Document BrkmXM4rgxd0MM4RoJMOQpyL

AR226-2768 FOR D PONT USE ONLY E. I. du PonC de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkeon Road, Newark Delaware 19711 HASKELL LABORATORY REPORT NO. 600-81 Material Tested 1 Oetanolc acid, pentadecafluoro*-, ammonium salt* : Haskell No. 12,037 Other Codes rjUAMuA C-8 Study Inltiated/Completed 4/7/81 - 7/15/81 .Material Submitted Z CR&D Department Haskell Lab LIVER HEIGHT COMPARISON IN CASTRATED AND OVARIECTOMIZED RATS VS. NORMAL RATS I.! ' |' " ' ' ---------------- ' ------------------- | ! Procedure: The test material,as a suspension in corn oil, was administered by intragastrlc Intubation in single doses to 3 groups of 10 castrated male and 3 groups of 10 ovarlectomlxed female Crl:CD rats; this is identified here as a Range-Finding LD50 test. To evaluate the effect of|the compound in the liver weights of rats, 50 male and 50 fenale Crl:CD rats were divided into the following groups: Gp . ( 1 ) Male - control - corn ( 2) Female - control - corn (3) Male - 200 mg/kgj (4) Female - 200 mg/kgj (5) Male - 100 mg/kg] (6) Feale - 100 mg/t (7) Male - control castrated ' (8) Female - control - - ovarietomited (9) Male - 200 mg/kg1 ( 10) Female - 200 mg/kg castrated ovariectomlzed The test material and corn oil (controls) were administered in the same manner. Rats were weighed and observed during a 14-day recovery period and then sacrificed. Rats (except those in the Range-Finding LD50 study) were sent to Pathology where liver weights were recorded (tissue saved). - 1- Company Sanitized. Does not contain T SCA CBl Results: I. Range-Finding LD50 Test Males: Normal Average Dose- mg/kg Body Wt. 670 248 480 251 200 250 Castrated Dose mg/kg Average Body Wt. 670 249 480 248 200 245 Females : Normal Suspension X 4.0 ' 2.8 1.2 Average Dose (mL) 4.16 4.30 4.16 . Mortality Ratio 8/10 7/10 0/10 LD50 439 mg/kg Suspension X 4.0 2.8 ; 1 `2 Average Dose (mL) 4.17 4.25 ; 4.08 Mortality Ratio LD50 8/10 5/10 .0/10 491 mg/kg Dose mg/kg 670 480 200 Average Body Wt. 174 172 174 Ovarlectomized Average Dose mg/kg Body Wt. 670 197 480 202 200 203 Suspension iX 2.9 ` , 2.0 ! 0.8 Average Dose (mL) 4.03 4.12 4.34 Suspension jX \ 2.9 2.0 1.0 Average Dose (mL) 4.54 4.85 4.06 Mortality Ratio LD50 . 7/10 7/10 0/10 459 mg/kg Mortality Ratio LD50 9/10 8/10 0/10 400 mg/kg LD50 Confidence Limits: Normal Male Castrated Male Normal Female Ovarlectomized Female Upper 554 619 607 494 .* . Lower ' 294 . 276 315 259 Sloge 6.1 6.7 5.2 7.2 -2- Company Sanitized. Does noi contain TSCAC31 II. Liver Weight Comparison Teat Dose Sex Group Avg. Group Avg. Liver Wt/ Sex Status Final Body Wt (g) Liver Wt. Body wt. riadios Control (Corn Oil) Control (Corn Oil) 100 200 200 M M M M M Normal Castrated Normal Normal Castrated 330 337 331 329 335 14.84 14.65 19.81 18.89 15.95 4.50 4.35 5.99 5.74 4.76 Control (Corn Oil) Control (Corn Oil) 100 200 200 F Normal 223 F Ovarlectomijzed 249 F Normal : 218 F Normal 223 F Ovarlectomized 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 surgicallyHnodifled or not and included : sporadic weight loss, stained perlneai area and stained face. No deaths occurred in this phase of the experiment. ' Summary : moderately toxic when administered orally to young adult Crl:CD nmle and remale rats tha|t were untreated or surgically-modified (ovarlectomized or castrated), its LD50 is between 400 and 491 mg/kg of body weight. No changes in liver weight in liver tfl body weight ratios were seen in female rats gi"in single doses of up to 200 mgJpBB|^(ovariectomixed or normal). A single oral dose of either 100 or 7*111 m i l I I produced an Increase in liver weight of male;rats. Castration reduced the magnitude of the liver weight increase but rats castrated, and given 200 mg/kg had heavier^iveM^ than did the controls (not treated w i t h g S n f i Clinical signs seen treated cats included, stained face and perlneai area and sporadic weight loss. -3- Sam C o m P a tscacbi Report by: ^ rfi *. Lon Hinekle Technician Reviewed by: Study Director Approved by: ____ y. l________ : Gerald L. Kennedy1, 4r * Chief, Acute Investigations Section LH:jrg:W P:14.3 Date Issued; October 7, 1981 Report No. 600-81 i % * - 4- . sanitized. Ooes not co