Document J3N7qEOk4rMY1MM5kg6M4K5KZ
HAZLETON
vcaCA M C
Chemical & BioMedical Sciences Division
3301 KIN SM AN BLVD . P.O. BO X 7S4S M AD ISO N, W ISCONSIN 53707 PH O N E (80S) 241*4471 T U 7 0 3 9 H A Z R A L M D S UO
FINAL REPORT
ROGER G. PERKINS MINNESOTA MINING & MANUFACTURING
TOXICOLOGY SERUICES ST. PAUL, MN <56101
COMPANY
SAMPLE: T-4101 PURCHASE ORDER NUMBER: T837389-410 753
SAMPLE NUMBER: 70905392 SAMPLE ENTERED: 09/23/87 REPORT PRINTED: 01/21/88
ENCLOSED: ACUTE ORAL TOXICITY STUDY IN RATS COECD GUIDELINES!
o Key Personnel o Method o Summary o Individual Pathology Comments o References o Pathology Report o Raw Data Appendix
SIGNED:
STEUEN M. GLAZA STUDY DIRECTOR ACUTE TOXICOLOGY
Q
......... \7f \ r^ DATE
HAZLETON
3301 KIN SM AN BLVD . P O. BO X 7545 M AD ISO N, W ISCO N SIN 53707
Chemical & BloMadleal Sciences Division
PH O N E (SOS) 241-4471 T L X 703SSS H A Z R A L M O S UD
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
KEY PERSONNEL
Acute Toxicology
Steven M. Glaza Study Director
Calvin L. Horton Group Leader Support Services
Sharen L. Houery Report Coordinator
Quality Assurance
Debra Curley Arndt Manager
Anatomical Pathology
Thomas E. Palmer, PhD Anatomical Pathologist
Robert Salava Senior Section Supervisor
Dennis Hoffman Group Leader Necropsy
Anne Mosher Group Leader Pathology Data
Laboretorv Animai Ueter inar.ian
Cindy J. Cary, DUM Diplomate, ACLAM
@
HAZLBTOhl -- ---- ~
Chemical & BioMadical Sclencea Divlalon
3301 KIN SM AN BLVD . P.O. BO X 7545 M AD ISO N. W ISCONSIN 53707 P H O N E (BOB) 341-4471 TUC 703B6B H A 2 R A L M D S U0
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
3
OECD ORAL SCREEN
Objective: To determine the acute oral toxicity produced when a test material is administered by the oral route (gavage) to rats according to the Organisation for Economic Cooperation and Development's Guidelines
for Testing Chemicals.
Test Material: T-4101 Physical Description: Purity and Stability:
Storage and Retention:
Safety Precautions:
Clear, yellow liquid
Sponsor assumes responsibility for purity and stability dtermint ions. The test material was stored at room temperature. Any unused material will be discarded according to HLA Standard Operating Procedure. Normal handling procedures were used according to HLA Standard Operating Procedure.
Test Animal: Voung adult albino rats of the Sprague-Daw1ey strain were
procured, separated by sex, maintained in group cages in temperatureand humidity-controlled quarters, provided continuous access to Purina Rodent Chow and water, and held for an acclimation period of et least 7 days. A n i m a 1 husbandry and housing at HLA comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals". If variations from the prescribed environmenta1 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 st u d y .
Acclimated animals were chosen at random for the study. Test animals
were housed by sex in groups of five and identified by animal number
and corresponding ear tag. Food and water were available
libit um
throughout the study, except for an overnight period just before
test material administrat1 on when food, but not water, was withheld.
Reason for Species Selection: The rat is the animal classically used due to its small size, ready availability, and large amount of background data.
Method: Five male and five female rats weighing from 200 to 298 g were
used for each dose level. The study consisted of two dose levels
(0.50 and 5.0 g/kg).
Preparation and Administration of Test Material: An individual dose
was calculated for each animal based upon its fasted body weight and administered undiluted by gavage.
The dose volume of the test material varied per dose level based upon an average bulk density of 1.13 g/ml.
HAZLETON
3301 KIN SM AN BLVO . P-O- BO X 7S46 M AD ISO N. W ISCONSIN S3707
Chemical & BloMedical Sciences Division
PH O N E (608) 241-4471 T LX 7 0 3 8 H A Z R A L M D S UD
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
O E C D OR AL SCREEN
(CONTINUED)
Reason for Route of Administration: This is the method for administering a known quantity of test substance and has been the route of choice
historically.
Observations: The animals were observed for clinical signs and mortality at 1, 2.5 and 4 hours after test material administration and daily thereafter for at least 14 days.
All animals were weighed just before test material administration, at 7 days and at study termination (or at death).
Pathology: At study termination surviving animals were euthanatized. Animals which died on study or euthanatized at study termination ware subjected to a gross necropsy examination and abnorma1ities recorded. Following necropsy, animals were discarded and no tissues were saved.
Statistical Methods: Other than average body weights, no other statistical method 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.
H A Z L E T O N _______ _ _ _ _ _____________LtTTVOTSPigS ANC^CA.INC
Chemical & BloMadlcal Sciences Division
3301 KIN SM AN BLVO. P.O. BO X 7545 M AD ISO N. W ISCONSIN 53707 PH O N E (BOS) 241*4471 T LX 703SS6 H A Z R A l M D S UD
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
PAGE
OECD ORAL SCREEN
SUMMARY
(CONTINUED)
Test Animal: Albino Rats - Sprague-Dawley strain Source: Charles River Laboratories, Inc., Portage MI Date Animals Received: 09/08, 09/28, 10/12, and 10/26/07
Method of Administration: Oral Gavage
Date Test Started: 10/16/87
Date Test Completed: 11/20/87
Estimated Oral LD50: Male - Between 0.50 and 5.0 g/kg of body weight Female - Between 0.50 and 5.0 g/kg of body weight
Dose Level (g / k g )
0.50 5.00
0.50 5.00
Average Body ideights (g) Mortality (Number
Initial
Day 7 Termina 1 Dead/Number Dosed)
266 278
340
--
370
--
0/5 5/5
203 208
230 166
237 232
0/5 4/5
CLINICAL SIGNS (No. of Animals Affected)
____fclauxa____ ________________ Povs__________________________
1.0 2.5 4.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
DOSE LEUEL: 0.50 g/kg
Ma 1es
Appeared Normal 5 5 5
555555555
5555
5
Ferna 1es
Appeared Normal 5 5 5 5 5 5 5 5 5 5 5 5
5 555 5
@
HAZLETON -- 3P I S W A P C t W C
3301 KIN SM AN BLVD. P O. BO X 7S45 M AD ISO N, W ISCONSIN 53707
Chemical & BloMedlcal Sciences Division
PH O N E (60S) 241*4471 T LX 703BSB H A Z R A L M D S UD
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
PAGE 6
OECD ORAL SCREEN
(CONTINUED)
CLINICAL SIGNS (Continued) (No. of Anim al s Affected)
_____ H o u r s _____ 1.0 2.5 4.0
Devs
10 11 12 13 14
DOSE LEUEL: 5.0 g/kg
Ma 1es
Appeared Normal 3 0 0 0 0 0 0 0 0
Hypoact ivi ty At ax la
2 5 5 555310 0 0 5 5 05 3 1 0- - - - -- -- " --
Red-s ta ined face
* 0 0 0 14 5 3 1 0
:
Pa in re f 1ex absen t
0 0 0 0 042 10
_--
----
M ios is
0 0 1 000000
Val low-stained gen 1 1a 1 reg ion 0 0 0 0 0 2 1 0 0
_ _--
Dea th
0 0 0 00022 1
Eemalea
Appeared Normal 3 0 0 0 0 0 0 0 0 0 0 0 1 0 1 1 1
Hypoac t iv ity
2 5 5 533322 111 0 0 0 0 0
Ye 1low-stained
g e n it a 1 reg ion 0 1 1 5 3 3 3 2 2 1 1 1 0 0 0 0 0
Dia rrhea At ax ia
1 1 1 100000000 0 0 0 0 0 0 1 5 5 13322 101 0 1 0 0 0
Red-s tained
face
0 0 5 523322 110 0 0 0 0 0
Prost rat ion
0 0 0 100000000 0 0 0 0 0
T remo rs
0 0 0 100000000 0 0 0 0 0
Pa in reflex
absent
0 0 0 001110000 0 0 0 0 0
Cyan osis
0 0 0 100000000 0 0 0 0 0
Dea th
0 0 0 2* 0 0 0 1 0 1 0 0 0 0 0 0 0
* Animals died following a.m. observations.
HAZLETON
i ws/ewcA *\c
Chemical & BloMadlcal Scianca Division
3301 KIN SM AN BLVD . P.0 . BO X 7545 . M AD ISO N. W ISCONSIN 53707 PH O N E (605) 241-4471 . T L X 703S56 H A Z R A L M D S UD
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
OECD ORAL SCREEN
CC O N T l N U E D )
PATHOLOGY
DOSE LEUEL: 0.50 g/kg of body weight
A n lma 1 Number
Sex
Test Day Died Sacrificed
Necropsy Comments
C 03078 C03074
M M
- 14 - 14
No visible 1es ions No visible les ions
C03077
M
- 14
No visible les ions
C03076
M
- 14
No visible lesions
C03073
M
- 14
No visible 1es ions
C03245
F
- 14
No visible lesions
C03243
F
- 14
No visible 1es ions
C03246
F
- 14
No visible 1es ions
C03244
F
- 14
No visible lesions
C03327
F
- 14
No visible les ions
PAGE 7
HAZLETON --
3301 KIN SM AN BLVD . P.O. BO X 7546
A/S/eniCA uve M AD ISO N, W ISCO N SIN 53707
Chemical & BioMedleal Scianca Division
PH O N E (60S) 341-4471 T LX 703S66 H A Z R A L M O S UD
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
PAGE 8
OECD ORAL SCREEN
CC O N T I N U E D )
PATHOLOGY (Continued)
DOSE LEUEL: 5.0 g/kg of body weight
Animal Number
C00544
Sex M
Test Day Died Sacrificed
4-
Necropsy Comments
Perianal stains - tan; ocular discharge (bilateral) - red and black, crusted; gastrointestina 1 tract (GI) - severely autolyzed.
C00542
M
4
-
Perianal stains - tan; ocular
discharge (bilateral) - red and crusted; stomach - grandular mucosa diffusely red with multiple dark
brown linear areas, 4 x 1 mm.
CO 0545
M
4
-
Perianal stains - tan; stomach glandular mucosa, multiple dark brown linear areas, up to 3 x 2 mm.
CO 0551
M
5-
Perianal stains - tan; ocular discharge (bilateral) - red and crusted; stomach - glandular mucosa has two dark brown linear areas, both are 10 x 2 mm.
CO 0548
M
5-
GI tract - very autolyzed.
HAZLETON
I AfwCniCA. use
Chemical A BloMedical Sciaticas Division
3301 KIN SM AN BLVD . P.O. BO X 7545 M AD ISO N, W ISCONSIN 53707 PH O N E (SOS) 241-4471 T LX 703SS6 H A Z R A L M D S UD
SAMPLE NUMBER: 70905392 SAMPLE: T-4101
PAGE 9
OECD ORAL SCREEN
(CONTINUED)
PATHOLOGY (Continued)
DOSE LEUEL : 5.,0 g/kg of body we ight (continued)
An ima 1 Number
Sex
Test Day D ied Sac r if iced
Necropsy Comments
CO 0988
F
1
-
Perineum - stained brown; ocular discharge (bilateral) - red; stomach - contains green semi-solid 'mate ria1.
C00976
F
1' -
Perineum - stained brown; ocular discharge (bilateral) - red; paranasal discharge - red; stomach - contains clear, oily
ma te r ia 1.
C00987
F
- 14
No visible lesions.
C01005
F
5
-
Nasal discharge - red; perianal and inguinal stains - tan;
stomach - glandular mucosa has multiple, dark brown linear areas, up to 4 x 2 mm.
CO 0957
F
7
-
Stomach - glandular mucosa has multiple dark red linear areas, up to 3 X 1 mm.
1. H i t c h , R . K . , " A c u t e O r a l T o x i c i t y S t u d y , " P e s t i c i d e A s s e s s m e n t Guidelines, Su b d i v i s i o n F, Haza rd Evaluation: Huma n and D o me st ic
Animals, U.S. Environmental Protection Agency Office of Pesticide
and Toxic Substances Series 81-1, p p . 34-39 (November 1982).
2. 21 C F R 5 8 ( U n i t e d S t a t e s F o o d a n d D r u g A d m i n i s t r a t i o n ' s G o o d Laboratory Practices Regulations for Nonelinical Laboratory Studies).
3. N I H P u b l i c a t i o n No. 8 5 - 2 3 ( r e v i s e d 1985).
HLA LAB NO. 70905392
PATHOLOGY REPORT Acute Oral Toxicity
PAGE 10
Ten rats (five males, five females) from eacn of two dose levels (0.5 and 5.0 g/kg) were necropsied. Tne animals that died on test were refrigerated and necropsied within 24 nours, usually tne same day. All surviving animals were eutnanatized and necropsied at the termination of the study. The dose level, day of deatn and gross observations recorded for each animal are on pages 7 to 9 of this report.
The only recorded observations were in those animals that died on test. The stomach contained material of variable consistency and color which possioly represents test material mixed with ingesta. The gastric mucosa in some animals had focal red or brown linear areas wnich were possioly treatment related. All other observations were considered related to postmortem change or incidental findings which were not related to treatment.
Pathologist (1734mcs)
Date
Personnel Signature Sheet Acuta ToMcology
H U * 0 .1 te S 3 d J^
Jo> Title
Backy Backwlth
Sr. Lab. A M e e l Asst.
Stave Beloungy
Lab. Anlaal Asst.
Kan Bridges
Pat Crary
Sr. U b . Anlaal Asst. Sr. Lab. Anlaal Asst.
Shane Elth
U b Anlaal Asst.
Shawn Frazier
Lab Anlaal Asst.
Steven M. Glaze
Group Leader
Molly Hahn
Adarin. Clerk
Kevin Heal1ton
Lab. Anlaal Asst.
Jeff Hicks
Sr. Lab. Anlaal Asst.
Calvin Horton
Group Leader
Sharon L. Howory AdBlalstratlve Asst.
Gregory Johnson
Lab. Anlaal Tech.
Paul Krehs
Lab. Anlaal Asst.
Moyne Madison
Section Supervisor
Scott McConnell
Lab. Anlaal Tech.
Shelley McConnell Dawn Conant
Lab. Anlaal Tech. Sr. Lab. Anlaal Asst.
Den Mavis
Lab. Anlaal Asst.
Mahln Olson
Lab. Anlaal Asst.
Patricia Padghaa
Joseph J. Dawi
Teas Loader Lab. Anlaal Asst.
Michael Patzka
Lab. Anlaal Asst.
John Paulson
Sr. Lab. A M a a l Asst.
Jane Polnow
Lab. Anlaal Tech.
D e m i s B. Stainer Lab. Anlaal Tech.
RlchMl Thtslng Ub. Mllnl ASSt.
Paula 6. Vangen
Albert Olson
Administrative Asst.
Manpower
J1m Jlrschele
LTE
Ben Haley
Sr. Lab Animal Asst.
Eileen M. McConnell Admin. Clerk
Annette R. Turner Manpower
Signature
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Initials ___
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date. 8W-
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PoylaMd * > Q ^ ---J2M87
Dose level: O S
08SERVATI0NS (Individual)
Test Material: ~P~ H <Q I
HL ki l c f l o S V Z -
- Surviving animals submitted for terielna) necropsy. Technician / S V -
Data m /
- Surviving anlnuls
designated for sacrifice
Nfland discard.
Technician
f/>
Date N A_____
Indicates condition exists
SI Slight. - Condition not evident.
* found dead, P.H. check.
n A N u t Oioo f( iIctaulolIrr f i l l
Reviewed
Date: j_
Dose level: O . S "
OBSERVATIONS (Individual)
\Test Material : T~- M|Q
HLA:3
- Surviving anlaals submitted for teralnal necropsy. Technician / 5 4 r
Date
* < / 2-o / s ~7
- Surviving anlaals designated for sacrifice and discard. ..
Tpchnlc Ian Nf\_______
Oate fvilA______________
Indicates condition
exists
SI Slight.
- Condition not evident.
* found dead, P.N. check,
M hk>i
if
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OBSERVATIONS (Individual)
____________________ Tesi a te rlai:___ J- 4 ^ 0 J-----------
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Ko-
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lobaservatlons
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geared
Normal 4iv<
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OBSERVATIONS (Individual)
.Test Material:
T - 4 l O > \ _________
Pre-
Hours
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1-213 7
7
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Sttf4* P*K U L TI 11 13 14
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Surviving anlaals
subaltted for terminal
necropsy.
-.
Technician lilt-
Date ^ h o f f i
Surviving anlaals
designated for sacrifice
and discard. Technician
Ain* ___
Date A/ft
Indicates condition
eilsts SI Slight.
- Condition not evident.
found dead, P.N. check, ,
bivf A o p h c ^ L i e t i t //*-/7 Reviewed by: C t p _______ Date: &/(J h 7
