Document 5kgQ9rDp2drb1MqQOLv7qX2zN
3M General Offices
Zeno,
3M Center St. Paul. MN 55144-1000 651 733 1110
\& itt
September 24, 20Q3t
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Bv Hand Delivery
Document Processing Center (7407) Office of Pollution, Prevention and Toxics U.S. Environmental Protection Agency 1200 Pennsylvania Avenue, N. W. Washington, DC 20460 Attention: Section 8(e) Coordinator
Re: TSCA Section 8(e) Submissions
Dear Sir/Madam:
3M Company ("3M") requests that EPA place the attached studies in the TSCA Section 8(e) docket. We have included a master index for these studies identifying the study title, test substance and CAS number. A Confidential Business Information (CBI) version of this index and the studies also is being submitted today pursuant to EPA procedures. 3M has not provided CBI substantiation with this submission, but would be willing to do so at the Agency's request.
3M has concluded that data in these studies may not be, strictly speaking, "corroborative" of previously reported or published information as defined in EPA's reporting guidance or otherwise potentially may warrant 8(e) submission based on EPA's reporting guidance.
3M appreciates EPA's attention to this matter. Please contact the
undersigned if you have any questions or require further information regarding this r~o
submission.
cr>
Very truly yours,
CD
CD I -i T '
EHQ
Dr. Katherine E. Reed, Ph.D Staff Vice President Environmental Technology and Safety Services (651)778-4331 kereed@mmm.com
CO
CD ro
88040000247
804 000024 7
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on Septem ber 24, 2004 (Confidential Business Information Redacted)
Primary Eye Irritation Study -
Rabbits
1 1 I______________________ 1______
20% solids (Ethomeen S/12 1.0M with diethyl
sulfate 0.94M); 80% water [Ethomeen S/12 = R-
Guinea Pig Contact Dermal
N(Et)+<C2H40H)2 where R=C18 with 1-2
Irritation/Sensitization
double bonds]
20% {61791-24-0 with 64-67-5); 80% 7732-18-5
Primary Eye Irritation Study -
Rabbits
Butanoic acid, heptafluoro-, calcium salt
2366-98-5
Acute Oral Toxicity Screen with T-
2712CoC in Albino Rabbits
periluorohexanoic acid
307-24-4
Primary Skin Irritation Test with T-
2725Ec (Repeat Application) in
Albino Rabbits
l
Acute Ocular Irritation Test with T-
1I
]
2725Ec in Albino Rabbits
[
Sensitization Study with T-2741AC
11
I
in Albino Guinea Pigs
[
1I
Ora1Rangefinder Study of T-3140BS 1-[3'-(perfluorooctanesulfonate) anilino amide}-2
]
in Pregnant Rats
potassium 3,4,5,6-tetrachlorophthalate
57589-85-2
80% 1-[3'-(perfluorooctanesulfonate) anilino
amide]-2-potassium 3,4,5,6-
Oral Rangefinder Study of T-3139BS tetrachlorophthalate; 5% C7 homolog; 5% C5 80% 57589-85-2; 5% 68541-01-5 ; 5% 68541-02-6;
in Pregnant Rats
homolog; 5% C4 homolog; 5% C6 homolog 5% 68568-54-7; 5% 68815-72-5
Acute Occular Irritation Test with T- perfluoroethylcyclohexylsulfonic acid diethanol
2997CoC in Albino Rabbits
amine salt
salt of 133201-07-7 and 111-42-2
Sensitization Study with T-3386 in
Albino Guinea Pigs
(
l[
1
jn Vitro Microbiological Mutagenicity
Assays of 3M Company's
Compound T-3411
I______________________ 1____ I______________________ I______
SANiTtZEL,
1
Master Index to Studies Submitted Under TSC A 8(e) by 3M Company on September 24, 2004 (Confidential Business Information Redacted)
68% poiy(oxy-1,2-ethanediyl), alpha-[2-
[ethyl[(heptanedeca8uorooctyt)sulfonyl]amino]et
hylj-omega-hydroxy-; 12% polelhylene glycol;
7% water; 4.86% poly(oxy-1,2-ethanediyl),
alpha-[2-
(ethyl[(pentadecafluoroheptyl)sulfonyljamino]eth
yl]-omega-hydroxy-; 4% residual organic
fluorochemical; 3% heptadecafluoro-1-
octanesulfonic add; 0.81% poly(oxy-1,2-
ethanediyl), alpha-[2[ethyl[(undecafluoropentyl)sulfonyl]amir>ojethyl]-
omega-hydroxy-; 0.3% 1,4-dioxane; 0.2% n- 68% 29117-08-6; 12% 25322-68-3; 7% 7732-18-5; ethylperfluorooctanesulfonamidoethyl alcohol; 4.86% 56372-23-7; 4.05% 68298-79-3; 3.24%
Acute Oral Toxicity Screen with T- 0.03% linear n-ethyl
68298-81-7; 3% 1763-23-1; 0.81% 68298-80-6;
3448 in Albino Rats
perfluorooctanesulfonamide
0.3% 123-91-1; 0.2% 1691-99-2; 0.03% 4151-50-2
jn Vitro Microbiological Mutagenicity
Assays of 3M Company's
Compound T-3516
l
Acute Dermal Toxicily Study with T-
l1
1
3451 in Albino Rabbits
C8F17S02N(CH3).Na
Unknown
Acute Oral Toxicity - Method.
Summary, Pathology; Primary
Dermal Irritation - Method,
Summary; Primary Eye Irritation -
Method, Summary; Guinea Pig
Maximization - Method. Summary [ Acute Oral Toxicity - Method,
1I
1
Summary, Pathology; Primary
Dermal Irritation - Method,
Summary; Primary Eye Irritation -
Method, Summary;
[
]f
1
Dermal Sensitization Study in
[
1t
1
Guinea Pigs, Maximization Test -
Method, Summary 4 Hour Acute Aerosol Inhalation
[ [
]I 1[
I ]
Toxicity Study with T-3825 in Rats l Primary Eye Irritaiton/Corrosion
I t ....... .
1
Study in Rabbits 4-Hour Acute Aerosol Inhalation
[
. ] ... [
I
Toxicity Study with T-3825 in Rats I_______________________________ I I_______________________________ I
2
Master index to Studies Submitted Under TSC A 8(e) by 3M Company on Septem ber 24, 2004 (Confidential Business Information Redacted)
T-3820. Acute Inhalation Toxicity Test T-3821: Acute Inhalation Toxicity Test T-3845 Acute Inhalation Toxicity Test Evaluation of the Acute Inhalation Toxicity of T-3920 in the Rat Primary Eye Irritation Study in
Rabbits - Method, Summary Acute Oral Toxicity Study in Rats (OECD Guidelines) Acute Inhalation Toxicity Study with T-4129 in the Rat Acute Inhalation Toxicity Study with T-4130 in the Rat Acute Oral Toxicity Study in Rats; Acute Dermal Irritation Study in Rabbits; Acute Eye Irritation Study in Rabbits Dermal Sensitization Study in Guinea Pigs - Maximization Test
( i
heptafiuorobutyryl chloride
I 1
II
Decanoic add, nonadecafluoro-, ammonium salt 95% ammonium periluorodecanoate; 5% ammonium perfluorooctanoate
[] I1
I] [1
[1 I______________________ 1______
375-16-6
I______________________ I.... . ..
3108-42-7 5% 3825-26-1
[] t]
l] 11
Mutagenicity Test on T -4413 [ ]
Mouse Lymphoma Forward Mutation
Assay with Duplicate Cultures
t
Acute Inhalation Toxicity Study with
1[
1
T-4354 in the Rat
[
Primary Dermal Im'tatiorVCorrosion
II
1
Study in Rabbits
[
Acute Inhalation Toxicity Study in
1[
1
the Rat with T-4397 Primary Eye Irritation/Corrosion
l
1[
1
Study of T-5261 in Rabbits
lithium tetrafluoroethane-1,2-disulfonimide
Unknown
Acute Inhalation Toxicity Evaluation
on T-5231 in Rats
l
1[
1
4-Hour, Acute Inhalation Toxicity
Study with T-5305 in Rats 4-Hour, Acute Inhalation Toxicity
[
1[
1
Study (Limit Test) with T-5343.1 in
Rats 1______________________ 1____ 1______________________ 1
3
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on September 24, 2004 (Confidential Business Information Redacted)
4-Hour, Acute Inhalation Toxicity
Study With T-5306 in Rats
[
][
I
4-Hour, Acute Inhalation Toxicity
Study (Limit Test) with T-5357.1
[
I1
I
Acute Dermal Toxicity Study of T-
4201 in Rabbits
Lithium Bis(Trifluoromethanesulfonyljimide
90076-65-6
SubAcute 28-Day Oral Toxicity with
T-2816 by Daily Gavage in the Rat
Followed by a 14 Day Recovery
Period
[
]f
1
Subacute 28-Day Oral Toxicity with
T-2816 by Daily Gavage in the Rat
Followed by a 14-Day Recovery
Period
l
I1
J
Acute Inhalation Toxicity Evaluation
onT-5187 in Rats
I
T-4240 4-Week Oral Toxicity Study
]I
]
in Rats
[
] J______________________ ]
Dermal Sensitization Study of T-
5473 in Guinea Pigs - Maximization
Test 4-Hour. Acute Inhalation Toxicity
i
)[
1
Study With T-5698 in Rats
1
Acute Inhalation Toxicity Evaluation
][
I
On T-5708 in Rats T-5486 Assessment of Cardiac
l
I[
]
Sensitization Potential in Dogs
octafluoropropane
76-19-7
Acute Inhalation Toxicity Evaluation
on T-5655 in Rats
i
T-4201 4 Week Oral Toxicity Study
JI
1
in Rats with 2-Week Recovery
Period
Lithium Bis(Trifluoromethanesulfonyl)imide
90076-65-6
T-5658: Eye Irritation to the Rabbit 1
1[
1
Acute Inhalation Toxicity Evaluation
on T-5715 in Rats
[
Acute Inhalation Toxicity Evaluation
J[
I
on T-5716 in Rats
[
It
1
Acute Inhalation Toxicity Study of T-
5724 in Rats
[
Acute Inhalation Toxicity Study of T-
1[
I
5725 (Resin Solution) in Rats
I______________________ 1____ I______________________ 1
4
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on September 24, 2004 (Confidential Business Information Redacted)
Acute Inhalation Toxicity Study
(Limit Test) of T-5927 in Rats
t
Acute Inhalation Toxicity Study of T-
5928 in Rats (LC50)
I
Acute Inhalation Toxicity Evaluation
on T-5829 in Rats Single-Dose Intravenous
I
Pharmacokinetic Study of T-5963 in
Rabbits Single-Dose Intravenous
[
Pharmacokinetic Study of T-6030 in
Rabbits
[
1[ I[ 1[
1[
l[
] I I
I
I
87-93% fluorinated alkyl alkoxylates; 4-10%
linear N-ethyl periluorooctanesulfonamide; 2-
4% poly(oxyMt2-ethanediyl)..alpha.-[2-
[ethyl[(pentadecafluoroheptyt)sulfonyl]amino]eth
yt]-.omega.-methoxy-; 0-4% residual organic
fluorochemicals; 0-2% c8 sulfonamide; 0.1-1%
5-Daily Dose Dermal
1-heptanesulfonamide, N-ethyl-
Absorption/Toxicity Study of T-6029 1,1,2,2,3,3,4,4.5,5,6.6,7,7,7-pentadecafluoro-; 87-93% 68958-61-2; 4-10% 4151-50-2; 2-4%
and T-6032 in Rabbits
miscellaneous components (each less than 1%) 68958-60-1; 0-2% 31506-32-8; 0.1-1% 68957-62-0
Single-Dose Intravenous
Pharmacokinetic Study of T-6061 in
Rabbits Single-Dose Intravenous
[
1[
1
Pharmacokinetic Study of T-6065 in
Rabbits Single Dose Intravenous
I
lt
1
Pharmacokinetic Study of T-6063 in
Rabbits
[
Acute Inhalation Toxicity Study of T-
1[
1
6235 in Rats
[
Primary Dermal Irrittion/Corrosion
1 I_______________________________ 1________
Study of T-6402 in Rabbits
I
1[
I
Dermal Sensitization Study of T-
6402 in Guinea Pigs- Maximization
Test (EC Guidelines)
t
1
Acute Eye Irritation/Corrosion Study 1-Butanesulftnic acid, 1,1,2,2,3,3,4,4,4-
with T-6318 in the Rabbit
nonafluoro-, Sodium Salt
I 102061-82-5
1
5
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on September 24, 2004 (Confidential Business Information Redacted)
Primary Skin Irritation / Corrosion
Study with T-6567 in the Rabbit (4-
Hour Semi-Occlusive Application) t
J
Assessment of Contact
Hypersenitivity to T-6318 in the
Albino Guinea Pig (Maximization 1-Butanesulfinic acid, 1,1,2,2,3,3,4,4,4-
Test)
nonafluoro-. Sodium Salt
Single-Dose Intravenous
Pharmacokinetic Study of T-6502 in
Rabbits Single-Dose Intravenous
[
J
Pharmacokinetic Study of T-6504 in
Rabbits
[
1
Single Dose Intravenous
Pharmacokinetic Study of T-6506 in
Rabbits
[
A Study for Effect on Embryofoetal
1
Development of the Rat (Inhalation 20-80% methyl nonafluoroisobutyl ether; 20-
Administration)
80% methyl nonfluorobulylether
Bacterial Reverse Mutation Test of T
6695 5-day Inhalation Toxicity of
(
J
Perfluorocyclohexene (( ]; T-
70% crude perfluorocyclohexene; 30%
6878) in Rats
periluoromethylcyclopentene
5-Daily Dose Dermal
Absorption/Toxicity Study of T-6502
and T-6503 in Rabbits Primary Eye Irritation/Corrosion
[
1
Study of T-6786 in Rabbits
Lithium Bis(periluoroethylsulfonyl)imide
Primary Dermal Irritation/Corrosion
Study of T-6804 in Rabbits
Lithium Bis(peri!uoroethylsulfonyt)imide
5-Day Inhalation Toxicity Screen of
HFE [ 1
C-C6F110CH3
Primary Eye Irritation/Corrosion
Study of T-6804 in a Rabbit (OECD
Guidelines)
Lithium Bis(perfluoroethyisulfonyl)imide
Acute Oral Toxicity Study of T-6804
in Rats (OECD Guidelines)
Lithium Bis(perfluoroethylsulfonyl)imide
Dermal Sensitization Study of T6908 in Guinea Pigs, Mazimization Test (EC Guidelines)
[I
102061-82-5
f1
[I [1
20-80% 163702-08-7; 20-80% 163702-07-6 l1 70% 355-75-9
[ 132843-44-8 132843-44-8 4943-08-2
132843-44-8 132843-44-8
1
6
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on Septem ber 24, 2004 (Confidential Business Information Redacted)
Eye Irritation/Corrosion Study of T- N-Me Fos Amide-Triphenylbenzyl Phosphonium
4127 in the Rabbit
Chloride Complex; D-1624
31506-32-8
Single-Dose Intravenous
Pharmacokinetic Study of T-6924 in
Rabbits
[
1F
1
Dermal Sensitization Study of T6924 in Guinea Pigs- Maximization Test (EC Guidelines)
[
l .. 1
1
Dermal Sensitization Study of T-
7003 in Guinea Pigs - Maximization
Test (EC Guidelines)
I
1
Report of Sera and Liver Data for [ N-ethyl heptadecafluoro-N[2-
] Monoester - Preliminary ADME (phosphonooxy)ethyl] octanesulfonamide
Study in Rats
diammonium salt
[ ) Diester-Pharmacokinetic
Study in Rats (Study No. T-7043.1. ammonium
DT-26)
bis[ethvl(perfluorooclane)sulfonayl]phosphate
Single Dose Intravenous
Pharmacokinetic Study with T-7082
in Rabbits
[ N-ethyl heptadecafluoro-N[2-
]
[ ] Monoester - Pharmacokinetic (phosphonooxy)ethyl] octanesulfonamide
Study in Rats (Study No. T-6997.2) diammonium salt
Determination of PFOS Presence
and Concentration in Serum from
the Dermal Absorption Studies of T-
7106 and T-7107 in Hra:(NZW)SPF
Rabbits Dermal Sensitization Study of T-
t
]
7285.5 in Guinea Pigs -
Maximization Test (EPA/OECD
Guidelines)
1
Twenty-eight Day Repeated-Dose
J
Oral Toxicity Study of T-6861 in
Rats
Lithium Bis(perfluoroethylsulfonyl)imide
Twenty-eight Day Repeated Dose
Oral Toxicity Study of T-7005 in
Rats
[
1
[ 67969-69-1 30381-98-7 1 67969-69-1
1 I
ll
i 132843-44-8
J
I_______________________________ I
7
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on September 24, 2004 (Confidential Business Information Redacted)
Acute (4-Hour) Inhalation Toxicity of
Test Atmospheres Obtained after
Healing (
] in Rats
Toxicokinetic Study of
I
l
Perflurooctanesulfonamidoacetate ([
1; T-7071.2) in Rats
periluorooctanesulfonamido carboxylic acid
[ 2806-24-8
I
Acute Nose-Only Inhalation Toxicity
Study of T-7087, T-7088, T-7089
and T-7090 in Rats (Limit Test)
[
]
[ Acute Ocular Irritation Study of T-
I
7485 Applied to New Zealand White
Rabbits
potassium nonafluorobutanesulfonate
Toxicokinetic Study of
Perfluorooctane Sulfonamide
(PFOSA; T-7132.2) in Rats
perfluorooctanesulfonamide
Acute Four-Hour Inhalation Study in Perflurobutanesulfonyl Fluoride (96-98%) And
Rats
Perfluorosulfolane (2-4%)
Primary Eye Irritation/Corrosion
Study of T-7508.2 in Rabbits MV31 K-Salz; Test for Primary
[
]
Dermal Irritation in the Rabbit
[
Assessment of Acute Oral Toxicity
]
with T-7560 In The Rat (Acute Toxic
Class Method)
[
Acute Eye Irritation/Corrosion Study
I
with T-7560 in the Rabbit
[
]
[ ) Potassium bis-
(periluorobutanesulfonyl)imide
Repeat Dose ADME Study in Rats Potassium bis(perfluorobutanesulfonyt)imide
Toxicity Study by Repeat Dose
Inhalation Administration to CD Rats Perflurobutanesulfonyl Fluoride (96-98%) And
for 4 Weeks
Perfluorosulfolane (2-4%)
[ i
29420-49-3
] ]
754-91-6 96-98% 375-72-4; 2-4% 42060-64-0
[l
r1
I_______________________________ 1________ i_______________________________ I
129135-87-1
96-98% 375-72-4; 2-4% 42060-64-0
A Sub-acute( 28 Day) Inhalation
Toxicity Study, Including a Recovery 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3
Study, with T-7479 in Rats
pentanon
756-13-8
Xenochemical Receptor trans-
Activation by Periluorooctane-based
Chemicals
perfluorooctanesulfonamide
754-91-6
8
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on September 24, 2004 (Confidential Business Information Redacted)
84% 1-octanesulfonicacid,
1.1,2.2.3,3,4,4,5,5,6,6.7,7,8,8.8-
heptadecafluoro-, potassium salt; 5.5%
potassium (periluorohexyl)sulfonate; 4%
potassium nonafluorobutanesuifonate; 4%
potassium periluoroheptanesuifonate; 2%
potassium periluoropentanesulfanate; 0.5% 84% 2795-39-3; 5.5% 3871-99-6; 4% 29420-49-3;
unknown
4% 60270-55-5; 2% 3872-25-1
95% N-ethylperfluorooctanesulfonamidoethyl
alcohol; 5% 1-heptanesulfonamide N-ethyl-
1.1,2.2.3,3.4.4,5.5.6,6.7,7.7-pentadecafluoro-N-
(2-hydroxyethyl)-
95% 1691-99-2; 5% 68555-73-7
Acute Inhalation Toxicokinetic Study
of Periluoroctanesulfonyl Fluroide
(POSF) T-7098.4
periluorooctanesulfonyi fluoride
307-35-7
Five-Day Inhalation Toxicity Study of
HFE [ 1in Male CD Rats
C-C6F11-CF2-0-CH3
181214-67-5
Acute Toxicity Screen of
Perfluorocydohexene (T-6878) in 70% crnde perfluorocydohexene; 30%
Rats
perfluoromelhylcydopentene
70% 355-75-9
[ ] (T-7056)
Toxicokinetic Study in Rats
1 JI N-Methyl Perfluorobutylsulfonamide = 95% 1-
I
Assessment of Acute Oral Toxicity Butanesulfonamide, 1,1.2,2,3,3,4,4,4-
with T-7601.3 in the Rat (Acute
Nonafluoro-n-Methyl; 5% N-Methyl-4-Hydrido-
Toxic Class Method)
Perfluorobutytsulfonamide
68298-12-4
Subchronic 90-Day Oral Toxicity
Study with T-7320 By Daily Gavage
in the Rat Followed by a 28-Day
Recovery Period
[
1[
I
84% 1-octanesulfonic add,
Protein Binding of Perfluorobutane 1.1.2,2,3,3,4,4,5,5,6,6,7.7,8,8,8-
Sulfonate. Periluorohexane
heptadecafluoro-. potassium salt; 5.5%
Sulfonate, Perfluorooctane Sulfonate potassium (perfluorohexyl)sulfonate; 4%
and Perfluorooctanoate to Plasma potassium nonafluorobutanesuifonate; 4%
(Human, Rat. and Monkey), and potassium periluoroheptanesuifonate; 2%
Various Human-Derived Plasma potassium periluoropentanesulfanate; 0.5%
Protein Fractions
unknown
potassium nonafluorobutanesuifonate
potassium (perfluorohexyl)sulfonate
84% 2795-39-3; 5.5% 3871-99-6; 4% 29420-49-3; 4% 60270-55-5; 2% 3872-25-1 29420-49-3 3871-99-6
9
Master Index to Studies Submitted Under TSCA 8(e) by 3M Company on Septem ber 24, 2004 (Confidential Business Information Redacted)
potassium perfluorooctanoate
Five Day Inhalation Toxicity Study of
[ JMonochloride. [ ], and
HCFC225cb in Male CD Rats
C4F9-OCH2CI
C-C6F11-CF2-0-CH3
CF2CICF2CHCIF
Toxicokinetic Screen of [
] (T-
7483) in Rats
C7F15C{0)N(H)CH3
84% 1-octanesulfonic acid,
1,1,2.2,3,3,4,4,5,5,6,6.7.7.8,8.8-
heptadecafluoro-, potassium salt, 5.5%
potassium (perfluorohexyl)sulfonate; 4%
Low Level Oral
potassium nonafluorobutanesulfonate; 4%
Perfluorooctanesuifonate (PFOS) potassium periluoroheptanesutfonate; 2%
Dose Toxicokinetic Study in Rats: potassium periluoropentanesutfanate; 0.5%
Serum and Liver PFOS
unknown
2395-00-8 205367-42-6 (n-isomer) and 221617-86-3 (Iisomer) 181214-67-5 507-55-1 89685-56-3
84% 2795-39-3: 5.5% 3871-99-6; 4% 29420-49-3; 4% 60270-55-5; 2% 3872-25-1
10
Experiment No.: Conducted At : Da te s Conducted : Conducted By:
Acute Oral Toxicity Screen with T-2712COC in Albino Rats
0479AR0680
Safety Evaluation Laboratory Riker Laboratories, Inc., St. Paul, Minnesota December 7, 1979 to December 26, 1979
K. L. Ebbens, BS
Date
Supervisor, Acute Toxicology
Study Director
/
1.
Summary An acute oral toxicity screen with T-2712CoC was conducted from December
7, 1979 to December 26 , 1979 at Riker Laboratories, Inc., St. Paul, Minnesota using male albino rats ranging in body weight from 159 tc 270 grams. The test article was administered by gastric intubation at dosage levels of 5,000, 1,000 and 500 mg/kg body weight with mortalities of 5/5, 5/5 and 1/5 noted respectively. The untoward behavioral reactions which occurred during the 14 day observation period generally consisted of ataxia, dyspnea, emaciation, hypoactivity, sal ivation, prostration, and unkempt appearance. The onset of the reactions oc curred from 1-30 minutes to 5 days post dose and all reactions subsided by day 5 or death precluded recovery. Body weight losses were noted for 3/4 animals from the 500 mg/kg dose group which survived the 14 day test period. Gross ne cropsies performed at the end of the 14 day study generally revealed hemorrhagic vas deferens and one incidence of atrophic testes. Chemical burns of the stomach and intestines were generally noted in the animals which lied acutely, however, autolysis precluded gross tissue evaluation of two animals. The approximate oral LD50 of T-2712CoC is less than 1,000 mg/kg and greater than 500 mg/kg in fasted male albino rats. Introduction
a The objective of this study-- was to approximate the acute oral LD50 of T-2712CoC in fasted male albino rats. The study, which was initiated at Riker Laboratories, Inc., St. Paul, Minnesota on December 7, 1979 and completed on December 26, 1979, was not conducted to support a government submission or marketing permit, and is therefore not regulated by the Good Laboratory Practices Act of 1978. The raw data generated by the Study Director and final report are stored in the conducting laboratory's archives.
-- Riker Toxicity Experiment N o . : 0479AR0680, Test Method 605A
2.
Method and Results .a
Young albino rats-- were used in this test. All animals were held under quarantine for several days prior to testing with only animals which appeared to be in good health and suitable as test animals at the initiation of the study used. The rats were housed in suspended, wire-mesh cages in temperature and humidity controlled rooms and permitted a standard laboratory diet-- plus water ad libitum except during the 16 - 20 hour period immediately prior to gastric intubation when food was withheld.
The rats were administered the test article at pre-selected dosage levels. All doses were administered directly into the stomachs of the rats using a hypodermic syringe equipped with a ball-tipped intubating
After gastric administration of the test article, the rats were returned to their cages and observed for the following 14 days. Initial and final body weights, mortalities (Table 1) and adverse reactions (Table 2) were r corded. A necropsy was conducted on all animals that died during the study as well as those euthanatized at the end of the 14 day observation period (Table 1). The protocol, principle personnel involved in the study, composition characteristics, and Quality Assurance statement are contained in Appendices I - IV.
Charles River Breeding Laboratories, Inc., Wilmington, Massachusetts Ralston Purina Laboratory Chow, Ralston Purina, St. Louis, Missouri Popper and Sons, Inc., New Hyde Park, New York
mini u|
TABLE 1 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS
with T-2712COC Mortality, Necropsy and Body Weight Data
Dose-
Animal
(mqAg) Sex Number
Individual Body Weights (g)
Test Day Number:
Number Dead
0 14 Number Tested
5,000 M 9R21177 9R21178 9R21179 9R21180 9R21181
179 168 180 178 174
(1 Hour) (2 Hours) (1-30 Minutes) (1 Hour) (1 Hour)
5/5
1,000 M
9R21184 9R21185 9R21186 9R21187 9R21188
183 181 167 191 159
(2 Days) (3 Days) (2 Days) (6 Days) (2 Days)
5/5
500 M 9R20680 9R20681 9R20682 9R20683 9R20684
247 243 250 254 270
(5 Days) 186 171 289 205
1/5
3.
Percent Dead 100
100
20
Note: Figures in paretheses indicate time of death The approximate acute oral LD50 is less than 1000 mg/kg and greater than 500 mg/kg in fasted-male mice.
-- The test article was administered undiluted
Necropsy Findings: Necropsy of the animals which died acutely generally revealed chemical burns of the stomach and intestines, however, autolysis precluded gross tissue evaluation of two animals. Necropsy of the animals which survived the 14 day observation period re vealed an atrophic testicle (1/4), and hemorrhagic vas deferens (3/4).
TABLE 2
ACUTE ORAL TOXICITY SCREEN - ALBINO RATS
with T-2712CoC
Summary of Reactions
Dose (mg/kg)____Sex
Time of Onset
Cessation of Reaction t)
Number Affected Following Dose
Following Dose
Time of Death
Reaction________Number Dosed Administration___________ Administration_________ Following Dose
5,000 1,000
500
M Dyspnea Hypoactivity Salivation
M Dyspnea Emaciation Hypoactivity Prostration Salivation Unkempt Appearance
M Ataxia Dyspnea Hypoactivity Mucous in mouth Salivation Unkempt Appearance Vocalization
4/5 5/5 4/5
5/5 1/5 5/5 1/5 5/5 1/5
5/5 2/5 5/5 1/5
5/5 1/5
1/5
1 Hour 1-30 Minutes 1-30 Minutes
1-30 Minutes 4 Days 1-30 Minutes 5 Days 1-30 Minutes 4 Days
1 Day 1-30 Minutes 1 Day 3 Days
1-30 Minutes 3 Days
1 Day
Until Death Until Death Until Death
2 Days Until Death 5 Days Until Death 1 Day Until Death
3 Days Until Death Until Death Until Death
1 Day Until Death
2 Days
1-30 Minutes-2 Hours 2 - 6 Days
5 Days
a -- Time indicates when first animal in the dose group exhibits the reaction. b. -- Time indicates when no animal in the dose group exhibits the reaction.
APPENDIX I PROTOCOL
Riker Experiment No. ;^)C|
TEST: ____ _________ f i l t r i Q s d SPONSOR: 3M Company ________ C . r v i~-^ (
___________________________ _ ______________ Division
CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc., st. Paul, Ilinnesoi
TEST ARTICLE:
- f - J K O . C C-_____________________________________________
CONTROL ARTICLE: ju,-[ f t ____________________ ^_______ :_______________________ __ PROPOSED STARTING/COMPLETION DATE OF TEST: /;'! / j r. - . } { $ r > _______________
TEST SYSTEM AND SOURCE:
' K&
sex: c T Number; J Weight Range: i f a -
OBJECTIVE:
The objective of this test will be to characterize the acute _____ C T C -fiO "_______ toxicity of the test article in albino
were selected as a test system for reproducibility of response, historical use, ease in handling and general availability.
METHOD:
The animals will be housed in stainless steel suspended wire mesh
cages in temperature and humidity controlled rooms during both the
quarantine and test periods, with food-- and water offered ad
libitum-- . Each animal will be identified by color coding, accord
ing to the laboratory's standard operating procedure, which will
correspond to a card affixed to the outside of the cage. A single
dosage of S Q O O
m g A g will be administered to each animal. The
test article^will be administered to the animals in the form re
ceived from the sponsor, after which the animals will be returned
to their cages and observed for any untoward behavioral reactions
for the following 14 days. Initial and final body weights will be
recorded. A gross necropsy which will include, but not be limited
to; heart, lungs, liver, kidneys and general gastrointestinal 'tract
will be conducted on all animals which die during the conduct of
the test as well as the animals surviving the test period. Any
gross abnormalities which are observed during the conduct of j the
necropsy will be recorded with specific mention to the organ and/or
site observed. All raw data and the final report will be stored in
the Riker Laboratories Archives, St. Paul, Minnesota.
-- Purina Laboratory Chow, Ralston Purina, St
b A
* 'L *. >. i, ._ ./.
"V> titu w .. -,
^ 'v
Louis, Missouri ivv'.'V A -1.tri
` V
jin '*'-
Sponsor
'A /*/o
Date
Study D irctfor'
Date
RiJeer Experiment No. : OMVif.fcivSO
APPENDIX I(concluded)
~"
Amendaent to Protocol
6*
Study Director
Date
3.
Study Director
Date
4.
Study Director
Date
5.
Study Director
Date
6.
Study Director
Date
7.
Study Director
Date
8.
S t u d y Di r e c t o r
Oat
APPENDIX II Principle Participating Personnel Involved in the Study
7.
Name Jt. L. Ebbens, BS K. D. O 'Malley, BS J . A . Skroms G. C. Pecore
Supervisor, Acute Toxicology Study' Director
Advanced Toxicologist Technical Writer
Acute Toxicology Senior Laboratory Technician
Coordinator Animal Laboratory
APPENDIX III Composition Characteristics
This study is not regulated by the Good Laboratory Practice Act of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study.
APPENDIX IV Quality Assurance Statement
This study is not regulated by the Good Laboratory Practice Act -of 1978 and therefore a statement signed and prepared by the Quality Assurance group is not applicable. This study was, however, audited by the Quality Assurance group. In addition to the data audit, different significant phases for studies underway in the Biocompatibility Laboratory are inspected weekly on a recurring cycle, and the facilities are examined by Laboratory Quality Assurance on a three month schedule.
