Document ByL6XL2eo5LkGNxaMMRbjenm
M&S.6 _ 066S
PFOA
Acute Toxicity - /
000814
gg) HAZLETON
l a b o r a t o r e s a v e r c a ,SC 3301 KINSM AN BLVD., P.O. BO X 7S45 MADISON. Wl 53707 U SA
FINAL REPORT
Karen Armstrong 3M Toxicology Services Building 220-2E-02 St. Paul, MN 55144-1000
Sample: T-4416
HLA Number: 91201739
Enclosed: Acute Oral Toxicity Study in Rats (OECD Guidelines)
o Key Personnel o Methodology o Summary of Results o Individual Pathology Comments o References o Pathology Report o Raw Data/Appendix
Study Director Acute Toxicology
PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD
Date
HAZLETON
LABORATOR6 S AMEF1CA. SC.
3301 KIN SM AN BLVD., P.O. BO X 7545 MADISON. W l 53707 U SA
HLA Number: 91201739 Sample: T-4416
Acute Toxicology Steven M. Glaza Study Director Section Supervisor Steven R. Sorenson Study Coordinator Patricia Padgham Group Leader Sharen L. Howery Report Coordinator
Qua!itv Assurance Deborah L. Keller Manager
Page 2
KEY PERSONNEL
Laboratory Animal Veterinarian Cindy J. Cary, DVM Dipl ornate, ACLAM
Anatomical Patholoav Thomas E. Palmer, PhD Anatomical Pathologist Dennis Hoffman Group Leader Necropsy Anne Mosher Group Leader Pathology Data
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i oom njm ia Laboratory Sarveaa Company
000516
HAZLETON
l a b o r a t o r c s a v e fic a ,rsic
3301 KIN SM AN BLVD., P.O. BO X 7S4S MADISON, W l S3707 U SA
HLA Number: 91201739
Sample: T-4416
Page 3
METHODOLOGY
Objective: To assess the acute oral toxicity produced when a test material is administered by oral gavage to rats.1
Test Material : T-4416 Physical Description: Purity and Stability:
Storage and Retention:
Safety Precautions:
Clear colorless liquid Sponsor assumes responsibility for purity and stability determinations (including under test
conditions). The test material was stored at room temperature. Any unused material will be returned to the Sponsor according to HLA Standard Operating Procedure. Normal handling procedures were used according to HLA Standard Operating Procedure.
Test Animal: Adult albino rats, Crl:CDBR, were procured, separated by sex, maintained in group cages in temperature- and humidity-controlled quarters, provided continuous access to Rodent Chow 5001, Purina Mills, Inc., and water, and held for an acclimation period of at least 7 days. Animal husbandry and housing at HLA comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals".2 If variations from the prescribed environmental conditions existed, they were documented and considered to have no effect on the study outcome. No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.
Acclimated animals were chosen at random for the study. Five male and five female rats, weighing from 204 to 299 g, were used for each dose level. The study consisted of three dose levels (0.2, 1.0 and 5.0 g/kg of body weight). Test animals were housed by sex in groups of five and identified by animal number and corresponding ear tag. Food and water were available ad libitum throughout the study, except for an overnight period just before test material administration when food, but not water, was withheld.
Reason for Species Selection: Historically, rats have been used as a representative of a rodent species and are preferred by various regulatory agencies.
Preparation and Administration of Test Material: The test material was administered as received. An individual dose of the undiluted material was
calculated for each animal based upon its fasted body weight and administered by gavage.
The dose volume of the test material varied for each dose level based upon the bulk density of the material of 1.28 g/mL.
PHONE (606) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HA2RAL MDS UD
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000S 17
HAZLETON la b o r a t o r e s a m e b c a ,im c. 3301 KINSM AN BLVD., P.O. BO X 7545 MADISON. W l 53707 U SA
HLA Number: 91201739
Sample: T-4416
Page 4
Reason for Route of Administration: Historically, the oral route has been the route of choice for administering a known amount of test material.
Observations: The animals were observed for clinical signs and mortality at 1, 2.5 and 4 hours after test material administration. The animals were observed daily thereafter for 14 days for clinical signs and twice daily for mortality.
Animals were weighed just before test material administration. Surviving animals were weighed again at Day 7 and at termination of the experimental phase or at death (when survival exceeded 1 day).
Pathology: All animals whether dying on test or euthanatized at termination of the experimental phase were subjected to a gross necropsy examination and all abnormalities were recorded. After necropsy, the animals were discarded and no tissues were saved.
Statistical Methods: The LDcg value for males, females and the combined sexes was calculated based upon tne observed mortality using a computer program utilizing a modified Behrens-Reed-Muench Cumulant Method.3 No other statistical analysis was performed.
Location of Raw Data and Final Report: The raw data and a copy of the final report will be retained in the archives of HLA.
PHONE (606) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD
O O H N W O Laboratory S a rvcN Company
000818
.(fi) HAZLETON LABORATORIES A M E R C A fMC. 3301 KINSM AN BLVD., P.O. BO X 7545 MADISON, Wl 53707 U SA HLA Number: 91201739
Sample: T-4416
Page 5
SUMMARY OF RESULTS
Test Animal: Albino Rats - Crl:CDBR Source: Charles River Laboratories, Inc., Portage MI Date Animals Received: 12/04/89, 12/18/89 and 01/08/90
Method of Administration: Oral Gavage
Start Date (In-life): 12/28/89
End Date (In-life): 02/16/90
Estimated Oral LD50 : Male - 1.8 g/kg of Body Weight 95% Confidence Limits - 0.7 to 4.9 g/kg
Female - 0.6 g/kg of Body Weight 95% Confidence Limits - 0.2 to 1.5 g/kg
Sexes Combined - 1.0 g/kg of Body Weight 95% Confidence Limits - 0.4 to 2.4 g/kg
Sex Male
Female
Dose Level __ (g/kg)
0.2 1.0 5.0
0.2 1.0 5.0
Average Body Weights fo1
Initial
Day 7
Terminal
290 332 272 264 274 --
362 315 --
211 247 233 257 230 --
254 268 --
Mortality (Number Dead/Number Dosed 1
0/5 1/5 5/5
0/5 4/5 5/5
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(**) HAZLETON LABORATORES AM EHCANC 3301 KINSM AN BLVD., P.O. BO X 7545 M ADISON. Wl 53707 U SA HLA Number: 91201739
Sample: T-4416
Page 6
Observation Appeared normal
Clinical Signs (Number of Animals Affected)
nuui
L lO Z A A 1 Z
col
1 lfl i l 11 11 11
Hales i(Q -L -q /k a l 5 5 5 555555555 5 5 5 5 5
Appeared normal
Females (0.2 Q/kq) 5 5 5 555555555 5 5 5 5 5
Males H .O Q/kq)
Appeared normal Hypoactivity Red-stained face
5 5 5 521112333 3 3 3 4 4 0 0 0 032222111 0 0 0 0 0 0 0 0 0 12221111 1 1 0 0 0
Yellow-stained
urogenital area 0 0 0 0 1 3 3 3 1 1 1 1 1 1 1 0 0
Ataxia
0 0 0 000001111 0 0 0 0 0
Thin appearance
0 0 0 000001111 1 0 0 0 0
Diarrhea
0 0 0 0000000 11 0 0 0 0 0
Death
0 0 0 0 10000000 0 0 0 0 0
Females (1.0 a/kg)
Appeared normal
5 5 5 511111111 1 1 1 1 1
Hypoactivity
0 0 0 022 100000 0 0 0 0 0
Red-stained face 0 0 0 0 2 2 1 0 0 0 0 0 0 0 0 0 0
Ataxia
0 0 0 001000000 0 0 0 0 0
Prostration
0 0 0 000 100000 0 0 0 0 0
Death
0 0 0 0 12 100000 0 0 0 0 0
PHONE (608) 241-4471 FACSIMILE (60S) 241-7227 TELEX TLX 703956 HAZRAL MDS UD
O O B W N O Laboratory Sotvicm Compony
000820
HAZLETON
LABORATORIES AMEBCA, MC
3301 KIN SM AN BLVD., P.O. BO X 7545 M ADISON. Wl 53707 USA
HLA Number: 91201739
Sample: T-4416
Page 7
Clinical Signs (Continued) (Number of Animals Affected)
Observation
Hour
_____________________ D M ________________________
1.0 2.5 4.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Males (5.0 o/kg)
Appeared normal
1 0 00
Diarrhea
4 4 41
Hypoactivity
0 4 41
Red-stained face 0 2 4 1
Lacrimation
0 0 10
Ataxia
0 0 01
Death
0 0 1 4'
* - One animal found dead after the morning observation.
Females (5TQ q/kq)
Appeared normal
2 0 00
Diarrhea
3 3 20
Hypoactivity
1 3 20
Lacrimation
0 2 20
Ataxia
0 1 10
Red-stained face 0 1 1 0
Death
0 2 12
PHONE (608) 241-4471 FACSIMILE (606) 241-7227 TELEX TLX 703956 HAZRAL MDS UD
. OCRAHNO Uboc.wr,
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000821
HAZLETON
LABORATORIES A M E H C A .N C
3301 KINSM AN BLVD.. P.O. BO X 7545 MADISON. W l S3707 U SA
HLA Number: 91201739
Sample: T-4416
INDIVIDUAL PATHOLOGY COMMENTS
Dose Level: 0.2 g/kg of Body Weight
Animal
Test Dav
Number Sex Pied Sacrificed NecroDSV Observatio
C50366
M
-
14 No visible lsions
C50367
M
-
14 No visible lesions
C50363
M
-
14 No visible lesions
C50369
M
-
14 No visible lesions
C50370
M
-
14 No visible lesions
C50501
F
-
14 No visible lesions
C50502
F
-
14 No visible lesions
C50503
F
-
14 No visible lesions
C50504
F
-
14 No visible lesions
C50500
F
.
14 No visible lesions
Page 8
PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UO
OORIMIMO Laboratory S arvicw Company
000822
HAZLETON
LABORATOH eSAM 6flCA.NC
3301 KINSM AN BLVD., P.O. BO X 7545 MADISON, W l 53707 U SA
HLA Number: 91201739
Sample: T-4416
Page 9
INDIVIDUAL PATHOLOGY COMMENTS (continued)
Dose Level: 1.0 g/kg of Body Weight
Animal
Test Dav
Number Sex Died Sacrificed NecroDsv Observation
C49861
M
-
14 No visible lesions
C49862
M
-
14 No visible lesions
C49863
M
-
14 No visible lesions
C49864
M
2
- Stomach, Glandular Mucosa: diffusely red
C49860
M
-
14 No visible lesions
C49921
F
3
- Stomach, Glandular Mucosa: diffusely red
C49917
F
2
-
No visible lesions
C49918
F
4
Perinasal Discharge: red Stomach, Glandular Mucosa: multiple dark areas, up to 2 x 4 mm
C49919
F
3
- Stomach, Glandular Mucosa: diffusely red
C49920
F
-
14 No visible lesions
PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD
HAZLETON
LABORATORIES A M ERC A , MC
3301 KIN SM AN BLVD., P.O. BO X 7545 M ADISON. Wl 53707 U SA
HLA Number: 91201739
Sample: T-4416
Page 10
INDIVIDUAL PATHOLOGY COMMENTS (continued)
Dose Level: 5.0 g/kg of Body Weight
Animal
Test Dav
Number Sex Pied Sacrificed Necropsy Observation
C49191
M
1
-
No visible lesions
C49192
M
1
-
No visible lesions
C49193
M
1
"
Stomach, Glandular Mucosa; multiple brown areas, up to 3 x 1 mm
C49194
M
0
-
Stomach, Glandular Mucosa: diffusely dark red
C49490
M
1
-
No visible lesions
C49131
F
0
-
Stomach contents: clear white fluid
C49132
F
1
-
Stomach, Glandular Mucosa: multiple brown areas, up to 4 x 2 mm
C49128
F
0
-
Stomach Contents: clear white fluid
C49129
F
0
-
Stomach Contents: clear white fluid
C49130
F
1
-
No visible lesions
PHONE (60S) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 H AZR Al MDS UD
O O P N jwQ Laboratory Sarvic-- Company
000824
HAZLETON
LA BO RA TO RES AM ERGA.IM C.
3301 KIN SM AN BLVD.. P.O. BO X 7545 MADISON, W l 53707 U SA
HLA Number: 91201739
Sample: T-4416
Page 11
REFERENCES
1. "Acute Oral Toxicity," Organisation for Economic Cooperation and Development's Guidelines for Testing of Chemicals, Section 401 (adopted May 12, 1981).
2. NIH Publication No. 86-23 (revised 1985).
3. Thakur, A. K. and Fezio, W. L., "A Computer Program for Estimating LD50 and its Confidence Limits Using a Modified Behrens-Reed-Muench Cumulant Method," Drug and Chemical Toxicology, 4(3):297-305 (1981).
PHONE (60S) 241-4471 FACSIMILE (606) 241-7227 TELEX TLX 703956 HAZRAL MDS UD
O O R N W O LaborM ary Sarwc-- Company
(00825
HAZLETONLABORATORES AMERCA.VIC.
3301 KINSM AN BLVD.. P.O. BO X 7545 M ADISON. W l 53707 USA
HLA Number: 91201739
Sample: T-4416
Page 12
PATHOLOGY REPORT
There were 10 rats (5 males, 5 females) from each of 3 dose levels (0.2, 1.0, and 5.0 g/kg) necropsied. The animals that died on test (DOT) were refrigerated and necropsied within 24 hours, usually the same day. All surviving animals were euthanatized and necropsied at the termination of the study. The dose level, day of death, and gross observations recorded for each animal are on page 8 through 10 of this report.
All animals in the 5.0 g/kg dose group died on test. At necropsy, the only changes observed were in the animals that died on test. The most frequently recorded observations pertained to the content and coloration changes in the mucosa of the stomach. These findings possibly represent test material mixed with ingesta, postmortem change, or both. All remaining observations in the DOTs were considered postmortem change, incidental, and unrelated to the test material. There were no visible lesions in the sacrificed animals.
Pathologist (91201739.cjr)
Date
PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD
* O O W N W O Laboratory Sorvtcoa Company
000826
HLA: ^ n o n 3 C1
PERSONNEL SIGNATURE SHEET ACUTE TOXICOLOGY
Name
Job Title
Signature
Initials
Becky Beckwith Ann Bursaw
Lab Animal Technician Sr. Clerk
'i.ak^-ffghuiLtJj /p7ioijE>OAjOassr'
Anthony Cass
Lab Animal Assistant
D kA v,/Twq C o Jxa.
Cindy J. Cary, DVM Lab Animal Veterinarian
Kari Gassen
Sr. Lab Animal Assistant j^oJLi
Steven M. Glaza
Section Supervisor
Ben Haley
Sr. Lab Animal Assistant
Jeff Hicks
Lab Animal Technician
Sharen L. Howery Research Assistant
Jim Jirschele
Lab Animal Assistant
J,L J L s A / V
Wayne Madison
Senior Section Supervisor C ()"? "t Q.
oj
Bud McDonald Eileen McConnell
Sr. Lab Animal Assistant Administrative Clerk
rtk*_P .-iX.r'x-/
Henry Mikula Albert Oleson
Lab Animal Assistant Sr. Lab Animal Assistant M & u f Q u , r s
A O __
Patricia Padgham
Jane Pol now
Steven R. Sorenson
Dawn Thieding
t
Annette R. Turner
'2> 1___
(09/11/89)
-
000827
BEST COPY AVAILABLE
DOSE AUI11HISIRATI0II/0DY UCIGtt/HORl
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HLA: g? U l S
Study T t t ls l Acute OrI T o xicity
Test M a te ria l; ~7~~- *4 *4 I
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(g/kol Fested Date/T Ina/Taclinlcten 2. -I
/ 3 :o 5~ii -w-/ C lh l Root Ho. ) & '2 --
Route of A dm inistration; Orel Gavage
Dose Volume 0,lC) (ad./kgl
Sex: rileie^Fcieele
Animel No.
CS' o g c . Oli'l
Pretested Body Weight (q)
NA
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BEST COPY AVAILABLE
Dose leve
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Surviving animals submitted for terminal necropsy. A , Technician V _____
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Surviving animals designated for sacrifice and discard. Technician NA__________
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SI Slight-. - Condition not evident.
* found dead, P.H. check.
NA Not applicable
Reviewed by:
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Date: ________
000829
BEST COPY AVAILABLE
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Dose level: O .*2.
OBSERVATIONS (Individual) ________________ _Test material: ) - I C-?
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000830
BEST COPY AVAILABLE
DOSE AUtllHISIRATIOII/OOY WEIGIII/HORTA. f RECORD
HLA: l l Z n f 1 3 7
Study T itle s Acute OrI T o xicity
le s t H a te rla l; ~7~ - *-/ *4 I O ____________ Vehicle; N A ___________________
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best copy available
Dose level: 1 . 0
OBSERVATIONS (Individual) _________________Test material: / - Q-*4 I
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Surviving animals
submitted for terminal
necropsy.
,
Technician Mr-/_____
Date
Surviving animals designated for sacrifice and discard. Technician M __________
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exists SI Slight. - Condition not evident.
* Found dead, P.M. check.
NA Not applicable Reviewed by: *37/_____ Date: ________ -90________
000832
BEST CPY AVAILABLE
Dose level: / &
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Surviving animals
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NA Not applicable Reviewed by: J 7 / _____ Date: ______ ____________
000833
BEST COPY AVAILABLE
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DOSE AUMiNISlftATlOfl/DCJUY WE IGIIT/MORIAL.. f RECORD
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,HA 'li
HA - Hot Applicable
Reviewed Dy S ? / Data
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Dose level:
C>
OBSERVATIONS {Individual) Test material : / - *-1*4 I
HLA: U l & m i y
lo A<~ m iz z<? ^ 9
- Surviving animals
submitted for terminal
necropsy.
.
Technician N
Date A)ft_________
- Surviving animals designated for sacrifice and discard. Technician NA__________
Date NA
JbOO
Indicates condition
exists
SI Slight.
- Condition not evident.
Cfl * Found dead, P.H. check.
NA Not applicable Reviewed by: j?/_____
Date:
___
Oose level: <5**. O
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OBSERVATIONS (Individual) Test material: ~7~- *V /C
h i.ft:
'7 3 * 7
Surviving animals submitted for terminal necropsy. Technician _
Date A)f\
Surviving animals designated for sacrifice and discard. Technician MA__________
Date NA_______________
Indicates condition
exists SI Slight. - Condition not evident.
* Found dead, P.H. check.
HA Not applicable
Reviewed by:
-7 7 /
D a t e : _________