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US ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND, MARYLAND 21010-5425

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EVALUATION OF EUTHYMIC HAIRLESS GUINEA PIGS [Crl:IAF(HA)BR] AS AN ANIMAL MODEL FOR VESICANT INJURY

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D. Marlow Mershon MillardW.M.Mitcheltree

-""Denver

ju,"I z 1 ,S69

"Larry

John P. Petrali Gerald P. Jaax

May 1.989

Apptovod for public rl.s.

dilttribution unlimrited

US ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND 21 701-5012 FORT CETRICK, MARYLAND

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DISP•ITICH N

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Destroy this report when no longer reeded.

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Do riot return to the originator.

DISCIAIMER The findings contained herein are the private views of the author(s) and are not to be aaxtnrus as official or as reflecting the views of the Anry or the Deparient of Defense. In cactlzq the research deribed in this report, the :Lwestigators adhered to the Okife for the Care and Use of L= torv Animmls, National Irstitutes of I•mth Publicaticon Mtber 85-23. The use of trade naam herein does not Contitute an official ndorsemnt or approval of the use of suh comiercial harrme or softwre. This dcwmnt may not Do cited for purpoes of advertisawnt.

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UNCLASSIFIED SECURITY CLASS1 mm) ...... 3 Eschar formation (necrosis) ......

TABLE 4:

4 Blister formation .................

MEAN GROSS LESION DIAMETER, MEDIAN ERYTHEMA/ESCHAR SCORE, AND MEDIAN EDEMA/BLISTER SCORE AT 24 AND 48 HOURS POST-EXPOSURE IN HAIRLESS GUINEA PIGS. 24 HOURS POST-EXPOSURE

HD DOSE (ul)

4

DIAMETER (3m)

ERYTHEMA/ ESCHAR SCORE

EDEMA/ BLISTER SCORE

48 HOURS POST-EXPOSURE DIAMETER (m)

ERYTHEMA/ ESCHAR SCORE

EDEMA/ BLISTER SCORE

0.05

3.17

3.50

1.00

n/a

n/a

n/a

0.1

5.08

3.00

1.00

n/a

n/a

n/a

0.2

6.75

3.00

1.00

n/a

n/a

n/a

0.4

6.83

4.00

2.00

n/a

n/a

n/a

0.5

8.75

3.50

1.00

8.75

4.00

1.50

1.0

13.50

3.50

1.50

13.62

3.50

2.00

2.0

16.38

4.00

1.50

13.88

4.00

2.00

4.0

19.75

4.00

2.00

17.62

4.00

2.00

ERYTHEMA/ESCHAR SCORE: No errythema .................... Slight erythema

(barely seen)....1

!W-4erate erythema (pink) ......... Severo erythema (beet red) ....... Eachar formation (necrosis) .....

EDEMA/BLISTER SCORE: 0 No edema. ........................ Slight edema (barely seen) ....... 2 Moderate edone (wll defined) .... 3 Severe edema (raised >1 mm) ...... .4 Blister formation ................ 24

2 3 4

1.

lley-Mendoza, C.E.; Bhatti, T.; Bannard R.A.a.; and Casselman, A.A.. ?:ni of Creams for Efficacy Against Mustard. 197th American Chemical Society tional Meeting, Agridcemicals Section, Abstract No. 25., Dallas, TX, April 9- 4, 1989. 2. 3.

Daniel, Wayne W.. Biostatistics: Sci• 3rd Edition, 1983.

A Fturdation For Analysis in the Health

Eisk mp, D.M.W; Verzanivoort, C.A.M.; and Cohen, Z.M..

and Decc tminaticn in Man and Animals. Large Kl. iweg 139, .Ljswijk, ZH. 1973.

Skin Penetration

Medisch Biologisch Laboratorium Inc.,

4. Kmpwey, C.D. zind Pittman, F.E.. A Simple Methylenm Blue, Azure 11, and Basic Fumhsin Stain for Epoxy Embedded Tissue Sections. Stain Techno1oxv, Vol. 49, 1974. 5. McDoell, E.M. and Trump, B.F.. Histologic Fixative Suitable for Di Light ard Electron Microscopy. Arch. Pathol. Lab. Med., Vol. 100, PP. 405414, 1976. 6. Mit _eltree, L.W.; Mershon, M.M.; Wall H.G.; and Pulliam, J.D.. Microbli.s•_r Formation in Vesicant-Exposed Pig Skin. Journal of Toxiciolov auid Ocular Toxicooloy, Vol. 8, No. 3, 1989.

-

7. Natio al Defense Research Committee (NRfC). dhemical Warfare Agents and ft~latad Q ical Problem~s. Vol. 2, Part III, pp. 479-520, 1946. 8. Pap•Jreister, B.P.; Gross, C.L.; Petrali, J.P.; and Meier, H.L.. Pathology u by MUstard Gas in Human Skin Grafted in Athymic Rude Mice. Part II -

Ultrastrtural Chne.

Journal of Toxicol=u - =uAneg= and Ocular

, Vol. 3, No. 4, p. 393-408,

T

1984.

9. Phartgdn Research International, Inc.. Comparative Delayed Contact Hypersensitivity in Haired Versus Hairless Guinea Pigs. M marma.kon Study No. PH 424-EXP-ý67-86, 7 Jul 1987. 10. American Vbterinary Medical Association. 1986 Report of the AVMA Panel on Euthanasia, Journal of the American Veterinary Medical As• m i• , Vol. 188, No. 3, 1P86. 11.

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of Federal Regulaticr. Method of Testin Primary Irritant , 2. II, Part 1500.41, pp. 348-349, 1 Jan 1987.

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