AD-AlGa 041 ARMY ENVIRONMENTAL HYGIENE AGENCY ABERDEEN PROVING GR-ETC F/G 6/20TOPICAL HAZARD EVALUATION PROGRAM OF CANDIDATE INSECT REPELLENT--ETC(U)APR GO A W SINGER

UNCLASSIFIED USAEHA-7T-51-OO15"O NL7END

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UNITED STATES ARMYENVIRONMENTAL HYGIENE

AGENCYABERDEEN PEIVINI 11880 MI 211

TM-1 TOPICAL HAZARD EVALUATION PROGRAMOF CANDIDATE INSECT REPELLENTS

A13-341559 1-(4-CHLOROPHENOXY)-2-(2-METHOXYETHOXY)-ETHANE ANDA13-34156, 1-(4-CHLOROPHENOXY)-2- (2-ETHOXYETHOXY)-ETHANEA STUDY NOS. 75-51-0015-80 AND 75-51-0016-80

FEBRUARY 1977 -APRIL 1980

Approved for public release, distribution unlimited.

80 627 087

SEURTYCASIYCAIN F HI A EWm AUnclassified I j

'L T#Ll e"~bt Topical Hazard Evaluation Program o TP FRPR 1PRO OEE

CoandaeIsc eelnsA3315,10-clro l Feb 77 - Apr 80US o Army (Health o ries oxy)enan , an. A13-34,156 :-

Fort4Sa ouopn, TX 78234N OO EPRNME

. PONRORING ORAMINCY NAME ADSI ADDRESSa Eor 'YAM~o~a O_.)I. EUIY S.4e e

IA.ELASS WORKTIUNI DON RAIN

11. CONTROISING STFIE MEN AD ES I&i REPORoDAT

Aprove faorublonc reeae ditrbtinuniitd

17. DISTRISUTION STATEMENT (of lie bte neel lck2,I s~rtbr Report)

1S. SUPPLEMENTARY NOTES

19. KEy woRDS (Coatimnua ros, r se~* ide Uf necessary aid tIdfr~ 6Y block -iab-)

A13-341 55 Topical Hazard Evaluation Programl-(4-chlorophenoxy)-2-(2-methoxyethoxy)-ethane Photo Irritation

,, 1 -(4-chlorophenoxy)-2-(2-ethoxyethoxy)-ethan.eSkin Sensitization25, AfSIRACI (conaau sispoffin ebb N nosessa mdientitr by block" mmli) r

'., Preliminary hazard evaluations of A13-34155 and A13-34156 were performed by

technical grade compounds did not cause skin, eye, or photo irritation. Theydid not prove to be skin sensitizers or to be acutely toxic by ingestion. Itwas recommended that both compounds be approved for further testing as candidateinsect repellents.

AN 7 DTes1~510~r UnclassifiedSECupiy CLASSIFICATION OF THIS PAGE ?Mm Dates Emaes

DEPARTMENT OF THE ARMY CPT SInger/lm/AUTOVONU. S. ARMY ENVIEONMENTAL HYGIENE AGENCY 584-3980

ABERDEEN PROVING GROUND. MARYLAND &1010

HSE-LT-T/WP JUN 19MSUBJECT: Topical Hazard Evaluation Program of Candidate Insect Repellents

A13-34155, 1-(4-chlorophenoxy)-2-(2-methoxyethoxy)-ethane, andA13-34156, 1-(4-chlorophenoxy)-2-(2-ethoxyethoxy)-ethane, StudyNos. 75-51-0015-80 and 75-51-0016-80, February 1977 - April 1980

Executive SecretaryArmed Forces Pest Management BoardForest Glen Section, WRACWashington, DC 20012

A summary of the pertinent findings and recommendations of the inclosedreport follows:

Preliminary hazard evaluations of A13-34155 and A13-34156 were performed bymeans of laboratory animal studies using rats, rabbits, and guinea pigs. Thetechnical grade compounds did not cause skin, eye, or photo irritation. Theydid not prove to be skin sensitizers or to be acutely toxic by ingestion. Itwas recommended that both compounds be approved for further testing ascandidate insect repellents.

FOR THE COMMANDER:

1 Incl OHN F. MAZURias (5 cy) U S

Director, Laboratory Services

CF:HQDA (DASG-PSP)Cdr, HSC (HSPA-P) Aces-aionForDir, Advisory Ctr on Tox, NRC JTI.S &61iSupt, AHS (HSA-IPM) WC TABUSDA, ARS (Dr. Terrence McGovern) Unm)iouncedUSDA, ARS-Southern Region ju!'t c6 fi C t _ -

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DEPARTMENT OF THE ARMYU.S . ARMY ENVIRONMENAL HYGIENE AGENCY

ABERDEEN PROVING GROUND. MARYLAND IM010

HSE-LT-T/WP

TOPICAL HAZARD EVALUATION PROGRAMOF CANDIDATE INSECT REPELLENTS

A13-34155, 1-(4-CHLOROPHENOXY)-2- (2-METHOXYETHOXY)-ETHANE andA13-34156, 1-(4-CHLOROPHENOXY)-2- (2-ETHOXYETHOXY )-ETHANE

STUDY NOS. 75-51-0015-80 and 75-51-0016-80FEBRUARY 1977 - APRIL 1980

1. AUTHORITY.

a. Letter, US Department of Agriculture - Agricultural Research Service,Southern Region, Insects Affecting Man Research Laboratory, Gainesville,Florida, 10 February 1977.

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 theUS Department of Agriculture, Agricultural Research, Science and EducationAdministration, titled, Coordination of Biological and Toxicological Testingof Pesticides, effective 23 January 1979.

2. REFERENCE. Toxicology Division Procedural Guide, US Army EnvironmentalHygiene Agency (USAEHA), 1972, revised 1976.

3. PURPOSE. The purpose of this program is to provide guidance for furtherentomological testing of the candidate insect repellents A13-34155 andA13-34156.

4. SUMMARY OF FINDINGS. Hazard evaluations of the candidate repellentsA13-34155 and A13-34156 were conducted by this Agency using New Zealand Whiterabbits for skin and eye studies, Hartley guinea pigs for a skinsensitization study and Sprague-Dawley rats for determination of oraltoxicity. A tabular presentation of animal toxicity data developed in thisAgency follows:*t

* In conducting the studies described in this report, the investigatorsadhered to the "Guide for the Care and Use of Laboratory Animals," USDepartment of Health, Education and Welfare Publication No. (NIH) 74-23,revised 1978.t The experiments reported herein were performed in animal facilities fullyaccredited by the American Association for the Accreditation of LaboratoryAnimal Care.

pproved for public release, distribution unlimited.

) * I

Study Nos. 75-51-0015-80 and 75-51-0016-80, Feb 77 - Apr 80

TABLE. PRESENTATION OF DATA

Test Results Interpretation

SKIN IRRITATION STUDIES

Rabbits

Single 24-hour appl i- Compounds A13-34155 USAEA Category Ication to intact and and A13-34166 did not (ref Appendix).abraded skin of New cause any irritationZealand White rabbits. of the intact skin or

of the skin surroundingan abrasion.

0.5 mL technical gradecompound applied to eachof six rabbits.

EYE IRRITATION STUDIES

Rabbits

Single 24-hour appli- Compounds A13-34155 USAEHA Category Acation of 0.1 mL technical and A13-34156 did not (ref Appendix).grade compound to one cause any irritationeye of each of six New to the eyes of rabbits.Zealand White Rabbits.

APPROXIMATE LETHAL DOSE (ALD)

Oral

Rats (male)-no diluent For A13-34155, the Neither compoundALD was determined presents much lethalto be 1125 mg/kg. hazard from accidentalFor A13-34156, the ingestion.ALD was 3300 mg/kg.

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Study Nos. 75-51-0015-80 and 75-51-0016-80, Feb 77 - Apr 80

Test Results Interpretation

PHOTOCHEMICAL SKIN IRRITATION STUDIES

Rabbits

A single 0.05 mL appli- Neither compound in Compounds A13-34155cation of a 25 percent ethanol caused a and A13-34156 did not(w/v) solution of each photochemical irrita- cause a photochemicalcompound and a 10 percent tion reaction under irritation reaction(w/v) Oil of Bergamot test conditions. under test conditionssolution (positive control) and are not expectedin 95 percent ethyl alcohol to cause a photo-were applied to the intact chemical irritationskin of six rabbits. Five in humans.minutes after application,the rabbits were exposed toUV light (365 nm) for 30minutes at a distance of10-15 cm.

Control

Following UV exposures of Positive control appli-the rabbits, 0.05 M. of cation and irradiationtest compound, positive caused greater irritantcontrol and diluent were effects than in unirra-applied to additional diated skin areas.skin areas to serve asunirradiated controlsites. Application areaswere checked for skinirritation at 24, 48 and72 hours.

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Study Nos. 75-51-0015-80 and 75-51-0016-80, Feb 77 - Apr 80

Test Results Interpretation

SENSITIZATION STUDIES

Guinea Pigs (Male)

Intradermalinjections of 0.1 nIof a 0.1 percentsolution (w/v) ofA13-34155, A13-34156or of dinitrochloro-benzene (DNCB)* ina mixture containing1 volume of propyleneglycol and 29 volumesof saline.

Ten test guinea pigs for Challenge doses of Compounds A13-34155each compound were given A13-34155 and A13-34156 and A13-34156 did notten sensitizing doses did not produce a sensi- produce sensitizationover a 3-week period. tization reaction, reactions under testAfter 2 weeks rest, they conditions and are notwere challenged with ID expected to produce sen-injections of each test sitization reactionscompound. in man.

Ten positive control Challenge dose of DNCB DNCB produced a markedguinea pigs were sen- in positive control reaction, indicating thesitized over 3 weeks with guinea pigs produced guinea pigs respond toDNCB. After 2 weeks a marked sensitization sensitizing agents.rest, they were chal- reaction in 10 outlenged with ID injections of 10 guinea pigs.of DNCB.

* A known skin sensitizer

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Study Nos. 75-51-0015-80 and 75-51-0016-80, Feb 77 - Apr 80

5. CONCLUSION. Technical grade compounds A13-34155 and A13-34156 did notcause any skin, eye, or photo irritation, no sensitization reaction, and didnot prove to be an acute ingestion hazard.

6. RECOMMENDATION. Under the provisions of the Memorandum of Understanding(paragraph 1b), it is reconmmnded that A13-34155 and A13-34156 be approvedfor further testing as candidate insect repellents.

ALLENI W. SINGERCPT, VCGeneral Veterinary OfficerToxicology Division

APPROVED:

AJHUR H. McCREESH, Ph.D.Chief, Toxicology Division

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Study Nos. 75-51-0015-80 and 75-51-0016-80, Feb 77 - Apr 80APPENDIX

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 intactskin and the skin surrounding an abrasion. (INTERPRETATION: Should not beused directly on the skin without a prophetic patch test having beenconducted on humans to determine irritation potential to human skin. May beused without patch testing, 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.

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

E. Compounds producing moderate injury to the cornea, and in additionproducing some injury to the conjunctiva. INTERPRETATION: Should be used

with extreme caution around the eyes and mucosa.

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

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