Document 5D0Gd0Ld3nX9yGEBGYGeOkq34
InterofficeCorrespondence 30"m",
c:kl.E.
J.D. B.W. R.A. F.A.
D.G.
Freier Lazerte Nippoldt Prokop Ubel
Weiblen
201-IS 236-1 201-lS 236-3B 220-2E
201-lS
Subit!ct
FC-143
Rat Toxicity Study
Request A67821
March 20, 1978
TO: J. E. LONG
220-2E
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 serum (ppm)
Male
5/5
0
0
Male
5/5
10
21
Male
5/5
30
34
Male
5/5
100
36
iiale
5/5
300
38
Male
5/5
1000
49
Female
5/5
Female
5/5
Female
5/5
Female
4/5
Female
4/5
Female
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 whole blood (ppm)
Male Male Male
0
0
1000
100
3000
not measured
Female Female Female
0
not measured
1000
1.5
3000
not measured
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 Singeres latest publication, I believe the following study should be initiated at once.
Proposed Study
GROUP
1 2
NUMBER Male
4 4
OF RATS Female 4 4
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 switched to control food (0 ppm FC-143) for an additional 10 days. At the end of this additional 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@z Belisle