Document wg68aQvqgOYk5d49z7Y7gRk8V

FOR DO POST d s e omi-y Copies to:! AR226-2782 Haskell ULatbaerrMatoot, for TeleTology" nul Indoatr"lacl'-M-e-d-i-c-i-n-eElkton Road, P. 0. Box 50, Newark, Delaware 19711 HASKELL LABORATORY REPORT NO. Material Tested 1> Octanolc acid, pentadeca- flubro-. amonlua tir (See page 4-5) Study Inltlated/CoapletpH *1'/1c oA*j//0e/#eazm Material Submitted hv Department & Develoeeent Haskell Laboratory S u m ary jfFFECT 0F|_ _____ I C J-A110NIUM PERFLHOBn |0N THE ELIMINATION OF a m o a t e FROM RATS AND MICE Adult nale rats and alee were given hours after dosing with [W CJ-a*sonim " Although a previous study Indie the acute lethal.effects of C-81 elimination of [^CJ-C-8 via th, Introduction l( H - W , 249) 2 (i1 -I=C=g) [could reduce of enhanced or exhaled air. a p p l i ^ " f^Ifi" i!!tan0atec,,Cld (C`8> 18 8 .pound used _n the notable toxicological effecrof0^ ^ 8^ ^ ^ S T h i S f and 18 i i S S p T L 'Z Z r "earof n L ^ n g ^ S S S S Z t ? ' * * toxici F, a that C-8 would undergo b i l L TM thC * * 60U*ht* Xt V*B (Boylan et al. 197^ , 7 e*fretion and reabsorption like Kepone ' 1978)' and thua susceptible to therapeutic removal by - 1- Company Sanitized. Does not contain TSCA CBI I I * previous s t u d y l ^ ^ M K L k . within 2 hours of C - ^ T ! - ^ ^ * BhOWed that dose8 of " ^ W l t h nonabsorbed C-8 in thl l L ? , ta due to interaction of " *ocpt1" - " r "1" ' " " ^ S S T - S S i E S S ? ^^iljinteraine y* a s a s iH s a reflect the unt of copo .,,J r.t.lned b, the to,,. "" * - trecot H.rk m W .tlll,tl,, Counter, *del 16882, Serf.! ,882020 !-- --- Oxiprep-2 -- Oxlsorb n--n->_2 .Bk._wiuu_e_r Aquasol-2 .Ulcer, Model ^ i Sertel ,202280 6 - Jenco Metabssrls* - ? _ D="is gxass mouse metabolism cages 8 glass rat metabolism cages ' Methods Intragastric intubftion/S )eighrCri"cD*8vSOll,tl!n W,S ^ "^ e r e d by adult male mice at a dose of 10 J / L ?^ ? adult rats.and to sis DPM - Dtsintigrations Per M i n u t e 1,13 * W * DPM/kg; where groups as follows: * 4rat8 and -- ce -s rc divided into three Group Control Control Treated Number Kats Mice 22 32 32 Treatment Sacrificed at 24 hours. Sacrificed at 96 hours. Dosed w i t h l t f H i ^ ^ g g ^ T i? C ll c'^e- sTM <(1000 mg/lc|5 24 hours after - 2Does not contain TSCA CBl Company Sanitized charters. Ertlfd NaOfl, followed by a m e T t m E^ L idiTldl,al g1" 8 et*boliw J., 1"plnger8 containing 1.0 H at 24 hours, A s l o u r s . X tlu l's ^ 1 TM T L ! ? " n* scintillation fluid. The samples were cleared and11<F?J5J?L.AS,OSSOl2 drops of glacial acetic acid. Feces were "lth 8everal water, Weighed, and 0.5 g was oxldiLril ! , approximately 1-2 mL tours, animals were sIcrlfT^L^- !fd ? COunted* At 2 hours and 96 syringe, approximately 1-2 mL Jf*1?8 * heparinized puncture and approximately 8 mL of Kinna e"owed froa the mice via heart cava of the raL ^ e r s w e r f r ^ o ^ l 8 " ^ fr" the lnf"ior vena weighed, and 0.5 g samples was o x l d l z L I ^ rats aad "Ice, homogenized, f a L c " rd ?ri^arS ^r.n f"OUn.tud- * - # * ** w s " .....8 C02'.b,orblr Z ^ 1 ? `S , TM 2" U " t*8 Results and Discussion A. Effect of on [14C]-C~8 Elimination. * * 4 " and distribution results for rats dosed with or without = S S H r n Z z r s J T " 1 - - s .'E r dlffernc i. **-?* tth PecleP.Jh. m p t l c M . . animals was not profound. Only ra^fecalexere^wwS* **v cntri S B S 5 ^ j g S iV iig " -- STSi be made lf rend* however statistical comparisons could S . S S L SZ SSL T iZ SJH l S . * 2 a - S " from t h ^ o d y ! ^ " * 88 laeffectlve in enhancing the elimination of C-8 of enhanc^C-^elimi11 rf ^ ^ T 0"8 ln blood llver confirms the lack blood concentrations for rate Induce! r e s j c t i v e l y ^ Th ^ J f i a= a t .ps significant differed in tissue coice *** [ m i " 'y L S Z 1 " " * * 1`" * - - m m b, 8> f i i M a 3 - . i c b .h<,d l - f c- 8- nonabsorbed C-8 then a s s o c i e ^ t 3 B B t * S i l8tered* ^ .bjorptio. could occur. oud rbu, procured the ,, J - 3- not contain TSCACBl Sanitized. Does Company *. Comparison of {14CJ-C-S Elimination in Bats and Mice. R *gmeaarte3d!KaLn-d tchoPnit!roWlfrseni"s0alDsO.tabthiee digff*efrfetn?ce between1 v P*r5 on of the specie--specific lifunnstn. Pcxe were pooled asd rats vsa mice was m S e disposition and exertion of C-8 in Table 1 presents a comparison of male rat vs. male moose [id J a grater fflc}-* !H r a i f JereB" ln urinary excretion was reflected- 1 , J concentration in mouse liver (53.2 vs. 30.7 u* eou f S ts S JV fzi ^ t i o n a l l y , the liver/blood ra tio w S I S concentrating t ^ r 6^rat liver and/or retainin^f I fCJ-iC-r8 " to a "8e liver ** capable of greater extent than the i n_vi.oI v r ^ t S " h f w ayT L 8mEiuciri t^ucCl^aV1sCraif sCcUcBrpuslart:i^o0n*in ^ a*l i v e r_might tfes kioney excretes the conpound. 1 --- ? References c Haskell Laboratory. Unpublished Data: 2' L` f f ' - P- S` d 6 ) . "Cholescyraine: B-14,611 CAS Begis -Acontaiinn TSCA CBi C o m p 3")v 3an!?izcd. 0ss ncl H-14.249 Composition Report by: Approved by: TPP:tac:WP:l3.4 Date Issued: September 17 1982 Haskell Report fb. 405-82 ' ,,,, Cerald L. Kenned^?/ Section Supervisor I Acute Investigations -5- notcontainTSCA c' Sanitized- Doe* TABLE 1 Urine Expired Air Feces i emulative Percent of Dose Becovered (n)* ' ` Male Rat 24-Hour 46-Hour 6.5 + 1.7(8) 21.6 + 2.4(5) Hale House 24-Hour a7co_~Bn_our 4.2 + 2.2(5) 8 .8 + 6 .4 ( 4 ) 1.3 + 0.1(8) 4.4 + 1.4(8) 1.6 + 0.2(5) 6.5 + 2.1(5) 2.9 + 1.0(5) 3.8 +2.7(4) 5.4 + 0.9(4) 6.6 + 1.2(3) Liver Blood ug Equivalent C--8/g Tissue Hale Rat 24-Hour 96-Hour 34.9 + 2.8(2) 30.7 + 2.1(5) 24.8 -r 0.6(2) 18.0 + 1.6(5) Hale Mouse 24-Hour 96-ji..* 69.0 (1) 53.2 + 7.0(4) 18.5 (1) 10.2 + 0.7(4) Table 1. Ellnination end M.trlbntton of [14c|-C-8 in Bot. ond Mice &Q*'-**~*' corn*-- 1 wed. Does nc CUMULAT JVE PERCENT DOSE Figure feces, #1 and Elim ination of sxpired a ir of ra ts . in urine, 7not contain TSCA CBI Company sanitized. Does UC EQUIVALENTS C - 8 / 0 t is s u e Figure #2 - Microgram of liver and blood of equivalents rats. of C-8 per gram - 8- Company anmfezed. Does no! contain SCA.C3 CUMULA FIVE PERCENT Figure #3 - Cumulative % dose of 14c exc-eted in urine and C02 of mice. ' excreted m the - 9not contain 7SCA-CBI Sanitized-D es &on$an>i CUMULATIVE PERCENT DOSE o*m u vii Figure #4 - Cumulative % dose of 14C excreted in the feces of mice. Note: only one animal in treated group. - 10 - .A - s m s s " " 4' ft*,,00n*.2i ,w*' -- JJG EQUIVALENTS C - 8 / G TISSUE BO 70 80 50 40 SO 20 10 0 / / z a LIVER SB BLOOD / Figure #5 - Microgram equivalents of C-8 per gram liver and blood of mice. Note: only one animal in "control-24 hours" group. - 11 Company Sanitized. Does not contain TSCA CB1