Document 29D3emJjMgXBBpxnwpymX0dp

HAZLETON________________*i LASCFUCTCFIIES A M E R IC A . INC Chemical & BioMedical Sciences Division JS ? 3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD F IN A L REPORT ROGER P E R K IN S MINNESOTA M IN IN G MANUFACTURING TOXICOLOGY SERUICES S T . P A U L , MN 5 5 1 0 1 COMPANY SAMPLE: T -4 0 1 6 PURCHASE ORDER NUMBER: T 8 3 7 3 8 9 - 4 1 0 7 1 2 SAMPLE NUMBER: 7 0 1 0 0 3 5 SAMPLE ENTERED: 0 1 /0 7 x 8 REPORT PR IN TED : 0 2 x 0 5 x ENCLOSED: ACUTE ORAL T O X IC IT Y STUDY IN RATS - METHOD, SUMMARY, PATHOLOGY RAW D AT A A P P E N D I X SIGNED: STEUEN M. GLAZA STUDY DIRECTOR ACUTE TOXICOLOGY ............... DATE BY AND FOR HAZLETON L A BO R A T O R IE S A M E R IC A , IN C . RAW D A T A FOR T H I S S TU D Y ARE K E P T ON F I L E A T H A Z L E T O N L A B O R A T O R I E S AMERICA. I N C . , MADISON, WISCONSIN. HAZLETON LABORATORIES AN RICA. INC Chemical & BioMedical Sciences Division 3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD SAMPLE NUMBFR: 7 0 1 0 0 3 5 3 L A MP L E : T --4 0 1 6 PAGE ACUTE ORAL T O X I C I T Y Oh t e c f i u e : To d e t e r m i n e t h e a c u t e o r a l t o x i c i t y p r o d u c e d w h e n a t e s t m a te ria l is a d m in is te re d by the o ra l route (garage) to r a ts a c c o rd in g the U.S. E n viro n m e n ta l P r o te c t io n Agency's G u id e lin e s fo r T e s tin g P e s t i c i d e s and T o xic S ubstances. to Test M a te ria l: T-4G16 Physical D e scrip tio n : P u r i t y a nH P t s h i I i ti.r Thick brown l iq u i d Spono - assumes respons i t i 1 i ty s t a b ilit y determ inations. fo r p u rity end T e s t A n i m a 1: Y o u n q a d u l t m a l e a n d f e m a l e a l b i n o r a t s o f t h e S p r a g u e Dawleu s t r a i n were p ro c u re d , m a in ta in e d by sex in group cages in t e m p e r a t u r e - and h u m i d i t y - c o n t r o l l e d q u a r t e r s , p r o v i d e d c o n t i n u o u s access to P u r i n a R o d e n t Chow and w a t e r , and h e l d f o r an a c c l i m a t i o n p e r i o d o f at least 7 d a y s . A c c li m a t e d a n im a ls were chosen a t random f o r the s t u d y . Test a n im a ls lA,e r e h o u s e d b y s e x i n g r o u p s o f f i v e a n d i d e n t i f i e d b y a n i m a l n u m b e r a n d c o r r e s p o n d i n g e a r t a g . F o o d a n d w a t e r w e r e a v a i l a b l e ad 1 i b i t um t h r o u g h o u t th e s t u d y , e x c e p t f o r an o v e r n i g h t p e r i o d l u s t b e f o r e t e s t m a t e r i a l a d m i n i s t r a t i o n when f o o d , but not w a t e r , was w i t h h e l d . Reason f o r S p e c ie s S e l e c t i o n : The r a t is the a n im a l c l a s s i c a l l y used due to ! t sm all s i z e , ready a v a i l a b i l i t y , and la rg e amount o f b a c k g ro u n d d a ta . Me t hr, d : F i v e m a l e a n d f i v e f e m a l e r a t e w e i g h i n g f r o m 2 0 3 t o ' 2 9 3 g we r c used for a s in g le dosage level of 5.0 g /kg . P r e p a r a t i o n a n d A d m i n i s t r a t i o n o f T e s t M a t e r i a l : An i n d i v i d u a l d o s e mas c a l c u l a t e d f o r e a c h a n i m a l b a s e d u p o n i t s f a s t e d b o d y w e i g h t and a d m i n i s t e r e d u n d i l u t e d by gawage. T h e d o s e v o l u m e o f t h e t e s t m a t e r i a l w a s 4 . 6 3 m 1/ k q o f b o d y w e i g h t b a s e d upon an a v e r a g e b u l k d e n s i t y o f 1 . 0 8 g / m l . Reason for Route of A d m i n i s t r a t i o n : a known q u a n t i t v o f t e s t s u b s ta n c e h i s t o r i c a l 1y . This is and has the method fo r been the ro u te adm inistering of choice ^ HAZLETON LABORATORIES AMERICA. INC Chemical & BioMedical Sciences Division 3301 KINSMAN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD AMPLE NUMBER: 7 0 1 0 0 3 7 3 AMPL. E : T - 4 0 16 hHbt ELITE OPAL T O X I C ! TV (CONTINUED) Oh .=e r w a t i o n s : T h e a m ma 1s we r e o b s e r w e d f o r c l i n i c a l s i g n s a n d mo r t a 1 i 1 y a t l . 2-P and 4 h o u rs a f t e r t e s t m a t e r i a l a d m i n i s t r a t i o n . The a n i m a l s were o b s e rv e d d a i l y t h e r e a f t e r f o r 14 days f o r c l i n i c a l s i g n s and t w i c e d a i l y f o r mo r t a 1 l t y . A ll anim als were weighed just b e fo re te s t m a te ria l a d m i n i s t r a t i o n . S u r u i v i n o a n im a ls were weighed a g a in at 7 days and at s t u d y t e r m i n a t i o n . F'atholoqw: At s t u d y t e r m i n a t i o n s u r v i v i n g a n im a ls were e u t h a n a t i z e d . Animals which died durinq the s t udy or were e u th a n a t i z e d received a gross n e c r o p s y e x a m i n a t i o n and all a b n o r m a l i t i e s we re recor d e d . H ^ lZ ^ E T I O r N l- A B a R n 3R IE S A M ERICA. INC 3301 KINSMAN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 Chemical & BioMedical Sciences Division PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD s a m p l e NUMBER : Y 0 1 0 0 3 5 3 SAMPLE: T-40'16 PAGE ACUTE ORAL T O X I C I T Y SUMMARY ( CONTINUED) Ts=. t A n l ma 1 : A l b i n o Ra t s - S p r a o u e - D a u 1e y Source: C h a r l e s R l u e r L a b o r a t o r 165 , I n c . , Da t e A n i m a 1s R e c e l we d : 1 2 / 2 2 / 8 s tra in Portage M1 M e t h o d o f A d m i n l s t r a t i o n : Or a 1 Gawage Date Test S ta rte d : 01/08/87 Date Test Lom pleted: 01 , " 2 2 / 8 7 E s t i m a t e d O r a l LD5 0 : M a l e - G re a t e r t h a n 5 . 0 g / L q o f b o d y we 1 q h t F e ma 1e - G r e a t e r t h a n 5 . 0 g / k q o f b o d y we 1 g h t fnsA np Le^e 1 ( q /V g 1 Male F e ma 1 e 5-0 5.0 Aweraqe Body Lleiqhts (q) In l t 1a 1 Day 7 Terminal 264 325 361 2 G9 224 234 Mo r t a 1 l t y ( N u m b e r Dead /N um ber Dosed 0/ 5 1/ 5 C 1 l n l ca 1 S igns Hour 1 n 9 c 4 . 0 1X 9 7 /; F Ma 1 e s Da v s A7o 9 A n p ^ a f e d N o r m a 1 X Hunoflct i u 1 t v ji Red-stained face i F * r e s s i ''6' s a l i '-J3 t l o n 0 4 1 1 0 X r 5 5 5 5 5 F 5 C 1 000000000 1 0 0 0 0 0 0 1] 0 1 Cl 0 0 0 0 0 0 0 0 F e ma 1es --n " -r o H KJp r rrta s 7 7 7 o 4 4 4 4 4 a 4 Hunnan t 1u l t u Tj. Red-stained face 9 1 n 1 9 110 00000 -> <--> 1 1 0 0 0 0 0 0 F vc e s s iw e sailw ation At 9 x ja E nia c l a t i o n De a t h n l 9 00000000 0 0 0 0 0 0 10 0000u 0 0 0 Cl 0 1 0 0000 0 u 0 0 0 0 1*0 0 0 n 0 0 Found dead in p . m. 0 T *1 `I ' 5F 00 00 00 44 00 00 00 00 00 00 0 0 0 0 0 0 0 0 0 HAZLETON LABORATORIES AMERICA. INC 3301 KINSMAN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 Chemical & BioMedical Sciences Division PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD SAMFL E NUMBER: 7 1 0 03E? AnPL E : T - - li i 6 ?h L t o k I C I T Y PATHDLOC Y ( CONT I NI JEO ) D o s a g e L e ' >e 1 : A n i ma 1 Nurnbe r r >, 6 3 RA Sex M B . fl a / T q o f b o d u we i o h t T e s t Da y D i e d Sac r i f i c e d _1 N e c r o p s y Comments CT rv i n s d i ' *- b f Olu I . firm , rubbery, porous m a te ria l. C6 6 3 8 2 M - 14 Stomach - c o n ta in s d a r k - b r o w n . firm , rubbery, porous m a te ria l. C6 6 A 1 0 M - 14 Stomach - c o n ta in s d a rk -b ro w n , firm , rubbery, porous m a te ria l. C 6 6 3 8 ij M - 14 Stomach - c o n ta in s d a rk-b ro w n , firm , rubbery, porous m a te ria l. Cn6439 M - 14 S t o ma c h - c o n t a i n s d a r k - b r o w n , firm , rubbery, porous m a te ria l. C6 6 3 2 3 F - 14 Stomach - c o n ta in s d a r k - b r o w n , firm , rubbery, porous m aterial , u l c e r a t e d a r e a s on n o n q l a n d u l a r DOr t ' n . C6 6 E2 4 F - 14 S t o ma r. hi - c o n t a i n s d a r k - b r o uin . firm , rubbery, porous m a te ria l. C 6 F 19 F - 14 Stomach - c o n ta in s d a rk -b ro w n , f i r m , r u b b e r y , porous, m a t e r i a l . C 478 F - 1- C66E1E F *7 _ Stomach - c o n ta in s d a r k - b r o w n , f i r m , r u b b e r y , n o r ous. m a t e r i a l . u l c e r a t e d a r e a s on n o n q l a n d u l a r port ion. Stomach - c o n ta in s d a rk -b ro w n , f i r m, rubbery, porous m a te ria l, a n d e x h i b i t e d d i f f u s e 1y r e d a r e a s on g l a n d u l a r p o r t i o n , end u l c e r a t areas, on o l a n d u l a r a n d n o n q 1a n d u 1 port ions. HAZLETON LABORATORIES AM ERICA. INC 3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 Chemical & BioMedical Sciences Division PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD SAM PLE NLIMRFR : 7 G1 G0 ~ F Fa MPLF : 7 -4 0 1 6 P A L, ACIJT- OPAL TO a C TTY (CONTINUED) References: i H, t c h , R . K . , " A c u t e O r a l T o x i c i t y S t u d y , - " P e s t i c i d e A s s e s s m e n t Guide) i n es , S u b d i v i s i o n F, Hazard E v a l u a t i o n : Human and Domes t i c A n i m a l s , IJ-S- E n v i r o n m e n t a l P r o t e c t i o n A g e n c y O f f i c e o f P e s t i c i d e and T o x i c S u b s t a n c e S e r i e s 8 1 - 1 , p p . 3 4 - 3 9 , N o v e m b e r 19 8 2 o i r- c' p c o (i *n i *c d S p a t e s S e e d a n d D >g A d m i n i s t r *. . r .^ 3 p C r ,ri L a b o r a t o r y P r a c t i c e s R e g u l a t i o n s f o r N o n c l i n i c a l L a b o r a t o r y S t u d i e s ). DHHS P u b l i c a t i o n No . ( N I H 8 F - 2 3 1 9 8 9 ) G u i d e f o r t h e C a r e a n d Use of Laboratory Animals. o OACUTE ORAlrtOXICm Dose Administration/ Body Weight/ Mortality Recrfrd Tret H a te rla l: T 4 0 l( o Vehicle I l i f t Ht.A ko. I_ B ulk b a n a lt y i_ l | / a U Spec le a - l b l B a d - ou rc a : C k n r lft t'P .u g r a t e iv . d n a - a a - 'S a b o a * b e w a il___ 3 . 0 ) < / H > a a ta d l D a ta |-~7-'S7 T l- a j3 1 i2 0 t Te* c h n lc ta n i^ r W c lo o m Mo. 3 5 0 aai /fulaTfanala 1 O.S)k DoaaTlx Q Q'.<3Qm Technician bata calaDead / (jiaT) u4/0 frt34 Urn- HA lift , liav1lodvWeialt la) nayII bodyWaieht It) (07(3 (074 (043 3712 (0*8 1,3) 1,4 |.3 1,3 e.iajtr r?72> 5511 3M1] 3Coii> ^00 ?>ao 3*57 3MSf 3(gi.- (irtic __ i ^nic... .lls_ 12_ QE.vpfainrifil)ladb?y:_--_ ___ftnv //s.. Ky^ aJ/so/? 6>_ far.n 150^ HeadBodyUaiaht It) lutee V elitele <L Cl ^ t a L / k t ) 1 m om m m l a t i Ml ____________I o t a T l t a i ^ : 5 S a m l T e c h n ic ie n ia ti ) U n . lf/ //iS ( 0 2 > (fl+W ( 4 7 7 f p l S \ JKC.. D a ta W ( c a la Deed MA \ ----------------------- V |>relatad lu d v U e ith t i l ) Vested Rode W eiebt te l a c tu a l bo a e lade) Kev 1 Rod U e iu h t t e ) nay U Body W e ltlit I t ) A ftf -- r 0 l4 o en ( C n s |,.C > 101 .% o ,4 h lO O i 7 <<3 o iri 0 ,4 1 (0C>> ( 0 0 7 q ,s $ _Q\1 ^7 0 'M V Feuul O ftO t-- \ \ \ \ \ ( Mt -l|g - t o ^v9 a ^smc. jJL )fo b& 7 66 K -T o AJ / 5 t > 7 ( S Q < ? _____ Jaad Body Wei a l i i I t ) -- n a l-T 7 T T J >\ Ilnu r a boaa 0- A Lavai baa MORTALIT T MO. U U D /M O . D O S ) e ry f& n e d l t-Q ^ e -ty n L (Q p r iA j/i/v jS i /5 > -**> 6 ? g p T e clin ic Ia n D ata iqSTI J L NA - N ot A p p lic a b le * - 1i o m | c a l c u l a t e d , b u t n o t a d a ln ia t e r e d uiiuaed ail le a I re tu rn e d t o atocfc R eview ed Ry /-< s a ^ .7 o acute oral t o x ic it y T-T e s t M a t e r i a l : In d iv id u a l C lin ic a l O bservations ___________________Dose L e v e l: MLA Ho* ! 70100?^ , / - Sign p re s e n t. S I Sign p re s e n t, s lig h t - Not ev id e n t. R e v ie w e d By: C~W ? D ate: o oo acute oral t o x ic it y Test M a te ria l! In d iv id u a l C lin ic a l O bservations T- 4Ctk> _____________ Dose L e v e l: __ - f i. ^ HLA No. : ~ |0 \0 Q & & 2 > jr~ & '3 -f7 y Sign p re s e n t. S I " Sign p re s e n t, s lig h t . - Not e v id e n t. Reviewed By: D ate: I