Document rejBpg8303vew2kyG9vd63dMe
HAZLETON LABORATORIES AM ERICA. INC.
/W U2C -0331
Chemical & BioMedical Sciences Division
3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD
$ EST COPY AVAILABLE
FINAL REPORT
R O G E R G. P E R K I N S MINNESOTA MINING & MANUFACTURING TOXICOLOGY SERUICES ST. PAUL f MN 55101
COMPANY
SAMPLE: T-4102 PURCHASE ORDER NUMBER; T837389-410 754
SAMPLE ENTERED: 09/25/8: REPORT PRINTED: 01/21/81
ENCLOSED:
P R I M A R Y D E R M A L IRRI TA T I O N / C O R R O S I ON S T U D Y IN R A B B I T S (OECD GUIDELINES)
o Key Personnel o Method o Summary o References o Raw Data Appendix
S IGNED
S T E U E N M. G L A Z A STUDY DIRECTOR
ACUTE TOXICOLOGY
..........\ r > . V X ? DATE
000564
H A Z L E T O N LABORATORIES AMERICA, INC.
Chemical & BioMedical Sciences Division
3301 KINSMAN BLVD. P.0. BOX 7545 ' MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD
S A M P L E N U M B E R : 7 G 9 0 5 7 63 SAMPLE: T-4102
PARE
2
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KEY PERSONNEL
Acute Toxicology
S t e v e n M- G t a z a Study Director
C a l v i n L. H o r t o n Group Leader Support Services
S h a r e n L. H o w e r y Report Coordinator
Quality Assurance Debra Curley Arndt Manager
Laboratory Animal Veterinarian C i n d y 3. C a r y , D U M Diplomats, ACLAM
000565
H A Z L E T O N LABORATORIES AMERICA. INC.
Chemical & BioMedical Sciences Division
3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD
S A M P L E N U M B E R : 7 0 9 0*5763 SAMPLE: T-4102
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OECD DERMAL IRRITATION
Objective: To determine the relative level of p r im ar y skin irritation/ corrosion of a test substance on rabbits under semioccluded conditions a c c o r d i n g to the 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 Guidelines for Testing Chemicals.
Test Material: T-4102 Physical Description: Purity and Stability:
Storage and Retention:
Safety Precautions:
Dark amber liquid Sponsor assumes responsibility for
purity and stability determinations. The test mate ri al was st o r e d at room temperature. Any unused material will be discarded according
to HL.A S t a n d a r d O p e r a t i n g P r o c e d u r e . Normal handling procedures were used according to H L A S t a n d a r d O p e r a t i n g Pr oc ed ur e.
Test Animal: Young adult rabbits of the New Zealand White strain were procured,, 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 led q u a r t e r s , p r o v i d e d a c c e s s to w a t e r ad l i b i t u m 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 d a y s . A n i m a l h u s b a n d r y a n d h o u s i n g
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 t h e " G u i d e f o r t h e C a r e a n d Lise o f 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 t h e p r e s c r i b e d e n v i r o n m e n t a l c o n d i t i o n s exis te d, they were d o c u m e n t e d and c o n s i d e r e d to have no effect
on the s t u d y outcome. No c o n t a m i n a n t s were e x p e c t e d to ha ve be en present in th e 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 or a f f e c t e d the results of the study.
Three a c c l i m a t e d animals, w e i g h i n g fr om 2202 to 2 3 2 3 g , were ch os en at r a n d o m for the test, t r e a te d, and m a i n t a i n e d d u r i n g the o b s e r v a t i o n period as specified for the acclimation period. Test animals were identified by animal number and co rr es p o n d i n g ear tag. A p p r o x i m a t e l y twenty-four hours before treatment the hair was clipped from the back o f e a c h a n im a 1.
Reason for Species Selection: Historically, the New Zealand White albino rabbit has been the animal of choice for evaluating the effect of chemicals on the skin.
Pr e p a r a t i o n and Administrat ion of Test Material: received. The pH was d e t e r m i n e d to be 9.1.
The sample was dosed as
000566
H A Z L E T O N LABORATORIES AM ERICA, INC.
Chemical & BioMedical Sciences Division
3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD
SAMPLE NUMBER: 70905763 SAMPLE: T-41Q2
COPY AVAILABLE
4
O E C D DERMAL. IR RITATION
(CONTINUED)
T r e a t m e n t : The test m a t e r i a l wa s a p p l i e d to the intact s k i n of e a ch r a b b i t in the a m o u n t of 0.5 ml. T he t r e a t e d a r e a w a s c o v e r e d w i t h a 2.5 x 2.5-cm gauze patch secured with paper tape and overwrapped with Sa ra n Wr ap and El as to p l a s t tape to p r o v i d e a s e m i o c c l u s i v e dressing. C o l l a r s w e re a p p l i e d to r e s t r a i n the test a n i m a l s for the 4 - h o u r e x p o s u r e
period.
Reason for Route of Administration: based on the method of Draize.
Historically, the route of choice
Ohservat ions: After the exposure period, the patches were removed. The
test sites were washed using lukewarm tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. Thirty minutes following removal of the test material, the de gr ee of erythema and edema was read a c c o r d i n g to the Dr ai ze technique. S u b s e q u e n t e x a m i n a t i o n s were ma de at 24, 48 and 72 ho urs af te r pa t c h removal.
Individual b o d y we ig ht s were taken just pr io r to s t u d y initia tion.
P a t h o l o g y : At s t u d y t e r m i n a t i o n all a n i m a l s we re e u t h a n a t i z e d and discarded.
Statistical Methods: Other than average dermal irritation scores, no other statistical method was performed.
Location of Raw Data and Final Report: The raw data and a copy of the final r e p o r t w i l l b e r e t a i n e d in t h e a r c h i v e s o f H L A .
000567
H A Z L E T O N LABORATORIES AMERICA, INC.
Chemical & BioMedical Sciences Division
3301 KINSMAN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD
SAMPLE NUMBER: 70905763 SAMPLE: T-4102
BEST COPy AW!f
PAGE
5
OECD DERMAL IRRITATION
(CONTINUED)
SUMMARY
Teat Animal: Albino Rabbits - New Zealand White Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 10/20/87
Date Test Started: 11/02/87
Date Test Completed:
11/05/87
A n im a 1. Nu mb e r Sex
F20309 F20349 F20311
M F M
Mean
IN D IU ID U A L D E R M A L I R R I T A T I O N S C O R E S
Erythema
Ederna
Ho urs 4 24 48 72
Hou rs 4 24 48
1111 0000 0111
101 000 000
0.3 0.7 0.7 0.7
0.3 0.0 0.3
72
0 0 0
0- 0
PRIMARY DERMAL IRRITATION SCORES *
Ob serva t ion Period
3 Rabbit Mean
4 Hours: 24 Hours: 48 H o u r s :
72 Hours:
0.7 0.7 1.0 0.7
T h e P r im a r y D e rma 1 I r r i t a t i o n S c o r e is th e t o t a l d e r m a 1 i r r i ta t io n s c o r e f o r all th e an ima Is ( e r y t h e m a a n d e d e m a ) d i v i d e d b y the n u m b e r of t e s t
s i t e s (3 ) at e a c h o b s e rva t ion p e r i o d .
000568
H A Z L E T O N LABORATORIES AMERICA. INC
Chemical & BioMedical Sciences Division
3301 KINSMAN BLVD. P.O. BOX 7545 MADISON, WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 HAZRAL MDS UD
S A MP LE NUMBER: 7(1905763 S A M P L E : T - 4 1 02
BEST COPY AVAILABLE PAGE 6
OECD DERMAL IRRITATION
(CONTINUED)
Re fe renees :
1. O r g a n i s a t i o n f o r 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 e l i n e s for Testing of Chemicals, Section 404, Acute Dermal Irritation/ C o r r o s i o n , a d o p t e d May 12, 1981.
2. O E C D ' s 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 (Final
3- D r a i n e , J . H . , " A p p r a i s a l of the 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 Cosmetics - Dermal Toxicity", As sociation of Food and Drug Officials of the U.S., p p . 46-59 (1975).
4. N I H P u b l i c a t i o n No, 8 6 - 2 3 ( r e v i s e d 19 85 ).
000569
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Personnel Signature Sheet Acute Toxicology
HLA MO. lC'9C<Sl(j>3
ms.
Job Title
SlJPfttgre
Initials
Becky Beckwith
Sr. Lab. Animal Asst.
Steve Beloungy
Lab. Animal Asst.
Ken Bridges Pat Crary
Sr. Lab. Animal Asst. Sr. Lab. Animal Asst.
Shane E1th
Lab Animal Asst.
Shawn Frazier
Lab Animal Asst.
Steven M. Glaza
6roup Leader
Nolly Hahn
Admin. Clerk
Kevin Hamilton
Lab. Animal Asst.
Jeff Hicks
Sr. Lab. Animal Asst.
Calvin Horton
Group Leader
Sharen L. Howery Administrative Asst.
Gregory Johnson
Lab. Animal Tech.
Paul Krebs
Lab. Animal Asst.
Wayne Nadlson
Section Supervisor
Scott McConnell
Lab. Animal Tech.
Shelley McConnell Dawn Conant
Lab. Animal Tech. Sr. Lab. Animal Asst.
Don Navis
Lab. Animal Asst.
Robin Olson
Lab. Animal Asst.
Patricia Padgham Joseph J. Daun
Team Leader Lab. Animal Asst.
Michael Patzka
Lab. Animal Asst.
John Paulson
Sr. Lab.' Animal Asst.
Jane Polnow
Lab. Animal Tech.
Dennis B. Steiner Lab. Animal Tech.
Michael Theslng
Lab. Animal Asst.
Paula 6. Vangen Albert Olson
Administrative Asst. Manpower
Jim Jirschele
LTE
Ben Haley
Sr. Lab Animal Asst.
Eileen M. McConnel Admin. Clerk
Annette R. Turner Manpower
000570
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DERMAL IRRITATlOH/BOOY WEIGHT RECORD (4-Hour Exposure)
HtA: 1 0 9 0 7 7 7 ( ^ 3
Study l i t l e : M w r > Derm) Irrita tio n
T eil Material:_______ Physical Description:
\-- m O Q . O M a V CLC
U ^ U t cl
*! Rsulti_ 1 1
with Henne Meter Mo. 6690
I W : __ O . S /n<-
P#r SII
Jlolstened with 0.9* Saline
Pale Animals Received: I0 '2 0 ~ % 7 Souarrccee//Sattraln/Specles: Hatleton Research Products/Mow Tmltwl Whlte/Rabblt Room Huadiur: I f a !
TechnicUn/Date Animals Clipped:____ Kfi / 11l/l/fi~7
Iniittiiaatteedd by::_
frS
Patel
7
ShIn Preparation: ^ Intact Aj/? Abraded (with a clipper blade) Reviewed by:
fr=-
Date
Animal Huxd.er/Sex
e T &-03U
Q S aorIn itia l Body Weight (a)
2
>3
Recorded
Technician
by
07
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-- J&_____ - K f t J jZ l - J flp ________
o / -Pay Rudy Weight (a)
o 14 Pay Body Weight (g)
0 il-Pay Body Weight (g)
01
Observation
Per tod
h*
o .C i..1 lluuri rythe"*
/
'S "
\ t O ol ..1 lluuri
Edema Erythema
/
o
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Edema frytbema
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no
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7 Huuri
Edema trfth a M
/1
<7 0 n1
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9b Hours
Edema
Er/TW*ma -w .
0
0
0
s
Dormal Irrita tio n Score
^ Stu. IH H O
S*/. 0.1 nP USAl ^ site \ | -^ 0
"-3 071 fP tf-S-V
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? Due
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Erythema EdeiM
.
\ \ h.
1 1 Paul Erythema
-I Due
Edema Erythema
[s ,,
Edema
HA Not applicable.
A - Subcutaneous hemorri^i.
8 - Blanching.
'
N - Possible necrotic area.
U - Unable to determine pH.
A ll animals appeared normal just prio r to dosing.
Tec!nHclM^/!^^Datir^7~P~0 7
Surviving animals designated fo r sa c rific e and discard. Technician V-- Date f t ~.< r - J 2
Data reviewed by:
_________ Date;
(llll.'h |/v ll )
w)(2>wfe tsfvrg TEtEb tr H/a/QT
HLA: 7 0 9 0 5 7 ^
PRIMARY OERMAL IRRITATION SCORING SCALE (DRAIZEl TECHNIQUE)
(1) .Erythema and Eschar Formation
No erythema Very slight erythema (barely perceptible) Well-defined erythema Moderate to severe erythema Severe erythema (beet redness) to slight eschar
formation (Injuries 1n depth)
Highest possible erythema score
(2) Edema Formation
No edema Very slight edema (barely perceptible) Slight edema (edges of area well-defined by
definite raising) Moderate edema (raised approximately 1 mm) Severe edema (raised more than 1 mm and
extending beyond area of exposure)
Highest possible edema score
0 1 2 3 __4
4
0 1 2
3 4
4
1 Dralze, J. H.t "Appraisal of the Safety of Chemicals In Foods, Drugs, and Cosmetics - Dermal-Toxicity." Association of Food and Drug and Drug Officials of the U.S., pp. 46-59 (1975).
(00261/vmt)
000572
