Document ba7yL9mzyV3kv12OO7Dn45xRD

AR226-2921 FOR DU PONT USE ONLY E. I . du Pont de Nemours and C o ., In c. H a s k e ll L a b o ra to ry fo r T o x ic o lo g y and I n d u s t r ia l M e d icin e E lk fo n Road, P . 0 . Box 50 Newark, Delaware 19714 HASKELL LABORATORY REPORT NO. 584-84 1 SUMARY S in g le doses o f] __ were a d m in iste re d by in t r a g a s t r ic in t u b a tio n t o m ale r a t s . The LD50 w il determ ined to be 1900 mg/kg o f body w e ig h t. C l i n i c a l s ig n s were noted in l e t h a l l y and n o n - le t h a lly dosed a n im a ls . Deaths occurred w it h in 6 days a f t e r d o s in g . T h is m a t e r ia l i s c o n sid e re d s l i g h t l y t o x ic when a d m in iste re d as a s in g le o r a l dose ( i . e . , LD50 between 500 and 5000 mg/kg). INTRODUCTION ^ ^ ^ T h ^ p u r p o s e o f t h is t e s t was to determ ine the LD50 fo r] m ^ H j m | n i n r a t . The LD50 i s d e fin e d as th a t d o le w h ic h w h e n a d m x n is c e re ^ a s a s in g le dose, i s expected to k i l l 50% o f dosed anim als w it h in 14 days o f d o s in g . W h ile th e e v a lu a tio n o f c l i n i c a l s ig n s o f a b n o rm a lity and g ro ss p a th o lo g ic changes observed a fte r dosing are u se fu l in a ssessin g the t o x ic it y o f a te s t m a te ria l, these data are not used in the c a lc u la tio n o f the LD50. Company Sanitized. Does not contain TSCA CBI HLR #584-84 Page 1 o f 4 MATERIALS AND MFTHfin A. Animal Husbandry ' M ale* 7 -w e k -o ld , CrliCD(SD)BR ra ta were re ce ive d from C h arles R iv e r Breeding L a b o ra to rie s , K in g sto n , New Y o rk . Rats were housed a s 2 i i i J i naSU8? ende^ s t e e l, wire-mesh cages. Each r a t was a ff ix e d fn**' h I*6 id e n t if ic a t io n number which was recorded on a card . , ,th f ca9e` , Animal rooms were m aintained on a t im e r - c o n tr o lle d 12 hour/12 hour lig h t / d a r k c y c le ; th e r e la t iv e h u m id ity range was 32-58S and the tem perature range was 23-26" C lib it"TM o V ie<J R0d8nt Ci 0W #5002 w ater were a v a ila b le ad Rats. wara quarantined, weighed, and observed fo r geneFST ofd vlenadPoPsredXU,ately " " Prir t0 testi"9* Rats -- TM ks B. Protocol S in g l e o r a l d o se s o f th e t e s t m a t e r ia l were made uo as . . . . s a c r if ic e d . The LD50 v a lu e s were c a lc u la te d from the m o r t a lit y d a ta u sin g th e method o f D. 3. F in n e y .1 C. Test M a te rial Form: P urity: S ta b ility : C o m p o sitio n : J jj te to tan powder The m a te ria l was assumed to be s ta b le under J:hg c o n d itio n s o f t h is study. Synonyms: Submitted by: ^ ^ " ^ rr o d u c ts Department Washington Works D* Raw Data and F in a l Report Storage A l l raw d a ta and the f in a l re p o rt w i l l be s to re d in the Mm eedaiicciinnee , Et . 1r ^. dduu PoVnot ndte^. ?N^em0o^urs fand rCToo.,x iIcnocl.3, y NewaI rk. IDn edluaws tarriea l o r in the Du Pont H a ll o f R e co rd s/ Wilmington, D e l a t e ! Company Sanitized. Does not contain TSCA CBI HLR #584-84 Page 2 o f 4 RESULTS A * D osing In fo rm a tio n and M o r t a lit y Data The d o sin g in fo rm a tio n , fa s te d mean body w eig h ts, and m o r t a lit y r a t io s are g ive n below: Dose (mq/kq) 1200 1500 1800 2000 Average Body Weight (s) 254 241 243 243 Suspension (mg/mL) 200 200 200 200 Average Dose (nL) 1.5 1.8 2.2 2.4 M o rtality R a tio 0/10 4/10 6/10 4/10 t Thf *;D50 fo r male r a t s *a s 1869 m9 A g w ith a 95 co n fid e n ce in t e r v a l o f 1617-3343 mg/kg and a s lo p e o f 6 .9 p r o b it s / lo g (m g/kg). B. C lin ic a l 5iqns jjo n -L e th a l Doses: Commonly observed c l i n i c a l s ig n s in c lu d e d r u f f le d f u r , h y p e r a c t iv it y , lim p n e ss, hunched p o stu re and a brown d is c h a rg e from the nose. M L e th a l Doses: Commonly observed c l i n i c a l s ig n s in c lu d e d brown or s ksined and/or wet perineun, hunched p o stu re , d ia rrh e a , red, y e llo w and/or brown d is c h a rg e s from the e y e s, nose and mouth and moderate to severe weight lo s s ( i . e . , 5-15 o f body weight) g e n e ra lly la s t in g from 1-6 days a ft e r d o sin g . Other c li n i c a l sig n s in clu d e d r u f fle d fu r, h y p e ra c tiv ity , lim pness, ra p id and/or labored reach in g , lim p n o ise , a ta x ia , h a ir lo s s , low posture, general p a r a ly s is and le t h a r g y . Deaths o ccu rre d w it h in 3-6 days a f t e r d o s in g . CONCLUSION /. The_ L? 58 determ ined to be 1900 mg/kg o f body w eig h t under th e c o n d itio n s o f t h i s t e s t . T h is m a te ria l i s c o n sid e re d s l i g h t l y t o x ic when a d m in iste re d in s in g le o r a l doses to male r a t s ( i . e . , LD50 between 500 and 5000). Acknowledgement: Bruce A. Burgess and Rayanne L . Ferenz a ls o p a r t ic ip a t e d in t h is stu d y . Company Sanitized. Does not contain TSCA CBI HLR #584-84 Page 3 o f 4 Work and Report by: JL -, ' /L t a lv in N. W ylie ~ r T e c h n ic ia n Study D ire c to r: '" David B. W arheit, Ph.D. Research T o x ico lo g ist Approved by: CNW/DBW/egg:0.12 Date Issued: 1/16/85 Study Initiated/Com pleted: ^5/23/84-6/26/84 T ia s k e ll Lab. Report No. *64-84 Nunber o f pages in t h is rep o rt: 4 Section Supervisor Acute In ve stig a tio n s 1F in n e y , D. 3 ., P r o b it A n a ly s is , 3d E d ., Cambridge U n iv e r s it y P re s s , 1971. Company Sanitized. Does not contain TSCA CBl HLR #584-84 Page 4 o f 4