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AR226-2768 FOR DU FONT USE ONLY Copies co: E. I. du PonC de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, Newark, Delaware 19711 HASKELL LABORATORY REPORT NO. 600-81 Material Octanoic acid, T e s t e d H a s k e l l pentadecafluoro^, TSo\ 12,037 ammonium salt* : Study Initiated/Completed 4/7/81 - 7/15/8i .Material Submitted b? CR&D Department Haskell Lab LIVER HEIGHT COMPARISON IN CASTRATED AND OVARIECTOHIZED RATS VSc NORMAL RATS Procedure t The test material, |as a suspension in corn oil, was administered by intragastric intubation in uingle doses to 3 groups of 10 castrated male and 3 groups of 10 ovariectomi.ied female Crl:CD rats; this is identified here as a Range' Finding LD50 tost. To evaluate the effect ofjthe compound in the liver weights of rats, 50 male and 50 fee ale Crl;CD rats were divided into the following groups: Gp.. (1) Hale - control - corn oil (2) Feipale - control (3) Male - 200 ng/kgi (4) Female - 200 og/kgl (5) Male - 100 mg/kgj (6) Fei&ale - 100 mg/kg< -(7) (8) (9) (10) Male - Female Male Female - control control - 200 mg/kg 200 mg/kg1 castrated ovariectooized castrated ovariectomized The test material and corn oil (controls) were administered in the same manner. Rats ware weighed and observed during a 14-day recovery period and then sacrificed. Rats (except those in the Range-Finding LD50 study) were seat to P&thology where liver weights were recorded (tissue saved). Company Sanitized. Does not contain TSCA CBl Results: I. Range-Finding LD50 'Test Males; Normal Dose. ing/kg Average Body We. Suspension Z 670 248 4.0 480 251 2.8 200 250 1.2 Castrated Dose mg/kg Average Body Wt. Suspension Z 670 249 480 248 200 245 4.0 2.8 : 1-2 Females: Normal Dose mg/kg 670 480 200 Average Body Wt. 174 172 174 Suspension ; X 2.9 , 2.0 1 0.8 Ovarlectomized Dose mg/kg 670 480 200 Average Body We. 197 202 203 Suspension Z , i 2.9 2.0 1.0 LD50 Confidence Limits: Normal Male Cascraced Male Normal Female Ovariectonized Female Upper 619 607 494 Average Dose (mL) 4.16 4.30 4.16 Mortality Ratio 8/10 7/10 0/10 LD50 439 mg/kg Average Dose (mL) 4.17 4.25 . 4.08 Mortality Ratio 8/10 5/10 .0/10 LD50 491 mg/kg Aves-age Dose (mL) 4.03 4.12 4.34 Mortality Ratio . 7/10 7/10 0/10 LD50 459 mg/kg Average Dose (mL) 4.54 4.85 4.06 Mortality Ratio 9/10 8/10 0/10 LD50 400 Bg/kg Lower ' -294- , 276 315 259 ^ 6.7 5.2 7.2 2 - CoTnpa"y ^Sannwif-r-eecid. ^C-"--oes^ccr^TSCA^ II. Liver Weight Comparison Teat Dose <g/^) Sex Group Avg. Sex Status Final Body Wt (g) Group Avg. Liver Wt. Liver We/ Body wt. radios Control (Corn Oil) M Normal 330 Control (Corn Oil) M Castrated 337 100 M Normal 331 200 M Normal 329 200 M Castrated 335 14.84 14.65 19.81 18.89 15.95 4.50 4.35 5.99 5.74 4.76 Control (Corn Oil) Control (Cora Oil) 100 200 200 Normal 223 Ovariectomijzed 249 Nonaal i 218 Normal 223 Ovariectomized 239 9.75 10.22 9.94 10.37 10.34 4.37 4.10 4.56 4.65 4.28 Clinical Signs: Clinical signs (at each dose tested) were similar for all raes whether the rats were surgicallyi-aodified or not and included: sporadic weight loss, stained perinea! area and stained face. No deaths occurred in this phase of the experiment. ' Summax y-s moderately toxic when administered orally to young adult CriTCD male andIr^eemmaale rats Cthhaajlt were untreated or surgically-modified (ovarieccomized or castrated), fits LD50 is between 400 and 491 ing/kg of body weight. No changes in liver weight in liver cobodvweight ratios were seen in female rats gi"n single doaes of up to 200 ngHBBBBpS (ovariectoaized or normal). A single oral dose of either 100 or ZOOmgm^BAcg produced an increase in liver weight of male rats. Castration reducedche magnitude of the liver weight increase but racs castrated, and given 200 mg/kg had heavier^Livers. than did the controls (not created wichaBAQ Clinical signs seen iayBBa treated rats included, sceined face and perinea! area and sporadic weight loss. ^containTSCACBi Sanite^0005 Corop^ Report by; -A</ ,,T^^. If< 1 0 /H/;ijf^er^^A'.Ge Loo Hinckle Technician Reviewed by: Study Director Approved by: ! jafe^aJ y. ^----^. ^ Gerald L. Kennedy1, ^r. Chief, Acute Investigations Section LH:jrg;WP:14.3 I Q Date Issued: October 7, 1981 Report No. 600-81 4 - n^iconiamTSCACM . , , co^p^!^^