Document oDgBao3212gjbN63r9aErazBr

Interoffice Correspondence c :H .E . F r e i e r J.D. Lazerte B.W. Nippoldt R. A. P r o k o p F.A. bel D.G. Weiblen 201-1S 236-1 201-1S 236-3B 220-2E 201-1S ARaofc-oM^ Subject FC-143 Rat Toxicity Study Request A67821 March 20, 1978 TO: J. E. L O N G 2 2 0 - 2 E FROM: JON BELISLE: -201-is Samples of serum from the rats surviving the IRDC 90-day sub-acute rat toxicity study (reference 137- 089) were received for analysis of FC-143 RAT SURVIVAL DOSE (ppm) 143 in s e r u m (ppm) Male Male Male Male Male Male 5/5 5/5 5/5 5/5 5/5 5/5 0 10 30 100 300 1000 0 21 34 36 38 49 Female Female Female Female Female Female 5/5 5/5 5/5 4/5 4/5 5/5 0 10 30 100 300 1000 0 not measured 0.15 not measured 0.25 0.65 Samples of whole blood from the rats surviving the IBT 28-day oral toxicity study (reference 8532-10654) were analyzed for FC-143. RAT DOSE 143 in w h o l e b l o o d (ppm) Male Male Male 0 1000 3000 0 100 not measured Female Female Female 0 1000 3000 not measured 1.5 not measured 001667 2 DISCUSSION Needless to say, it is most surprising to see a male rat accumulate and retain FC-143 at a level approximately 100 times greater than a female rat. To confirm the difference between the male and female, serum from the 1000 ppm dosage level was analyzed for total fluorine content. RAT Male - 1000 ppm Female - 1000 ppm TOTAL FLUORINE 61 2.5 (ppm)^' ^ A new sampling technique (not yet fully calibrated) was used. In past analysis, approximately 1 g of serum solids was analyzed; with this new technique, only 0.02 g serum solids was used. It should be kept in mind that due to the limited sample size and to reduce analysis time, all values are the result of a single determination. Sufficient sample remains for further characterization if desired. Based on the above studies and the abstract to Professor Singer's latest publication, I believe the following study should be initiated at once. Proposed Study GROUP 1 2 NUMBER OF RATS Male Female 44 44 DOSAGE LEVEL 1000 ppm 1000 ppm Group 1 - at the termination of the 10-day study period, the serum should be collected and submitted as Group 1 - male; Group 1 - female. Group 2 - at the end of the 10-day feeding study, the rats would be s w i t c h e d to c o n t r o l f o od (0 p p m FC-143) for an a d d i t i o n a l 10 days. At the end of this ad di t i o n a l 10 days (total study time = 20 days) the serum would be collected and submitted as Group 2 - male; Group 2 - female. The purpose of this experiment is to verify the difference between male and female rats in the accumulation of FC-143 and for the first time, Group 2 will show whether FC-143 is cleared from the serum with time. n Belisle 001668