Document 58eBjrwayV6rXGBO0BMkK1yD
Study NO.T-7098.1; DT35
Title: &zu 4 69 5
Pharmacokinetic Study of Perfluorooctanesulfonyl Fluoride {POSF) FollowinE a Single Oral Gavage Dose In Rats
3M Strategic Toxicology Laboratory Corporate Toxicology
3M Medical Department 3M Center, Building 270-SB-3 14
St. Paul, MN 55144 Final Report
January 31,2004
Study Director: Andrew M. Seacat, Ph.D., DABT, Toxicology Specialist Study Toxicologist: Deanna J. Luebker, M.S., Advanced Research Toxicologist Sponsor: 3M Specialty Chemicals Division 3M Center Bldg 236 St. Paul, MN 55144
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T-7098.1; ST35 Final Report
Summary
Rats received a single oral dose of 5 mg/Kg perfluorooctanesulfonyl fluoride. Necropsies were
- performed on days 1,4, and 29 post dose. POSF was metabolized to PFOS which was maximum
in the liver on day 4 post-dose at approximately 11 ppm, or 10% of the dose. PFOS was present in sera at approximately one tenth of the level found in the liver. Thus, perfluorooctanesulfonyl fluoride (POSF) was absorbed and metabolized to perfluorooctanesulfonate (PFOS) by rats following and oral dose.
Study Objective
The objective of this study was to assess the potential for oral absorption, urinary and fecal clearance, and biological persistence of perfluorooctanesulfonyl fluoride (POSF) in male Sprague Dawley rats after a single oral dose. POSF is the starting material for the synthesis of a variety of perfluorooctane sulfonate (PFOS) based materials. Data gathered in this study help define the rate of metabolism of POSF to PFOS by the liver and provide data for proper risk characterization of POSF.
Method Summary
This study was performed in the 3M Strategic Toxicology Laboratory under a defined protocol (1) and classified as a "Class B Study" as explained in TOX SOP 0950, Strategic Toxicology Lab GLP Program Procedure (2).
Briefly, the procedure was as follows. Thirty male Sprague Dawley rats (obtained from Harlan Laboratories), 6-8 weeks in age and approximately 150-250g, were divided into the following dose groups:
Euthanasia day 1 post dose day 4 post dose day 29 post dose day 1 post dose day 4 post dose day 29 post dose
Rats received either a 5 mlKg dose of vehicle control (2% Tween SO), or a 5 mLKg dose of a 1 mg/mL POSF suspension in 2% Tween 80 (final dose = 5 mgiKg) via oral gavage on day zero of the study. Three specified rats from groups 3 and 6 were housed individually in metabolism cages for portions of the study. Urine and feces were collected on days 1,2,4, 14, and 29-post dose. Necropsies were performed on days 1,4, and 29 post dose. At necropsy, liver and sera were collected from each animal. For metabolite analysis, these specimens were packed in dry ice and shipped to Kris Hansen, 3M Environmental Technology and Safety Services for FC
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j T-7098.1; ST35 Final Report
analysis. Liver and sera were analyzed and the raw data was reported (3) . Urine and feces
analysis was not performed and was canceled. Results Treatment with PFOS at 5 m a g had no effect on body weight or liver weight (Table lA, B). Extraction and analysis of the tissues showed that PFOS was detected in the livers of all POSF dosed animals at all time points and was maximum in the liver on day 4 post-dose at approximately 11 ppm (Table 2). Trace amounts of perfluorooctanesulfonamidoacetate (PFOSAA, M556) were also reported for liver samples from POSF treated animals on days one and 4 post-dose (Table 2). The origin of the M556 in the liver samples is unknown, and all samples were near the practical quantitation limit for PFOSAA of 0.06 pg/g. Approximately 10 % of the dose was present in the liver as PFOS on day 4 post dose as calculated fiom the sum of the liver PFOS and liver PFOS equivalents from PFOSAA (Table 3). The PFOS levels in the sera of the rats were approximately one tenth of the level found in the liver sample extracts and were maximal on day one post dose (Table 4). No other metabolites were detected in the sera. Approximately 0.1 % of the dose was present in the sera as PFOS on day 1 post-dose (Table 4).
Conclusions These data support the conclusion that perfluorooctanesulfonyl fluoride (POSF) can be absorbed by rats following a single oral gavage dose, and metabolized to perfluorooctanesulfonate (PFOS).
,
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L T-7098.1; ST35
Final Report
k.
List of Tables 1. Table 1: Biological Parameters
1A: Control Group 1B: POSF Dose Group. 2. Table 2: Liver PFOS and PFOSAA (M556) 3. Table 3: Liver PFOS equivalents and Percent Dose in Liver 4. ;Table4: Serum PFOS and Percent Dose in serum
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\., T-7098.1; ST35
Final Report
Table 1A: Biological Parameters. Control Group
Time Dose Point
animal # Initial Terminal Kidney Liver wt 9ROO-xxx BW (g) BW (g) Weight (g) (g)
Day1 Omgkg
00 1
202
207
1.7
8.7
Day1 Day1 Day1 Day1
Omgkg Omgkg Omgkg Omgkg
002
204
213
003
188
196
004
203
207
005
200
207
1.7
9.3
1.6
8.4
1.7
9.5
1.6
9
Avg SD Range Min
MU N
199
206
6
6
188
196
204
213
5
5
5
1.7
9.0
0.1
0.4
1.6
8
1.7
10
5
5
Day4 Day4 Day4 Day4 Day4
Omgkg Omgkg Omgkg Omg/kg Omgkg
006
193
206
007
198
215
008
204
228
009
204
220
010
191
209
1.6
8.2
1.7
8.6
1.8
9.5
1.7
9.1
1.7
9.1
Avg SD Range Min
Max N
198
215
6
9
191
206
204
228
5
5
5
1.7
9
0.1
1
1.6
8
1.8
10
5
5
Day29 Omg/kg
01 1
196
275
2.1
11.9
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T-7098.1;ST35 Final Report
Table 1:
'Table 1B: Biological Parameters. POSF Dose Group
/Time Point
Dose
animal ## Initial Terminal 9ROO-xxx BW (8) BW (g)
Kidney Weight (8)
>
Liver wt (g)
Day1 Day1 Day1 Day1 Day1
5mg/kg 5mgkg 5mg/kg 5mg/kg 5mgkg Avg
03 1
21 1
215
032
199
203
033
204
213
034
197
205
03 5
212
216
205
210
1.6 10.0
1.6
8.7
1.9
9.8
1.5
8.7
1.7
8.6
1.7
9
~ SD Range Min
Max N
7
6
197
203
212
216
5
5
5
0.2
1
1.5
9
1.9
10
5
5
Day4 Day4 Day4 Day4 Day4
5mgkg 5mgkg 5mg/kg 5mg/kg 5mg/kg
Avg SD Range
N
Min Max
036
215
240
037
195
216
038
200
22 1
039
203
229
040
199
224
202
226
7
9
195
216
215
240
5
5
5
1.9 10.2
1.7
9.0
1.7
9.3
1.9
9.8
1.7
9.3
1.8
10
0.1
0
1.7
9
1.9
10
5
5
Day29 Day29 Day29 Day29 Day29
5mg/kg 5mg/kg 5rngkg 5mg/kg 5mgkg
Avg SD Range Min
Max N
04 1
202
3 10
042
205
30 1
043
196
3 06
044
202
295
045
203
288
202
300
3
9
196
288
205
310
5
5
5
2.3 13.0
2.2
11.4
2.2
11.7
2.1
11.0
2.0
10.6
2.2
12
0.1
1
2.0
11
2.3
13
5
5
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T-7098.1; ST35 Final Report
Table 2: Table 2: Liver PFOS and M556 in the POSF dose Group Time Point Dose POSF animal # 9ROO-xxxLiver [PFOS] ppm Liver [M556]ppm Liver M556 PFOS eq (ppm)
Day 1 5 m a g
03 1
2.35
0.125
0.11
Day 1 5 mg/kg
032
3.41
0.0957
0.09
Day 1 5 m a g
033
13.80
0.08 15
0.07
Day 1 5 mg/kg
034
3.73
0.1 14
0.10
Day 1 5 m a g
03 5
11.20
SE
Avg
6.90
0.10
0.09
SD
5.22
0.02
0.02
Day 4
5 mg/kg
036
6.76
0.0166
0.01
Day 4
5 mg/kg
037
6.79
0.033 1
0.03
Day 4
5m a g
038
8.22
SE
Day 4
5 mg/kg
039
12.50
0.0125
0.01
Day 4
5 mg/kg
040
19.70
SE
Avg
10.79
0.02
0.02
SD
5.50
0.01
0.01
Day29 Day29 Day29 Day29 Day29
5mg/kg 5mg/kg 5mg/kg 5mg/kg 5mg/kg
04 1
2.55
<PQL
042
3.30
<PQL
043
7.54
<PQL
044
5.47
<PQL
045
2.57
<PQL
Avg
4.29
SD
2.17
1. Liver M556 PFOS equivalents = Liver M556 concentration * (MW PFOSMW M556) = Liver M556 * ( 499/556)
PQL = practical quantitation limit in liver for M556 = 0.060 ug/g SE = sample evaporated, no sample remaining
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T-7098.1; ST35 Final Report Table 3:
I I Table 3: Liver PFOS equivalents and Percent Dose in Liver
Time Point IDose POSF Ihimal# PFOS eq in Total PFOS eq in PFOS eq. In % PFOS eq dosed
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T-7098.1; ST35 Final Report
lDay4 5 m g k g
03 7
0.094
7.0
0.7
968.2
Day4 5mgkg
03 8
0.0712
7.1
0.5
992.5
: b a y 4 5m*g
03 9
0.121
7.4
0.9
1009.4
lDay4 5mg/kg
040
0.119
7.2
0.9
989.6
I
Avg
0.10
7.3
0.7
1005.2
I SD
0.02
0.3
0.2
Day29 5rngkg
04 1
0.0523
10.0
0.5
37.1 1004.0
lDay29 5mglkg
042
0.0928
9.7
0.9
1020.4
Day29 5mg/kg
043
0.2 1
9.9
2.11
975.6
Day29 5mgkg
044
0.152
9.5
1.4)
1002.5
~Day29 5mgkg
045
0.0671
9.3
0.61
1009.4
Avg
0.11
9.7
1.11
1002.4
SD
0.07
0.3
0.61
16.5
1. There are 32.3 mL Plasma per Kg of rat.
~2T. otal PFOS equivalents in sera (ug) = PFOS equivalent concentration in sera @pm) * serum volume (ml) 3. PFOS equivalents in dose (ug) = Initial BW (g) * dose (mgkg) * MW PFOS/ MW M556 = BW*5*(499/556) 4. % PFOS equivalents dosed in serum = (PFOS equivalents in sera (ug)/ PFOS equivalents in dose (ug)) * 100
0.07 0.05 0.09 0.09 0.07 0.02 0.05 0.09 0.2 1 0.14 0.06 0.1 1 0.07
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DT 35; T-7098.1
Final Report
Signatures: Prepared By:
Advanced Research Toxicologist Study Toxicologist
Andrew Seacat, Ph.D. Toxicology Specialist Study Director
Date /
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! . DT 35;T-7098.1 Final Report
References 1. 3M Medical Department, Study No. T-7098.1. 3M Strategic Toxicology Protocol Number: DT35. Title: PHARMACOKINETIC STUDY OF POSF IN RATS. 2. 3M Medical Department, Corporate Toxicology Strategic Toxicology Laboratory
Standard Operating Procedure (TOX SOP) No. 0950 - GLP Program Procedure,
1999. 3. Hansen K. Laboratory Report Final Report of Data for POSF (T-7098.1)
Phannacokinetic Study in Rats. Laboratory Report No. FACT-TOX-116. 3M Testing Laboratory 3M Environmental Technology & Safety Services 3M Environmental Laboratory Fluorine Analytical Chemistry Team (FACT) 2-3E-09 935 Bush Avenue, St. Paul, MN 55106.
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