Document 1QNz1y4rLzK1j5oydj1LGKebm
,0"""-"4 7-11-A
TECHNICAL REPORT SUMMARY
TO: TECHNICAL COMMUNICATIONS
CENTER - 201-2CN
important- Ifreportisprintedon both sidesofpaper,sendtwo copiestoTCC.)
C)tvision
CRL
- Analytical
and Properties
Research
Project
Trace Fluorochemicals
in the
Report Titi
IRDC l@7-088:
FM-3422/Monkey
Environment
To
J.E. Long
Author(%)
Jon Belisle
Notebook Reference
Laboratory
SECURITY 111-
1:1 Open
KEYWORDS: (Selectterms from 3M Thesaurus. Suggest other
aPPlicable terms.)
Ck Clomd
CURRENT
OBJECTIVE-
Requestor:J.E.
Central Research Analytical ReporlChemical/Analysi!;
Long;
3M CHEMICAL REGISTRY
Request #A69503;
04@/16/7 8
Dept. Number
0502
1'rolocNtumbor
A000006
We-p-c-wt-w-u-m-vor
995
EmployeeNumber(%)
88240
No. of Tages Including Cov*rsheat
3
Now Chemicals Reported
0 Yes
CX No
Project #9172110004
REPORT ABSTRACT: (200-250words)Thisabstracitnformatioinsdistributbeyd theTechnicaClommunicationsCenterto alert3M'arstoCompan@ R&D. ItisCompany confidentimaalterial.
CLOSED ABSTRACT
The level of FM-3422 was determined in the serum and livers
of monkeys from the IRDC subacute study 137-088.
Furthermore
total fluorine content was determined in selected serum samples and the metabolism of FM-3422 characterized by
FINMR.
CENTRAL
ANALYTICAL
LABORATORY
Report No. --- 6995 ------------
August Date-----
16, 1978 - --
----
ibject: IRDC 137-088: Fm-3422/Monkey
eque stor: --q --@-- Iglk_q....
Dept. Name
equest No. -h@2@Q@ --------
D a ted
eport:
----------- Proi. No.21.2,@@16PL00
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
30, 100, 300, 1000 mg/kg/day. The study was revised with levels: 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 1
IV v
Dosage Level
0
1 mg/kg/day
3
11
10
to
30
Survival, 4/4 4/4 4/4 4/4 3/4
SERUM ANALYSIS
@l@k e
a@e@'
7470M
0
7493F
0
FM-3422
in Serum 0 0
(ppm)
Total F in Serum (ppm) nmO nm
7467M
1
0
ran
7489F
1
0
nm
7469M
3
0.1
nm
7474M
3
nm
75
7487F
3
0.1
nm
#6995
-2
7475M 7498F
(2) Dosage
10 10
FM-3422 in Serum nm 0.4
7472M
30
0.5
7499F
30
0.7
August 16, 1978
pm) Total F in Serum (ppm) 150 nm
375 nm
(DM = Male, F = Female z@In mg/kg/day (2)nm= 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% linear). 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
@@ke@
Dosage(Z
7 4 6 9 ',1
3
7487F
3
FM-3422 in Liver(Pg_) 110 190
FM-3422 in Liver(ppm'). 1.3 2.6
7472M
30
7499F
30
(Din mg/kg/day
1300 4600
14.3 59.2
A.I@. #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 F14-3422 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 rrele. 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.
IODN Belisle jz
