Document Dd3L3R08J8goYLgq4XGq8vwpa
AR226-0136 9 }
STUDY CODE: K01-1802
[Receipt No. T96-2481
[Report No. T-4637
3)
FINAL REPORT
BACTERIAL REVERSE MUTATION TEST
oOiF
September, 1996
Hi Research Libraries
Chemical Biotesting Center
Chemicals orn Inspection & Testing Institute
a ee
02000
QUALITYASSURANCESTATEMENT
HCihtemaiRceaslesaIrncshpeLcatbioornato&riTeess,tiCnhgeImincsatlBii,oteJsatpianngCenter TSiS ploen:soU r. MBacI terialT reve3rO sMemLutM IaMtiIoTnO EteDstof -1 Studycoder KOL1802
`ThisreportwasauditedbytheQuality AssuranceSection.
t1h,ethoreguinndaelrsiJgapnaende,sheerreepboyrdteclarethat thisreportreflects
Section Chie,Quality Assurance
ou Jaswan5g 1997
Siganr) (Gp >
Keiji ShiraisBh.iS,.
COR001
Kol-1802
1, the undersigned, hereby declare that this report provides
a correct English translationofthe Final Report. (Study code No. KO1-1802 issued on September 25, 1996)
ae) Joraany 1. 777
Shozo Ogura Hita Research Laboratories Chemical Biotesting Center
Chemicals Inspection &
`Testing Institute, Japan.
02002
Kol-1802
`SGLTPATEMENT
'Hita Research Laboratories, Chemical Biotesting Center (Chemicals Inspection & Testing Institute, Japan
SpS onsoU r MITO3MM LIMO ITED
Title:
Sndy CodeNo:
K0l:1802 Bacterial reversemutationtest of 7-1
1, the undersigned, hereby declare that this study was conducted in compliances with
"Standards to be observed by Testing Institutions for Toxicity Investigations" (Japan's MOL, No.76, September 1, 1988).
Management: _Signedinoriginal September 25, 1996 Shigetaka Yamane, Ph D.
0003
`SGLTPATEMENT
Hita Research Laboratories, Chemical Biotesting Center
Chemicals Inspection & Testing Institute, Japan
SpS onsoU r MITO3MMLIMO ITED
Tite
Bacterial reverse mutation tet of 7-1
Study CodeNo--__Ko1-1802
1, the undersigned, hereby declare that this study was conducted in compliances with "Standards to be observed by Testing Institutions for Toxicity Investigations" (Japan's MOL, No.76, September 1, 1988).
"This was reissued becauseofthe final report amendment.
Management:
_Sig inon rigine al d Shigetaka Yamane, Ph. D.
November 27, 1996
02004
Ko1-1802
`QUALITYASSURANCESTATEMENT
Hita Research Laboratories, Chemical Biotesting Center `Chemicals Inspection & Testing Institute, Japan
SpS onsoU r: MITO3MM LIMO ITED
Tide:
Bacterial reverse mutation test of T-1
StCudyode_N _KOoI-1: 802
"This study was audited by the Quality Assurance Section and the study procedures were inspected on the following dates.
DatesofInspections DatesofReports to Datesof Reports to
and Audits
Study Director
Management
August 15,1996
SSeepptteemmbb22ee05rr,, 11999966
1,theundersigned, hereby declare that this report provides an accurate descriptionofthe
`methods and procedures used in this study and that the reported results accurately reflect
the raw data obtained.
Section Chief, Quality Assurance: Signedinoriginal Keiji Shiraishi, B.S.
September 25, 1996
C02005
QUALITYASSURANCESTATEMENT
Hita Research Laboratories, Chemical Biotesting Center Chemicals Inspection & Testing Institute, Japan
SpS onsoU r MITO3MM LIMO ITED
Title:
Bacterial reverse mutation tes of T-1
StudyCodeNo. K01-1802
"This study was audited by the Quality Assurance Section on the following dates.
uditor
DateofAudit | DH ofReportto | DateofReport to
Study Director __| Management
`This statement was added to the Quality Assurance Statement issued on September 25, 1996.
Section Chief, Quality Assurance: _Siginon rigienald
Keiji Shiraishi, B.S.
November 27, 1996
OR006
Ko1-1802
Studycode:
KO1-1802
Test substance code: HR3272
Sponsor code: 5030
TITLE Bacterial reverse mutation testof 7-1
SPONSOR SUMITOMO 3M LIMITED 8-8, Minami-Hashimoto 3-chome Sagamihara-shi, Kanagawa, 229 Japan
`TESTING FACILITY Hita Research Laboratories, Chemical Biotesting Center `Chemicals Inspection & Testing Institute, Japan 822, 3-chome, Ishii-machi, Hita, Oita 877, Japan
PURPOSE OF STUDY The purpose of this study was to determine the mutagenic potential of the test substance using Salmonella typhimurium and Escherichia coll,
`TESTING METHOD `This study was conducted in accordance with the following guidelines: "Standards for Toxicity Investigations" (Japan's MOL, No.77, September 1, 1988),
`GLP COMPLIANCE `This study was carried out in compliance with the following GLP requirement: "Standards 10 be observed by Testing Institutions for Toxicity Investigations" (Japan's MOL, No.76, September 1, 1988)
PERIOD OF STUDY Commencementoftest Dose finding test: `Completionofobservation: Presentation offinal report:
August 21, 1996 September 10, 1996 September 17, 1996 September 25, 1996
C0007
Kol-1802
LOCATION AND PERIOD FOR RETENTION OF RAW DATA Data and test substance are retained in the archives and the test substance storage roomofHita Research Laboratories for 10 years following the dateof the notification specified under Item 1 ofArticle 57-2 ofIndustrial Safety & Health Law, respectively. After termination of the retention period, any measures taken are done so with the approvalofthe sponsor.
PERSON CONCERNED WITH STUDY Study Director
Siginn origie nal d
Shozo Ogura.
September 25, 1996
Hita Research Laboratories
Mutagenicity Section
Study Staff: Person in chargeofStorage:
Tsunehiko Inai, B.S. Shizuka Kouda
ANY UNEXPECTED SITUATIONS AND DEVIATIONS FROM PROTOCOL. There were no unexpected situations and deviations from protocol which might have affected the test results.
2008
K01-1802
CONTENTS
MATERIALSAND METHODS
1. TEST SUBSTANCE AND POSITIVE CONTROLS~~ sssssssssssssssess 2
2. BACTERIAL STRAINS
aesvermrermr--
4. PRE-CULTURES
JE
5. PREPARATION OF TEST SUBSTANCE AND POSITIVE
CONTROLS
Cerenren 7
6. METHODS
FG
7. MICROSCOPIC OBSERVATION AND COLONY COUNTING === 8 8. INTERPRETATION OFRESULTS +++sssssssssssssssssnssmmssssssssssss Q
CONCLUSION
JET
APPENDIX TAB ANDLFIE GURSES resevsssssssssssssssssssssssssssssssss 1.6.
OR003
Ko1-1802
SUMMARY The reverse mutation test of 7-1 was performed on Salmonella typhimurium strains TAL00, TAIS3S, TA98, TA1S37 and Escherichia coli strain WP2 ur using the preincubation method with and without metabolic activation. `The results showed that the numbersoftheir revertant colonies for all strains in groups which were treated with the test substance were less than twice that of each negative control, with and without $9 Mix. `The numbersof the revertant colonies in the negative control and the postive controls were withinthebackground daintouar laboratories Based upon the above results, 7-1 was judged to have no reverse mutagenic potential `under the preseat test conditions.
02010 --1-
Ko01-1802
MATERIALS AND METHODS
1. TEST SUBSTANCE AND POSITIVE CONTROLS 1.1 Test substance (Information provided bythesponsor)
1) Name Reaction productsofperfluorodimethylcyclohexylsulfonyl fluoride,
perfluoroalkyl (C=0-2) cyclohexylsulfonyl fluoride, potassium carbonate and
`sulfuric acid Other name: 7-1 `CAS No.: 67584-42-3(themain component A(n=2))
29 2) LotNo.
3) Supplier
SUMITOMO 3M LIMITED
4) Structural formula or rational formula (Outlineofmanufacturing method, in case
both were unknown)
A Cif
Ge )sox (1=0-2)
6%
B CE oryon
CFy
Cc CF`mFam 1S03K.
(m=8)
20%
3%
D KS205,04
04%
Others
06%
5) Purity (molecular formula --)
100 w/w
6) Impurities
7) Physicochemical properties
Appearance at ordinary temperature: ~ white powder +
Molecular weight:
about 500
-2-
cozo11
Ko1-1802
Stability: Melting point: Boiling point: Vapor pressure: Parition coefficient: Solubility: Degreeofsolubility: 8) Storage conditions room temperature
stable Water. S$ 01% DMSO: Z sweet Acetone: about 5% Others:
methanol about 5% * Examined in our laboratories
9) Care on handling
Gloves, amask, aheadcapand alabcoatwerewornwhenhandling.
12 Positive controls
1) 2:(2-Faryl)-3-(5-nitro-2-furylacrylamide (AF-2)
Manufacturer: Wako Pure Chemical Industries, Ltd
LotNo: LEN0STI
Properties: reddish-orange crystalline powder
Puity:
9.5%
Grade:
special grade
2) Sodiumazide (NaNs)
Manufacturer: Wako Pure Chemical Industries, Ltd.
Lot No. DLP2438
Properties: white crystalline
Purity:
99.4%
Grade:
special grade
3) 2:Methoxy-6-chloro-9-{3-(2-chloroethyl)-aminopropylamincacridine 2HC
acR-191)
Manufacturer: Polysciences, Inc
LotNo.: 412795
Properties: yellow crystalline powder
Purity:
-
Grade:
-
-3-
o2012
K01-1802
4) 2-Aminoanthracene (2AA)
MLaontuNfaoc.turer: DWLaRk7o8P6u9re Chemical Industries, Ltd.
Properties:
yellowish-green-brown powder
Purity:
95.7%
Grade:
-_--
5) Storage conditions
A cold and dark place
6) Care on handling Gloves, a mask, a head cap and a lab coat werewornwhen handling.
2 BACTERIAL STRAINS
2.1 Strains selected
Salmonella typhimurium strains TA100, TASS, TA1S35 and TAIS37 were
obtained from Dr. B.N. Ames, UniversityofCalifornia, U.S.A. ,on June 20, 1990.
A Escherichia coli strain WP2 uvrA was obtained from Japan Bioassay Laboratories, on April 6, 1995.
8. typhimurium strains TA100, TA1535andE. colistrainWP2 uvrA were used for the detection of base-pair substitution mutation, while S. typhimurium strains
22 'StToAr9a8gaend TA1537 for the deteocfftramiesohinft mutation.
The test strains were stored as frozen stock cultures (0.045 ml of dimethyl sulfoxide (DMS0)*/0.5 mlofbroth culture) at -80C (ultra-deep freezer MDF291, Sanyo).
* Purity 2 99.0%, Lot No. CF103, Dojindo Laboratories
02013
Cae
01-1802
23 Characterization ofthe stains 1)_Characterisicsofthestrains
Strains
Mutation on Mutation on Membrane Refactor synthesisof excision mutation (pKM101) amino acid _ repair as)
Salmonella typhimurium
TALS3S
HisG46 vr ofa -
TAIS37
HisC3076 DurB ofa -
TAS
hisD3052 ~~AuwB ofa +
TA100
HisGi6 LawrB. fa +
Escherichia coli
We2 7A
mw
Duvrd +
-
`The amino acid requirement for growth was demonstrated by using histidine for
S. typhimurium strains and tryptophan for E. coli strain. The presence of R-
factor, membrane mutation and mutation on the ability to repair DNA lesions were
confirmed by ampicillin resistance, sensitivity to crystal violet and UV sensitivity,
respectively.
2) Dateof characterization
Salmonella typhimurium
TAIS3S
July 18, 1996
TALS37
June 7, 1996
TA
June 7, 1996
TA100
March 6, 1996
Escherichia coli
We2 urd
April 18, 1996
3. MEDIUM AND $9 MIX
31 Medium
1) Minimal glucose agar plate (prepared inourLaboratories)
`The medium was prepared as follows, and poured 30 ml into a petri dish.
Components
Amount included in one litre
20 x Vogel-BomneEr
50m
40 wiv% Glucose
som
Agar
15g
W) Agar
`Bacto-Agar (Lot No. 84707AJA, Difco Laboratories)
(2) Manufacturing date: dose finding teston August 29, 1996
main test on September , 1996
c02014
ass
Ko01-1802
2) Soft agar
`The solution containing 0.5 mM histidine and 0.5 mM biotin for S. typhimurium
strains or 0.5 mM tryptophan for E. coli strain was added to the soft agar solution containing 0.6 w/\% agar (Bacto-Agar, Lot No. 71892AJB, Difco
32
Laboratories)
$9Mix
and
0.5
w/v%
NaCl
in
a
ratio
of1
:
10.
1) Ratliver $9 (Kikkoman Co., Ltd.)
Induction method:
SD male rats, 7-week-old (203-254 g), were
intraperitoneally administrated phenobarbital (30 mg/kg
1 time, 60 mg/kg x 3 times) and 5,6-benzoflavone
(80 mg/kg x 1 time).
Lot No.
Storage:
RAA-350 (manufactured on August 23, 1996, purchased on September 4, 1996)
80C (ultra-deep freezer MDF-291, Sanyo)
2) Cofactor for S9 Mix (Oriental Yeast Industries, Ltd.)
LotNo.:
999601
Storage:
20C (bio-freezer GS-2603, Nippon Freezer Ltd. )
3) Composition of $9Mix
NOnAeDPmlHo,f4$p9mMoilxNcAoDntHa,ine1d008
pmol
pmol
MogfC0.l2,M33suodmioulmK-CphIo,sphpamtoelbGuf-f6e-rP,(p4Hp7m.o4l)
and 0.1 ml $9.
4. PRE-CULTURES From the stock cultures, 20 pl of bacterial suspension was inoculated to L-tube containing 10 ml nutrient broth No.2 (Lot No. 194 56443, OXOID Ltd, J), the bacterialculture was incubated at 37 + 0.5C for 8 h with `shaking at 50 times/min by the Monod shaker (MONOSIINTA-, Taitec Co., Ltd.) The viable cell counts
EE Te calculated from the values which were determined at 660 nm by`spectrophotometry (Novaspec, LKB Japan) at the endofincubation are shown below.
[T |raisw es [wezwea] o tase | aise|
[viable cells |finding
10m) aineess| 19 | 21 | 56 | 25 | 20 |
--6-
02045
Kol-1802
5. PREPARATION OF TEST SUBSTANCE AND POSITIVE CONTROLS 51 Test substance
1). Preparation `The test substance was dissolved in DMSO (Lot No. CF103) to make 5 wiv% concentration and diluted with the same solvent to give appropriate concentrations.
2) Stabilityofthetest solution No denaturation of the test solution was observed to a color and exothermic reaction until 2 hours afer preparation.
3) Preparation ime Prepared immediately before use and used within 0.5h at room temperature.
52 Positive controls 1) Preparation NaN, was dissolved in distilled water (Distilled water for injection, Lot No, K6B74, Otsuka Pharmaceutical Factory). AF-2, ICR-I91 and 2AA were dissolved in DMSO (Lot No. CDO69) 2) Preparationtime and storage condition Prepared on every 3 months and stored at ~80C (ultra-deep freezer MDF-291, Sanyo).
6. METHODS The test was carried out for S. pphimurium strains TAIS3S, TAIS37, TASS, TAI00 and a E. coli strain WP2 uvrA using the pre-incubation method both with and without metabolic activation system. The plating was done in triplicate for the negative control and in duplicate for the test substance and positive controls
6.1 Procedures After0.1 mlof thetestsubstancesolution, 0.5 mlof0.1 M sodium phosphate buffer(pH7.4) or $9 Mix,and 0.1mlofthe bacterialculturewereadded to atube, the mixtures were incubated for 20 min at 37 0.5C. Two mlofthe soft agar `wasthenaddedtoeachtubeand poured onto a minimal glucose agar plate. Afer incubation for 48 h at 37 0.5C, the number of revertant colonies were counted.
02016
y=
K01-1802
As the sterility test, each 0.1 ml of each bacterial suspension, test substance solution, $9 Mix or 0.1 M sodium phosphate buffer (pH 7.4) were smeared on a minimal glucose agar plate and incubated at 37 + 05C for 48 h, and then checked the bacterial contamination. DMSO was used as 2 negative control, and the following positive controls were used for each bacterial strains.
TAI0 TAIS3S WP2uwd TA9 TASS
SOMx() __AF2 NaN, AF2 AF2 CRS
001
0s
001
01
1
SOMix (+) __ 24A 284 24
24A 284
1
2
10
0s
2
62 Dose selection
(ug/plate)
1) Dose finding test
`The test was carried out at the highest doseof5,000 pg/plate and 6 doses of
1,000, 500, 100, 50, 10 and 5 gplate. As a result, growth inhibition
observed at doses of more the 1,000 ug/plate for 5. typhimurium strains TA100,
TAIS3S, TAIS37 and E. coli strain WP2 ud and 5,000 pg/plate for S.
typhimurium strain TA98 without $9 Mix.
Growth inkibition observed at dose of 5,000 pg/platefor S. typhimurium strains
`TAI00, TAIS3S, TALS37and E. coli WP2uve with S9Mix.
2) Maintest
Basedontheresults ofthedosefindingtest, amaintestwith S9Mixwas
performed at the highest dose of 5,000 pg/plate and lower doses diluted with a
geometric progression of2. Without $9 Mix, a maximum dose was decided
1,250 pg/plate in the caseofS. phimurium strains TAL00, TAIS3S, TAIS37
and E. col strain WP2 uvrA and 5,000 pglplate in the case ofS. pphimurium
strain TA98 and $ lower doses were decided in each bacterial strain by dilution
with a geometric progression of2.
7. MICROSCOPIC OBSERVATION AND COLONY COUNTING 7.1 Microscopic observation
`The stateofrevertant colonies (size and numberofcolonies), depositionofthe test substance and the growth inhibition were examined with a stereo microscope.
wg
02017
Ko1-1802
72 Colony counting `The numberofcolonies were counted with a manual counter or a colony analyzer (CA, Toyo-sokki Co., Ltd). Correction for counting errors was made for `measurements with the colony analyzer. Each plate was measured three times, and the average of these three measurements was adopted as the number of revertant colonies on the plate. The average for each dose was calculated from the valuesofthe plates used. Decimalsofthe average figures were rounded off.
8. INTERPRETATION OF RESULTS The test substance was judged to be positive, when the number of revertant colonies was twice or moreofthe negative control, and the dose-relationship and the reproducibility were obtained. Any statistical procedures were not used. RESULTS
`The numbersoftheir revertant colonies for all strains in groups which were treated with the test substance were less than twice thatofeach negative control with and without 59 Mix. `The growth inhibition was observed at more than 1,000 ug/plate in S. typhimurium strains TA100, TAIS35, TAIS37andE. col strain WP2 wr and at 5,000 ugplaintSe. yphimurium strain TAS without $9 Mix. `The growth inhibition was noted at 5,000 pg/plate in S. typhimurium strains TA100, TAIS3S, TAI537and E. coli strain WP2 urd wiS9tMihx. `The positive controls showed the distinct increaseofrevertant colonies, and the positive controls and the negative control were within a rangeofthe background data in our laboratories. There were no fuctuations which affected the test results since the sterility test confirmed the absence ofany micro-organisms.
62018
--o-
01-1802 CONCLUSION In conclusion, 71 wasjudged to have no reverse mutagenic potential under the present test conditions. REFERENCES 1. Ministry of Labor (1991) Guidebook on Mutagenicity Tests using Micro `organisms, New Edition (in Japanese) published by Japan Industrial Safety and HealthAssociation, 2 Green MHL. and W.J. Muriel (1976) Mutagen testing using Trp* reversion in Escherichia coli, Mutation Res., 38: 3-32. 3. Maron, DM, and BN. Ames (1983) Revised methods for the Salmonella mutagenicity test, Mutation Res, 113: 173-215.
02049
--10-
Dose finding test
Test substance:T=1
fe
witha) | copentrotion| Busecparsubotiationtype |_ Frameshifttype |
|= [Fem]fon]Em E>a) in) Sx Galsate) "ra100[7A1685|WP2uvmd|Th98 |TA1697|
shi T HECo RfCET HfmE]BoEm]E2aE] [[oTna[ [C wo Sfow nn]]a SZoon] ]n] oow)] [on mn] olEw]Z|J
[zm [3m] Ea Eom)
rita [on[Con 20m] Som]tom)
Puitios
Bote |_Me | ou | wm | ow |ow| wm |
mol TE | ow[es|r] oui
(ug plate)
pFe on oelf 20 "AP-2: 2-(2-Furyl)-3-(5-nitro-2-furyl)ecrylanide
Tats
-9-(3-(2-chloroethyl)-aninopropylasino)
Cio
scridine-2HC) 62020
Main test
fore
ent mts
iSax) || CGeethli)n[[1r1p00smi16n0i5|vteheare|d|2P8a3e6n|it r1e67|]
[zr[fw]som]Bo Bom]ou]
[[oCoa[[MEomm EEcoClaEcona]--l% _i--cma]]
FE
EEHTHEHHE E
[om[S edae ]Sat ]tn]
=[acalFw[dcniiacol]
[oo[Can SC]Sm 2m
[= ~~ Tea --|
IE
a i ed
FEE
soe | [oom][Col Cm|Fo]fom]
w [EE=N[ HE SH o $CE n]i EFH HmT]Hn dE Ei] IE HEHEHEHE E
FO I ENFEEE TERT HE)E rreSpHraiEng |[m i[malagte CO [|oS Cwom[a |2=2Cw o [3w 2Cor [o122wam]|
JaTSTeE urmo|so uifE inI TrmL[5 Com[58 Cen[2 ca [13 0)
"oKEntt e:ie ot <brsh tape r) dio1
"2: 2-Asinoanthracene
cO2071
ao
Dose
1
finding
test
25 10
2
8
i2s
'
K01-1802
0Sa:m1r11a0
5 10
50 100
500 1000
Fig. 1 Dose-response curve without 9 Mix
wefat0 e)
Es
=E 10
3
a
O:TA 100
O:1A 1535 A:WP2urrd
5 10
50 100
500 1000
Fig. 2 Dose-response curve with 9 Mix
--5-
(fe0t0e) c02022
Dose finding test py
PE
Hor-1802
om 8
O:TA 1537
i 10
&
50
5 100
500 1000
Fig. 3 Dose-response curve without $9 Mix
(ug/5p0l00ate)
2x
8 Za
8
31
O:TA 88 O:TA 1837
Fi.g.
5
4
0
Dose-response
50 100
curve with
500
$9 Mix
1000
--y-
(ue/5p00l0ate) 0R2023
Main test
g 3 LI 2
1-180 OOTTA 1105035 py)
EN
8.1 15
ES
os
Fig. 5 Dose-response curve without 59 Mix
0
sate
hs
O14 100 OTA 15%
per
=
3 8 2s 2
15%
a3 625 1250 2500 5000
Fig. 6 Dose-response curve with $9 Mix
(ug/plate)
-F =
oR024
Main test a
3a
i s EI
2
Brig oomm 15
WL WL 5 a 5 uw Fig. 7 Dose-response curve without $9 Mix
m0 gw
(ug/plate)
5
om
ot 1551
2
2 8 5 5
iZ a
21
15 sis 625 1250 250 sito
Fig. 8 Dose-response curve with 0 Mix
(ug/plate)
--6--
COR02S
[EINALREPORTAMENDMENT
Hita Research Laboratories, Chemical Biotesting Center Chemicals Inspection & Testing Institute, Japan
1. Title (Study code) Bacterialreverse mutationtest of 7-1 (K01-1802)
2. Amendment (Items) CAS No. and structural formula or rational formula (Annex 1)
3. Authorization Study Director
--Signedinoriginal Shozo Ogura
November 27, 1996
i=
C2026
Amex1
LI Test substance (Information providedbyth sponsor) Page 2
Belore changes: 1) Name
Reaction products of perfuorodimethyloyclohexylsulfonyl
Muoridepecuoronliyl (C02) cyelohexylsufony] potassium carbonate and sulfuric acd
fluoride,
Othername: 7-1
CAS No. 67584423
4)
Structural
method, in
formals or rational formula
case both were unknown)
(Outine
of
manufacturing
Go Cram Gysom =o
CF;
CFs CoFmSOK (med) KaS0 (molecular formula =)
Cae
CGRez?
After changes: 1) Name
Reaction products of perfluorodimethylcyclohexylsulfonyl
fluoride, perfluoroalkyl (C=0-2) cyclohexylsulfonyl
`potassium carbonate and sulfuric acid
Othername: 7-1 CAS No.: 67584-42-3(themaincomponentA(=2))
fluoride,
4) Structural formula or rational formula (Outline of manufacturing `method, in case bothwere unknown)
A Coan Gyo (=02)
26%
B CF.
{ > >--SOK
CFy
C CoFamSOK
D K2S04
Ohes
(molecular formula
(m=8)
0000
~y
20%
%
04%
06%
Reason for changes: To document new information supplied by the sponsor.
Date effective:
November 13, 1996
-3-
020238