RD-RI39 966 TOPICAL HAZARD EVALUATION PROGRRM OF CANDIDATE INSECT i/iREPELLENTS AI3-3827..(U) ARMY ENVIRONMENTAL HYGIENERGENCY ABERDEEN PROVING GROUND RD J V MADE 03 APR 84

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UNITED STATES ARMYENVIRONMENTAL HYGIENE

AGENCYABERDEEN PROVING GROUND, MO 21010

TOPICAL HAZARD EVALUATION PROGRAMOF

CANDIDATE INSECT REPELLENTSA13-38274. A13-38276, and A13-38279A US DEPARTMENT OF AGRICULTURE PROPRIETARY CHEMICALS

STUDY NOS. 75-51-0417-84, 75-51-0419-84AND 75-51-0421-84

FEBRUARY -NOVEMBER 1983

Approved for public release; distribution unlimited.

UnclassifiedSECURITY CLASSIFICATION OF THIS PAGE (39,.m Dno Aor .

REPORT DOCMENTATION PAGE READ INSTRUCTIONSBEFORE COMPLETING FORM

I. REPORT NUMBER 2. GOVT ACCESSION NO S. RECIPIENT'S CATALOG NUMBER

75-51-0417, 0419, 0421-84 _

4. TITLE (M.swmit.)Topical Hazard Evaluation Program of S. TYPE OF REPORT & PERIOD COVEREDCandidate Ingect Repellents A13-38274, A13-38276, Final, February 1983 -and A13-38279, US Department of Agriculture November 1983Proprietary Chemicals, Study No. 75-51-0417-84, 75- 6. PERFORMING ORO. REPORT NUMBER

51-0419-84 and 75-51-0421-84, February 1983 -November 1483

7. AUTHOR(e) 8. CONTRACT OR GRANT NUMRERi')

John V. Wade, DVM, CPT(P), VC

9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASKAREA & WORK UNIT NUMBERS

CommanderUS Army Environmental Hygiene AgencyAberdeen Proving Ground, MD 21010

i1. CONTROLLING OFFICE NAME AND ADDRESS I&.' REPORT DATE

Commander February 1983 - November 1983US Army Health Services Command -s. NUMBER OF PAGES

Ft Sam Houston, TX 78234 814. MONITORING AGENCY NAME S ADDRE 1sS Eftf. km, comngtr OffI.A) 1S. SECURITY CLASS. (of iffe repet)

Unclassified

IS&. DECLASSIFICATIONIOOWNGRADINGSCHEDULE

IS. DISTRIBUTION STATEMENT (of Sis R*aW)

Approved for public release; distribution unlimited.

17. DISTRIBUTION STATEMENT (of 00. abstact ,teod In Slock , I2 0.t ff t bm pRoiwt)

IS& SUPPLEMENTARY NOTES

19. KEY WORDS (Ciehnc.m .. sde itf eibes oWl dmC&tvl by Meck mmbr)

A13-38274 Skin IrritationA13-38276 Topical Hazard Evaluation ProgramA13-38279 USDA Proprietary ChemicalsEye IrritationPhotochemical IrritationSASTRACT (loon M b MVmi OM by NoWoeS MdII- F60kM=680

"Jhe technical grade chemicals produced no greater than mild primary irritationof the intact skin and of the skin surrounding an abrasion. The 24 percent (w/vsolutions of these chemicals in 95 percent ethanol which were applied duringphotoirritation studies produced mild to moderate primary irritation of theintact skin, without ultraviolet (UV) irradiation. Chemical A13-38276 produceda photochemical irritant reaction upon irradiation with UV light which wassignificantly more severe than the primary irritation previously noted. Addi-tionally, although these ethanol solutions were colorless, they produced a -

P A N 1073 9ION oF NOV 6OSONSTE Unclassified

SECUSITY CLAIEFICATfOW OF THIS PAGE (MM Dt* BiWoe)

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4'.%...

Unclassified9 CUiATY C A IFICATi@N OF THIS PAGEr(IMM Daa fh4)i

20.A/marked yellow discoloration of the skin upon application. All three

chemicals produced moderate injury to the cornea and, in addition,produced some injury to the conjunctiva.,

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4.

Unclassified

*4SECURITY CLASSIPICATION OP THtS PAGE(VIbIn Daee £~nfmtd)

DEPARTMENT OF THE ARMY CPT(P) WADE/orl/AUTOVON584-3627U. t ARMY ENVIRONMENTAL HYGIENE AGENCY

ABERDEEN PROVING GROUND. MARYLAND 21010

KPL TOATTENTION OF

HSHB-OT/IP f APR 1q84SUBJECT: Topical Hazard Evaluation Program of Candidate Insect Repellents

A13-38274, A13-38276, and A13-38279, US Department of AgricultureProprietary Chemicals, Study Nos. 75-51-0417-84, 75-51-0419-84. and75-51-0421-84, February - November 1983

Executive SecretaryArmed Forces Pest Management BoardForest Glen Section, WRAMCWashington, DC 20307

EXECUTIVE SUMMARY

The purpose, essential findings, and major recommendations of the inclosedreport follow:

a. Purpose. The purpose of this program is to provide guidance forfurther entomological testing of the Candidate Insect Repellents A13-38274,A13-38276, and A13-38279 by means of laboratory animal studies using NewZealand White rabbits.

b. Essential Findings. The technical grade chemicals produced no greaterthan mild primary irritation of the intact skin and of the skin surrounding anabrasion. The 25 percent (w/v) solutions of these chemicals in 95 percentethanol which were applied during photoirritation studies produced mild tomoderate primary irritation of the intact skin, without ultraviolet (UV)irradiation. Chemical A13-38276 produced a photochemical irritant reactionupon irradiation with UV light which was significantly more severe than theprimary irritation previously noted. Additionally, although these ethanolsolutions were colorless, they produced a marked yellow discoloration of theskin upon application. All three chemicals produced moderate injury to thecornea and, in addition, produced some injury to the conjunctiva.

c. MaJor Recommendations. Disapprove chemicals A13-38274, A13-38276, andA13-38279 for further testing.

FOR THE COMMANDER:

1 Inc] I C.,GA S. ,.D.as (5 cy) Colonel, MC

Director, Occupational and t,Environmental Health

CF:HQDA (DASG-PSP) wo inclCdr, HSC (HSCL-P)Comdt, AHS (HSHA-P) R I 1.

Dir, Advisory Cen on TOX, NRC (2 cy) TUSDA, ARS (Dr. Terrence McGovern)USDA, ARS-Southern Region (3 cy)Cdr, USAMRDC [SGRD-DPM/LTC(P) Reinert] epic

4 Al0Coo,

Id..

DEPARTMENT OF THE ARMYU.S. ARMY ENVIRONMENTAL HYGIENE AGENCY

ABERDEEN PROVING GROUND. MARYLAND 21010

AKPLV TOATUTON OF

HSHB-OT/WP

TOPICAL HAZARD EVALUATION PROGRAMOF

CANDIDATE INSECT REPELLENTSA13-38274, A13-38276, and A13-38279

US DEPARTMENT OF AGRICULTURE PROPRrETARY CHEMICALSSTUDY NOS. 75-51-0417-84, 75-51-0419-84

AND 75-51-0421-84FEBRUARY 1983 - NOVEMBER 1983

1. AUTHORITY.

a. Letter, US Department of Agriculture - Agricultural Research, SouthernRegion, Insects Affecting Man and Animals Research Laboratory, Gainesville,Florida, 10 February 1983.

b. Memorandum of Understanding between the US Army Environmental HygieneAgency; the US Army Health Services Command; the Department of the Army,Office of The Surgeon General; the Armed Forces Pest Control Board; and the USDepartment of Agriculture, Agricultural Research, Science and EducationAdministrations; titled Coordination of Biological and Toxicological Testingof Pesticides, effective 23 January 1979.

2. REFERENCE. Toxicology Division Topical Hazard Evaluation ProgramProcedural Guide, US Army Environmental Hygiene Agency (USAEHA), January 1982.

3. PURPOSE. The purpose of this program is to provide guidance for furtherentomological testing of candidate insect repellents A13-38274, A13-38276, andA13-38279, US Department of Agriculture (USDA) Proprietary Chemicals.

4. SUMMARY OF FINDINGS. Hazard evaluation of the candidate insect repellentsA13-38274, A13-38276, and A13-38279, USDA Proprietary Chemicals were conductedby this Agency using New Zealand White rabbits for skin, eye, andphotochemical irritation studies. A tabular presentation of animal toxicitydata developed by this Agency follows: *t

* In conducting the studies described in this report, the investigators

adhered to the "Guide for the Care and Use of Laboratory Animals," USDepartment of Health, Education, and Welfare Publication No. (NIH) 80-23,revised 1978.t The studies reported herein were performed in animal facilities fullyaccredited by the American Association for the Accreditation of LaboratoryAnimal Care.

a fr p

hpproval for public release; distribution unlimited. I"II_________________________________________.

Study Nos. 75-51-0417-84, 75-51-0419-84, and 75-51-0421-84, Feb 83 - Nov 83

TABLE. PRESENTATION OF DATA

TEST RESULTS INTERPRETATION

SKIN IRRITATION STUDIES

Rabbits

Single 24-hour application Chemical A13-38279 USAEHA Category Ito intact and abraded skin did not produce (ref Appendix A)of the New Zealand White irritation of therabbits. intact skin and no

greater than mild0.5 mL technical grade irritation of thechemical applied to each skin surrounding anof six rabbits. abrasion. Chemicals.. USAEHA Category II

A13-38274 and A13-38276 (ref Appendix A)produced mild primaryirritation of the

a" intact skin and of theskin surrounding anabrasion.

EYE IRRITATION STUDIES

Rabbits

Single 24-hour application Chemicals A13-38274, USAEHA Category Eof 0.1 mL technical grade A13-38276 and A13-38279 (ref Appendix A)chemical to one eye of produced moderate injuryeach of nine New Zealand to the cornea and, inWhite rabbits. Three of addition, produced somethe nine rabbits had the injury to the conjunctiva.eye flushed with warm waterfor 1 minute, 25 seconds Washing with warm waterafter application, did not significantly

decrease the amountof occular injury noted.

2

Study Nos. 7,5-51-0417-84. 75-51-0419-84, and 75-51-0421-84, Feb 83 - Nov 83

TEST RESULTS INTERPRETATION

PHOTOCHEMIGAL SKIN IRRITATION STUDIES

Rabbits

A single 0.05 mL Chemical A13-38276 Chemical A13-38276application of a 25% (w/v) produced a photo- could produce a

solution of each chemical chemical irritation photochemicalor a 10% (w/v) Oil of reaction under tesT irritation reactionBergamot solution (positive conditions. Chemicals in humans.control) in 95 percent A13-38274 and A13-38279 Chemicals A13-38274ethyl alcohol were applied did not produce a and A13-38279 areto the intact skin of photochemical irrita- not expected tosix rabbits. Five minutes tion reaction. .. produce photochemicalafter application, the Irritation in humans.rabbits were exposed toultraviolet (UV) light(365 nm) for 30 minutes ata distance of 10-15 cm.

Control

Following UV exposure Positive control applicationof the rabbits, 0.05 mL and irradiation resultedof test chemicals, pos- in greater irritant effectstive control and diluent than without irradiation.were applied to additional Ethanol solutions of theskin areas to serve as test chemicals produced mildunirradiated control sites. to moderate primary irritationApplication areas were of the intact skin at the siteschecked for irritation at of applicati-on, both irradiated24, 48, and 72 hours and unirradiated. They also

produced a yellow discolorationof the skin. Irradiation ofchemical A13-38276 followingapplication significantlyincreased the irritant response.

5. CONCLUSION. Technical grade chemicals A13-38274, A13-38276 and A13-38279

produced no greater than mild primary irritation of the intact skin and of the

skin surrounding an abrasion. The 25 percent (w/v) solutions of thesechemicals in 95 percent ethanol which were applied during photoirritationstudies, produced mild to moderate primary irritation of the intact skin,without UV Irradiation. Chemical A13-38276 produced a photochemical irritantreaction upon irradiation with UV light which was significantly more severe

3

_a

Study Nos. 75-51-0417-84, 75-51-0419-84, and 75-51-0421-84, Feb 83 - Nov 83

than the primary Irritation previously noted. Additionally, although theseethanol solutions were colorless, they produced a marked yellow discolorationof the skin upon application. All three chemicals produced moderate injury tothe corneaand, in addition, produced some injury to the conjunctiva. Thesestudies were monitored by the Analytical Quality Assurance Office (seeAppendix B).

6. RECOMMENDATION. Recommend that chemicals A13-38274, A13-38276, andA13-38279 be disapproved for further testing as candidate insect repellents(under the provisions of the Memorandum of Understanding, para lb, thisreport).

e JOHNV. WADE, .DVMCPT(P), VC "

Laboratory AnimalVeterinary Officer

Toxicology Division

APPROVED:

'MARW14. WEEKSChief, Toxicology Division

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Study Nos. 75-51-0417-84, 75-51-0419-84, and 75-51-0421-84, Feb 83 - Nov 83

APPENDIX A

TOPICAL HAZARD EVALUATION PROGRAMDEFINITIONS OF CATEGORIES OF COMPOUNDS BEING

CONSIDERED FOR ACUTE SKIN APPLICATION

CATEGORY I - Compounds producing no primary irritation of the intact skin orno greater than mild primary irritation of the skin surrounding an abrasion.(INTERPRETATION: No restriction for acute application to the human skin.)

CATEGORY II - Compounds producing mild primary-irritation of the intact skinand the skin surrounding an abrasion. (INTERPRETATION: Should be used onlyon human skin found by examination to have no abrasions or may be used as aclothing Impregnant.)

CATEGORY III - Compounds producing moderate primary irritation of the intact, skin and the skin surrounding an abrasion. (INTERPRETATION: Should not be

pused directly on the skin without a prophetic patch test having beenconducted on humans to determine irritation potential to human skin. May beused without patch testinb, with extreme caution, as clothing impregnants.Compound should be resubmitted in the form and at the intended useconcentration so that its irritation potential can be reexamined using othertest techniques on animals.)

CATEGORY IV - Compounds producing moderate to severe primary irritation ofthe intact skin and of the skin surrounding an abrasion and, in addition,producing necrosis, vesiculation, and/or eschars. (INTERPRETATION: Shouldbe resubmitted for testing in the form and at the intended use concentration.Upon resubmission, its irritation potential will be reexamined using othertest techniques on animals, prior to possible prophetic patch testing inhumans, at concentrations which have been shown not to produce primaryirritation in animals.)

CATEGORY V - Compounds impossible to classify because of staining of the skinor other masking effects owing to physical properties of the compound.(INTERPRETATION: Not suitable for use on humans.)

EYE CATEGORIES:

A. Compounds noninJurious to the eye. INTERPRETATION: Irritation ofhuman eyes is not expected if the compound should accidentally get into theeyes, provided it is washed out as soon as possible.

B. Compounds producing mild injury to the cornea. INTERPRETATION:Should be used with caution around the eyes.

C. Compounds producing mild injury to the cornea, and in addition someinjury to the conjunctiva. INTERPRETATION: Should be used with cautionaround the eyes and mucosa.

0. Compounds producing moderate injury to the cornea. INTERPRETATION:Should be used with extreme caution around the eyes.

E. Compounds producins moderate inJury to the cornea, and in additionproducing some Injury to the conjunctiva. INTERPRETATION: Should be usewith extreme caution around the eyes and mucosa.

F. Compounds producing severe injury to the cornea and to theconjunctlva. INTERPRETATION: Should be used with extreme caution. It isrecommended that use be restricted to areas other than the face.

A-1

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Study Nos. 75-51-0417-84, 75-51-0419-84, and 75-51-0421-84, Feb 83 - Nov 83

APPENDIX B

ANALYTICAL QUALITY ASSURANCE

The Analytical Quality Assurance Office certifies the following:

a. These studies were conducted in accordance with:

(I) Standing Operating Procedures developed by the ToxicologyDivision, USAEHA.

(2) Title 21, Code of Federal Regulations (CFR), 1983 rev, Part 58,Good Laboratory Practice for Nonclinical Laboratory Studies.

(3) Final Rule, Pesticide Programs; Good Laboratory PracticeStandards; 48 Federal Register (FR) 53963-539691, Z9 November 1983.

b. Facilities were inspected during its operational phase to ensurecompliance with paragraph a above.

c. The information presented in this report accurately reflects the rawdata generated during the course of conducting these studies.

PAUL V. SNEERINGER, Ph.D.Chief, Analytical Quality

Assurance Office

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