Document M1gpVeoRyjanzLNwNB6e7YOk
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TECHNICAL REPORT SUMMARY
ORIGINALTO: TECHNICAL COMMUNICATIONS CENTER - 201-2CN
, important -- I f report sprinted on both sides o f paper, send two copies to TCC.)
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O iv isio n
CRL - Analytical and Properties Research Laboratory
Project
Trace Fluorochemicals in the Environment________________
Report Title
IRDC 137-088: FM-3422/Monkey
To
J.E. Long
A u rhor(s)
Jon Belisle
N otebook R afarance
SECURITY
O Open
3< Closed
KEYWORDS: (Select terms from 3M Thesaurus. Suggest other applicable terms.)
CURRENT OBJECTIVE:
Requestor :J.E. Long;
Central Research Analytical Repor : Chemical/Analysi:>
3M CH EM ICA L R E G IS T R Y
Request #A69503;
Qept. Number
0502
t'rolact Number
AO 00006
Report Number
995
Employee Number))
88240
No. of Page* Including Covarshaat
__________ 3_______
New Chemicals Reported
Yes
C X No
Project #9172110004
R EP O R T A B ST R A C T: (200-250 words) This abstract information is distributed by the Technical Communications Canter alert 3M`ers to Company R&O. It is Company confidential material.
CLOSED ABSTRACT
The level of FM-3422 was determined in the serum and livers of monkeys from the IRDC subacute study 137-088. Furthermor total fluorine content was determined in selected serum samples and the metabolism of FM-3422 characterized by F/NMR.
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CENTRAL ANALYTICAL LABORATORY
Report No.
6995
Date
August 16, 1978
bject: IRDC 137-088: FM-342 2/Monkey
eq u e s t o r t.L o n g _____
Dept. Nam e _.T o x ic o lo g y ._
e q u e st N o. _A69 5 0 3___ ______
D a t e d ---- _ _ _ _ _ _ _ _ _ _ _
eport:
Proj. No.917_211_0004
Reference 137-088 by IRDC was a 90 day subacute Rhesus monkey toxicity study of FM-- 3422. The original study was set at the following dosage levels: 30, 100, 300, 1000 mg/kg/day. The study was revised w i t h dosage levels of 10, 30, 100, 300 mg/kg/day. It appears (see Table below) that the dosage levels were lowered again prior to the study. The serum and livers were each individually submitted for analysis. Each group contained 4 monkeys, 2 male and 2 female as follows:
Group I
II III
IV V
Dosage Level 0
1 mg/kg/day 3 10 30
Survival 4 /4 4 /4 4 /4 4 /4 3 /4
SERUM ANALYSIS
M o n k e yC^D DosageQ)
FM-3422 in Serum (ppm)
Total F in
7470M
0
0
nm
7493F
0
0
nm
7467M 7489F
1 1
0 0
nm nm
7469M 74 7 4M 7487F
3
3
3
0.1 nm 0.1
nm
75
nm
7 L
'v.K. #6995
M o n ,k e yCU 7475M 7498F
Dosaqe 10 10
- 2-
August 16
FM-3422 in Serum (ppm) nm 0.4
Total F in ! 150 nm
7472M 7499F
30 30
0.5 0.7
375 nm
^ 4 = Male, F = Female <2\ ^ln mg/kg/day
^im = not measured
The analysis of the serum for FM-3422 indicated that this compound was present at a very low concentration. Total fluoride analysis indicated the presence of a significant level of fluoride. Therefore the serum of 7472M was prepared for F/NMR analysis.
The NMR spectra indicated (Richard Newmark) the presence of. FC-95 with no other significant fluorine peak noted. A very high branched content was observed (80% branched/20% line a r ) . The branched/linear ratio of FM-3422 used in the feeding study was found to be 40% branched/60% linear. Perhaps the branched isomer is retained to a greater extent than the linear.
The fact that a high level of FC-95 was found in the serum and essentially no FM-3422, indicates that FM-3422 is metabolized to the sulfonic acid. Furthermore, the study would indicate that FM-3422 is cleared from the body rather rapidly, that is before it is completely converted to FC-95 since the monkey tolerates FM-3422 at concentrations approximately 10 times greater than FC-95; this suggests that FC-95 builds up slowly with time.
LIVER ANALYSIS
Monkey 7 4 6 9M 7487F
Dosage^ 3 3
FM-3422 in Liver(yg) 110 190
FM-3422 in Liver(ppm) 1.3 2.6
7472M
30
7499F
30
0 in mg/kg/day
1300 4600
14.3 59.2
77/ S i
A.H. #6995
3 August 16, 1978
The high values of FM-3422 found in the liver when compared to the low level in the blood may indicate conversion of FM-3422 to the sulfonic acid (see above F/NMR data on serum) in the liver. The data shows that the female accumulates and/or retains FM-3422 at a level 2 to 3 times higher than the male. In addition, the only animal to die during the study was a female, perhaps again suggesting a greater sensitivity of the female to this compound.
n Belisle /jz
