1 m r> ? ? E B 6 b nn b? E s* tm T> D nn b b 1b D B V Df i b> p b> T> by* T> ? JL_ 6 DO D X) > p DP ? mO nn O bO mD pE e /I t- _ m -to > D P Ab J _ Xb F ? o n p C- JD -D D * D 1T O 0 T> O Reviewed By:____________________ M _____ Date:____ t i S M ________________ RT 01.14.00 EC2-04b 000013 t 002956 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 30 MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE l-l-ol \-lo\ 12 M , I-&O l'rtf i'T-ef f-3-Oi l -9-01 )-10-0 NI-oi M3C\ HVI 3 4 5 6 7 8 9 10 11 12 13 14 Animal Number 13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950 b b D Gb "P B b D P vn P fn P) t > P n 'P ? V p P m OO Vp p. M D -D T> ' b t > e> p T> p bP _ l P rn O eL DP m bi p G E. b DP rn b b jd D V\ K 6 P p ? P. 1 Pc D ~ e ' O a m P P f , DD D "b b m F m n D e 01 b V p p no f . P O DD b P n P P- b P rA (7)C l 'O t Reviewed By:__________________f l ) _ Date: 000014 h i * !_____________ RT 01.14.00 EC2-04b /ff q iu l 002957 PROTOCOL: 418-020 DOSAGE: 0 (Vehicle) MKD P = Proestrus E = Estrus M = Metestrus Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus DATE 'tiO l Hat I <" Ink* M * w 1 2 3 4 5 d 7 8 9 10 11 12 13 Saline Pre-Check 'M i-/ * * Tech/Time HStT UW n^> IlZu / n JSC ant vm-/ Saline PostCheck Tech/Time lZ06 |P*lL lift Smears Taken Tech/Time Start ULmc. ic ^ f Smears Taken Time End I2W Smears Read Vfa'/ Tech/Time Start ivn )H0 \\SM m J tl4 3 Smears Read Time End 12HI iza* ia y f ^6 IJCO n a i t lia i," .<te fW w iOOl IlS ^ |>3 && It \\2H <*** ____ 1 1 / Animal Number 13801 13802 13803 13804 13805 13806 13807 13808 13809 p ?r b b tr D&o ' P6 t> b b p 0 Pz b b D p h i? p z 0 Vp Pp D V f z, V D P m t/\ T> hP b? ? f/ m Pn r> fA 0 p Pp 6 13810 P V p) 13811 13812 t D t> _Cl_ 5 L . D Reviewed By: p p JD " D? De n 0 Date: inifwJ- n jicri'la ju Lt?< ^S (irf^< !J> cJ. "aCtf '// /j, RT 01.14.00 EC2-04a 000015 EXACT COPY 002958 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 APFO Estrous Cycle Evaluation DOSAGE: GENERATION: ROUTE: SPECIES/STRAIN: 0 (Vehicle) MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE j.lSoi i n oi m-| l"l`V'<|( l'Z'O'Ol 1-21-*1 12 34 5 6 7 8 Animal Number T7 9 10 11 12 13 A / 13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827 b E f. (fl 0 P tv\ V P em Di e m D? pn P 0 P (r m b E 6 P Yr' m T> P P l= pn &ED m DV E P & f . rn D P k ? f r IY D P P ? L fn D ? (T P Z rn D E P(Y \ ) b hD Dp JP E fO D P C O 6 TO rn p p 6 6 e m t "7 T / 13828 bp D PP 13829 13830 > p f P0 6 PDP 0p Reviewed By: Date: 000016 RT 01.14.00 EC2-04b /VT 002959 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: AP FO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 1 MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estais M = Metestrus D = Diestais DATE Animal Number 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849 N io l t-ib-S l-r7N m-oi 1234 bP b P1 JL_ cW gP P b P D P rtf P p p 6T ? P B bf P b N ? ?r b p b b T> Pb i> f 0 P f t on /V) P P S b? B P no \> b Pp e 0 P f, b p (T) b HS-oi l-zo-ol W W y 5 6 7 8 9 10 11 12 13 r / DEm O T) e PB in P r> PD 0b e "7 / y / / / /f J 0n D / if r> T) D D6 J/f 0nn / T) D DPB DD P T y Do P / 0 e / 0 D? / 9e / P m/ Reviewed By: Date: 000017 RT 01.14.00 EC2-04 r x A C T c ri) PROTOCOL: 418-020 DOSAGE: 1 MKD P = Proestrus E = Estrus M = Metestrus Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage) 002960 TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus Reviewed By: Date: 000018 RT 01.14.00 EC2-04b ,A/r^W tf y q iu i jV PROTOCOL: 418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metestrus Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage) 002961 TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus Reviewed By: ____ Date: 000019 ______________ RT 01.14.00 EC2-04b ( exact copy ^lu/o> PROTOCOL: 418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metestrus Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage) 002962 TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus C ) erjri'i Jy A^~ 000020 RT 01.14.00 EC2-04b qiu^od. 002963 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: AP FO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 10MKD P Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE ,di l-tU-Ol 1-n.oi H8-M l-Sto-ol f-ai-ot / 41 2 3 4 5 6 7 8 9 10 11 12 13 Animal Number / 13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909 T> Z m O Db f a P !> P zD D o T> E vn P t gp bD m p \> E ?D peD p bb D f s E PF PO D pG T> T ) E P ?. m D ? bb T P D 7) ?P P E P ? mD MP Pz P P p f, m J_ P E- SL D D6 PE t) P DD mD DO P) D? $0 Z P6 D > oO 6 r> PB nP / -O P / p 6/ / / / / / /_ / / / ! Reviewed By: Date: RT 01.14.00 EC2-04 000021 eaACT C O F f \ R iu lo i. f PROTOCOL: 418-020 DOSAGE: 10 MKD P = Proestms E = Estais M = Metestrus Argus TEST ARTICLE/SUBSTANCE: APPO GENERATION: P ROUTE: Orai (Gavage) 002964 t y p e o f TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus ifo) Reviewed By:______________________________________ Date:______ RT 01.14.00 EC2-04 000022 Q c q lui 03- 002965 PROTOCOL: 418-020 DOSAGE: 30 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE Animal Number 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939 Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus l'frol / M 12 llil 34 l-to-ol -aioi 567 8 9 D (S D h> pF p D P p T D D P p0 P PMr f j ) P e m Pe O? p e D(E m P T D p tT t> V P E D P mA P P ?y mP r> p f v &0 D E jVl e P 5" D in D P ? e ? 6 pV 0 6D b p on D e b p ? - fio D ? i m b t> f r V E D D P D&** v P D e N\ y m V P ? DD / m > 6O 71 10 11 12 13 / / / / (/ ___ 1 / / / _________ J / / / Reviewed By: Date: . ' g - s p a rs t; (p u '/vO RT 01.14.00 EC2-04b 000023 EXACT COPY y t qtiWos. PROTOCOL: 418-020 DOSAGE: 30 MKD P = Proestrus E = Estais Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: P ROUTE: Oral (Gavage) 002966 TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus 000024 01243 ESTROUS CYCLE EVALUATION F1 GENERATION FEMALE RATS 000025 IXC1 Rfni 03l PROTOCOL: 418-020 DOSAGE: 0 MKD P = Proestrus E = Estrus M = Metestrus Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: F1 Oral (Gavage) 012432 TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus DATE /--ol sh/*> T O 'hid 5'Pl >' fiS-* f-n-o iliaci f'/f-v! 5 ao* -Zhoi 12 4 5 6 7 8 9 10 11 12 13 14 Saline Pre-Check r*PH ff Tech/Time !Z3$ /3>'~ /^ - P |i<f C> lYV^ (a3| > iHI i)C iywH) w xT^s IWF ^yi4> tJA J?3t (0b'< (d I t+x>* ?1 1 * Saline PostCheck Tech/Time 1 032- 031> OP > iwcr- |30 Vi'*-' >c ac 257 CM. *1 ISfiE )JC 7 * ' use m /34C. Smears Taken t&l *S3 Tech/Time Start T" Smears Taken Time End r5t>% /33o uri A3 l33(p (3V /3f Br. Oc (31 f WM)/ tSOM -V rn it'i "IX)%3, (J*/*/ {ipb V}0le |2^ |3H V35" m 1 3 | 9 ^ r A l&Z /JZvl Smears Read ,\*p Y Tech/Time Start i3o U7V Yb lf \3 \\ (Vi^ i-oa- M A13O1'1r"M/ i ht /3CG I37 |2-r7 :wO y/>3 ib (fc Smears Read Time End H trf Hoi, Uro )3M^ 133s" I35& K # 133*7 ivi I3Q 0Y7 Animal Number VbO^L rb o H l? > 0 fe I3DS *Da* <)L\ e XD Z> ? C 6D V m 2> r P > D re c x> P ? e DP e Pr P p\ T) f D I'blO 1*31^ P fc eC M P I3 li T) c P p ~ e t m m j) r .. lP > 9 - l T) p / ____ eV e Reviewed By:__ p p 3 P0 X ) t> C/ P ?E D E Eh P E K t> f Ob EE 0 PP E D?C0 eM H\ b f ?E Date: J r /fio j fW tU ci w f fv_ wj. U<JU Y C**ua> W4^***j O-e^uJU^ tpuW>- .y-'ntiit 000026 M v~ O E D E b iP ' t> r m /O F E > b b/ AA--Z7 D D i> D b E x> D B P P ET m 0D ED AA 0 r > h t P PC D 1> PE AA D 'L<bf I JL . RT 01.14.00 EC2-04a o iU b/A- '%,.. `lik v /o ^ p 01243: Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE F1 Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus d./., f/uLt 5Mf-ei iS-' /-/(-61 7'(ll /ir-c S'ib-ti <h 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Animal Number n f b c , (Y\ D f l3> T> D D \33H T l f r t?ybS ,1? ? /33> T ) D ? I3 3 S 13 VO T> : M eD 13-7/ O ET T 1347 in T) c r Ti P f OE r 0 m. T r n>HS T c D lib o e c b 13 5 3 T O D /35S r* _P) f )2>58 T) ? r 135e) X) P D - ' --4 T O P D ?P D T> 6 / I "D f r D D ? E T P D ? t> P e H PP P D 0 X Pe D DP P p X> P D Pe t (f IA /h 1> P E E D P N4 t> T> D P NA D X PC D P o D6 Pf *b O P f? T e M T> P D li e m. b f e / n TT P E F 7 f ry h t M b iT f b /I b Z9 (h J> i> P > p ]> b $ r * T) b Dp p D br P D /v\. D 0 nu > P m TT T p T ~ f w 0 F E C P F /n -D P C Dp F H) > P r F m 7> D r A\ b f F (K D D 0 ( F D b P F PP r C D rxP H 1 @ CC5-i7-ci Reviewed By: - -- -_______Date: l RT 01.14.00 EC2-04b 000027 EXACT COPY 012434 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 1 MKD F1 Oral (Gavage) Rat/Cri:CD (SD) IGS BR VAF/P!us P = Proestrus E = Estrus M = Metestrus D = Diestms DATE sh /o i hki s'/o/; 4 > k S-chA 5ivo 5-iH-oi >-a-6 ^-n-oi . M j Hi 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Animal Number ^Ls^ \ rLb T ? P5?/ |2 > ? 5 e. D O P " M > e F /n > P Pi V P b D ? E Fl M 4 . T> D f fn O V fc M 0 F e D P f IA T> P F 1r P (Y] J> f i> O T t M b F T) D O m D P P F M $ P f d T> ? E D > p D D i> 0D D DD T D mu I3?X e Dp e T> p j> p E 1> D *A O P F P D Df F /\A F DP 3> S S ! e > p E. D D T F P Q F 7> G > 9 ? O P B /il 3> ta . "O P r 1-1 D "b f ? A Al 0 p H b D E P D 0 > f IS S H T> T r> > E E P T) F F r> b p i^ 9 ? f3>8") i^ a rb T S 1> D r r > D ? M P P FD jp D T> P ? TA r> P /). P p f |A 1> ? t M P e P p f /A > "O f F <r 0 Z> r ?>?? P r b f E _n_ D D T- -o l > " <><>* Reviewed By: Fi- -- Date: S p /o ! RT 01.14.00 EC2-04b 000028 ^ T~C O P Y ) ^(u (o- ! 012435 PROTOCOL: 418-020 DOSAGE: 1 MKD P = Proestrus E = Estais M = Metestnjs D = Diestajs DATE Animal Number n IH Ol IH M IH07 Hon N ID IH K ms NN H l% Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: F1 Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus Sfajo 5/ 7/0/ if'l'i Jt/L 5-iioi F-ifol S V HTci 5-N-cl $H\ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 /?m D ? r pn D ? A b - A J> T) ? F ) fe 0p bP ? C rl D ? t> f 7 A- mD D ? er > D ?e /n D y Z) D D ? c> D ? E t i> /O ,_D p T r r e r T > D ? m J> p P f T V 0 ? fc D V r P b F D 07> ? 'T> ? /i X > T> b p er X > PPb pv X P 6 fh b p p E f F .p P * m E fi j> C f Reviewed By: Date: 000029 RT 01.14.00 EC2-04b f- qiu (os- 01243 J PROTOCOL: Argus TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: 3 MKD P = Proestrus APFO GENERATION: F1 ROUTE: Oral (Gavage) Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus E = Estais M = Metestajs D = Diestrus DATE Animal Number m\ \H7> IH3-9, /H 3 0 /4 3 \ IH 3 fe H ' J m o. IW U H 5C W 52 )H S 5 IH 5 L m sE ljh 5'llt sfr/L 1 234 5 cb ro D f CM D D P fl D T) ? 2> V T> E> rY) b t> 7b D S> 17 DO 7) P D P 17 7 C J7 e D > GDB "D > \Abc 5-l1"0l D r (Y] P /r m 2) Dp T n PB P ) J7 X BD n> b bP Pe r pU- B 3/U/.I SrW-M 5mW 5-n-ci S-t'i-ci j i f/Voi 6 7 8 9 10 11 12 13 14 b P e ? fA t> 6 P D D /> r T r \> P h> D D /Y D 0 D PP P T f P P yvi B f Al r A B P D y' P 56 fA P P es* A1 D T f F /Q D T) P E b f- D L-r>- T] f V S) P0 e M A Lc_ d D f B r>> D F jC J 'TN D P b P E /) * V f P E ) P P Xb b P P p V) l t - a ? A P O P F, pA " P i /G (K B 0 0P f) Yb P z D V e ?, P if n B t KA TA A\ . * D r ? P r G. m 1) A . P B h Reviewed By: >.J Date: 4- RT 01.14.00 EC2-04b 000030 & X A C T C O P Y "! tlu (os. 01243 PROTOCOL: 418-020 DOSAGE: 3MKD P = Proestrus E = Estais M = Metestrus Argus TEST ARTICLE/SUBSTANCE: APFO GENERATION: F1 ROUTE: Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus DATE Animal Number HS3! ...H > l l LlU 'h M fo S IH U 'Z H 7 -JH 7(e H 7? m s/rfoi ? h k imiti f/i'Joi Si?v 3o< 5-I4-6I s-M '/t-el iTD! '/W 5-t-tj S M 21 3 4 5 6 7 8 9 10 11 12 13 P 7? f D t> jp f -7^ ? / T rri D > 9 P A fil f T D T> P E p M A i /> e n T> E P M D F D D p e n V E i W6 C Pf > 0T I? D / d P , F (TL e c X> D > P f if fl'l P D T) i b b P /n jlF A? e D V r E0 P P li P ce T) V r 6 0 P f D P C T> T> P P O D Y 0 P M! ) 14 M P D M i) r i) D Reviewed By: a . Date: RT 01.14.00 EC2-04b 000031 EXACT COPY ^^U tlO u 012438 Argus PROTOCOL: 418-020 DOSAGE: 10MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE Animal Number / m M ite ms H lo N IH m n I50C , 15oa I5 5 1507 /5 0 8 1511 1573. f t iH IS IL __ 15/7 TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: F1 Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus e lisic i 4,-L f/fiJ n 12 3 <r\&0\ 5M a' 5-4 oi 5-)5-<5'lk-fc!. 5-17-fl* 5 'r tq y-T-vi 3M 4 5 6 7 8 9 10 11 12 13 14 6M r p > > H bPP p b D P0b P / ) S T D P0 L Pc D P CD Et i t V D P p M B f) & D C c P > p e: ]> 5 pF .> P r 'b f r pr> > 6 D ? (Z D DP > D p P NA .0 Et k z ,p' D D ~ P <r b p D PP TT) T D h D P > p peD P iA D P Yp P D PO E P (=. P P Fi 0 P P P b E n TP j) ? D D D P ? r> 0 D E /n D L 0 D e" T> D e D P> 6 f D T T P E 0 c= ? 6 b > D /A D P P D X) E f fn B fr0) P) .D e b P f P ? P P e T D > C > x> f & f D 0 P PP ) P E F- D h. P p P b b f e DO IA X) p l P b> <2)rvj3rtS--y-o * Reviewed By: L tx . Date: -5 7 ^ / 0 / RT 01.14.00 EC2-04b 000032 rt & 012439 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 10MKD F1 Oral (Gavage) Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estais M = Metestrus D = Diestrus DATE Sfa/ot *H/0i slJot //a) -p*t S lil Jli-C 5'iiroi 5-17-CI KO 5-p-l f/ult) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Animal Number is n D I5 2 l 152?) 163-1 P 6D T> 150-7 153-% 1531 h D D (5 3 3 D 1631 1537 /5 3 7 r T) D eD D T> D ? e D r D T> P D > P \Y\ T> D P P T? p Q J> tA > ? r> D P r h D t> J? r nr\ 0 f E D DP E 0 r T> D ? PD ' P P D Di B Al f ) = i 0 D e M pP P /I D Z1 r P P r B tfi m P % E" i) D E /U /n P p p D P J T P O A > r M f $ r D P P ~^r P J) 000033 ^ <71(o> 012440 Argus PROTOCOL: 418-020 DOSAGE: 30MKD TEST ARTICLE/SUBSTANCE: APFO GENERATION: F1 ROUTE: Oral (Gavage) TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE sfcf* 1 f*A12VTM/i ^L3L\ 5-IPW%1li|015-14-cl S'/Irt5-17-c SS4L/?-cf sfuk 4 5 6 7 8 9 10 11 12 13 14 Animal Number i5 hi )5HH 5H5 HdHo SH9 1550 /55a 1555 T P ~ r Al > g e D tM P D Pe mP t r> ~D O f V P T T> P m P B P Pe De Pt ~P MD MB p rp t W0 D E DDP DP f J2_ P jD b D E __L L t= P 1_ M DL.E E JL. E > f JDL - E V E /) D /w JX ft 4 L ~ J L D E D SI E E D 155? T f B T> ? D D X . O b tk / 5 5 S 6 O B T E 6 IA 0 P E 5 p /5/tf) 150, S )<L9 5 7 f K 75 I57L, is n "P r B Df mT i e: r e DD TDr JL mT J> r BP r P BP Z9 0 ni <ET D O D D R ? P V P 0 E V no E E /> /il E l) dJJ- D E m J) /VI b t /to D > M TJ D t: E /W t> " b D D D <P r B T> 0 ? D r> j . D J -- T D D / 6 P E f D 0 E E F. T) P E e D E D E E M G&lkS-W \ Reviewed By: Date: RT 01.14.00 EC2-04b 000034 A A V vwMr 01244 Argus PROTOCOL: TEST ARTICLE/SUBSTANCE: TYPE OF TEST: 418-020 DOSAGE: APFO GENERATION: ROUTE: Estrous Cycle Evaluation SPECIES/STRAIN: 30 MKD F1 Oral (Gavage) Rat/Cri:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus DATE bh h ti 4 4 1 *(L S<*l` i - i f f 1 2 3 A5 6 7 5'lh-Di 5\l-b\ K'USC1Ai'h'l sw# 8 9 10 11 12 13 14 Animal Number /5 ? 7 Th F C b f b V Fp Pb F e fi ~D 0 D t> f T D 9 r\ D b h D p F /J B l% l 6 D d Pp D h a t> D P P fb DP b f) e P ra D r 1 "h ? C E P D ? f - D D i5% 1 a H D D P E M D i /T} P r I5i) P r DP 0 ? h pa P F T T! & ? > ? C D D ? E N\ O P t> -p B \^ 8 T) b ? C m 0 P P b T T P J) Hoo o f T> F h 9 P -- D B E b Reviewed By: Date: 000035 A RT 01.14.00 EC2-04b EXACT COPY ff 012442 Argus PROTOCOL: 418-020 DOSAGE: 0 MKD P = Proestrus E = Estais M = Metestrus D = Destais Date Saline Pre-Check Tech/Time Saline Post-Check Tech/TIme Smears Taken Tech/Time Start Smears Taken Time End Smears Read Tech/Time Start Smears Read Time End Test Article/Substance: APFO GENERATION: ROUTE: F1 Oral (Gavage) 5U2l di 1 w m S'-& l 2 P- /a 3 ^ 5--34-C7/ 3 Ft-- nn . Hr LiU'*** w m l4oi )V n H tf I3?T> |3>? tin ^i-- j 4 /Sor P -" X.l^ Ilf H nsi p" IUT- |3V Type of Test: Estrous Cycle Evaluation Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus S oi 5M-?/o\ 56 TV**' WOZ- sA/<>i 7 DC 05 r\ \m 7 ow/ W / I iV5*-* ii 5o uno. e** rw.* DK 1 M37 W c T n fo ii5 o ^v / i * 4 avu> ) X 3 - rzz/o ANIMAL NUMBER 13 o a I'b D H /3>ip I3 0 S I3 ic 13 / 4 7 3 13 3SM 1^5 1330 Reviewed By: P MD FE D pe D0 p c /n 0 P 6 rA D e A1 0 p 0 m p0 Df t F/? c> f Pp bD p (A Op I) r r/i O D B D0 D i> E 0 p "T //I D 0 P /* PD P T ) F> f *4 nn O B e /V\ D e _ 2 ____ . v .... Date: i 0 P * W * J r >1*1- b.1- a ta* ; W ru.lL-'- /'t H ll1' 1 RT 01.14.00 EC1.04a :j jy \ WW* 000036 i ,<t 'Alloa- 012443 Argus PROTOCOL: 418-020 Test Article/Substance: APFO Type of Test: Estrous Cycle Evaluation DOSAGE: 0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus Date GENERATION: F1 ROUTE: Oral (Gavage) Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus < 24>& 5-43 0( T ' J ) 5-Z-0 -au-t.' -T 27-4 5-zo 12345 67 ANIMAL NUMBER 31 E M i^ y i M P pi c , r/i y^D C l?>H I D v D 1344 D, f D #' /M t |3 4 ? t) D e iM P /3 5 b z. 0 Z, 1355 135% X) t p 2- O b m m P yi D /n P D //\ D ^7 P 6: r 09 OD p DM t D DD j M M i* pe O0 P .0 pD P 50 /A P\ 0 F D PP Pc 0P r pP rv) A 't /n r H Reviewed By: 000037 Date: l RT 01.14.00 EC1-04b E.X )T & 012444 Argus PROTOCOL: 418-020 Test Article/S ubstance: APFO Type o f Test: Estrous Cycle Evaluation DOSAGE: 1 . 0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus Date GENERATION: F1 ROUTE: Oral (Gavage) S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus S-*3-| 12 3 o y *~3tf-%*\ 45 5 V 7 - ' 5 28-01 67 ANIMAL NUMBER i'bhQ XKb I-LH I3 L 7 /> ? \K 7\ I5 7 5 l3 7 ? , / 3 7! m\ im L3S3 . ;3 3 V 1387 i'b n Iy t2 > 1377 .. . .IH D t___ By: D D P b P V e i> d d p b a M . .b F. p r. P p p p D t D P D D Al D m p AO /VI __]__ AI m c D m t /Tl O D P D D p m 5 v Al P D rA D m D D D /T) nO D O P p no D p p , O Dt e9 t D O rF ED D i> T VA V ? S' O D O DF P D if E: O t. r eD VA D E no E EP n0 O D . m __ no Date: S '/z^ /o ( .. . RT 01.14.00 EC1-04b 000038 HlXAOT CO' { R/h / ^- 012445 Argus PROTOCOL: 418-020 Test Article/S ubstance: APFO Type o f Test: Estrous Cycle Evaluation DOSAGE: 1 . 0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus Date GENERATION: F1 ROUTE: Oral (Gavage) S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus 5 fri 1 5-AYol 5-2H-0I SS.d] 'il r " 5"- A T 0 1 TT28-) 23 4 5 6 7 ANIMAL NUMBER H W l'io ? M oi P C ni P e J h ____ D h 0Pf J tlO HA D D P IHIlr |4 i? r> p t > i MD e (A 0 p D ? K yA D t> l/vv 05 5 D0 D 43 D P P m /'v Reviewed By: ( Q ., ____________ 000039 P e te : ------------- R T 0 1.1 4.00 EC1-04 exact copy glutei 012446 Argus PROTOCOL: 418-020 Test Article/Substance: APFO Type o f Test: Estrous Cycle Evaluation DOSAGE: 3 . 0 MKD GENERATION: F1 ROUTE: Oral (Gavage) S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus Date E'VII s-avoi S M-al S3.S&) 12 3 4 y n-o/ iS-ZB-o] 567 ANIMAL NUMBER w al IHd-L? H9% 1 m iH ~b3 mi mi \HH2i IHLfb m (o IW f* H 5o ma ms b h b b P D 9, f r> E^c^ b b b b b D > D D P 0 t/\ t M L tA f YA (f\ 0 D D J> e p t D f m t 0 tA t D m D m o .. p t t (A F f ** fc 0 (A P D D D p D P f\ 6 t t P AA ,\A E : ywA D D P ? > E P E A P O \> e DB Op DE DE 0 DP E0 DE V > bP 2. ___ D p t> JE Pf /n 0P DD PP R eview ed By: Q > ^ d f 7 . ________ D ate: i S / ^ U -------------R T 0 1.14.00 EC1-04b 000040 (TXACf c o p y ' 5 t 4iui<& Argus 012447 PROTOCOL: 418-020 Test Articie/Sufastance: APFO Type o f Test: Estrous Cycle Evaluation DOSAGE: 3 . 0 MKD P = Proestrus E = Estais M = M etestnjs D = Diestrus Date GENERATION: F1 ROUTE: Oral (G avage) S p e c ie s /S tra in : R at/C rl:C D (S D ) IGS BR V A F /P lu s 5VLb\ S'-37-0, S-2H ai S-3LS-01 5-Z<r'* ` 1234 5 jr-ze-i 67 ANIMAL NUMBER /4 L 3 l^(s>7 li? 2 . /V 7 V H?> /W /4<2>D . I> .h b C b > 'h fr\ F r t i rf\ P f D D t- e tD t .... fA . D t mM D oD > F P > cS- AA D tM rA O Dc fH X> fH P ? fc P Ef 0D R eview ed By: 170 000041 D ate: (_________ RT 01.14.00 EC1-04b IbA /A t ^w /> PROTOCOL: 418-020 DOSAGE: 1 0 . 0 MKD Argus Test Article/Substance: APFO GENERATION: ROUTE: F1 Oral (Gavage) P = Proestrus E = Estrus M = Metestrus D = Diestrus Date 5-3 oi 12 ANIMAL NUMBER m3- D D W jLp IH V i Pt hP DD 50 |4 ? / IHW m? E - (O b S - nO Dp ? I5 c 0 1505 i5 b 7 /5 OS 1511 /5 /3 iS H 1 5l<<? b 15 b ------ e. p . D r> p F p no O p 15 l 7 iS h p P 15 3 -\ 31 p R eview ed By: U c L ^ J l - S-aM'Oi 3 P m P ? P D D (V\ D m e P r*0 D D D - 4 P D rP c P D p Ki P P D /*) /V) (A ? p 000042 012448 Type of Test: Estrous Cycle Evaluation Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus 5-2A-* 5 Sz8c 1 67 A DE E D D 0P 0 DE D 0F PO D E PE /V\ A D p e a O 5E p M D P = P fE D rP A pD 0 00 v> r t D DB P OB Prt Date: S R T 01.14.00 EC1-04b A f t , ; ' . 3 j A ;V 012449 Argus PROTOCOL: 418-020 Test A rticle/S ubstance: APFO Type o f Test: Estrous Cycle Evaluation DOSAGE: 1 0 . 0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus Date GENERATION: F1 ROUTE: Oral (Gavage) S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus 5Vu>[ 5-3.3 0) SM-oi 1 23 <35-01 4 5-^7 S-Z8 oj 567 ANIMAL NUMBER |5 3 3 15117 )5 3 3 i'T'] 1555 )5 3 lI /5 3 7 iS 'A D D "D - T) > P P ? X? B D e A P t M D P /Tl 0 in P tM AA p Pp ?E DP i? mp DD PB B- PB O n DP ZD P6 * * Reviewed By: \ fi __________ Date: * r fa f0 ( R T 01.14.00 EC1-04b 000043 EXACT COPY f it ^iulo- Argus 012450 PROTOCOL: 418-020 Test Articie/Substance: APFO Type of Test: Estrous Cycle Evaluation DOSAGE: 3 0 . 0 MKD GENERATION: F1 ROUTE: Oral (Gavage) Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus P = Proestrus E = Estrus M = Metestrus D = Diestrus Date tu>\ 1 5`^ 3 i 5-dH-ot 5-oiS.O/ $ V j -o\ S'Tia) Szt>-o) 2 345 67 ANIMAL NUMBER 15Hl lf)W /5 5 M DD ? DD 1O S'" p 0 p. D Dp E E mn 1550 DD KL /v\ _ o f E cf *V) P p r t> D P p p lS fQ , /6 5 S Di ) t An 0 E cM r ir |5 5 7 ? P] D 5 .0 155% bD ep DE 15 0 0 \5 b t\ DP e i /n r .0 p p \5U 5 50$ l 7 l 157% D P f rA D P t /V\ 0 e n /r? J D ____ I D D 0& D p DG0 E 1 O D 1 5 7 0 F> p M D E \5 7 k DD Dr b 1577 D E DS 1 5 V ) & P pn P > R eview ed By: Q. 00 ____ D a te : y fz r fiu ,----------- RT 01.14.00 EC 1-04b 000044 !EXACT COPY 1 P*ih 1 Argus PROTOCOL: 418-020 DOSAGE: 3 0 . 0 MKD Test Articie/Substance: APFO GENERATION: ROUTE: F1 Orai (Gavage) P = Proestrus E = Estrus M = Metestrus D = Diestrus Date $'Tu>\ 1 ANIMAL NUMBER (5 3 7 /5 -& M b i^ 7 /5 s 5 e. o e. m\ l5 T > \< ,n I p DO t > > b 2 D P t t b D D p P 5" 34 t ri tm Pi x> f/J D DO PP f P rn e _ 012451 Type of Test: Estrous Cycle Evaluation Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus S'-ZO-O'I 5'o?l;0/ 5 -3 8 0 1 567 " T - P p P P E bA P p P P p m 0 P r> 5 /A D 0 0 Reviewed By: - _______ 000045 ;i \ Date: RT 01.14.00 EC1-04