Document EvbqBNxVaGOpgyqa96LN5dqag

HAZLETON< * UABOPW CTDRIES A f W C A . IN C Chemical & BioMedical Sciences Division ` 3301 KINSM AN BLVD. P.0. BOX 7545 MADISON, WISCONSIN 53707 PH O N E (608) 2414471 TLX 703956 H A Z R A L M DS UD FTKII R E P O R T R O G E R G. P E R K I N S MINNESOTA MINING & MANUFACTURING TOXICOLOGY SERUICES ST. P A U L , MN 55101 COMPANY SAMPLE: T-4016 PURCHASE ORDER NUMBER: T837389-410 712 SAMPLE NUMBER: 70100354 SAMPLE ENTERED: 01/07/87 REPORT PRINTED: 02/26/87 ENCLOSED: P R I M A R Y D E R M A L I R R I T A T I O N S T U D Y IN R A B B I T S - M E T H O D , S U M M A R Y RALJ D A T A A P P E N D I X SIGNED: S T E U E N M. G L A Z A STUDY DIRECTOR ACUTE TOXICOLOGY ...... i n t t & r . ' & r S ? . DATE So *1-'V V ST BY AND FOR H A Z L E T O N L A B O R A T O R I E S A M E R I C A , INC. RAW DATA FOR THIS STUDY ARE KEPT ON FILE AT HAZLETON LABORATORIES AMERICA, INC., MADISON, WISCONSIN. <i*f--,,*. 'VS'L HAZLETON LABORATORIES AMERICA. IISC Chemical & BioMedical Sciences Division 3301 KIN SM AN BLVD. P.0. BOX 7545 MADISON. W ISCONSIN 53707 PH O NE (608) 241-4471 TLX 703956 H A Z R A L M DS UD SAMPLE NUMBER: 70100354 SAMPLE: T-4016 PRIMARY DERMAL IRRITATION Objectl^e: To d e t e r m i n e the relative level of p r i m a r y skin irritation of a test m a t e r i a l on rabbits under o c c l u d e d c o n d i t i o n s a c c o r d i n g to the F e d e r a l H a z a r d o u s S u b s t a n c e s Act R e g u 1at i o n s . Test Material: T-4016 Physical Description: Purity and Stability: Thick brown liquid Sponsor assumes responsibility for purity and stability determinations. 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 a n d h u m i d i t y - c o n t r o l l e d 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 urn and a m e a s u r e d 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. Three male and three female a c c l i m a t e d a n i m a l s , w e i g h i n g from 2 4 1 4 g to 2 7 3 8 g, w e r e c h o s e n at r a n d o m for the test, t r e a t e d , a n d m a i n t a i n e d d u r i n g S h e observation period as s p e c ified for the acclimation period. Test animals were identified by animal number and c o r r e s p o n d i n g ear tag. Approximately twenty-four hours before treatment the hair was clipped from the back and flanks of each animal. Reason for Spe c i e s Selection: H i s t o r i c a l l y , the New Zealand White albino rabbit has been the animal of choice for e v a l u a t i n g the effect of chemicals on the skin. Preparation and Administration of Test Material: received. The pH was not determined. The sample was dosed as Treatment: Just before the test material was applied, c r i s s c r o s s epi d e r m a l a b r a s i o n s w e r e made on one e x p o s e d a r e a of e ach rabbit to p r o v i d e one abraded and one intact test site. (The abrasions were sufficiently deep to p e n e t r a t e the s t r a t u m c o r n e u m , but not d e e p e n o u g h to p e n e t r a t e to the dermal layer and cause bleeding.) T h e test m a t e r i a l w a s a p p l i e d to th e t w o t es t s i t e s on e a c h r a b b i t in the amount of 0.5 ml per site. E a c h t r e a t e d a r e a was c o v e r e d w i t h a 5.0 x 5.0-cm gauze patch secured with paper tape and overwrapped with S a r a n W r a p a n d t l a s t o p i a s t t a p e to m a i n t a i n the t e s t m a t e r i a l in c o n t a c t with the skin and decrease the rate of evapor a t i o n . Collars were used to r e s t r a i n the test a n i m a l s d u r i n g the 2 4 - h o u r e x p o s u r e period. Reas o n for R o u t e of A d m i n i s t r a t i o n : based on the method of Draize. H i s t o r i c a l l y , the route of choice -VSs LA B O FW D R 'ES AMEPUCA. "SC Chemical & BioMedical Sciences Division 301 KIN SM AN BLVD~"* P.O. BOX 7545 MADISON. WISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 H A Z R A L MDS UD SAMPLE NUMBER: 70100354 SAMPLE: T-4016 PRIMARY DERMAL IRRITATION (CONTINUED) Ob s e r v a t i o n s : After the exposure period, the patches were removed. The test material was removed with acetone and then the test sites were washed using lukewarm tap water and d i s p o s a b l e paper towels. Care was t a k e n to r emove the test m a t e r i a l as t h o r o u g h l y as p o s s i b l e w i t h o u t irritating the skin. Thirty minutes following removal of the test mat e r i a l , the degree of erythema and edema was read D r a i z e t e c h n i q u e . A s e c o n d r e a d i n g was t a k e n at 72 the primary dermal irritation index for the sample, vat io ns w e r e c o n d u c t e d at 96 h o u r s , a n d at 7 a n d l<* a c c o r d i n g to the h o u r s to d e t e r m i n e Additional obser- davs . I n d i v i d u a l b o d y w e i g h t s w e r e t a k e n just p r i o r to s t u d y i n i t i a t i o n and at w e e k l y i n t e r v a l s t h r o u g h o u t the s t u d y pe r i o d . 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 were e u t h a n a t i z e d and d i s c a r d e d . HAZLETON LABORATORIES AMERICA. INC 3301 KIN SM AN BLVD. P-O. BOX 7545 MADISON, WISCONSIN 53707 Chemical & BioMedical Sciences Division PH O NE (608) 241-4471 TLX 703956 H A Z R A L MDS UD SAMPLE NUMBER: 70100354 SAMPLE: T-4016 PRIMARY DERMAL IRRITATION (CONTINUED) SUMMARY Test Animal: Albino Rabbits - New Zealand White Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 12/16/86 Date Test Started: 01/08/87 Date Test Completed: 01/22/87 Primary Dermal Irritation Scores * Observation Period 24 Hours 72 Hours 96 Hours 7 Days: 14 Days : 6 Rabbit Mean 2.0 1.8 1.4 0.7 0. 0 Primary Dermal Irritation Index**: 1.9 * The P r i m a r y D e r m a l I r r i t a t i o n S c o r e is the t o t a l d e r m a l i r r i t a t i o n s c o r e for all the animals (erythema and edema) divided by the number of test s i t e s (12) at e a c h o b s e r v a t i o n p e r i o d . * * T h e P r i m a r y D e r m a l I r r i t a t i o n I n d e x is the s u m of the 2 4 a n d 7 2 - h o u r p r i m a r y dermal i r r i t a t i o n s c o r e s , d i v i d e d by two and r o u n d e d to the nea rest ten th . Commen ts : Tape or mechanical irritation was o b s e r v e d on the test sites of two animals u n e a n i m a l e x m b i t e d s u b c u t a n e o u s h e m o r r n a g i n g w i t h i n D o t h test s i t e s at 24 hou r s and w i t h i n the a b r a d e d test s i t e at 72 and 96 hours. Sl i g h t s c a b f o r m a t i o n was o b s e r v e d w i t h i n the a b r a d e d test s i t e of this a n i m a l at D a y 7 C o n c l u s i o n : A c c o r d i n g to F H S A r e g u l a t i o n s , t h i s t es t m a t e r i a l is not a primary skin irritant. HAZLETON LABORATORIES AMERICA. INC 3301 KINSM AN BLVD. P.O. BOX 7545 MADISON, W ISCONSIN 53707 Chemical & BioMedical Sciences Division PH O NE (608) 241-4471 TLX 703956 H AZR AL MDS UD SAMPLE NUMBER: 70100354 SAMPLE: T-4016 PRIMARY DERMAL IRRITATION (CONTINUED) Re f e r e n c e s : 1. C o d e of F e d e r a l R e g u l a t i o n s , T i t l e 16 S e c t i o n 1 5 0 0 . 3 : F e d e r a l H a z a r d o u s S u b s t a n c e s Act R e g u l a t i o n s , pp. 3 2 5 - 3 4 2 , ( J a n u a r y 1, 1 9 8 5 ) . 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 Cosmetics - Dermal Toxicity", Association of Food and Drug O f f i c i a l s of the U.S., pp. 4 6 - 5 9 (1975). 3 21 CFR 58 (United States Food and Drug A d m i n i s t r a t i o n ' s Good Laboratory Practices Regulations for N o n c l i m c a l L a b oratory Studies) 4. D H H S P u b l i c a t i o n No. ( N I H 8 5 - 2 3 1985) G u i d e for the C a r e a n d U se of Laboratory Animals. 7 0 i O 2>tD H ' PRIMARY SKIN IRRITATION SCORING SCALE (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 in depth) Highest possible erythema score 0 1 2 3 4 (2) Edema Formation No edi-- _ 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 o o M lH AH t DfcUlAL IM IT A I IO* ITU M o x VVi a V ^ v t L ' . rtx e t n- Y- f t ? > r4ct^ O n ^ouina.