Document wR3gyoeqymavx9DvyG357XV6
R O G E R G. P E R K I N S MINNESOTA MINING t MANUFACTURING
TOXICOLOGY SERUICES ST. PAUL, MN 55101
COMPANY
SAMPLE: T-4101 PURCHASE ORDER NUMBER: T8373B9-410 753
SAMPLE NUMBER: 70905793 SAPTLl ENTERED: 09/23/87 REPORT PRINTED: 01/17/88
ENCLOSED:
A C U T E D E R M A L T O X I C I T Y S T U D Y IN R A B B I T S (OECD GU I D E L I N E S )
o Key Personnel
e Method
o Summary
o Individual Pathology Comment
o Reference*
.
o Pathology Report
o Rev Date Appendix
SIGNED:
S T E U E N M. C L A Z A STUDY DIRECTOR ACUTE TOXICOLOGY
......... V W . 1 & DATE
Ljacng g im
sc
Chemical* BloMadlcal Sciences Division
3301 KINSMAN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 PHONE (8M) 241-M71 TLX 7 0 M M H A Z I U l MOS UD
_ SAMPLE NUMBER: 70905393 SAMPLE: T-4101
PAGE 2
KEY PERSONNEL
Acute Toxicology
S t e v e n M. G l a z e Study Director
C a l v i n L. H o r t o n Group Leader Support Services
S h ar en L. H o w e r y Report Coordinator
ualitv Assurance
Debra Curley Arndt Manage r
Anatomical Pathology
T h o m a s E. P a l m e r , P h D Anatomical Pathologist
Robert Salava Senior Section Supervisor
Dennis Hoffman Group Leader Necropsy
Anne Mosher Group Leader Pathology Data
Laboratory Animal Ueterinanan C i n d y J. Ca r y , D U M Diplomate, ACLAM
SAMPLE NUMBER: 70905393 SAMPLE: T-4101
OECD DERMAL SCREEN
O
b
jective:
of a test Organisat
i
To
ma on
t
essess
erial for Ec
w o
the
hen nom
i
sy
it c
stemic
is a p Cooper
p a
toxi
lied tion
c
ity
to and
and the
Dev
s e
relat kin a lopme
i c n
ve co t'
r s
skin ding
Gui
d
irritan to the elines
c
y
for Testing of Chemicals.
Test Material: T-4101 Physical Description: Purity and Stability:
Storage and Retention:
Safety Precautions:
Amber liquid Sponsor assumes responsibility for pur ity and s t a b i l i t y dtermint i o n s The test mate ri al was stor ed at r o o m temperature.
Any unused material will be discarded according
to H L A S t a n d a r d O p er at in g P r oc ed ur e. Normal handling procedure were used according
to H L A S t a n d a r d O p e r a t i n g P r oc ed ur e.
Test Animal: Young adult rabbits of the New Zealand White strain were p r o c u r e d , m a i n t a i n e d i n d i v i d u a l l y in s c r e e n - b o t t o m c a g e s in t e m p e r a t u r e and h u m i d i t y - c o n t r o l l e d qu ar te rs , p r o v i d e d access to w a t e r * 1 and a measured amount of Purina High Fiber Rabbit Chow, and held for an a c c l i m a t i o n p e r i o d of at least 7 days. A n i m a l h u s b a n d r y " * ; " " * * "2 UaB at H L A c o m p l y w i t h s t a n d a r d s o u t l i n e d in the G u i d e for th e C a r e a n d Use of L a b o r a t o r y A n i m a l s " . If v a r i a t i o n s f r o m the p r e s c r i b e d e n v i r o n m e n t a 1 c o nd it io ns existed, they were d o c u m e n t e d and c o n s i d e r e d to ha ve no f f on the study outcome. No co nt am in an ts were expected to have been present in the f e e d or w a t e r w h i c h w o u l d h a v e i n t e r f e r e d w i t h o r a f f e c t e d the
results of the study.
Five male and five female acclimated rabbits, weighing between 2041 g and 2343 g, were chos en at random, treated, and m a i n t a i n e d d u r i n g the o b s e r vation period as specified for the acclimation period. Test animals were identified by animal number and corresponding ear tag. P P roximately twenty-four hours before test material application, each rabbit s back was shaved with an electric clipper. The shaved area made up approximately 20* of the total body surface.
Reason for Species Selection: Historically, the New Zealand White albino rabbit has been the animal of choice due to the large amount of background information on thia apse ies.
Preparation of Test Material: The sample was dosed as received. An individual dose was calculated and weighed out based upon each animal s
b o d y weight at initiation.
@
HAZLETON
tjmp ca Ksc
Chemical & BloMadlcal Science Division
_3 S _,, K IN S M A N B!LVuDn. . DP-nO. BO X 7545 . M A D ,S O N , W .S C O N S .N 53707 P H O N E .oa, 241-4471 . T L X 7 0 3 .5 . H A Z R A L O S D
SAMPLE NUMBER: 70905393 SAMPLE: T-4101
OECD DERMAL SCREEN
(CONTINUED)
PAGE
pi t q last tape fnd !hS b^ckl er. JEt- S:P5 ~ S - S T - T
during the 24-hour
Twenty-four hours later the bandages were removed washbd ,, u h lukaar. tap uatar and uipad m t h d.apaa-
C o n . r a u.r. appliad ta r.a.r.in ,h. t.at a m n . ! .
exposure period.
R e a s o n for R o u t e of Administration: H i s t o r i c a l l y , th is is the ro u t e of choice based on the method of Draire.
Observations: Each animal was observed for clinical signs and mortality 1 n c .,,cl a h o u r s a f t e r test m a t e r i a l a d m i n i s t r a t i o n . T h i r t y e'ter ^amovi! of the test material the initial dermal rr.ta .on
:::x ;;
s u b s e q u e n t r e a d i n g s of d e r m a l rr,r
on S t u d y D a y s 3, 7, 10 an d 14. The a n i m a l s w e r e o b u r i a d d. iJv Jor
clinical signs and twice daily (morning and afternoon) for "'tality. The an t m a l s were w e i g h e d just pr i o r to test m a t e r i a l a p p l i c a t i o n , at
7 d a y s and at s t u d y t e r m i n a t i o n .
Pathology: At st u d y te rmination, all an i m a l s w e r e e u t h . n . t i s e d , s u bj ec te d
to a gross n e c r o p s y ex a m i n a t i o n and all a b n o r m . 111 i.s war. recorded. After necropsy, animals were discarded end 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 r e t a i n e d in the a r c h i v e s of HLA.
HAZLETON
AfweniCA *
Chemical & BloMadlcal Sciences Division
3301 KINSMAN BLVD. . P.O. BOX 7545 MADISON, WISCONSIN 53707 . PHONE (S06) 241-4471 TLX 703*56 H AZhAL MDS UD
SAMPLE NUMBER: 70905393 SAMPLE: T-4101
PAGE 5
OECD DERMAL SCREEN
SUMMARY
(C O N T I N U E D )
Test Animal: Albino Rabbits - New Zealand White Source: Hazleton Research Products, Inc., Denver PA
Date Animals Received: 11/03/87
Method of Ad mi nistration: Dermal Application
Date Test Started: 11/16/87
Date Test Completed: 11/30/87
Estimated Dermal LD50: Male - Greater than 2.0 g/kg of body weight Female - Greater than 2.0 g/kg of body weight
Dose Leve 1 (G / K G )
2.0
0-4 nF
00
1 F
00
MORTALITY SUMMARY __ D a y s ______
9%4
MF MF MF
(NUMBER OF
MF
6 MF
DEATHS)
7-14 MF
Total M F Both
00 00 00 00 00
0 0 0/5 0/5 0/10
A v e r a g e B o d y W e i g h t s (g)
Initial
Day 7
Terminal
Male Female
2209 2130
2275 2038
2495 2194
Cl in ica 1 S i g n s (No. of A n im al s Affected)
H o u r s ----1.0 2.5 4.0
Devs 78
10 11 12 13 14
Males (2.0 g / k g )
Appeared Normal 5
5 55555
Females (2.0 g/kg)
Appeared Normal
Few feces H y po ac t ivi ty Loss of
appet ite Thin appearance
5 555532111 0 000012334 0 000023333
0 0
o0 o0 o0 o0 o0 o1 o2 o2 o3
111 444
33
333 000
Comments: Dermal irritation observed during the study consisted of slight to m o d e r a t e e r y t h e m a and ed e m a and s l ig ht a t o n i a and d e s q u a m a t i o n .
2 1 3
1 1
HAZLgTOfM
3301 KINSMAN BLVO. P O. BOX 7546 MADISON. WISCONSIN 53707
Chemical & BloMedieal Sciences Division
P H O N E (60S) 241*4471 T L X 703956 H A Z R A L M D S UD
SAMPLE NUMBER: 70905393 SAMPLE: T-4101
PAGE
OECD DERMAL SCREEN
PATHOLOGY
(CONTINUED)
Dose Level: 2.0 g/kg of body weight
Anima 1 Number
F20529
Se M
Test Day Died Sacrificed
14
Necropsy Comments
A x i l l a r y ly m p h n o d e s ( b i l a t e r a l ) d i f f u s e l y d a rk red .
F20468 F20516
M M
14 Treated akin - di ffusely thickened.
14 Treated skin - diffusely thickened with subcutaneous tissue under neath the treated skin having multiple red areas, up to 3.5 x 2.5 cm.
F20513 F20515 F20531
M M F
F20519
F
F2O490 F20496 F20569
F F F
14 No visible lesions.
14 No visible lesions.
14 Animal appears thin} ce cu m serosal surface has multiple red areas, up to 0.3 x 0.2 cm; cecum, colon and stomach contain green fluid; perianal stains - green.
14 Tr e a t e d skin - d i f f u s e l y th ic ke ne d with subcutaneous skin under neath the treated skin having mu l t i p l e red areas, up to 1.0 x 2.0 cm.
14 No visible lesions.
14 No visible lesions.
14 No visible lesions.
6
HAZLEtON LAaoMTomes AiweacA use
3301 K IN S M A N B LV O . P .0 . B O X 7546 M A D ISO N . W IS C O N S IN 53707
Chtmical & BloMadlcsl Sciences Division
P H O N E (608) 241-4471 T L X 703956 H A Z R A L M D S UO
SAMPLE NUMBER: 70905393 SAMPLE: T-4101
page
y
OECD DERMAL SCREEN
(CONTINUED)
References:
1. O r g a n i s a t i o n for E c o n o m i c C o o p e r a t i o n a n d D e v e l o p m e n t ' s G u i d a i m e for Testing of Chemicals, Section 402, Acute Dermal Toxicity, Adopted May 12, 1981.
.2 D r a i z e , J . H . , " A p p r a i s a l of th e S a f e t y of C h e m i c a l s in F o o d s , D r u g s , and C o s m e t i c s - De rmal T o x i c i t y " , A s s o c i a t i o n of Food and D r ug O f f i c i a l s of the U.S., pp. 46-5 9 (1975).
3. O E C D P r i n c i p l e s of G o o d L a b o r a t o r y P r a c t i c e , A n n e x 2, C ( 8 1 ) 3 0 ( F i n a l ) 4. N I H P u b l i c a t i o n No. B 5 - 2 3 ( r e v i s e d 1 9 8 5 ) .
HLA LA NO. 7U9053yj PATHOLOGY REPORT Acute Dermal Toxicity
PAGE 8
Ten rabbits (five males, five females) were eutnanatized and necropsied at tne
termination of tne study. The dose level, day of deatn, and gross oDservations recorded for each animal are on page 6 of tnis report. Tne treated sxin of tnree raooits was diffusely tnicxened; two of tne tnree nad multiple red areas in the subcutaneous tissue. All otner observations were
considered incidental findings unrelated to treatment.
Pathologist (1734mcs)
Date1
Personnel Signature Sheet Acute Toxicology
HLA 0. 7 M C S
BUI
Job T 1 t H
Becky Beckwith Stovo Soloungy Ron Bridges Pat Crary
Sr. lab. Animal Asst. Lab. Anlaal Asst. Sr. Lab. Anlaal Asst. Sr. U b . Anlaal Asst.
Shan* E1th Shawn Frazlor Stovon N. Ginza Nolly Halm Ravin Hamilton
Lab Anlaal Asst. Lab Anlaal Asst. Group Loader Adaln. Clark U b . Anlaal Asst.
Jeff Hicks Calvin Horton Sharon L. Hawary Gregory Johnson Paul krahs Wayne M M 1son
Sr. Lab. Anlaal Asst. ftroop Loader Adalbistrativa Asst. Lab. Anlaal Tech. Lab. Anlaal Asst. Section Supervisor
Scott HcConnall
Lab. Anioni Tech.
Shallay HcConnall Dawn Conant
Lab. Anlaal Tech. Sr. Lab. Anlaal Asst.
Don Navis
Lab. Anlaal Asst.
Robin Olson Patricia Padgbaa Joseph J. Dean
Lab. Anlaal Asst. Teas Lander Lab. Anlaal Asst.
Nlchaal Patzfcn John Poolson
Lab. Anlaal Asst. Sr. Lab. Anlaal Asst.
Jana Polnow
Lab. Anlaal Tech.
Dennis B. Stalnar Lab. Anlaal Tech.
Nlchaal Tlmslity
U b . Anlul Asst.
Paula 6. Vangan Albert Olson
Administrative Asst. Manpower
J1n Jlrschele
LTE
Ben Haley
Sr. Lab Animal Asst.
Eileen M. McConnell Adnrin. Clerk
Annette R. Turner Manpower
Signatura /H. i rfk.,L ~lja
I nalili (HK
HU: --,-r a -r --yO ' ACUTE DERMAL APPLICATION LDS0 ih NEW ZEALAND WHITE RABBITS
Test Material: T - *tlO I. Physical Description: Dosage Level (g/R9>: Date Animal Received:
Vehicle: A lDSaoituaer&ce^':i""Hlaz^il*eCutloninnpipReed"s:e*a.r'c/Tf;hnt/i,iP<iiri/oi*ao-iu?cts...
--- 3 1 -
,,l,,ec,,nmMcoia.n: Room "0 ..
-lb'- . 11 )
''
Ap ''1" 1 Rnv weions.
j 5icin
Sex -- 5--
------ h -- n--
i="7. r>^3Q X
( p j 2 iS 2l _22lC. ..34QGL
nMiiP O^lia
X -c
(T ^ 2 3 i L .3313- _ 2 i S S _ <r JU122. aLi^_
Ofti'R,
X X
(f &
aua. _2ax3 _ a a Q L GiRetorrddlAa e o r
S
1: X-
9 \2Cfil-- i t 1-1 ? flUQ- _lML
TVft-Ao*MMa> affli
Hooet
b o o m --
noQP nv%>
X X
? Si 3Q-. jlihL.
-to 0DDM?*lbV6
9 <S|la1_ j q s _ - 2 2 5 C - iV-Z'WS'l.
> -c
J23S- a o a A09et>-WAA TSJDAMFIWC.
A*. fife-
Scale Used________
'flu V
7a.
. _ m L . jj-zaa.
73&_
Vt-ZA-W*
1 - inxicx
,^ .
A - Abraded (with a clipper blade)
Reviewed By iO*a(00261/vmt)
nt* /cQ . - U & 7
Test Material: T ' 4101
MORTALITY REpORO
Hose level: n?. Oj / Kj
HLA:_!2j
HLA: i M O S M ?
OBSERVATIONS (Individual)
Dose level: ,-C7. O ^ / A r . ____________________ Tesl Material: J . r A t O L
Anlaal Hmbtr
.Ye ^
Observations__________
Predose
__ Hours 1_____,_____
study Da
_ L ?r?
4 _L
2i
3
JL
UL
7 r7
i z
z
jO _z
n
nO 1
r^*1 -- --
--
-- .
--- - ___
LU U llI'lIEIlgl
12
y Z "7
L, je ! z z H Z
JL
13 z;
14 . "Z "
UL _____ " 7 "7 r >s
et-
fZ -
Appeared Nonna 1 _
0SH
fl~ '1--j ' J i n i T i ' M i j i O S 13
2y ----
z_
1 .2
---
z 7" 7
'
2zz
"7 HZ
Surviving animals submitted for terminal necropsy. Technician
Oate ,jjI z J a ?
** _ _
lZ 2 z z
-k^
~ -- -- ----
t _l
!
Surviving anlauls designated for sacrifice and discard. Technician Lift_______
** ___ hlfl____________
n05/5
Appeared Normal
z
j2 z z
~ 'y
Z"
" -- .--
~"KS=
_ -- __
-- -- -- __ __ -- ____
---- -- --
--
~ -
---- ---- --
Tenths
""" mmt M l MM
Collected bv
r TM i r d r ^ r n n M ? a r ? n i r i r . i ( : i r . T i TM r / 7 m VTfifl R 1
i i i s ______________ IM Z.
Dfi ^ r a v/g ir n ctt h s i Uffl r o s i
M ft * K^orr fWiacaatt x 8 M/3o/Q7
Indicates condition exists
SI Slight. - Condition not evident. * found dead, P.N. check.
Reviewed by: OfeQ Oate: t Q b f t f
Dose level: c-.j/Kcj Nale/feele)
OBSERVATIONS ( Individual)
Jest aaterlal:
___________
HLA: 7. VQg. fi-,
Surviving antaals
subaitted for tornino I necropsy. Technician j(f6_____
wA '
Surviving onlaals designated for sacrifice and discard.
Tpchnldan O A ________
Date
.Ufl
JllL W M m %M' RWMliflFCflE*EJTEg b51B5OlVJiVmBRIll'c'q
(URttvrJ-n. error tSAu/nfr. .1/3*16-7
Indicates condition eitsts
SI Slight. - Condition not evident. * Found dead, P.N. check.
Reviewed
Date: _|fl&R i t t
Test auterlal: D o lovoi: J.ri tkr.
ACUTE DERMAL IRRITATION OBSERVATIONS
HLA: -l^, S l o t
!_________ m i
A . A_____________ 51112_________________
JJL
1
"/at, ,V*3C
Fetaales
uA :i j ' i U
10 "Ul
1 14 'A
1
Animi 1 No.: F2-0SJS m a d / A b r a d e d J___Animal No.: F i - o i Uitacl/Aradftd
Erythema_______ ._J______ I__
Edema
t/
Atonla_________ __ Q__ 0
1 1
/ t o
1. a1 o0
A 1 <4 D ! 1 11 O0A<
Pesouamatlon
-- __ Q
o
O
0
0 D 0 OA
Coriaceousness F1ssur1no
n n
o a o ri o O fi __ __ __ 2 __ ____ ___ __ ______ Ci_____A __
ri
r> a
__ "
1 Animal No .:Fi .q m u ? fntthbraded 1 Animal No. :
Ibraded
Erythema
_ l ___ 1
1'
Q
1
/O
AO
Edema___________ -XI__
Atonla__________ - ___
Pesouamatlon
- ___
ft o o
& ri o
O o
oo o
on
O Ci /> O
oO
/T O
D /O
o
Coriaceousness F1ssur1na
0o
o
oA
oo
o,,
0 _ _ ___ o ___ ____o __ __ ___ O __ __r~> C> o
Animal No.rfa-osiu fnuS/Abraded
Erythema
_ jS___ 1 J 1
1
i i w ___________ Atonla
S.___ - ___
1 O
-1 A
Desquamation
_i2___ n
ft
Coriaceousness - ___ -- __ r>
F1ssur1no
-- __ __
/ ri o r> o n /S
__ ___ ___
Anlaml No. :FZ.-OW?
1 /n o oo n oA n ot ri O O
n (S
]5taS/Abrdd r> C- n
OA OA O ri O "V
Erythema Edema Atonla
Pesouamatlon Coriaceousness F1ssur1no
Animal No.:P2.-n;i^ rnMgfr Abraded
-- L___ / Q/
1 "/ oo
1 o
nn
ri o ft
0 o r> o o
- Q ___ n ri O A
o __ __ fi__ __ ____
Animal No.: n .-rylol ntitJi'A braded
.3 D 1 rs 1 O
1----
1o
o
O
-z--
rs
o
ts
A
r? r\ rt
o
A n r> O o
____ o A r> o
Anima
Erythema________ 1
Edema
_i
No.: r !
n - os is rntact>Abraded 1 fn O 0n
-anil__________ -Q _ ___ ri
o
Pesouamatlon
-____
_ Q ____ D
Ci
Coriaceousness F1ssur1na
J2____ n
-fOi___
____ 9 0
-l O
Technician
lS '
y
jiaia______la o _ . M . M -- H/J3 /
AMaul No.rfZ-ns* i
> a l i /
1 9 tO
r o A Ci
A oA
0
oA
n
UHI.es*
-J____
CM
traded fJ
A
r.
w^i^m ' R iy
A - Subcutaneous hemorrhage. B - Blanching.
C - Scab formation. D - Eschar.
E - Exfoliation.
Qftttorl.y errors'B 'iu/f? Reviewed by:_QjQ_______
Date: /<!/,,fi7
inn?^i/wdifi
HU:
SCALE FOR SC0RIN6 ACUTE DERMAL REACTIONS
ERYTHEMA
0 - Non 1.0 - Slight 2.0 - Moderata (wall defined) 3.0 - Severe (beet red)
0 - None 1.0 - Slight (barely perceptible to well defined by definite
raising) 2.0 - Moderate (raised approximately lae)
3.0 - Severe (raised more than 1 ami)
ATONIA
0 - None 1.0 - Slight (slight Impairment of elasticity)
2.0 - Moderate (slow return to normal) 3.0 - Marked (no elasticity)
DESQUAMATION
0 - None 1.0 > Slight (slight scaling) 2.0 - Moderate (scales and flakes) 3.0 - Narked (pronounced flaking with denuded areas)
CORIACEOUSNESS
0 - None 1.0 - Slight (decrease 1n pliability) 2.0 - Moderate (leathery texture) 3.0 - Narked (tough and brittle)
FISSURIMO
0 - None 1.0 - Slight (definite cracks 1n epidermis) 2.0 - Moderate (cracks 1n dermis) 3.0 - Narked (cracks with bleeding)
(00261/vmt)
