## UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### MEMORANDUM

Date: 6/29/2015**SU~CT:** 

### Tetrachlorvinphos (Gardona): Data Evaluation Records (DERs) for EDSP
Tier 

### 1 Assays

PC Code: 08370 2



### Decision No.: 436352, 458689, 462384 463315,464569,468404

471437

, 481869,481870


### Petition No.: NA DP Barcode: D379676

, D396880, D399849
D4007 1 8

, D401619, D404438 D406501, D413982

, D413983 

### Registration No.: NA

Risk Assessment Type: NA

TXR No.: 0056284


### MRID No.: See Ta bl e Regulatory Action: NA
Case No.: NA CAS No.: 22248- 

### 79-9
40 CFR: NA

FROM: Greg Akerman, Ph.D. 

# bes-**~** Immediate Office
Health Effects 

### Division (7509P)



### THROUGH: 

### Jess Rowland

# r~_.n--­ Deputy Director
Health Effects Division



### TO: Jolene Trujillo Biologist/Chemical 

### Review Manager
Risk 

### Management and Implemen tation Branch V

Pes ticide Re-evaluation Division (7505P)



### I. ACTION REQUESTED Ver.Apr. 2010



### The Pesticide 

### Re-evaluation Division (PRD) 

### of OPP has requested that the Health Effects
Division (HED) review the Endocrine Disruptor Screening Program (EDSP) Tier 1 assays

Page J 

### of2Page 2 of 2 

### submitted in response to the agency’s Test Order for tetrachlorvinphos: Test Order # CON083702-14.

II. RESPONSE

Attached are the EDSP Tier 1 assay DERs for tetrachlorvinphos.

III. MRID Table

Chemical: Tetrachlorvinphos (Gardona) PC Code: 083702
Guideline Assay MRID
890.1100 Amphibian Metamorphosis Assay (Frog) 48688401
890.1150 Androgen Receptor Binding (Rat Prostate) 48703101
890.1200 Aromatase Assay (Human Recombinant) 48673801
890.1250 Estrogen Receptor Binding 48765001
890.1300 Estrogen Receptor Transcriptional Activation (Human Cell Line HeLa-9903) 48619501

890.1350 Fish Short-Term Reproduction 48838201
890.1400 Hershberger (Rat) 48946701
890.1450 Female Pubertal (Rat) 49186901
890.1500 Male Pubertal (Rat) 49186901
890.1550 Steroidogenesis (Human Cell Line – H295R) 48805201
890.1600 Uterotrophic (Rat) 48880601ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԡԹՌԹԯԽՉՍՁՊԽՅԽՆՌ    ԢԭԞԡԭԟԹՊԻ ՇԼԽ  

ԬԢԠԡԡԹՌԹԭՇՁՆՌ  

ԢԭԞԪԯԦԡ    

ԢԭԞԤՍՁԼԽՄՁՆԽ   

      ԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊ ՈՀՇՋՁՋԞՋՋԹՑ
ԣՊՇԿ

ԱԽՋՌԪԹՌԽՊՁԹՄ  ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ   ԭՍՊՁՌՑ
 

ԠՇՅՅՇՆԫԹՅԽ ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԠՀԽՅՁԻԹՄԫԹՅԽ  ԦԲԭԞԠ   
ԷԻՀՄՇՊՇ
ՌՊՁԻՀՄՇՊՇՈՀԽՆՑՄՎՁ ՆՑՄԼՁՅԽՌՀՑՄՈՀՇՋՈՀԹՌԽ

 ԠԞ԰ԫԹՅԽ  
ԷԻՀՄՇՊՇ
ՌՊՁԻՀՄՇՊՇՈՀԽՆՑՄԽՌՀԽՆՑՄԼՁՅԽՌ ՀՑՄՈՀՇՋՈՀԹՌԽ

ԠԞ԰ԫՇ  

԰ՑՆՇՆՑՅՋ  ՋՌՁՊՇԾՇՋԠԳԪԭ

ԢԭԞԭԠԠՇԼԽ 

ԯԽՎՁԽՏԽՊ ԫԹՅԽ ԧՇԺԱՁՌՄԽ ԡԹՌԽ ԞԾԾՁՄՁԹՌՁՇՆ

ԭՊՁՅԹՊՑ

ԹՆԼԣՁՆԹՄ ԠԹՌՀԽՊՁՆԽԞՍԺԽԽ ԟՁՇՄՇԿՁՋՌ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌ

ԬԭԭԢԣԢԡԢԯԟԦԳ ԧԹՆՍԹՊՑ

ԧՍՆԽ ԢԭԞ

԰ԽԻՇՆԼԹՊՑ ԪԹՊՑԠՄՇԻՃԯՍՋՌ ԟՁՇՄՇԿՁՋՌ

ԬԭԭԢԣԢԡԢԯԟԦԳ ԣԽԺՊՍԹՊՑ ԢԭԞ

ԡԹՌԽԢՎԹՄՍԹՌՁՇՆԠՇՅՈՄԽՌԽԼ #ԼԼՅՅՅՑՑՑՑ%

ԠՁՌԹՌՁՇՆ ԪԯԦԡ

԰ԻՀՆԽՁԼԽՊ԰ԷԱԷԨԽՆԼԹՄՄԹՆԼԥԬԨՊՍԽԿԽՊԱԽՌՊԹԻՀ ՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԞՅՈՀՁԺՁԹՆ

ԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԾՇՊՌՀԽԡԽՌԽԻՌՁՇՆՇԾԱՀՑՊՇՁԼԞԻՌՁՎԽ԰ՍԺՋՌԹՆ ԻԽՋԴՁՄԼՄՁԾԽԦՆՌԽՊՆԹՌՁՇՆԹՄԩՌԼ

ԢԹՋՌՇՆԪԡԭՊՇՂԽԻՌԫՇԞ԰ՈՇՆՋՇՊՋԨԪԤԟԽՊՆՍՌՀԦՆԻԹՆԼԱԥԪԠ԰ՌՍԼՑԠՇՅՈՄԽՌՁՇՆ

ԡԹՌԽԡԽԻԽՅԺԽՊ   MARY
CLOCK-RUST Digitally signed by MARY CLOCKRUST DN: c=US, o=U.S. Government, ou=USEPA, ou=Staff, cn=MARY CLOCK-RUST, dnQualifier=0000002342
Date: 2015.06.09 11:12:02 -04'00'ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԫՇՌԽ ԱՀԽԲ԰ԢԭԞԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅ
Ԣԡ԰ԭԱՁԽՊՋԻՊԽԽՆՁՆԿԺԹՌՌԽՊՑՁՋԻՇՅՈՊՁՋԽԼՇԾԽՄԽՎԽՆ

ՋԻՊԽԽՆՁՆԿԹՋՋԹՑՋՁՆՌԽՆԼԽԼՌՇՁԼԽՆՌՁԾՑԹԻՀԽՅՁԻԹՄ0ՋՄՁՃԽՄՑԽՆԼՇԻ ՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՁԽՁՌՋՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀ

ՌՀԽԽՋՌՊՇԿԽՆԹՆԼՊՇԿԽՆՇՊՌՀՑՊՇՁԼ
ԢԞՇՊԱՈԹՌՀՏԹՑՋԱՀԽՊ ՇԺՍՋՌՆԽՋՋՇԾՌՀԽԱՁԽՊԺԹՌՌԽՊՑՁՋԺԹՋԽԼՇՆ

ՌՀԽՋՌՊԽՆԿՌՀՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՌՇՁԼԽՆՌՁԾՑՈՇՌԽՆՌՁԹՄԽՆ ԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՏՁՌՀԻՇՅՈՄԽՅԽՆՌԹՊՑԽՆԼՈՇՁՆՌՋ

ՏՁՌՀՁՆՌՀԽԹՋՋԹՑՏՀԽՊԽԹՎԹՁՄԹԺՄԽԹՆԼՊԽԼՍՆԼԹՆԻՑԹԻՊՇՋՋՌՀԽԺԹՌՌԽՊՑԱՀՍՋՌՀԽՊԽՋՍՄՌՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄ

ԹՋՋԹՑՋՀՇՍՄԼՆՇՌԺԽԻՇՆՋՁԼԽՊԽԼՁՆՁՋՇՄԹՌՁՇՆԺՍՌՊԹՌՀԽՊՋՀՇՍՄԼԺ ԽԻՇՆՋՁԼԽՊԽԼՁՆՌՀԽԻՇՆՌԽՐՌՇԾՇՌՀԽՊԹՋՋԹՑՋ

ՁՆՌՀԽԺԹՌՌԽՊՑԹՋՏԽՄՄԹՋԬՌՀԽՊ԰ԻՁԽՆՌՁԾՁԻԹՄՄՑԯԽՄԽՎԹՆՌԦՆԾՇՊՅԹ ՌՁՇՆ
Ԭ԰ԯԦԦՆՇՊԼԽՊՌՇԼԽՌԽՊՅՁՆԽՁԾԹԻՀԽՅՁԻԹՄ

ՀԹՋՌՀԽՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀՌՀԽԢԞՇՊԱՈԹՌՀՏԹՑՋԹԴԽ ՁԿՀՌՇԾԢՎՁԼԽՆԻԽ
ԴՇԢԽՎԹՄՍԹՌՁՇՆՇԾԱՁԽՊ

ԹՋՋԹՑՊԽՋՍՄՌՋՁՆԻՇՅԺՁՆԹՌՁՇՆՏՁՌՀՌՀԽԾՁՆԼՁՆԿՋՁՆՌՀԽԬ԰ԯԦՋՀ ՇՍՄԼԺԽՍՆԼԽՊՌԹՃԽՆ
ՊԽԾԽՊՌՇՌՀԽԴՇԢ

ԡՇԻՍՅԽՆՌ

ԢԵԢԠԲԱԦԳԢ԰ԲԪԪԞԯԶ

ԱՀԽԼԹՑԹՋՋԹՑՇԾՌԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ
ԹՁՇՆԹՅ ՈՀՁԺՁԹՆՅԽՌԹՅՇՊՈՀՇՋՁՋՇԾՌՀԽԞԾՊՁԻԹՆԻՄԹՏԽԼ

ԾՊՇԿ ԵԽՆՇՈՍՋ ՄԹԽՎՁՋ ՏԹՋ ԻՇՆԼՍԻՌԽԼ ՍՆԼԽՊ ԾՄՇՏՌՀՊՇՍԿՀԻՇՆԼՁՌՁՇՆՋ ԞՅՈՀՁԺՁԹՆ ՄԹՊՎԹԽ 
ԾՇՍՊ ՊԽՈՄՁԻԹՌԽՋ ՈԽՊ

ՌՊԽԹՌՅԽՆՌՄԹՊՎԹԽՈԽՊՊԽՈՄՁԻԹՌԽԹՌԫՁԽՍՏՃՇՇՈԣԹԺԽՊ
ԫԣ԰ՌԹ ԿԽՏԽՊԽԽՐՈՇՋԽԼՌՇՆԽԿԹՌՁՎԽ
ԼՁՄՍՌՁՇՆՏԹՌԽՊ

ԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՅԿԩԼՁՅԽՌՀՑՄԾՇՊՅԹՅՁԼԽԡԪԣ ԹՆԼԱԠԳԭՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾ

ԹՆԼՅԿԹՁԩԪԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԱԠԳԭՏԽՊԽՅԿԹՁԩ
ԩԬԮՁՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԹՆԼԹՆԼՅԿԹՁԩՁՆՌՀԽՌԽՋՌ ՁՌԽՅՌՊԽԹՌՅԽՆՌՋԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋՅԹՁՆՌԹՁՆԽԼ

ԹՌՌՇոԠ
ՅԽԹՋՍՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑՏՁՌՀԹՈԥՇԾՌՇ 

ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԹՄՄԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻ ՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ

ԠՄՁՆՁԻԹՄ ՋՁԿՆՋ ՇԾ ՌՇՐՁԻՁՌՑ 
ՁԽ ԺԽՀԹՎՁՇՊԹՄ ԹՆԼ ՇՌՀԽՊ ՋՍԺՄԽՌՀԹ Մ ԽԾԾԽԻՌՋ ՏԽՊԽ ՆՇՌԽԼ ԹՌ  ՅԿ ԹՁԩ

ՁՆԻՄՍԼՁՆԿՁՆԻՄՍԼՁՆԿՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅ ԹՆԼՄՑՁՆԿՇՆՌՀԽԺՇՌՌՇՅՇԾՌՀԽՌԹՆՃՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՏՇՌԹԼՈՇՄ ԽՋ԰ՈՁՆԹՄ

ԻՍՊՎԹՌՍՊԽ
ԻՊՇՇՃԽԼՌԹՁՄՏԹՋՇԺՋԽՊՎԽԼՁՆԻՇՆՌՊՇՄՋԹՆԼՁՆԽՎԽՊՑ ՌՊԽԹՌՅԽՆՌԽՐԻԽՈՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

ԞՌԡԹՑՌԹԼՈՇՄԽՋՀԹԼՋՀՇՊՌԽՊՆՇՊՅԹՄՁՒԽԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩ ԩԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՅԿ

ԹՁԩ  ՌՀԹՆ ՁՆ ՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ 
Ո Ԟ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌ ԼԽՄԹՑ
ՇՆԽ ՋՌԹԿԽ ՇԾ ՅԽԼՁԹՆ ԫԣ

ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋՇԺՋԽՊՎԽԼԹՌԡԹՑ
ՈԼԹՑՋԹՌ ՅԿԹՁԩԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋ

ՇԺՋԽՊՎԽԼԢԾԾԽԻՌՋՇՆՌՀՑՊՇՁԼԿՄԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՏԽՊԽՇԺՋԽՊՎԽԼԹՌՅԿԹՁԩԥՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԽԾԾԽԻՌՋ

ՁՆԻՄՍԼԽԼՁՆԻՊԽԹՋԽՋՁՆԿՄԹՆԼՀՑՈԽՊՌՊՇՈՀՑԿՄԹՆԼՋՁՒԽԾՇՄՄՁԻՄԽՋ ՁՒԽԹՆԼԾՇՄՄՁԻՄԽԹՋՑՅՅԽՌՊՑԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽ

ԻՇՆՌՊՇՄԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԰ՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋՇՆԿՊՇՏՌՀՈԹՊԹՅԽՌԽՊՋ
Ո ՁՆԻՄՍԼՁՆԿՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀԹՆԼԺՇԼՑՏԽՁԿՀՌՏԽՊԽ

ՇԺՋԽՊՎԽԼԹՌԺՇՌՀՌՀԽԼԹՑԹՆԼԼԹՑՋԹՅՈՄՁՆԿՈՇՁՆՌՋԹՌՅԿ ԹՁԩԦՆԻՊԽԹՋԽԼԿՊՇՏՌՀՏԹՋՋԽԽՆԹՌՌՀԽ

ՄՇՏԽՋՌՌՊԽԹՌՅԽՆՌ
ՅԿԹՁԩԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆ ՌՊՇՄՋԹՆԼՏԹՋԻՇՆՋՁՋՌԽՆՌՏՁՌՀՇԺՋԽՊՎԹՌՁՇՆՋՁՆ

ՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋ ԳԹՄՁԼՁՌՑԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹՏԽՊԽԿԽՆԽՊԹՄՄՑՅԽՌԹՄՌՀՇՍԿՀ ՅՁՆՇՊԼԽՎՁԹՌՁՇՆՋԾՊՇՅՌՀԽԿՍՁԼԽՄՁՆԽՏԽՊԽՆՇՌԽԼ

ԞԼԼՁՌՁՇՆԹՄՄՑՋՇՄՎԽՆՌՁՆՌԽՊԾԽՊԽՆԻԽՏԹՋԹՈՈԹՊԽՆՌԦՆՌՀԽՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄԿՊՇՍՈՌՀԽՊԽՏԹՋԹՋՁԿՆՁԾՁԻԹՆՌՁՆԻՊԽԹՋԽՁՆ

ԼԹՑԺՇԼՑՏԽՁԿՀՌԹՆԼ԰Գԩ
ՈԹՆԼԼԹՑԺՇԼՑՏԽՁԿՀՌ԰Գԩ ԥԩԩԹՆԼՆՇՊՅԹՄՁՒԽԼԥԩԩ
Ո

ԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋԠՇՅՈԹՊԽԼՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌ ՊՇՄԡԹՑԺՇԼՑՏԽՁԿՀՌ԰ԳԩԹՆԼԫԣՋՌԹԿԽ


ՋՌԹԿԽՋՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑԼԽԻՊԽԹՋԽԼ
ՈԹՌՌՀԽՀՁԿՀԽՋՌՌԽ ՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԡԹՑԺՇԼՑՏԽՁԿՀՌ԰Գԩ

ՆՇՊՅԹՄՁՒԽԼԥԩԩԹՆԼԫԣՋՌԹԿԽ
ՋՌԹԿԽՋՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑԼԽԻՊ ԽԹՋԽԼ
ՈԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԠՇՅՈԹՊԽԼ ՌՇ ՌՀԽ ՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄ ՌՀԽ ՇՆՄՑ ՆՇՌԽՏՇՊՌՀՑ ՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄ ԾՁՆԼՁՆԿ ՏԹՋ ԹՆ ՁՆԻՊԽԹՋԽ ՁՆ ԾՇՄՄՁԻՄԽ

ԹՋՑՅՅԽՌՊՑԱՀԽՅՁՆՇՊԿՍՁԼԽՄՁՆԽԼԽՎՁԹՌՁՇՆՋԹՆԼՌՀԽՈՊՇՅՇՌՁՇՆՇԾ ԿՊՇՏՌՀՇԺՋԽՊՎԽԼՁՆԹՋՋՇԻՁԹՌՁՇՆՏՁՌՀՌՀԽՋՇՄՎԽՆՌ

ԼՇՆՇՌԹՈՈԽԹՊՌՇՀԹՎԽՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌԽԼՌՀԽՇՎԽՊԹՄՄՊԽՋՍՄՌ ՋՇՊՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽՋՌՍԼՑ

ԱՀԽԹՋՋԹՑ ՋԹՌՁՋԾՁԽՋ ՌՀԽԢԡ԰ԭԱՁԽՊԱԽՋՌԬՊԼԽՊՊԽՉՍՁՊԽՅԽՆՌԾՇՊԹՆԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇ ՊՈՀՇՋՁՋԞՋՋԹՑ
ԬԠ԰ԭԭ

ԤՍՁԼԽՄՁՆԽ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌՇՊԿԹՆՁՋՅԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

ԱԽՋՌՇՊԿԹՆՁՋՅՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՇՈՌՁՇՆԹՄՆՇՌՊ ԽՈՇՊՌԽԼ

ԢՐՈՇՋՍՊԽՌՑՈԽԣՄՇՏՌՀՊՇՍԿՀԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽ  ԰ՍՅՅԹՊՑ ՇԾ ԡԽՎԽՄՇՈՅԽՆՌԹՄ ԹՆԼ ԱՀՑՊՇՁԼ ԭԹՌՀՇՄՇԿՑԥՁՋՌՇՈԹ ՌՀՇՄՇԿՑ ԢԾԾԽԻՌՋ   ՁՆ ՌՀԽ ԞՅՈՀՁԺՁԹՆ

ԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԞԪԞՏՁՌՀ dĞƚƌĂĐŚůŽƌǀŝŶƉŚŽƐ;dsWͿ



ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ

԰ՌԹԿԽ ԥՁՆԼԩՁՅԺ

ԩԽՆԿՌՀ  ԞՋՑՆԻՀՊՇՆՇՍՋ

ԡԽՎԽՄՇՈՅԽՆՌ ԱՀՑՊՇՁԼԤՊՇՋՋ

ԹՆԼ

ԥՁՋՌՇՈԹՌՀՇՄՇԿՑ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

 ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ

 ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ

 ԶԽՋ ԫՇ ԫՇ ԶԽՋ ԫՇ ԫՇ ԶԽՋ

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԡՁԾԾ ԡՁԾԾԽՊԽՆԻԽ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ

 ԞՑԽՋՁՆԼՁԻԹՌԽՋԹՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇ ՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄՍՆՄԽՋՋ

ՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼ

 ԱՀԽԻՊՁՌԽՊՁԹԾՇՊՋՁԿՆՁԾՁԻԹՆԻԽԹՊԽԼԽՋԻՊՁԺԽԼՁՆՌՀԽԯԽՎՁԽՏԽՊ	Ջ ԞՆԹՄՑՋՁՋԹՆԼ԰ՌԹՌՁՋՌՁԻԹՄԳԽՊՁԾՁԻԹՌՁՇՆՋԽԻՌՁՇՆՋՇԾՌՀԽ

ԡԢԯԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀ ՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼ

ՈԹՌՀՇՄՇԿՁՋՌ

 ԥՁՆԼՄՁՅԺՄԽՆԿՌՀՁՋՆՇՊՅԹՄՁՒԽԼՌՇՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰Գԩ

Ԧ ԪԞԱԢԯԦԞԩ԰ԞԫԡԪԢԱԥԬԡ԰

ԤՍՁԼԽՄՁՆԽԣՇՄՄՇՏԽԼ

ԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ
ԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԱՀԽԾՇՄՄՇՏՁՆԿԼԽՎՁԹՌՁՇՆՏԹՋՆՇՌԽԼ

• ԣԽԽԼՁՆԿՊԹՌԽՋԼՍՊՁՆԿՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌՏԽՊԽԹՈՈՊՇՐՁՅԹՌԽՄՑՀԹՄ ԾՌՀԽՊԹՌԽՋՊԽԻՇՅՅԽՆԼԽԼՁՆՌՀԽԢԭԞ

ԿՍՁԼԽՄՁՆԽ

ԱՀՁՋԼԽՎՁԹՌՁՇՆԼՇԽՋՆՇՌՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌՌՀԽՊԽՋՍՄՌՋՇՊՁՆՌ ԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽՋՌՍԼՑ

ԠՇՅՈՄՁԹՆԻԽ

԰ՁԿՆԽԼԹՆԼԼԹՌԽԼԤԩԭԮՍԹՄՁՌՑԞՋՋՍՊԹՆԻԽԹՆԼԡԹՌԹԠՇՆԾՁԼԽՆՌՁԹՄՁՌ ՑՋՌԹՌԽՅԽՆՌՋՏԽՊԽՈՊՇՎՁԼԽԼԱՀԽՋՌՍԼՑՏԹՋ
ԻՇՆԼՍԻՌԽԼՁՆԻՇՅՈՄՁԹՆԻԽՏՁՌՀԤԩԭ԰ՌԹՆԼԹՊԼՋ#Բ԰ԢԭԞԠԣԯԭԹՊՌՋ ԹՆԼԹՆԼԬԢԠԡԢԫԳԪԠԠԥԢԪ
%ՏՁՌՀՌՀԽԾՇՄՄՇՏՁՆԿԽՐԻԽՈՌՁՇՆՋՆՇՌԽԼՁՆՌՀԽՋՌՍԼՑՊԽՈՇ ՊՌԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  • ԱՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽԻՀԹՊԹԻՌԽՊՁՒԹՌՁՇՆԹՆԼՋՌԹԺՁՄՁՌՑՍՆԼԽՊԻՇՆԼՁՌՁ ՇՆՋՇԾՋՌՇՊԹԿԽՏԽՊԽՆՇՌԼԽՌԽՊՅՁՆԽԼՁՆ

ԻՇՅՈՄՁԹՆԻԽՏՁՌՀԤԩԭ

• ԭԽՊՁՇԼՁԻԻՇՆՌԹՅՁՆԹՆՌԹՆԹՄՑՋՁՋՇԾՏԹՌԽՊՏԹՋՆՇՌԻՇՆԼՍԻՌԽԼԹԻԻՇՊԼ ՁՆԿՌՇԤԩԭԺՍՌՏԹՋՈԽՊԾՇՊՅԽԼՍՋՁՆԿ

ԹԻԽՊՌՁԾՁԽԼՄԹԺՇՊԹՌՇՊՑԹՆԼՋՌԹՆԼԹՊԼԲ԰ԢԭԞԹՆԹՄՑՌՁԻԹՄՅԽՌՀՇԼՋ

• ԭՊԽՄՁՅՁՆԹՊՑԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՁՇԼՁԼԽՁՆՏԹՌԽՊՏԹՋՆՇՌԼԽՌԽՊՅՁՆԽԼ ԹԻԻՇՊԼՁՆԿՌՇԤԩԭ

ԞԱԽՋՌԪԹՌԽՊՁԹՄ    ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԠԞ԰ԫՇ 

ԡԽՋԻՊՁՈՌՁՇՆ

ԴԹՌԽՊՋՇՄՍԺՁՄՁՌՑ ՅԿԩԹՌոԠ

ԢՐՈՁՊԹՌՁՇՆԡԹՌԽ ԧՍՆԽ

ԬՌՀԽՊՈԹՊԹՅԽՌԽՊՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ

ԬԢԠԡՊԽԻՇՅՅԽՆԼՋԼԽՋԻՊՁԺՁՆԿՏԹՌԽՊՋՇՄՍԺՁՄՁՌՑՋՌԹԺՁՄՁՌՑՁՆՏԹՌԽՊ ԹՆԼՄՁԿՀՌՈԨԹԭՇՏՇՊԨՇՏԨՇԻՎԹՈՇՊՈՊԽՋՋՍՊԽ

ՇԾՌԽՋՌԻՇՅՈՇՍՆԼԽՐՈՁՊԹՌՁՇՆԼԹՌԽ

ԩՇՌԫՇԟԹՌԻՀԫՇ ԱԵ

ԭՍՊՁՌՑ    

ԦՅՈՍՊՁՌՁԽՋ

ԫՇՁՅՈՍՊՁՌՁԽՋՏԽՊԽՊԽՈՇՊՌԽԼ

԰ՌԹԺՁՄՁՌՑՇԾԠՇՅՈՇՍՆԼ

ԱՀԽՋՌԹԺՁՄՁՌՑՇԾՌՀԽՌԽՋՌՁՌԽՅՏԹՋՆՇՌՊԽՈՇՊՌԽԼՁՆՌՀԽԠԽՊՌՁԾՁԻ ԹՌԽՇԾԞՆԹՄՑՋՁՋՇՊԼԽՌԽՊՅՁՆԽԼՍՆԼԽՊԽՐՈԽՊՁՅԽՆՌԹՄ

ԻՇՆԼՁՌՁՇՆՋ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾԱԽՋՌԠՀԽՅՁԻԹՄՋ

ԱՀԽՌԽՋՌՅԹՌԽՊՁԹՄՏԹՋՊԽԻԽՁՎԽԼՇՆԧՍՆԽԹՆԼՏԹՋՋՌՇՊԽԼՍՆԼԽՊԹՅԺՁԽՆՌԻՇՆԼՁՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԟԱԽՋՌԬՊԿԹՆՁՋՅԱԹԺՄԽԤԽՆԽՊԹՄԦՆԾՇՊՅԹՌՁՇՆԞԺՇՍՌՌՀԽԱԽՋՌ԰ՈԽԻՁԽՋԹՆԼԭԹՊԽՆՌԹՄԠԹՊԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՈԽԻՁԽՋԻՇՅՅՇՆՆԹՅԽ ԞԾՊՁԻԹՆԻՄԹՏԽԼԾՊՇԿ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԞԾՊՁԻԹՆԻՄԹՏԽԼԾՊՇԿ ԵԽՆՇՈՍՋՄԹԽՎՁՋԴԽՋՌԽՊՆ#ԞԾՊՁԻԹ%ԻՄԹՏԽԼ ԾՊՇԿ԰ՁՄՍՊԹՆԹ
ԵԽՆՇՈՍՋՌՊՇՈՁԻԹՄՁՋՅԹՑԺԽ ՍՋԽԼԹՋԹՆԹՄՌԽՊՆԹՌԽՋՈԽԻՁԽՋ ՀՇՏԽՎԽՊԹՄՁՋՌ ՇԾԹՄՄՇԾՌՀԽՆԽԻԽՋՋԹՊՑՈՊՇՌՇԻՇՄԼԽՎՁԹՌՁՇՆՋՌՇ ԹԻԻՇՅՅՇԼԹՌԽՌՀՁՋՋՈԽԻՁԽՋՁՋՊԽԻՇՅՅԽՆԼԽԼ ԾՇՊՁՆԻՄՍՋՁՇՆՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌԱՀԽԿՍՁԼԽՄՁՆԽ ՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹ ՍՋԽԼՌՇՋՍՈՈՇՊՌՌՀԽՊԽՄՁԹԺՁՄՁՌՑՇԾՌՀԽՌԽՋՌԺԽ

ՁԼԽՆՌՁԾՁԽԼ԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԵԽՆՇՈՍՋՄԹԽՎՁՋ԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼ ԴԽՊԽՈԹՊԽՆՌՋՅԹՁՆՌԹՁՆԽԼԹՋՁՆՀՇՍՋԽՋՌՇԻՃ!ԶԽՋ  ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՄԹՊՎԹԽ ՍՋԽԼ ՁՆ ՌՀԽ ԹՋՋԹՑԺԽԼԽՊՁՎԽԼԾՊՇՅՁՆՀՇՍՋԽԹԼՍՄՌՋԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅԱՁԽՊԞՋՋԹՑՋ
ԬԠ԰ԭԭԱԽՋՌԤՍՁԼԽՄՁՆԽ԰ԽՊՁԽՋԪԹՊԻՀԬԾԾՁԻԽՇԾԠՀԽՅՁԻԹՄ԰ԹԾԽՌՑԹՆԼԭՇՄՄՍՌՁՇՆԭՊԽՎԽՆՌՁՇՆ
ԬԠ԰ԭԭԴԹՋՀՁՆԿՌՇՆԡԠՀՌՌՈՏՏՏԽՈԹԿՇՎԽՆԼՇՈՍԺՋԹՋՋԹՑՎԹՄՁԼԹՌՁՇՆԻՄԹՊՁԾՁԻԹՌՁՇՆԼՇԻՈԼԾԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԽՊԽՈԹՊԽՆՌԹՄԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!ԫՇ ԫՇՌՊԽՈՇՊՌԽԼԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԾՇՊՈԹՊԽՆՌԹՄԾՊՇԿՋ
ՁԾԹՈՈՄՁԻԹԺՄԽԼԹՑՋԫՇՌՊԽՈՇՊՌԽԼԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄԾԽԽԼՁՆԿ ԫՇՌՊԽՈՇՊՌԽԼԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄՀԽԹՄՌՀ ԫՇՌՊԽՈՇՊՌԽԼԱԹԺՄԽԩԹՊՎԹՄ԰ԽՄԽԻՌՁՇՆԹՆԼԠԹՊԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԟԽՋՌՋՁՆԿՄԽՋՈԹՏՆ!ԫՇԞՄՄԽԿԿՋՏԽՊԽԻՇՄՄԽԻՌԽԼՇՆՌՀԽՋԹՅԽԼԹՑ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌՀԽԺԽՋՌ ՁՆԼՁՎՁԼՍԹՄՋՈԹՏՆՋՏՁՌՀԹՅՁՆՁՅՍՅՇԾ ՄԹՊՎԹԽՋՈԹՏՆԺԽԽՎԹՄՍԹՌԽԼՌՇՁԼԽՆՌՁԾՑՌՀԽ ԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆԹՆԼՌՀԹՌՌՀԽՄԹՊՎԹԽՋԽՄԽԻՌԽԼ ԾՇՊՌԽՋՌՁՆԿՇՊՁԿՁՆԹՌԽԾՊՇՅՌՀԽԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆ

ՁԽ ՌՀԽՋՈԹՏՆՋԹՊԽՆՇՌԻՇՅՁՐԽԼԫՍՅԺԽՊՇԾՋՈԹՏՆՋԽՎԹՄՍԹՌԽԼ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫՇՌՊԽՈՇՊՌԽԼԫՍՅԺԽՊՇԾԽԿԿՋՋԹՅՈՄԽԼՈԽՊՋՈԹՏՆ ԫՇՌՊԽՈՇՊՌԽԼԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ԡԽՌԽՊՅՁՆԽԼՍՋՁՆԿԼՁՋՋԽԻՌՁՆԿՅՁԻՊՇՋԻՇՈԽ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԺԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԼԹՑՋՈՇՋՌԾԽՊՌՁՄՁՒԹՌՁՇՆԼՈԾ ՁՆՁՌՁԹՌԽԼՏՁՌՀՄԹՊՎԹԽԹՌԫՁԽՍՏՃՇՇՈԣԹԺԽՊ ԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ  ԼԹՑՋ ՈՇՋՌԾԽՊՌՁՄՁՒԹՌՁՇՆԪԽԹՆՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՁԾՊԽՈՇՊՌԽԼՅՅ ԫՇՌՊԽՈՇՊՌԽԼԯԹՆԿԽՇԾՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՊԽՈՇՊՌԽԼԾՊՇՅՌՇՅՅ ԫՇՌՊԽՈՇՊՌԽԼԴԹՋՌՀԽՇՈՌՁՇՆԹՄՋՁՒԽՋԽՄԽԻՌՁՇՆՅԽՌՀՇԼՍՋԽԼ!ԫՇ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՄԹՊՎԹՄՋԽՄԽԻՌՁՇՆ ԱԹԼՈՇՄԽՋՏԽՊԽՋԽՄԽԻՌԽԼՁԾՌՀԽՑԹՈՈԽԹՊԽԼՆՇՊՅԹՄԹՆԼՀԽԹՄՌՀՑԹՆԼՀԹԼՊԽԹԻՀԽԼԫԣՋՌԹԿԽԱԹԼՈՇՄԽՋՌՀԹՌՅԽՌՌՀԽՋԽԻՊՁՌԽՊՁԹՏԽՊԽՁՆԼՁՋԻՊՁՅՁՆԹՌԽՄՑՋԽՄԽԻՌԽԼԹՆԼՈՄԹԻԽԼՁՆՌՇՌՊԹՆՋԾԽՊՎԽՋՋԽՄՋԢԹԻՀՌՊԹՆՋԾԽՊՎԽՋՋԽՄՏԹՋՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇԹՌԽՋՌԻՀԹՅԺԽՊՇՆԻԽՌՀԽՎԽՋՋԽՄԻՇՆՌԹՁՆԽԼՌԹԼՈՇՄԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԩՇԹԼՁՆԿՊԹՌԽ
ՊԽԹՊՁՆԿԼԽՆՋՁՌՑ ՄԹՊՎԹԽԩԱԹԼՈՇՄԽՋՏԽՊԽԹԻԻՄՁՅԹՌԽԼՁՆԹԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՍՆԼԽՊՌՀԽՋԹՅԽԻՇՆԼՁՌՁՇՆՋԹՋՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌՁՆԻՄՍԼՁՆԿՏԹՌԽՊԾՇՇԼՌՑՈԽՌԽՅՈԽՊԹՌՍՊԽ
ԼԽԿԠԹՆԼՈՀՇՌՇՈԽՊՁՇԼ
ԱՀԽՈԥԼՍՊՁՆԿՄԹՊՎԹՄԹԻԻՄՁՅԹՌՁՇՆՊԹՆԿԽԼԾՊՇՅԹՆԼԡԬՊԹՆԿԽԼԾՊՇՅՅԿԩ
 ՋԹՌՍՊԹՌՁՇՆ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՊԽԹՊՁՆԿ ԼԽՆՋՁՌՑ ՄՇԹԼՁՆԿ ՊԹՌԽ ՆՇՌ ԽՐԻԽԽԼ ԹՈՈՊՇՐՁՅԹՌԽՄՑ  ՄԹՊՎԹԽԩ ԻՍՄՌՍՊՁՆԿ ՋՑՋՌԽՅ ԾՇՊ ԾՄՇՏՌՀՊՇՍԿՀ ՋՑՋՌԽՅՋ ՇՊ  ՌԹԼՈՇՄԽՋԩ ՁՆ ՋՌԹՌՁԻՊԽՆԽՏԹՄ ԽՐՈՇՋՍՊԽՋՑՋՌԽՅՋԱՑՈԽՇԾԾՇՇԼ԰ԽՊԹԪՁԻՊՇՆն ԢԭԞՊԽԻՇՅՅԽՆԼՋ԰ԽՊԹԪՁԻՊՇՆ ն ՌՀՊՇՍԿՀՇՍՌ ՈՊԽԽՐՈՇՋՍՊԽ
ԹԾՌԽՊԫԣՋՌԹԿԽԹՆԼ ԼՍՊՁՆԿՌՀԽԽՆՌՁՊԽԼԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԦԾ ԹՆՇՌՀԽՊԼՁԽՌՁՋՍՋԽԼՌՀԽՋՌՍԼՑՊԽՈՇՊՌՋՀՇՍՄԼ ՈՊՇՎՁԼԽԹՆԹՄՑՋՁՋՇԾՁՇԼՁԼԽԻՇՆՌԽՆՌԹՆԼՈՇՌԽՆՌՁԹՄ ԻՇՆՌԹՅՁՆԹՆՌՋԹՆԼՌՀԽԼՁԽՌՋՀՇՍՄԼ ԼԽՅՇՆՋՌՊԹՌԽԽՉՍԹՄՈԽՊԾՇՊՅԹՆԻԽՌՇ԰ԽՊԹ

ԪՁԻՊՇՆ ն ԰ՇՍՊԻԽՇԾԾՇՇԼ԰ԽՊԹԫՇՊՌՀԞՅԽՊՁԻԹԪՇՆՌԿՇՅԽՊՑՎՁՄՄԽԭԞԦՇԼՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆԼՁԽՌ
ՁԾՃՆՇՏՆԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿՌՁՅԽՋԼԹՑ ԡՍՊՁՆԿԹԻԻՄՁՅԹՌՁՇՆՌԹԼՈՇՄԽՋՏԽՊԽԾԽԼԺԽԿՁՆՆՁՆԿԾՇՍՊԼԹՑՋԹԾՌԽՊԽԿԿԻՇՄՄԽԻՌՁՇՆ԰ԽՊԹԪՁԻՊՇՆՏԹՋԼԽՄՁՎԽՊԽԼԹՋՅԿՅԩՋՍՋՈԽՆՋՁՇՆ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾԽԽԼՁՆԿՇԻԻՍՊԹՌՄԽԹՋՌ

ՌՏՁԻԽՈԽՊԼԹՑԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿՊԽԿՁՅԽ ԡՍՊՁՆԿՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌՌԹԼՈՇՄԽՋՏԽՊԽԾԽԼՌՀՊԽԽՌՁՅԽՋԼԹՁՄՑԽՐԻԽՈՌՇՆՌՀԽՄԹՋՌԼԹՑՏՀԽՆՌՀԽՑՏԽՊԽԾԽԼՇՆՄՑՇՆԻԽԣԽԽԼՁՆԿՊԹՌԽՋԼՍՊՁՆԿՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌՏԽՊԽԹԼՂՍՋՌԽԼԾՇՊՌԹԼՈՇՄԽԿՊՇՏՌՀՌՇՅԹՁՆՌԹՁՆԹԻՇՆՋՌԹՆՌԾԽԽԼՁՆԿՊԹՌԽԡԹՑՅԿԹՆՁՅԹՄԼԹՑԡԹՑՅԿԹՆՁՅԹՄԼԹՑԡԹՑՅԿԹՆՁՅԹՄԼԹՑԡԹՑՅԿԹՆՁՅԹՄԼԹՑԡԹՑՅԿԹՆՁՅԹՄԼԹՑԲՆԽԹՌԽՆԾՇՇԼԹՆԼՏԹՋՌԽՏԹՋՊԽՅՇՎԽԼԺՑՋՁՈՀՇՆՁՆԿԼԹՁՄՑ ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋԼՍՊՁՆԿՌՀԽ ՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԺԽՁՆԻՊԽԹՋԽԼԹՄՇՆԿՏՁՌՀ ՄԹՊՎԹՄԿՊՇՏՌՀՌՇԹՈՈՊՇՐՁՅԹՌԽՄՑ ՅԿՄԹՊՎԹԼԹՑԺՑՌԽՋՌՁՆՁՌՁԹՌՁՇՆԢԭԞԹՆԼ ԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋՁՆԻՊԽԹՋԽ ԾՊՇՅՅԿՄԹՊՎԹԼԹՑԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
԰ՌՍԼՑ ԡԹՑՌՇՅԿՄԹՊՎԹԼԹՑՁՆՌՀԽՄԹՋՌՏԽԽՃ ՇԾՌՀԽՌԽՋՌ
԰ՌՍԼՑԡԹՑԡՁԼԣԽԽԼՁՆԿԯԽԿՁՅԽԾՇՄՄՇՏԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋ!ԫՇ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԠԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱՑՈԽՇԾԽՐՈՇՋՍՊԽԣՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏՌՀՊՇՍԿՀ

ՋՑՋՌԽՅԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅ
ՁԾԹՈՈՄՁԻԹԺՄԽԠՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋ  ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ ՊԽԻՇՅՅԽՆԼԽԼ ԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽ
ՁԾԹՈՈՄՁԻԹԺՄԽՅԩՅՁՆ ԞՈՈՊՇՐՁՅԹՌԽՄՑՎՇՄՍՅԽԹԼԼՁՌՁՇՆՋ
ԩԽԹԻՀՈԽՊԻՀԹՅԺԽՊՈԽՊԼԹՑ ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋ ՅԩՅՁՆ
ԻՇՅՈՄԽՌԽՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԻԹ
ԽՎԽՊՑՀՊՋԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋ
ՁԾԹՈՈՄՁԻԹԺՄԽ԰ՌՇԻՃՋՇՄՍՌՁՇՆՏԹՋԼԽՄՁՎԽՊԽԼՌՇՅՁՐՁՆԿԻՀԹՅԺԽՊՋՍՋՁՆԿԹՋՑՊՁՆԿԽՈՍՅՈ
ՌԹՊԿԽՌՊԹՌԽȝԩՅՁՆԯՇՌԹՅԽՌԽՊՋՏԽՊԽՍՋԽԼՌՇԻՇՆՌՊՇՄՌՀԽԾՄՇՏՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ
ՌԹՊԿԽՌՊԹՌԽՅԩՅՁՆՌՇԽԹԻՀՅՁՐՁՆԿԻՀԹՅԺԽՊԱՀԽՅՁՐԽԼՌԽՋՌՋՇՄՍՌՁՇՆՏԹՋԼԽՄՁՎԽՊԽԼՌՇՌԽՋՌԻՀԹՅԺԽՊՋՍՋՁՆԿԹՈԽՊՁՋՌԹՄՌՁԻՈՍՅՈ
ՌԹՊԿԽՌՊԹՌԽՅԩՅՁՆԱԽՋՌՋՇՄՍՌՁՇՆՋՏԽՊԽՋՌՁՊՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑԹՆԼՈՊՇՌԽԻՌԽԼԾՊՇՅՄՁԿՀՌԭՍՅՈՋԹՆԼՊՇՌԹՅԽՌԽՊՋՏԽՊԽԻԹՄՁԺՊԹՌԽԼՈՊՁՇՊՌՇՌՀԽՌԽՋՌԹՆԼՏԽԽՃՄՑՌՀԽՊԽԹԾՌԽՊԣՄՇՏՊԹՌԽՏԹՋԻՀԽԻՃԽԼԾՇՊԽԹԻՀՊԽՈՄՁԻԹՌԽԹՆԼՅԹՁՆՌԹՁՆԽԼՇԾՌՀԽՅԽԹՆԾՇՊԹՄՄՊԽՈՄՁԻԹՌԽՋԱԽՋՌՋՍԺՋՌԹՆԻԽՏԹՋՁՆՌՊՇԼՍԻԽԼՁՆՌՇԻՀԹՅԺԽՊՋԽՁՌՀԽՊՌՀՊԽԽ
ՈՇԾՋՌՍԼՑՊԽՈՇՊՌՇՊՋՁՐՈԼԹՑՋՈՊՁՇՊՌՇՁՆՌՊՇԼՍԻՌՁՇՆՇԾՌԽՋՌՇՊԿԹՆՁՋՅՋԱՀԽՈՊՁՅԹՊՑՋՌՇԻՃՋՇՄՍՌՁՇՆ
ՅԿԹՁՅԩՏԹՋԼՁՄՍՌԽԼՈՊՇՈՇՊՌՁՇՆԹՄՄՑՌՇՈՊԽՈԹՊԽՌՏՇՋԽԻՇՆԼԹՊՑՋՌՇԻՃՋՇՄՍՌՁՇՆՋ
ԹՆԼՅԿԹՁՅԩ԰ՌՇԻՃՋՇՄՍՌՁՇՆՋՏԽՊԽՅՁՐԽԼԺՑՁՆՎԽՊՋՁՇՆԹՆԼՊԹՆԿԽԼՁՆԹՈՈԽԹՊԹՆԻԽԾՊՇՅԻՄԽԹՊԹՆԼԻՇՄՇՊՄԽՋՋՌՇԻՄԽԹՊԹՆԼՋՄՁԿՀՌՄՑՑԽՄՄՇՏԣՊԽՋՀԹՄՁՉՍՇՌՋՇԾՊԽԾՊՁԿԽՊԹՌԽԼՋՌՇԻՃՋՇՄՍՌՁՇՆՏԽՊԽԼԽՄՁՎԽՊԽԼՌՇՌՀԽԽՐՈՇՋՍՊԽՋՑՋՌԽՅՏԽԽՃՄՑ ԯԽԻՇՅՅԽՆԼԽԼՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊ ԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋԪՁՐՁՆԿԻՀԹՅԺԽՊՁՋ ՊԽԻՇՅՅԽՆԼԽԼԺՍՌՆՇՌՊԽՉՍՁՊԽԼԞԽՊԹՌՁՇՆ ՁՋՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՅՁՐՁՆԿԞ ԼԽՅՇՆՋՌՊԹՌՁՇՆՌՀԹՌՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՁՋ ԻՇՅՈՄԽՌԽՄՑՅՁՐԽԼԺԽԾՇՊԽՁՆՌՊՇԼՍԻԽԼՁՆՌՇՌՀԽ ՌԽՋՌՋՑՋՌԽՅՁՋՊԽԻՇՅՅԽՆԼԽԼԱՀԽ ՊԽԻՇՅՅԽՆԼԽԼԾՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑՁՋ

ՏՁՌՀՁՆԯԽՆԽՏԹՄՈԽՊՁՇԼԾՇՊՋՌԹՌՁԻՊԽՆԽՏԹՄ
ՁԾԹՈՈՄՁԻԹԺՄԽՀՊՋ  ԦԾՋՌԹՌՁԻՊԽՆԽՏԹՄՁՋՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋ ՀՊՊԽՆԽՏԹՄՊԽՆԽՏԹՄՈԽՊՁՇԼՁՋ ՊԽԻՇՅՅԽՆԼԽԼՆՇՌՌՇԽՐԻԽԽԼՀՇՍՊՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԽՊԹՌՁՇՆ!ԶԽՋԟԽԿՁՆՆՁՆԿՇՆԡԹՑԺԽԻԹՍՋԽՇԾԼԽԻՊԽԹՋՁՆԿԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆԡԬՄԽՎԽՄՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՅԹՁՆՌԹՁՆՁՆԿԼՁՋՋՇՄՎԽԼ ՇՐՑԿԽՆԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԹՁՊՋԹՌՍՊԹՌՁՇՆ

ՅԿԩ ԞԽՊԹՌՁՇՆՅԹՑԺԽՅԹՁՆՌԹՁՆԽԼ ՌՀՊՇՍԿՀԺՍԺԺՄԽՊՋԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՇՋԽՌ ԺՍԺԺՄԽՊՋԹՌՄԽՎԽՄՋՌՀԹՌԼՇՆՇՌԻԹՍՋԽՋՌՊԽՋՋ ՇՆՌՀԽՌԹԼՈՇՄԽՋ԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ ՆԹՌՍՊԹՄՏԹՌԽՊԴԽՄՄՏԹՌԽՊԡՁՄՍՌՁՇՆՏԹՌԽՊՏԹՋՇԺՌԹՁՆԽԼԾՊՇՅԹՆՇՆՋՁՌԽՏԽՄՄԹՈՈՊՇՐՁՅԹՌԽՄՑՅԼԽԽՈԹՆԼՏԹՋԻՀԹՊԹԻՌԽՊՁՒԽԼԹՋՅՇԼԽՊԹՌԽՄՑՀԹՊԼԴԹՌԽՊՏԹՋԾՁՄՌԽՊԽԼՌՏՁԻԽԾՁՊՋՌՌՇՍՅՍՋՁՆԿԹՋԹՆԼԾՁՄՌԽՊԹՆԼՌՀԽՆՌՇՍՅԹՆԼՍՄՌՊԹՎՁՇՄԽՌ
ԲԳՋՌԽՊՁՄՁՒԽԼՈՊՁՇՊՌՇՍՋԽ ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼ ՏԹՌԽՊՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄՏԹՌԽՊ ԺԽՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊ ՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊ ՈՇՋՋՁԺՄԽԻՇՆՌԹՅՁՆԹՆՌՋՁՆԻՄՍԼՁՆԿՃՆՇՏՆ ՋՍԺՋՌՊԹՌԽՋՇԾՌՀԽՁՇԼՁՆԽՌՊԹՆՋՈՇՊՌԽՊՇԾՌՀԽ ՌՀՑՊՇՁԼԿՄԹՆԼ
ԽԿ ԾՄՍՇՊՁԼԽԻՀՄՇՊԹՌԽ ՈԽՊԻՀՄՇՊԹՌԽԬԢԠԡԹԻԻԽՈՌՋԹՆՑՏԹՌԽՊՁՆ ՏՀՁԻՀՌՀԽՌԽՋՌՋՈԽԻՁԽՋՋՀՇՏԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄ ԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌ

ԿՍՁԼԽՄՁՆԽԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!ԶԽՋ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԦՇԼՁԼԽՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՆՏԹՌԽՊ!ԫՇ  ԦԾՊԽԻՇՆՋՌՁՌՍՌԽԼՏԹՌԽՊՁՋՍՋԽԼՇՊՁԾ ԺԹԻՃԿՊՇՍՆԼՄԽՎԽՄՋՇԾՁՇԼՁԼԽՁՆՆԹՌՍՊԹՄՏԹՌԽՊ ԹՊԽՄԽՋՋՌՀԹՆսԿԩՁՇԼՁԼԽ ՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՋՊԽԻՇՅՅԽՆԼԽԼԱՀՁՋ ՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՋՁՆԹԼԼՁՌՁՇՆՌՇՌՀԽ ՊԽԻՇՅՅԽՆԼԽԼԼՁԽՌԹՊՑՋՇՍՊԻԽՇԾՁՇԼՁԼԽ ԽԿՁՆ԰ԽՊԹԪՁԻՊՇՆԱԽՋՌՎԽՋՋԽՄՌՑՈԽՅԹՌԽՊՁԹՄՋ ԿՄԹՋՋԹՉՍԹՊՁԹ ԢԭԞ ԹՆԼ ԬԢԠԡ ՊԽԻՇՅՅԽՆԼ ՌՀԹՌ ՏԹՌԽՊԻՇՆՌԹԻՌ ՈՇՊՌՁՇՆՋ ՇԾ ՌՀԽ ՋՑՋՌԽՅ ՆՇՌ ԻՇՅՈՊՇՅՁՋԽ ՌՀԽ ՋՌՍԼՑ 
ԽԿ ԹՄՄ ԿՄԹՋՋ ՎԽՋՋԽՄՋՇՊԿՄԹՋՋՎԽՋՋԽՄՋՏՁՌՀՋՌԹՁՆՄԽՋՋՋՌԽԽՄ ԾՊԹՅԽՋԹՊԽԹԻԻԽՈՌԹԺՄԽԽՐԹՅՈՄԽՋԱԽՋՌՎԽՋՋԽՄՋՁՒԽ12 LԣՁՄՄՎՇՄՍՅԽԩԴԹՌԽՊԼԽՈՌՀՏԹՋԻՅԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽՋՑՋՌԽՅԱՀԽՌԽՋՌԻՀԹՅԺԽՊՋԹՆԼԼԽՄՁՎԽՊՑՋՑՋՌԽՅՏԽՊԽՅԹՁՆՌԹՁՆԽԼՁՆԹՌԽՅՈԽՊԹՌՍՊԽԻՇՆՌՊՇՄՄԽԼԽՆՎՁՊՇՆՅԽՆՌԹՄԻՀԹՅԺԽՊԱՊԽԹՌՅԽՆՌԿՊՇՍՈՋՇԾՌԽՋՌԻՀԹՅԺԽՊՋՏԽՊԽՊԹՆԼՇՅՄՑՈՇՋՁՌՁՇՆԽԼ
ԺՄՇԻՃԽԼԺՑՌՊԽԹՌՅԽՆՌՏՁՌՀՁՆՌՀԽԻՀԹՅԺԽՊԦՆԹԼԼՁՌՁՇՆՌՇՌՀԽՅԽԹՋՍՊԽՅԽՆՌՁՆՌԽՊՎԹՄՋԼԽՋԻՊՁԺԽԼՁՆԱԹԺՄԽՌԽՅՈԽՊԹՌՍՊԽՏԹՋՅԽԹՋՍՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑ
ՅՁՆՅԹՐՌՀԽՊՅՇՅԽՌԽՊՁՆՇՆԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՊԽՈՄՁԻԹՌԽԹՆԼԡԬՏԹՋՅԽԹՋՍՊԽԼՌՀՊԽԽՌՁՅԽՋՏԽԽՃՄՑԹԾՌԽՊԹԽՊԹՌՁՇՆՏԹՋՁՆՁՌՁԹՌԽԼՇՆԡԹՑ԰ՈԽԻՁԾՁԻԻՇՆԼՍԻՌԹՆԻԽՏԹՋԹՄՋՇՅԽԹՋՍՊԽԼՏԽԽՃՄՑՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈԬՆԡԹՑՌՀԽՊԽՏԹՋԹՋՄՁԿՀՌԹՆԼՌՊԹՆՋՁԽՆՌԼՊՇՈՁՆՌԽՅՈԽՊԹՌՍՊԽՁՆՇՆԽՊԽՈՄՁԻԹՌԽՇԾՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԫՇԹԼՎԽՊՋԽՁՅՈԹԻՌՋՇՆՌՀԽՌԹԼՈՇՄԽՋՁՆՌՀԹՌՊԽՈՄՁԻԹՌԽՏԽՊԽՊԽՈՇՊՌԽԼԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԥԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬ   ԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՀԹՊԼՆԽՋՋՌՇՅԿԩԹՋԠԹԠԬ

Ոԥ  ԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥչՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆՅԿԩ   ԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ԡԬ ՅԿԩ
 ԹՁՊ ՋԹՌՍՊԹՌՁՇՆԬԢԠԡՊԽԻՇՅՅԽՆԼՋ ԡԬԻՇՆԻԽՆՌՊԹՌՁՇՆ ՅԿԩ

ԹՁՊՋԹՌՍՊԹՌՁՇՆԱԽՅՈԽՊԹՌՍՊԽոԠ    ԻՇՆՌՁՆՍՇՍՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչ Շ ԠՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼ ՁՆՌԽՊՌՊԽԹՌՅԽՆՌԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼ Շ ԠԦՇԼՁԼԽ
սԿԩ   ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՉՍԹՌՁԻՁՇԼՁԼԽՊԹՆԿԽսԿԩ
ՋՍՈՈՄԽՅԽՆՌԹՄ ՁՇԼՁԼԽՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼսԿԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞՅՅՇՆՁԹ
սԿԩ    ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞ ՊԽԻՇՅՅԽՆԼՋՌՀԹՌՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋԺԽՅԽԹՋՍՊԽԼՁՆԹԻՇՆՌՊ ՇՄ ԹՆԼԹՌՇՆԽՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՄԽԹՋՌՏԽԽՃՄՑԦՆՋՌԹՌՁԻ ՊԽՆԽՏԹՄ ՋՑՋՌԽՅՋՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋՁՆԻՄՍԼՁՆԿԹՅՅՇՆՁԹՋՀՇՍՄԼԺԽ ՅԽԹՋՍՊԽԼՂՍՋՌՈՊՁՇՊՌՇՊԽՆԽՏԹՄԦՆԹԼԼՁՌՁՇՆԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹ ՌԡԬ ԺԽՅԽԹՋՍՊԽԼԹՌԽԹԻՀԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌ ՌԽՅՈԽՊԹՌՍՊԽԺԽՅԽԹՋՍՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑԬԢԠԡՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԡԬ ԹՆԼՌԽՅՈԽՊԹՌՍՊԽԺԽՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌՈԥԹՆԼ ՀԹՊԼՆԽՋՋԺԽՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌԹՌՌՀԽԺԽԿՁՆՆՁՆԿԹՆԼԽՆԼՇԾՌՀԽՌ ԽՋՌԣՄՍՇՊՁԼԽ
ՅԿԩ   ԭԽՊԻՀՄՇՊԹՌԽ
սԿԩ   ԠՀՄՇՊԹՌԽ
սԿԩ  ԞՄՃԹՄՁՆՁՌՑ
ՅԿԨԹՋԠԹԠԬ   ԼԹՑՋ԰ՈԽԻՁԾՁԻԠՇՆԼՍԻՌԹՆԻԽՍ԰ԻՅ   ԼԹՑՋԱԹԺՄԽԠՇՅՅԽՆՌՋ•ԱՀԽՅՁՆՁՅՍՅԹՆԼՅԹՐՁՅՍՅՅԽԹՋՍՊԽՋԾՇՊՌԽՅՈԽՊԹՌՍՊԽԹՊԽԾՊՇՅԻՇՆՌՁՆՍՇՍՋՅՇՆՁՌՇՊՁՆԿՁՆՇՆԽՊԽՈՄՁԻԹՌԽՇԾՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԪԽԹՆՌԽՅՈԽՊԹՌՍՊԽՋՈԽՊՌՊԽԹՌՅԽՆՌԼԽՌԽՊՅՁՆԽԼՏԽԽՃՄՑՊԹՆԿԽԼԾՊՇՅՌՇԼԽԿԠ•ԥԹՊԼՆԽՋՋԹՄՃԹՄՁՆՁՌՑԹՆԼՋՈԽԻՁԾՁԻԻՇՆԼՍԻՌԹՆԻԽՏԽՊԽՅԽԹՋՍՊԽԼՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄ ԡ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ!ԶԽՋ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!԰ՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌԽՋՌԻՇՅՈՇՍՆԼԞՈՈՊՇՐՁՅԹՌԽՄՑՅԿԹՁԩԺԹՋԽԼՇՆԾՍՆԻՌՁՇՆԹՄՋՇՄՍԺՁՄՁՌՑՌՊՁԹՄՋՁՆՏԽՄՄՏԹՌԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ  ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ԰ՈԽԻՁԽՋ ԵԽՆՇՈՍՋՄԹԽՎՁՋԫՇՌՋՈԽԻՁԾՁԽԼՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌՏՀՁԻՀՇՆՄՑՊԽԾԽՊՋՌՇՌԹԼՈՇՄԽՋԥՇՏԽՎԽՊԴՁՄԼՄՁԾԽԦՆՌՄԩՌԼԼՇԽՋՆՇՌԻՍՊՊԽՆՌՄՑՅԹՁՆՌԹՁՆԹՆՑՁՆՀՇՍՋԽՋՌՇԻՃՋՇԾՇՌՀԽՊԾՊՇԿՋՈԽԻՁԽՋԩՁԾԽՋՌԹԿԽՆՇՌՊԽՈՇՊՌԽԼԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԫՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽԹՆԼՅԿԹՁԩԱՀԽՊԽՏԽՊԽՆՇՇՎԽՊՌՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑՇՊՅՇՊՌԹՄՁՌՑԟՇԼՑՏԽՁԿՀՌՏԹՋՊԽԼՍԻԽԼԹՌՌՀԽՌՏՇՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼՄԽՆԿՌՀՏԹՋՊԽԼՍԻԽԼԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԺՇՌՀԻՇՅՈԹՊԽԼՌՇՈՇՇՄԽԼԻՇՆՌՊՇՄՋԟՇԼՑՏԽՁԿՀՌՏԹՋԻՇՆՋՁԼԽՊԽԼՌՀԽՅՇՋՌՋԽՆՋՁՌՁՎԽԽՆԼՈՇՁՆՌԡԪԣՏԹՋՍՋԽԼԹՋԹՋՇՄՎԽՆՌԞՆԹՄՑՌՁԻԹՄՊԽԻՇՎԽՊՁԽՋՊԹՆԿԽԼԾՊՇՅՇՆԼԹՑԺՍՌԹԻՌՍԹՄՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋ  ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ԼՍՊԹՌՁՇՆ ՇԾ ՌՀԽ ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԼԹՑՋԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ԰ՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌԽՋՌԻՇՅՈՇՍՆԼԞՄՋՇԻՇՆՋՁԼԽՊԽԼՊԹՆԿԽԾՁՆԼԽՊՊԽՋՍՄՌՋԹՆԼՃՆՇՏՆԩԠՎԹՄՍԽՋԾՇՊՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ  ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽԫԞ ԱՀԽՊԹՆԿԽԾՁՆԼԽՊՁՋԺՊՁԽԾՄՑԼԽՋԻՊՁԺԽԼՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌԾՇՊՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ՅԹՐՁՅՍՅ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՋԽՈԹՊԹՌՁՇՆ ԺԽ  ԹՆԼ ՌՀԽ ՅՁՆՁՅՍՅԺԽԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄՁԾԹՈՈՊՇՈՊՁԹՌԽԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!ԶԽՋ ԰ՌՇԻՃՋՇՄՍՌՁՇՆՋՏԽՊԽՈՊԽՈԹՊԽԼՇՆԻԽԹՆԼՌԽՋՌՋՇՄՍՌՁՇՆՋՏԽՊԽԹԼՂՍՋՌԽԼՌՇԹՁԺԹՋԽԼՇՆՌՀԽՊԽՈՇՊՌԽԼՌԽՋՌՋՍԺՋՌԹՆԻԽՈՍՊՁՌՑ
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋԿԽՇՅԽՌՊՁԻՅԽԹՆ ԠԽՆՌՊՁԾՍԿԽԼՋԹՅՈՄԽՋՏԽՊԽՍՋԽԼԹՌՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿԹՁԩ ԠԹՄԻՍՄԹՌԽԼԹՋՌՀԽՈՊՇԼՍԻՌՇԾՌՀԽՄՇՏԽՋՌԻԹՄՁԺՊԹՌՁՇՆՋՌԹՆԼԹՊԼ
ՅԿԹՁԩԹՆԼՌՀԽԼՁՄՍՌՁՇՆԾԹԻՌՇՊՇԾՅԹՌՊՁՐԺՄԹՆՃՋԹՅՈՄԽՋ
ԣՇՍՊՅԹՌՊՁՐԺՄԹՆՃՋՏԽՊԽԹՆԹՄՑՒԽԼԹՆԼՆՇՁՆՌԽՊԾԽՊԽՆԻԽԺԹԻՃԿՊՇՍՆԼՏԹՋՇԺՋԽՊՎԽԼԹՌՇՊԹԺՇՎԽՌՀԽԩԬԮ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡ ՅԿԹՁԩԫՇՌՊԽՈՇՊՌԽԼԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԼԹՑՋ ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ ԺԽՅԽԹՋՍՊԽԼՁՆՇՆԽՌԹՆՃԹՌԽԹԻՀՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԹՆԼԽՎԽՊՑՏԽԽՃ

ՌՀԽՊԽԹԾՌԽՊԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ  ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԽՍՋԽՇԾԹ ԻՇՆԻՍՊՊԽՆՌՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿ ԹԿԽՆՌՁՋՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՄԹՊՎԹԽՈԽՊՌՊԽԹՌՅԽՆՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ՌԹԼՈՇՄԽՋՈԽՊՌԹՆՃՐՌԹՆՃՋ
ՊԽՈՄՁԻԹՌԽՋՈԽՊՌՊԽԹՌՅԽՆՌԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ!ԶԽՋԭՊԽՄՁՅՁՆԹՊՑՌՊՁԹՄՋՏԽՊԽՍՆՋՍԻԻԽՋՋԾՍՄԹՌՅԹՁՆՌԹՁՆՁՆԿՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՌՌՀԽԾՍՆԻՌՁՇՆԹՄՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌ
ՅԿԹՁԩՏՁՌՀՇՍՌՍՋԽՇԾԹՋՇՄՎԽՆՌ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԡԪԣԥԭԩԠԿՊԹԼԽԼՁՅԽՌՀՑՄԾՇՊՅԹՅՁԼԽ
ԡԪԣԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁԾԹՈՈՄՁԻԹԺՄԽՅԩԩ ԰ՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՏԹՋՌՀԽՋԹՅԽԹԻՊՇՋՋԹՄՄՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԹՆԼՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌԽՐԻԽԽԼ

ՅՄԩ ԬԢԠԡՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՇՄՎԽՆՌ ՀԹՎԽՆՇԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊՈՊՇԼՍԻԽԹՆՑ ՇՌՀԽՊԹԼՎԽՊՋԽԽԾԾԽԻՌՋԹՆԼՌՀԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆ ՆՇՌԺԽԿՊԽԹՌԽՊՌՀԹՆՅՄԩ ԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏԞՉՍԹՌՁԻԱՇՐՁԻՇՄՇԿՑՈՈ-ԬԢԠԡ
ԤՍՁԼԹՆԻԽԡՇԻՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋՇՆԱԽՋՌՁՆԿԹՆԼԞՋՋԽՋՋՅԽՆՌԫՇԭԹՊՁՋԣՊԹՆԻԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԹՈՇՋՁՌՁՎԽԻՇՆՌՊՇՄՍՋԽԼ! ԫՇԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՋՁԾԹՈՈՄՁԻԹԺՄԽԫԞ ԭՀՇՌՇՈԽՊՁՇԼՄՁԿՀՌԼԹՊՃՀՊՋ ԞՅԺՁԽՆՌՄԹԺՇՊԹՌՇՊՑՄՁԿՀՌԾՄՍՇՊԽՋԻԽՆՌԺՍՄԺՋՋՁՅՁՄԹՊՌՇՆԹՌՍՊԹՄՋՍՆՄՁԿՀՌՏՁՌՀՅՁՆՍՌԽՌՊԹՆՋՁՌՁՇՆՈԽՊՁՇԼՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ

ՄՁԿՀՌԼԹՊՃԩՁԿՀՌՁՆՌԽՆՋՁՌՑԹՌՏԹՌԽՊ	ՋՋՍՊԾԹԻԽ ԨՄՍՐԩՁԿՀՌՁՆՌԽՆՋՁՌՑՊԹՆԿԽԼԾՊՇՅՌՇԨՄՍՐԹՆԼՏԹՋՅԽԹՋՍՊԽԼՏԽԽՃՄՑԹՌԾՁՎԽՁՆԼՁՋԻՊՁՅՁՆԹՌԽՄՑՋԽՄԽԻՌԽԼՄՇԻԹՌՁՇՆՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑԨՄՍՐ ԹՌՏԹՌԽՊ	ՋՋՍՊԾԹԻԽԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱԽՋՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑՏՁՌՀdĞƚƌĂĐŚůŽƌǀŝŶƉŚŽƐ;dsWͿԱՊԽԹՌՅԽՆՌԦԡԫՇՅՁՆԹՄԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԪԽԹՋՍՊԽԼԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԪԽԹՆԠԳԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑԫՇՎԹՊՁԹԺՁՄՁՌՑՏԹՋՇԺՋԽՊՎԽԼ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌԽՋՌ ՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՅԹՁՆՌԹՁՆԽԼԹՌ ԹԻՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ
ԠԳ  ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄԫՇՎԹՊՁԹԺՁՄՁՌՑՏԹՋՇԺՋԽՊՎԽԼԱԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ  ԱԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ ԱԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ ԟԹՋԽԼՇՆԻԽՆՌՊՁԾՍԿԽԼՋԹՅՈՄԽՋԪԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆԹՆԼԠԳԾՇՊՍՆԻԽՆՌՊՁԾՍԿԽԼԹՄՁՉՍՇՌՋԾՊՇՅՌՀԽՋԹՅԽՋԹՅՈՄԽՋՏԽՊԽՅԿԹՁԩԹՆԼՊԽՋՈԽԻՌՁՎԽՄՑԭՊԽԻՁՈՁՌԹՌԽՏԹՋՇԺՋԽՊՎԽԼՌՀՊՇՍԿՀՇՍՌՌՀԽՋՌՍԼՑԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ  ԢԬԺՋԽՊՎԹՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋ԰ՍՊՎՁՎԹՄԹՆԼԿԽՆԽՊԹՄՇԺՋԽՊՎԹՌՁՇՆՋՁՆԻՄՍԼՁՆԿՋՍԺՄԽՌՀԹՄԽԾԾԽԻՌՋՏԽՊԽՊԽԻՇՊԼԽԼԼԹՁՄՑԡԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՌՇՌԹՄՄԽՆԿՌՀԺՇԼՑՏԽՁԿՀՌ
ՏԽՌՏԽՁԿՀՌՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩԹՆԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩՏԽՊԽՊԽԻՇՊԼԽԼՇՆԡԹՑՋՍԺՋԹՅՈՄԽԼՌԹԼՈՇՄԽՋԹՆԼԡԹՑ
ՊԽՅԹՁՆՁՆԿՌԹԼՈՇՄԽՋ԰ԳԩԹՆԼԥԩԩՏԽՊԽՅԽԹՋՍՊԽԼՍՋՁՆԿԼՁԿՁՌԹՄՁՅԹԿԽՊՑԥԩԩՏԹՋՅԽԹՋՍՊԽԼԾՇՊՌՀԽՄԽԾՌՀՁՆԼՄՁՅԺԱՀՊՑՇՁԼՀՁՋՌՇՄՇԿՑՏԹՋԽՎԹՄՍԹՌԽԼԾՇՊՌԹԼՈՇՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽԾՇՄՄՇՏՁՆԿՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆԪԽՌՀՇԼՋՏԽՊԽԻՇՆՋՁՋՌԽՆՌՏՁՌՀԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԽՐԻԽՈՌԾՇՊՌՀԽԾՇՄՄՇՏՁՆԿԼԽՎՁԹՌՁՇՆՋ԰ՇՅԽՋՈԽԻՁՅԽՆՋ
ՌԹԼՈՇՄԽՋՋԽՄԽԻՌԽԼԾՇՊՀՁՋՌՇՈԹՌՀՇՄՇԿՑՏԽՊԽՊԽՈՄԹԻԽԼԺԽԻԹՍՋԽԹԼԽՉՍԹՌԽՌՀՑՊՇՁԼՋՄՁԻԽՋՏԽՊԽՆՇՌՇԺՌԹՁՆԽԼ԰ՄՁԼԽՋՏԽՊԽԺՄՁՆԼԽԼԺԽԾՇՊԽԺԽՁՆԿՋՍԺՅՁՌՌԽԼՌՇՌՀԽՈԹՌՀՇՄՇԿՁՋՌԾՇՊՊԽՎՁԽՏԢՎԹՄՍԹՌՁՇՆՇԾՌՀԽՌՀՑՊՇՁԼՏԹՋԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇԻՇՆՌՊՇՄՋԹՅՈՄԽՋԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ!ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՅՇՊՌԹՄՁՌՑԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆ ՋՇԻԻՍՊԼԹՁՄՑԹՌԹՅՁՆՁՅՍՅՇՌՀԽՊՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽՊԽԻՇՅՅԽՆԼԽԼ ԹՋԾՇՄՄՇՏՋԫԣ ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ
ԼԹՑՋԹՆԼԹՆՑԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽ ՆՌՁՆԼՁԻԹՌԽԼԺՑՌԹԼՈՇՄԽՋՌՀԹՌԻԹՆՆՇՌԺԽԹՋՋՁԿՆԽԼԹՆԫԣՋՌԹԿԽ ԼԹՑՋԹՆԼ ՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԼԹՑՋԹՆԼՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
ԼԹՑՋ ԹՆԼԺՇԼՑՏԽՁԿՀՌ
ՌԽՋՌՁՆՁՌՁԹՌՁՇՆԾՇՊՇՈՌՁՇՆԹՄՋՁՒԽԺԹՋ ԽԼՄԹՊՎԹՄՋԽՄԽԻՌՁՇՆ ԹՆԼՌՀՑՊՇՁԼԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑ
ԼԹՑ ԫՇՌԽՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՑՋԽԻՌՁՇՆՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԹՄՋՇՁՆԻ ՄՍԼԽՋՌՀՑՊՇՁԼԿՊՇՋՋ

ՈԹՌՀՇՄՇԿՑՇԺՋԽՊՎԹՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԦԦ ԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫ

Ԟ ԯԽՋՍՄՌՋ

ԪՇՊՌԹՄՁՌՑՁՆԻՊԽԹՋԽԼՋՄՁԿՀՌՄՑՏՁՌՀՌՀԽՁՆԻՊԽԹՋՁՆԿՌԽՋՌԻՇՆԻԽՆՌՊԹ ՌՁՇՆՋԬՎԽՊԹՄՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄՅՇՊՌԹՄՁՌՑ


ՇՊՏԹՋՋՄՁԿՀՌՄՑՀՁԿՀԽՊՌՀԹՆՅՇՊՌԹՄՁՌՑԹՌՌՀԽՌՏՇՄՇՏԽՊՌՊ ԽԹՌՅԽՆՌՄԽՎԽՄՋ
ԹՆԼՅԿԹՁԩ

ՅԽԹՆՅԽԹՋՍՊԽԼԪՇՊՌԹՄՁՌՑԹՌՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
Յ ԿԹՁԩՅԽԹՆՅԽԹՋՍՊԽԼՏԹՋ

ԱՀԽՊԽՏԹՋՆՇՅՇՊՌԹՄՁՌՑՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋ

ԱԹԺՄԽԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑՁՆ ĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐ



ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑ

ԡԹՑ  ԡԹՑ

Ն ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ Ն ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ

ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑ

ՁԾՍՋԽԼ      

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԡԪԣ      

      

      

      

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ

 ԰ԹՅՈՄԽՋՁՒԽԹՆԼԻՍՅՍՄԹՌՁՎԽՅՇՊ ՌԹՄՁՌՑՎԹՄՍԽՋԹՌԡԹՑՈՊՁՇՊՌ ՇՁՆՌԽՊՁՅՋԹԻՊՁԾՁԻԽ

ԱԹԺՄԽԠՇՅՅԽՆՌՋ

ԣՇՊՄԹՊՎԹՄՅՇՊՌԹՄՁՌՑՁՆՌՀՁՋՌԹԺՄԽՆՌՇՌԹՄՆՍՅԺԽՊՇԾԹՆՁՅԹՄՋՈ ԽՊՌՊԽԹՌՅԽՆՌ
ԡԹՑՊԽՈՄՁԻԹՌԽՅՇՊՌԹՄՁՌՑ
ՏՀԽՊԽԹՈՈՄՁԻԹԺՄԽ

• ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄԞ
ԟ
Ԡ
ԡ


• ՅԿԹՁԩԞ
ԟ
Ԡ
ԡ


• ՅԿԹՁԩԞ
ԟ
Ԡ
ԡ


• ՅԿԹՁԩԞ
ԟ
Ԡ
ԡ


ԡԹՑՊԽՈՄՁԻԹՌԽՅՇՊՌԹՄՁՌՑ
ՏՀԽՊԽԹՈՈՄՁԻԹԺՄԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  • ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄԞ  ԟ
Ԡ
ԡ


• ՅԿԹՁԩԞ
ԟ
Ԡ
ԡ


• ՅԿԹՁԩԞ
ԟ
Ԡ
ԡ


• ՅԿԹՁԩԞ  ԟ
Ԡ
ԡ  

ԪԽԼՁԹՆԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋՋՁՅՁՄԹՊԹԻՊՇՋՋՌՀԽԻՇՆՌՊՇՄՋԹ ՆԼՄՇՏԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ
ԹՆԼ

ՅԿԹՁԩԪԽԼՁԹՆԫԣՋՌԹԿԽՏԹՋԼԽԻՊԽԹՋԽԼԹՌՌՀԽՀՁԿՀԽՋՌ ՌՊԽԹՌՅԽՆՌՄԽՎԽՄԹՌԺՇՌՀԡԹՑ
ԫԣ

ԹՆԼԡԹՑ
ԫԣՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԫԣ ԹՆԼԫԣԹՌԡԹՑԹՆԼ

ՊԽՋՈԽԻՌՁՎԽՄՑԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋՊԽՈՇՊՌԽԼ

ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆ ĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐ ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽԹՆԼԞՋՑՆԻՀՊՇՆՇՍՋ

ԡԽՎԽՄՇՈՅԽՆՌ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽ

ԡԹՑ ԡԹՑ

Ն ԪԽԼՁԹՆ

԰ՌԹԿԽ ԞՋՑՆԻՀՊՇՆՇՍՋ Ն ԪԽԼՁԹՆ

԰ՌԹԿԽ ԞՋՑՆԻՀՊՇՆՇՍՋ

ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑ

ՁԾՍՋԽԼ      

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԡԪԣ      

      

      

      

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ

ԱԹԺՄԽԠՇՅՅԽՆՌՋ

ԦՆՌՀՁՋՌԹԺՄԽՆՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԩԹՌԽՋՌԹԿԽՌԹԼՈՇՄԽՋ
 ԫԣԹՆԼՅՇՊՌԹՄՁՌՁԽՋՏԽՊԽԽՐԻՄՍԼԽԼԾՊՇՅ ՋՍՅՅԹՊՑԻԹՄԻՍՄԹՌՁՇՆՋՇԾՅԽԹՋՍՊԽԼԽՆԼՈՇՁՆՌՋ

԰Գԩԥԩԩԥԩԩ԰ԳԩԟԴԹՋԾՇՄՄՇՏՋ

• ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄԯԽՈՄՁԻԹՌԽԡ"ԫԣԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  • ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄԯԽՈՄՁԻԹՌԽԞ"ԫԣԹՆԼ"ԫԣ
ԹՄՋՇՅՇ ՊՌԹՄՁՌՁԽՋ

• ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄԯԽՈՄՁԻԹՌԽԟ"ԫԣ
ԹՄՋՇՅՇՊՌԹՄՁՌՑ

• ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄԯԽՈՄՁԻԹՌԽԠ"ԫԣԹՆԼ"ԫԣ
ԹՄՋՇՅՇ ՊՌԹՄՁՌՑ

• ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄԯԽՈՄՁԻԹՌԽԡ"ԫԣ
ԹՄՋՇՅՇՊՌԹՄՁՌՑ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԞ
ՅՇՊՌԹՄՁՌՑ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԟ"ԫԣԹՆԼ"ԫԣ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԠ"ԫԣԹՆԼ"ԫԣ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԞ"ԫԣ
ԹՄՋՇՅՇՊՌԹՄՁՌՑ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԟ"ԫԣ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԠ"ԫԣԹՆԼ"ԫԣ
ԹՄՋՇՅՇՊ ՌԹՄՁՌՁԽՋ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԡ"ԫԣ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԞ
ՅՇՊՌԹՄՁՌՁԽՋՌՀԽՊԽՈՇՊՌԹՄՋՇԻՇՆՌ ԹՁՆԽԼԹԼԹՌԹԽՆՌՊՑԽՊՊՇՊԾՇՊԥԩԩԾՇՊՌԹԼՈՇՄԽ

ՌՀԽՎԹՄՍԽՏԹՋԺԹԻՃԻԹՄԻՍՄԹՌԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԠ
ՅՇՊՌԹՄՁՌՁԽՋ

• ՅԿԹՁԩԯԽՈՄՁԻԹՌԽԡ
ՅՇՊՌԹՄՁՌՁԽՋ

ԪԽԹՆԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼ ՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՊԹՆԿԽԼԾՊՇՅՌՇ

ՁՆՌՀԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ
ԱԹԺՄԽԟՑԡԹՑՆՇՊՅԹՄՁՒԽԼ ԥԩԩԹՎԽՊԹԿԽԼՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՁՆՌՀԽՄՇՏԹՆԼՅՁԼԻՇՆԻԽՆՌՊԹՌՁՇՆԿ ՊՇՍՈՋԹՆԼՁՆՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆԿՊՇՍՈ

ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆ ĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐ ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ
ԥԩԩ

ԡԹՑ ԡԹՑ

Ն ԪԽԹՆ

ՅՅ չ԰ԡ ԥԩԩ

԰Գԩ  Ն ԪԽԹՆ
ՅՅ չ԰ԡ ԥԩԩ

԰Գԩ 

ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊ

ՇՆՄՑՁԾՍՋԽԼ        

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ


ԡԪԣ        

        ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ
ԥԩԩ

ԡԹՑ ԡԹՑ

Ն ԪԽԹՆ

ՅՅ չ԰ԡ ԥԩԩ

԰Գԩ  Ն ԪԽԹՆ
ՅՅ չ԰ԡ ԥԩԩ

԰Գԩ 

        

        

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԰ԡ ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

 ԰ՍՅՅԹՊՑՊԽՋՍՄՌՋԾՇՊՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩԹՊԽՈՊԽՋԽՆՌԽԼՁՆՌՀ ԽՆԽՐՌՌԹԺՄԽ ԱԹԺՄԽ 

ԱԹԺՄԽԠՇՅՅԽՆՌՋ

ԦՆՌՀՁՋՌԹԺՄԽՆՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԡԹՑ԰ԳԩԹՎԽՊԹԿԽԼՅՅՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՁՆՌՀԽ ՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼԹՆԼՅՅ

ՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿ ՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽԟՑԡԹՑ

ՅԽԹՆ԰ԳԩՏԹՋՅՅՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՅՅՁՆՌՀԽՋՇ ՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼԹՆԼՅՅ

ՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿ ՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ

ԡԹՑՏԽՌՏԽՁԿՀՌԹՎԽՊԹԿԽԼԿՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼ

ԹՆԼԿՁՆՌՀԽՄՇՏՅՁԼԹՆԼՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽԡԹՑՏԽՌՏԽՁԿՀՌԹՎԽՊԹԿԽԼ

ԿՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ ԹՆԼԹՆԼԿՊԹՆԿԽԼԾՊՇՅ

ՌՇԿՁՆՌՀԽՄՇՏՅՁԼԹՆԼՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎ ԽՄՑ

ԱԹԺՄԽԩԹՊՎԹՄԤՊՇՏՌՀՁՆ ĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐ



ԱՊԽԹՌՅԽՆՌ
ՅԿ

ԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԰ՆՇՍՌԳԽՆՌԩԽՆԿՌՀ
԰Գԩ ԟՇԼՑԴԽՁԿՀՌ 

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

Ն ԪԽԹՆ

ՅՅ չ԰ԡ Ն ԪԽԹՆ

ՅՅ չ԰

ԡ Ն ԪԽԹՆ

Կ չ԰ԡ Ն ԪԽԹՆ

Կ չ԰ԡ

ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆ

ՏԹՌԽՊՇՆՄՑՁԾ

ՍՋԽԼ            

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ

ԡԪԣ            

            

            

            

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԫԡ ԫՇՌԼԽՌԽՊՅՁՆԽԼ ԰ԡ ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

 ԞՄՋՇՊԽԾԽՊՊԽԼՌՇԹՋՏԽՌՏԽՁԿՀՌՁՆՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽ

ԱԹԺՄԽԠՇՅՅԽՆՌՋ

ԦՆՌՀՁՋՌԹԺՄԽՆՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՀՑՊՇՁԼԿՊՇՋՋԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼԹՌԹԹՊԽՊԽՈՇՊՌԽԼՁՆԱԹԺՄԽՋԹՆԼԦՆՌՀՁՋՋՌՍԼՑՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌԻՇՅՈԹՊԽԼԹՄՄՋԹՅՈՄԽՋ
ՁՆԻՄՍԼՁՆԿՌՀՇՋԽԾՊՇՅՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌՇԹՋԽՌՇԾՊԽԾԽՊԽՆԻԽԻՇՆՌՊՇՄՋԱՀԽՊԽԾԽՊԽՆԻԽԻՇՆՌՊՇՄՋՏԽՊԽԻՇՅՈՊՁՋԽԼՇԾԹԼԼՁՌՁՇՆԹՄՋԹՅՈՄԽՋԾՊՇՅՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԦՆՌՀԽՌԹԺՄԽՋՌՀԹՌԾՇՄՄՇՏՊԽՋՍՄՌՋԾՇՊԺՇՌՀՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋԹՆԼՊԽԾԽՊԽՆԻԽԻՇՆՌՊՇՄՋԹՊԽԿՊՇՍՈԽԼՌՇԿԽՌՀԽՊԱՀՑՊՇՁԼՋԽԻՌՁՇՆՋՏԽՊԽԽՐԹՅՁՆԽԼԺՑՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌՌՇԽՆՋՍՊԽՌՀԹՌՌՀԽՑՏԽՊԽՇԺՌԹՁՆԽԼԾՊՇՅՌՀԽԹՊԽԹՇԾՅԹՐՁՅՍՅԿՄԹՆԼԼՁԹՅԽՌԽՊ԰ՇՅԽՋԽԻՌՁՇՆՋՏԽՊԽՋՍԺՋԽՉՍԽՆՌՄՑՊԽՈՄԹԻԽԼԺՑՆԽՏՋԽԻՌՁՇՆՋԾՊՇՅՊԽՈՄԹԻԽՅԽՆՌՌԹԼՈՇՄԽՋԾՊՇՅՌՀԽՋԹՅԽՊԽՈՄՁԻԹՌԽ
ՌՀՊԽԽՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌՏՇՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌՏՇՁՆՌՀԽՄՇՏՌՊԽԹՌՅԽՆՌԹՆԼՌՀՊԽԽՁՆՌՀԽՅԽԼՁՍՅՌՊԽԹՌՅԽՆՌԴՀԽՊԽՊԽՈՄԹԻԽՅԽՆՌՇԻԻՍՊՊԽԼՌՀԽՋՌՍԼՑՊԽՈՇՊՌՁՆԼՁԻԹՌԽՋՌՀԽՁԼԽՆՌՁՌՑՇԾԺՇՌՀՌՀԽՇՊՁԿՁՆԹՄՄՑՋԽՄԽԻՌԽԼՌԹԼՈՇՄԽԹՆԼՁՌՋՊԽՈՄԹԻԽՅԽՆՌԱԹԺՄԽԤՊՇՋՋԭԹՌՀՇՄՇԿՑԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑՇԾՌՀԽԱՀՑՊՇՁԼԤՄԹՆԼՁՆĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՋՍՊԽԼ%԰ԱՀՑՊՇՁԼԤՄԹՆԼԥՑՈԽՊՌՊՇՈՀՑԱՀՑՊՇՁԼԤՄԹՆԼԞՌՊՇՈՀՑԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥՑՈԽՊՌՊՇՈՀՑԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥՑՈԽՊՈՄԹՋՁԹՆԦՆԻՁԼՆԦՆԻՁԼՆԦՆԻՁԼՆԦՆԻՁԼԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑՁԾՍՋԽԼ                                 ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԡԪԣ                                ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՋՍՊԽԼ%԰ԱՀՑՊՇՁԼԤՄԹՆԼԥՑՈԽՊՌՊՇՈՀՑԱՀՑՊՇՁԼԤՄԹՆԼԞՌՊՇՈՀՑԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥՑՈԽՊՌՊՇՈՀՑԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥՑՈԽՊՈՄԹՋՁԹՆԦՆԻՁԼՆԦՆԻՁԼՆԦՆԻՁԼՆԦՆԻՁԼ                                                                                                 ԱՀՑՊՇՁԼԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑԹՊԽԿՊԹԼԽԼԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԬԢԠԡԫՇԾՇՊՊԽԾԽՊԽՆԻԽԞԺԺՊԽՎՁԹՌՁՇՆՋԦՆԻՁԼ-ԦՆԻՁԼԽՆԻԽ԰-԰ԽՎԽՊՁՌՑԱԹԺՄԽԠՇՅՅԽՆՌՋԦՆՌՀՁՋՌԹԺՄԽՆՌՀԽՆՍՅԺԽՊՇԾԹՆՁՅԹՄՋԽՐԹՅՁՆԽԼՈԽՊՌՊԽԹՌՅԽՆՌԹԻՊՇՋՋԹՄՄՊԽՈՄՁԻԹՌԽՋԱՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՁՆԻՄՍԼԽՋԹՆԹԼԼՁՌՁՇՆԹՄՋԽՌՇԾՊԽԾԽՊԽՆԻԽՋՈԽԻՁՅԽՆՋԾՊՇՅՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈԱՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌՈՊՇՎՁԼԽԼԹԼԼՁՌՁՇՆԹՄՋԽՎԽՊՁՌՑՋԻՇՊԽՋԾՇՊՌՀՑՊՇՁԼԿՄԹՆԼՋՁՒԽ
ՁՆԻՊԽԹՋԽԹՆԼԼԽԻՊԽԹՋԽԱՀՇՋԽՋԻՇՊԽՋԹՊԽՆՇՌՊԽՈՇՊՌԽԼՁՆՌՀՁՋՌԹԺՄԽՋՁՆԻԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾՌՀԽՑՅՁՊՊՇՊԽԼՌՀԽՋԻՇՊԽՋԾՇՊՌՀՑՊՇՁԼԿՄԹՆԼՀՑՈԽՊՌՊՇՈՀՑԹՆԼԹՌՊՇՈՀՑԦՆԼՁՎՁԼՍԹՄՋԽՎԽՊՁՌՑՋԻՇՊԽՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼԾՇՊԾՇՄՄՁԻՍՄԹՊԻԽՄՄՀՑՈԽՊՌՊՇՈՀՑՇՊԾՇՄՄՁԻՍՄԹՊԻԽՄՄՀՑՈԽՊՈՄԹՋՁԹԥՇՏԽՎԽՊՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌՊԽՈՇՊՌԽԼՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋԺԽՌՏԽԽՆՌՊԽԹՌՅԽՆՌՋԹՆԼՌՀԽԻՇՆՌՊՇՄԾՇՊԽՁՌՀԽՊՇԾՌՀԽՋԽԼՁԹԿՆՇՋԽՋ
ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌԽՋՌԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԱՀՑՊՇՁԼԤՄԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՋՍՊԽԼ%԰ԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆԞՊԽԹ
ԦՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆԞՊԽԹ
ԡԽԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥԽՁԿՀՌ
ԦՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥԽՁԿՀՌԡԽԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԠԽՄՄ԰ՀԹՈԽԤՄԹՆԼԞՋՑՅՅԽՌՊՑԦՆԻՊԽԹՋԽԣՇՄՄՁԻՄԽ԰ՁՒԽԦՆԻՊԽԹՋԽԣՇՄՄՁԻՄԽ԰ՁՒԽԡԽԻՊԽԹՋԽՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑՁԾՍՋԽԼ                                                                ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԡԪԣ                                                                                                                                                                                                ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՋՍՊԽԼ%԰ԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆԞՊԽԹ
ԦՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆԞՊԽԹ
ԡԽԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥԽՁԿՀՌ
ԦՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥԽՁԿՀՌԡԽԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊԠԽՄՄ԰ՀԹՈԽԤՄԹՆԼԞՋՑՅՅԽՌՊՑԦՆԻՊԽԹՋԽԣՇՄՄՁԻՄԽ԰ՁՒԽԦՆԻՊԽԹՋԽԣՇՄՄՁԻՄԽ԰ՁՒԽԡԽԻՊԽԹՋԽՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻՆԦՆԻ                                                                 ԱՀՑՊՇՁԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՁՋԿՊԹԼԽԼԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԬԢԠԡԫՇԾՇՊՊԽԾԽՊԽՆԻԽԞԺԺՊԽՎՁԹՌՁՇՆՋԦՆԻ-ԦՆԻՁԼԽՆԻԽ԰-԰ԽՎԽՊՁՌՑԱԹԺՄԽԠՇՅՅԽՆՌՋԦՆԼՁՎՁԼՍԹՄՋԽՎԽՊՁՌՑՋԻՇՊԽՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼԾՇՊԾՇՄՄՁԻՍՄԹՊՄՍՅԽՆԹՊԽԹ
ՁՆԻՊԽԹՋԽՇՊԼԽԻՊԽԹՋԽՊԽԾԽՊՊԽԼՌՇԹՋԻՇՄՄՇՁԼԹՊԽԹՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌԥՇՏԽՎԽՊՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌՊԽՈՇՊՌԽԼՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋԺԽՌՏԽԽՆՌՊԽԹՌՅԽՆՌՋԹՆԼՌՀԽԻՇՆՌՊՇՄԾՇՊԽՁՌՀԽՊՇԾՌՀԽՋԽԼՁԹԿՆՇՋԽՋ
ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌԽՋՌԱՀԽՎԹՄՍԽՋԾՇՊԾՇՄՄՁԻՍՄԹՊԻԽՄՄՀԽՁԿՀՌ
ՁՆԻՊԽԹՋԽԹՆԼԼԽԻՊԽԹՋԽՁՆՌՀՁՋՌԹԺՄԽԹՊԽՌՀՇՋԽՊԽՈՇՊՌԽԼԾՇՊԾՇՄՄՁԻՄԽԹՋՑՅՅԽՌՊՑ
ՁՆԻՊԽԹՋԽԹՆԼԼԽԻՊԽԹՋԽՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌԞՋՑՅՅԽՌՊՑՏԹՋԼԽԾՁՆԽԼՁՆՌՀՁՋՋՌՍԼՑԹՋՌՀԽՊԹՌՁՇՇԾՌՀԽՄՇՆԿԹՐՁՋՌՇՌՀԽՋՀՇՊՌԹՐՁՋՇԾՌՀԽՄԹՊԿԽՋՌԾՇՄՄՁԻՄԽԣՇՊՌՀԽՈՍՊՈՇՋԽՇԾՌՀՁՋՌԹԺՄԽԹՆՁՆԻՊԽԹՋԽՁՆԾՇՄՄՁԻՄԽԹՋՑՅՅԽՌՊՑՁՋՊԽՈՇՊՌԽԼԹՋԹՆՁՆԻՊԽԹՋԽՁՆԻԽՄՄՀԽՁԿՀՌԹՆԼԹԼԽԻՊԽԹՋԽՁՆԾՇՄՄՁԻՄԽԹՋՑՅՅԽՌՊՑՁՋՊԽՈՇՊՌԽԼԹՋԹԼԽԻՊԽԹՋԽՁՆԻԽՄՄՀԽՁԿՀՌԣՇՄՄՁԻՍՄԹՊԻԽՄՄՋՀԹՈԽՏԹՋՆՇՌՊԽՈՇՊՌԽԼԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ
ԻՊՇՇՃԽԼՌԹՁՄՏԹՋՇԺՋԽՊՎԽԼՁՆԹՄՄՊԽՈՄՁԻԹՌԽՋ ՇԾԻՇՆՌՊՇՄՋԹՆԼՁՆՄՇՏԹՆԼՅԽԼՁՍՅՌՊԽԹՌՅԽՆՌՋԫՇ

ՋՈՁՆԹՄԻՍՊՎԹՌՍՊԽՏԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԠՄՁՆՁԻԹՄ ՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑ
ՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅԹՆԼՄՑՁՆԿՇՆ

ՌՀԽՌԹՆՃԺՇՌՌՇՅՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՏՇՇԾՌՀԽՋՍՊՎՁՎՁՆԿՌԹԼՈՇՄԽՋՁՆՀՁԿՀՌՊԽԹՌՅԽՆՌԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԠՄՁՆՁԻԹՄ԰ՁԿՆՋԹՌԱԽՋՌԱԽՊՅՁՆԹՌՁՇՆՁՆ ĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐ


ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԠՄՁՆՁԻԹՄ԰ՁԿՆՋ 

ԱՑՈԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊ

ՇՆՄՑՁԾՍՋԽԼ ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ  

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ


ԡԪԣ ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ  

 ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ  

 ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ  

 ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ  

԰ՅԹՄՄԽՊՁՆՋՁՒԽԻՇՅՈԹՊԽԼՌՇԻՇՆՌՊՇՄՋՈԽԻՁՅԽՆՋ  

ԩՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅ  

ԩՑՁՆԿՇՆԺՇՌՌՇՅՇԾՌԹՆՃ  

ԱԹԺՄԽԠՇՅՅԽՆՌՋ

ԦՆՌՀՁՋՌԹԺՄԽՆՌՀԽՌՇՌԹՄՆՍՅԺԽՊՇԾՋՈԽԻՁՅԽՆՋՈԽՊՌՊԽԹՌՅԽՆՌ ԾՇՊՏՀՁԻՀՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽՊԽՈՇՊՌԽԼԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ

ԡԹՑԱՀԽՋՌՍԼՑՊԽՈՇՊՌԹՄՋՇՁՆԻՄՍԼԽՋՌՀԽՁՆԻՁԼԽՆԻԽՇԾԻՄՁՆ ՁԻԹՄՋՁԿՆՋԺՑԼԹՑՌՀՊՇՍԿՀՇՍՌՌՀԽՋՌՍԼՑ

ԟ ԰ՌՍԼՑԞՍՌՀՇՊ	ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

ԞԾՊՁԻԹՆԻՄԹՏԽԼԾՊՇԿ
ԵԽՆՇՈՍՋՄԹԽՎՁՋՌԹԼՈՇՄԽՋՏԽՊԽԽՐՈՇՋԽԼՌՇՌ ԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԹՌՅԽԹՆ

ՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩԾՇՊ ԼԹՑՋ԰ՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋՏԽՊԽ

ՈԽՊԾՇՊՅԽԼԹՋԾՇՄՄՇՏՋ

• ԰ՍՊՎՁՎԹՄԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ
ՇՆԽՋՁԼԽԼՌԹՆՃԹՋՊԽՈՄՁԻԹՌԽԣ ՁՋՀԽՊ	ՋԢՐԹԻՌ
ՇՆԽՋՁԼԽԼՁՆԼՁՎՁԼՍԹՄ

ՌԹԼՈՇՄԽ

• ԫԣՋՌԹԿԽՅՍՄՌՁՉՍԹՆՌՁՄԽԹՆԹՄՑՋՁՋԺԹՋԽԼՇՆԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ՌՏՇՋՁԼԽԼՌԹՆՃԹՋՊԽՈՄՁԻԹՌԽ

• ԞՄՄՇՌՀԽՊԽՆԼՈՇՁՆՌՋԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ
ՌՏՇՋՁԼԽԼՌԹՆՃԹՋՊ ԽՈՄՁԻԹՌԽԡՍՆՆԽՌՌ	Ջ
ՌՏՇՋՁԼԽԼՌԹՆՃ

ԹՋՊԽՈՄՁԻԹՌԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱՇԼԽՌԽՊՅՁՆԽՏՀԽՌՀԽՊԹՆԽՆԼՈՇՁՆՌԽՐՀՁԺՁՌԽԼԹՅՇՆՇՌՇՆՁԻՌՊԽԹՌՅԽՆ ՌՊԽՋՈՇՆՋԽՌՀԽՊԽՋՈՇՆՋԽՋՏԽՊԽ

ԻՇՆՎԽՊՌԽԼՌՇՊԹՆՃՋԹՆԼՌՀԽՆՊԽԿՊԽՋՋԽԼԹԿԹՁՆՋՌՌՀԽՌՊԽԹՌՅԽՆՌԻՇՆ ԻԽՆՌՊԹՌՁՇՆՍՋՁՆԿԹՉՍԹԼՊԹՌՁԻՈՇՄՑՆՇՅՁԹՄ

ՅՇԼԽՄԱՀԽԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽՊԽՄԹՌՁՇՆՋՀՁՈՏԹՋԻՇՆՋՁԼԽՊԽԼ ՌՇԺԽՅՇՆՇՌՇՆՁԻՁԾՌՀԽՉՍԹԼՊԹՌՁԻՌԽՊՅ

ՏԹՋՆՇՌՋՁԿՆՁԾՁԻԹՆՌ
Ո ՇՊՁԾԺՇՌՀՌՀԽՄՁՆԽԹՊԹՆԼՉՍԹԼՊԹ ՌՁԻՌԽՊՅՋՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌ
ՈԱՀԽ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽՏԹՋԻՇՆՋՁԼԽՊԽԼՌՇԺԽՆՇՆՅՇՆՇՌՇՆՁԻՁԾՌՀ ԽՉՍԹԼՊԹՌՁԻՌԽՊՅՏԹՋՋՁԿՆՁԾՁԻԹՆՌԹՆԼ

ՌՀԽՄՁՆԽԹՊՌԽՊՅՏԹՋՆՇՌՋՁԿՆՁԾՁԻԹՆՌԣՇՊԽՆԼՈՇՁՆՌՋՇՌՀԽՊՌՀԹՆ ԫԣՋՌԹԿԽՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼ

ՌԽՋՌՏԹՋԹՈՈՄՁԽԼՁԾՌՀԽՊԽՋՈՇՆՋԽՏԹՋԼԽՌԽՊՅՁՆԽԼՌՇԺԽՅՇՆՇՌՇՆՁԻ ԱՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌՏԹՋ

ԹՍՌՇՅԹՌՁԻԹՄՄՑԹՈՈՄՁԽԼԾՇՊԫԣՋՌԹԿԽ

ԱՀԽՋՌՍԼՑԹՍՌՀՇՊՋՋՌԹՌԽԼՌՀԹՌՆՇԽԾԾԽԻՌՋՏԽՊԽՇԺՋԽՊՎԽԼՇՆՋՍՊՎՁՎԹՄԿՊՇՏՌՀԹՆԼԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՁՆ

ՌՀԽԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՁՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԱՀԽՊԽՏԽՊԽՌՊԽԹՌՅԽՆՌ

ՊԽՄԹՌԽԼԹՆԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻՌՁՇՆՋՁՆԺՇԼՑՄԽՆԿՌՀ ՏԽՌՏԽՁԿՀՌՋՆՇՍՌՌՇՎԽՆՌՄԽՆԿՌՀԹՆԼ

ՆՇՊՅԹՄՁՒԽԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍ ՈՁՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ԱՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՁՆՌՀԽՀՁՋՌՇՄՇԿՑՏԽՊԽՄՁՅՁՌԽԼՌՇՌՀԽ ՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՅԿԹՁԩԹՆԼ

ՏԽՊԽԻՇՆՋՁՋՌԽՆՌՏՁՌՀԽԾԾԽԻՌՋՋԽԽՆՇՆԿՊՇՏՌՀԽՋՈԽԻՁԹՄՄՑՆՇՊՅԹՄՁ ՒԽԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀ԰ՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋՁՋ

ՇԾՌՀՑՊՇՁԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՇԺՋԽՊՎԹՌՁՇՆՋՏԹՋՈԽՊԾՇՊՅԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆ

ՌԽՋՌԟՄՁՆԼԽԼՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԽՎԹՄՍԹՌՁՇՆՇԾԾՁՎԽԿՊՇՍՈՋՇԾ ԵԽՆՇՈՍՋՄԹԽՎՁՋ ՌԹԼՈՇՄԽՋ
ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՄՇՏՅՁԼԼՄԽԹՆԼՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՎԽԹՄ ԽԼՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԻՀԹՆԿԽՋՁՆ

ԹՆՑՇԾՌՀԽԿՊՇՍՈՋԽՐԻԽՈՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈԱՀԽՀՁԿՀՌՊԽ ԹՌՅԽՆՌԿՊՇՍՈԻՀԹՆԿԽՋԹԻՀՁԽՎԽԼՌՀԽՄԽՎԽՄ

ՇԾՋՌԹՌՁՋՌՁԻԹՄՋՁԿՆՁԾՁԻԹՆԻԽ
ՈՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌ ՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈԺՍՌՆՇՌՏՀԽՆԻՇՅՈԹՊԽԼ

ՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈԱՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌՋՍԿԿԽՋՌԽԼՌՀ ԹՌՌՀՁՋՁՋԺԽԻԹՍՋԽՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈ

ՋՀՇՏԽԼՋՄՁԿՀՌՄՑՁՆԻՊԽԹՋԽԼ
ՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԿՄԹՆԼՋՁՒԽՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈ

ԦՆԻՊԽԹՋԽԼԾՇՄՄՁԻՄԽԹՋՑՅՅԽՌՊՑԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՋԹԾՁՆԼՁՆԿՌՀԹՌՁՋԹՋՋՇԻՁԹՌԽԼՏՁՌՀ

ՁՆԻՊԽԹՋԽԼԿՄԹՆԼՋՁՒԽԺՍՌԺՑՁՌՋԽՄԾՁՋՆՇՌԼՁԹԿՆՇՋՌՁԻՇԾՌՀՑՊՇՁ ԼԿՄԹՆԼՀՑՈԽՊՌՊՇՈՀՑ

Ԡ ԯԽՎՁԽՏԽՊ	ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԪՇՊՌԹՄՁՌՑՏԹՋԹՋՋԽՋՋԽԼՎՁՋՍԹՄՄՑԯԽՈՄՁԻԹՌԽՅԽԼՁԹՆՎԹՄՍԽՋԾՇՊԡ ԹՑԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԽՊԽ

ԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՍՋՁՆԿՌՀԽՇՆԽՋՁԼԽԼԧՇՆԻՃՀԽԽՊԽ ԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌ#԰Ԟ԰%

ԯԽՈՄՁԻԹՌԽՅԽԼՁԹՆՎԹՄՍԽՋԾՇՊԡԹՑԫԣՋՌԹԿԽԼՁԼՆՇՌՋՀՇՏԹԻՄԽԹ ՊՄՑՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽԹՆԼՏԽՊԽ

ՌՀԽՊԽԾՇՊԽԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՍՋՁՆԿՌՀԽՌՏՇՋՁԼԽԼ ԪԹՆՆԴՀՁՌՆԽՑՌԽՋՌԱՏՇՋՁԼԽԼ

ԻՇՅՈԹՊՁՋՇՆՋՇԾՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌՇՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԫԣՋՌԹԿԽՊԽՋ ՍՄՌՋՏԽՊԽՈԽՊԾՇՊՅԽԼՅԹՆՍԹՄՄՑՁՆԢՐԻԽՄ

ՍՋՁՆԿՌՀԽԪԹՆՆԴՀՁՌՆԽՑԲՌԽՋՌ

ԡԹՌԹԾՇՊԡԹՑՆՇՊՅԹՄՁՒԽԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩ԰ԳԩՏԽՊԽՎՁՋՍԹ ՄՄՑԼԽՌԽՊՅՁՆԽԼՌՇԺԽԻՇՆՋՁՋՌԽՆՌՏՁՌՀ

ԹՅՇՆՇՌՇՆՁԻԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԹՆԼՌՀԽՊԽԾՇՊԽՏԽՊԽԹՆԹՄՑՒԽԼ ՍՋՁՆԿՌՀԽՇՆԽՋՁԼԽԼ
ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌ#԰Ԟ԰%ԡԹՌԹԾՇՊՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ 
԰ԳԩԺՇԼՑՏԽՁԿՀՌՀՁՆԼՄՁՅԺՄԽՆԿՌՀ

ԹՆԼԡԹՑՆՇՊՅԹՄՁՒԽԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀՏԽՊԽՆՇՌԻՇՆՋՁՋՌԽՆՌՏՁՌՀ ԹՅՇՆՇՌՇՆՁԻԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ

ԱՀԽԼԹՌԹՏԽՊԽՌԽՋՌԽԼԾՇՊՆՇՊՅԹՄՁՌՑՍՋՁՆԿ԰ՀԹՈՁՊՇԴՁՄՃՋՌԽՋՌԹՆԼ ԾՇՊՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՍՋՁՆԿ

ԩԽՎԽՆԽ	ՋՌԽՋՌ#԰Ԟ԰%ԱՀԽՋԽԼԹՌԹՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՆՇՊՅ ԹՄՁՌՑԹՆԼՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽԹՆԼ
ՏԽՊԽՌՀԽՊԽԾՇՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՌՏՇՋՁԼԽԼԡՍՆՆԽՌՌ	ՋՌԽՋՌ#԰Ԟ԰ %ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋ

ՏԽՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈԹՆԼԹՊԽԺԹՋ ԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԣՇՊԻՇՆՌՁՆՍՇՍՋԽՆԼՈՇՁՆՌՋԻՇՅՈԹՊՁՋՇՆՋՇԾՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌՇՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՊԽՋՍՄՌՋՏԽՊԽՈԽՊԾՇՅԽԼՍՋՁՆԿ

ՌՀԽՌՏՇՋԹՅՈՄԽՌՌԽՋՌԹՋՋՍՅՁՆԿՍՆԽՉՍԹՄՎԹՊՁԹՆԻԽՋ
ԢՐԻԽՄ ՌՀԽՌՏՇՌԹՁՄԽԼՈՎԹՄՍԽՁՋՊԽՈՇՊՌԽԼ

ԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋՇԺՋԽՊՎԽԼ԰ՍՅՅԹՊՑՋՌԹՌՁՋՌՁԻՋ ՁՆԻՁԼԽՆԻԽՎԹՄՍԽՋԾՇՊՌՀՑՊՇՁԼ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋԽՋԹՊԽՈՊԽՋԽՆՌԽԼՁՆՌՀԽՈՊԽՎՁՇՍՋՋԽԻՌՁՇՆ ԺՍՌՆՇԹԼԼՁՌՁՇՆԹՄՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋՏԽՊԽ

ՈԽՊԾՇՊՅԽԼՇՆՌՀԽՋԽԼԹՌԹԺՑՌՀԽՊԽՎՁԽՏԽՊ

ԠՇՆԻՄՍՋՁՇՆՋ

ԡԽՎԽՄՇՈՅԽՆՌԹՄԼԽՄԹՑՏԹՋԹՈՈԹՊԽՆՌՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄ ՅԿԹՁԩՏՀԽՊԽՌՀԽՊԽՎՁԽՏԽՊ

ՁԼԽՆՌՁԾՁԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋՏՁՌՀՊԽՋՈԽԻՌՌ ՇԡԹՑԫԣՋՌԹԿԽ
ՇՆԽՋՌԹԿԽԽԹՊՄՁԽՊՀՁՆԼՄՁՅԺ

ՄԽՆԿՌՀՇՆԡԹՑ
ԹՆԼԡԹՑ
ԹՆԼՆՇՊՅԹՄՁՒԽԼՀՁՆԼՄ ՁՅԺՄԽՆԿՌՀՇՆԡԹՑ
԰ՁՆԻԽ

ՌՀՑՊՇՁԼԾՍՆԻՌՁՇՆՁՋՇՆՄՑԺԽԿՁՆՆՁՆԿԹՊՇՍՆԼՌՀԽԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹ ԿԽՊԽԹԻՀԽԼԺՑԡԹՑՌՀԽԡԹՑՊԽՋՍՄՌՋ

ԹՄՇՆԽԹՊԽՆՇՌՆԽԻԽՋՋԹՊՁՄՑՁՆԼՁԻԹՌՁՎԽՇԾՌՀՑՊՇՁԼԹՆՌԹԿՇՆՁՋՅԥՇ ՏԽՎԽՊՌՀԽԽԾԾԽԻՌՇՆՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԺՇՌՀ

ՆՇՊՅԹՄՁՒԽԼԹՆԼՆՇՆՆՇՊՅԹՄՁՒԽԼՏԹՋՅՇՊԽՈՊՇՆՇՍՆԻԽԼԺՑԡԹՑԹՆ ԼՏԹՋԻՇՁՆԻՁԼԽՆՌՏՁՌՀՌՀՑՊՇՁԼ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋՁՆԻՄՍԼՁՆԿՁՆԻՊԽԹՋԽՋՁՆԿՄԹՆԼՀՑՈԽՊՌՊՇՈՀՑԿՄԹՆԼՋՁՒԽԾՇՄՄՁԻՄԽՋՁՒԽԹՆԼԾՇՄՄՁԻՄԽ

ԹՋՑՅՅԽՌՊՑԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌՊԽՈՇՊՌԽԼՌՀԹՌՋՍԻՀՇԺՋԽՊՎԹՌՁՇՆՋՇԾՄԹՊԿԽՊ ԿՄԹՆԼՋՁՒԽԹՊԽԽՐՈԽԻՌԽԼՏՁՌՀՄԹՊԿԽՊՆՇՌ

ՋՅԹՄՄԽՊՌԹԼՈՇՄԽՋՌՀԽՊԽՎՁԽՏԽՊՁՆՌԽՊՈՊԽՌՋՌՀՁՋՌՇՅԽԹՆՌՀԹՌՌՀԽՀՁՋՌՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋՁՆՌՀՁՋԻԹՋԽԹՊԽՆՇՌ

ԻՇՆՋՁՋՌԽՆՌՏՁՌՀԹՈՍՊԽՄՑԿՊՇՏՌՀՅԽԼՁԹՌԽԼԽԾԾԽԻՌԹՆԼԻՇՍՄԼՌՀԽՊԽ ԾՇՊԽԺԽՊԽԾՄԽԻՌՁՎԽՇԾՋՇՅԽՇՌՀԽՊՌՑՈԽՇԾ

ՁՆՌԽՊԾԽՊԽՆԻԽ

ԟՇՌՀՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩԹՆԼԺՇԼՑՏԽՁԿՀՌ
ԟԴՏԽՊԽՋՁԿՆՁԾՁԻ ԹՆՌՄՑԼՁԾԾԽՊԽՆՌԾՊՇՅՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋ

ՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄՇՆԡԹՑ
԰ԳԩԟԴԹՆԼ ԡԹՑ
԰ԳԩԟԴ

԰ՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋՁՆ԰ԳԩԹՆԼԟԴՏԽՊ ԽԹՄՋՇՇԺՋԽՊՎԽԼՁՆՌՀԽՄՇՏՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ՅԿԹՁԩՀՇՏԽՎԽՊՌՀԽՋԽԽԾԾԽԻՌՋՏԽՊԽՇԾԹՈՈՊՇՐՁՅԹՌԽՄՑ ՌՀԽՋԹՅԽՅԹԿՆՁՌՍԼԽԹՋԽԾԾԽԻՌՋՁՆՌՀԽ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՌՀԽՊԽԾՇՊԽՅԹՑՀԹՎԽԺԽԽՆԼՍԽՌՇՋՇՄՎԽՆՌՁՆՌԽ ՊԾԽՊԽՆԻԽԱՀԽՊԽՏԽՊԽՋՌԹՌՁՋՌՁԻԹՄՄՑ

ՋՁԿՆՁԾՁԻԹՆՌՋՇՄՎԽՆՌԽԾԾԽԻՌՋՇՆԿՊՇՏՌՀԺՍՌՆՇՌՇՆԼԽՎԽՄՇՈՅԽՆՌԹՄ ՈԹՊԹՅԽՌԽՊՋ

ԬՎԽՊԹՄՄԼԽՎԽՄՇՈՅԽՆՌԹՄԼԽՄԹՑՋՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄԺԽԻԹՅ ԽՅՇՊԽՈՊՇՆՇՍՆԻԽԼՇՎԽՊՌՁՅԽԹՆԼՏԽՊԽ

ԻՇՁՆԻՁԼԽՆՌՏՁՌՀԽԾԾԽԻՌՋՇՆՋԽՎԽՊԹՄՌՀՑՊՇՁԼՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄՈԹ ՊԹՅԽՌԽՊՋ԰ՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋՇՆԿՊՇՏՌՀՏԽՊԽ

ՇԺՋԽՊՎԽԼԹՌՌՀԽՋԹՅԽՌՊԽԹՌՅԽՆՌՄԽՎԽՄԱՀԽՊԽՋՍՄՌՋԹՊԽԼՁԾԾՁԻՍՄ ՌՌՇՁՆՌԽՊՈՊԽՌԾՍՊՌՀԽՊԺԽԻԹՍՋԽՅՇՊՌԹՄՁՌՑՏԹՋ

ՁՆԻՊԽԹՋԽԼԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑՏԽՊԽԽՎՁԼԽՆՌՁՆՌՏՇՇԾ ՌՀԽՊԽՅԹՁՆՁՆԿՌԹԼՈՇՄԽՋՁՆՌՀԽՀՁԿՀ

ՌՊԽԹՌՅԽՆՌԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԡԽՎԽՄՇՈՅԽՆՌԹՄԹՆԼԱՀՑՊՇՁԼԤՊՇՋՋԭԹՌՀՇՄՇԿՑԥՁՋՌՇՈԹՌՀՇՄՇԿՑԢՆԼՈՇՁՆՌՋՁՆՌՀԽԞԪԞՏՁՌՀĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ#ՅԽԹՋՍՊԽԼ%ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽԥՁՆԼԩՁՅԺԩԽՆԿՌՀԞՋՑՆԻՀՊՇՆՇՍՋԡԽՎԽՄՇՈՅԽՆՌԱՀՑՊՇՁԼԤՊՇՋՋԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑԡԹՑԡԹՑԡԹՑԡԹՑԡԹՑԡԹՑԡԹՑԪԽԼՁԹՆՈԪԽԼՁԹՆՈԡՁԾԾՈԡՁԾԾՈԡՁԾԾՈԡՁԾԾՈԱՊԽԹՌՅԽՆՌԯԽՄԹՌԽԼԢԾԾԽԻՌՋ!
ԶԽՋԫՇԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑՁԾՍՋԽԼ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԡԪԣ        ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ        ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ        ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ        ԫԞ ԫԞ ԫԞ ԫԞ ԶԽՋ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌԾՇՊ԰ՁԿՆՁԾՁԻԹՆՌԡՁԾԾԽՊԽՆԻԽՋԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՇՆԽՋՁԼԽԼԪԹՆՆԴՀՁՌՆԽՑՌՏՇՋՁԼԽԼԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՇՆԽՋՁԼԽԼԡՍՆՆԽՌՌՌՏՇՋՁԼԽԼԫԞԫԞԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՇՆԽՋՁԼԽԼԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԥՁՆԼՄՁՅԺՄԽՆԿՌՀՁՋՆՇՊՅԹՄՁՒԽԼՌՇՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽԠՇՅՅԽՆՌՋ

ԣՇՊԫԣ԰ՌԹԿԽՌՏՇՋՁԼԽԼԻՇՅՈԹՊՁՋՇՆՋՇԾՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌՇՆԽԿԹՌ ՁՎԽԻՇՆՌՊՇՄՊԽՋՍՄՌՋՏԽՊԽՈԽՊԾՇՊՅԽԼ

ՅԹՆՍԹՄՄՑՁՆԢՐԻԽՄ
ՍՋՁՆԿՌՀԽԪԹՆՆԴՀՁՌՆԽՑԲՌԽՋՌԫՇՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽԾՇՍՆԼՇՆԽՁՌՀԽՊ

ԡԹՑՇՊԡԹՑ

ԞՌԡԹՑՌՀԽՌԹԼՈՇՄԽՋՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՏԽՊԽԹՌԹՆՇՎԽՊԹՄՄԽԹՊՄՁԽՊԫԣՋՌԹԿԽ
ՌՀԹՆՌՀՇՋԽՁՆՌՀԽ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ՈԫՇՇՌՀԽՊՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻ ԽՋՁՆԫԣՋՌԹԿԽՏԽՊԽՇԺՋԽՊՎԽԼՇՆԽՁՌՀԽՊ

ԡԹՑՇՊԡԹՑ

ԣՇՊՆՇՊՅԹՄՁՒԽԼԥԩԩԻՇՅՈԹՊՁՋՇՆՋՇԾՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌՇՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄՊԽՋՍՄՌՋՏԽՊԽՈԽՊԾՇՊՅԽԼՍՋՁՆԿՌՀԽ

ՌՏՇՋԹՅՈՄԽՌՌԽՋՌԹՋՋՍՅՁՆԿՍՆԽՉՍԹՄՎԹՊՁԹՆԻԽՋ
ԢՐԻԽՄՌՀԽ ՌՏՇՌԹՁՄԽԼՈՎԹՄՍԽՁՋՊԽՈՇՊՌԽԼԫՇ

ՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽԾՇՍՆԼՇՆԽՁՌՀԽՊԡԹՑՇՊԡԹՑ

ԱՀԽՇՆՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՁՆՆՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋՁՆՌՀԽՀՁ ԿՀՌՊԽԹՌՅԽՆՌ
ՅԿԹՁԩՇՆԡԹՑ

ՏՀԽՊԽՆՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋՄԽՋՋՌՀԹՆՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ Ո

ԫՇՆՆՇՊՅԹՄՁՒԽԼԥԩԩ
ՆՇՌՋՀՇՏՆՁՆԱԹԺՄԽՏԹՋԹՄՋՇԹՆԹՄՑՒԽԼՋՌ ԹՌՁՋՌՁԻԹՄՄՑՍՋՁՆԿԹՌՏՇՋՁԼԽԼԡՍՆՆԽՌՌ	Ջ

ՌԽՋՌ
԰Ԟ԰ՎԞՌԺՇՌՀԡԹՑԹՆԼԡԹՑՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆ Ռ
ՅԿԹՁԩՏԹՋՌՀԽՇՆՄՑՌՊԽԹՌՅԽՆՌ

ՋՁԿՆՁԾՁԻԹՆՌՄՑԼՁԾԾԽՊԽՆՌԾՊՇՅՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԡԹՑ ՈԡԹՑՈ

ԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌ
ՁԽՌԹԼՈՇՄԽՋՏՀՁԻՀԻՇՍՄԼՆՇՌԺԽ ՋՌԹԿԽԼՏԹՋՊԽՈՇՊՌԽԼՁՆՌՀՁՋՋՌՍԼՑ

ԣՇՊՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋԽՋՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁՋՌԼԽՌԽԻՌԽԼՋՌԹ ՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋԹՌՌՀԽՀՁԿՀ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ՅԿԹՁԩՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋ ՌԽՈԼՇՏՆՌԽՋՌԱՀԽՊԽՎՁԽՏԽՊԼՁԼՆՇՌ

ՎԽՊՁԾՑՌՀԽՋՌԹՌՁՋՌՁԻԹՄՇՍՌԻՇՅԽՋՁՆՌՀՁՋԻԹՋԽՋՁՆԻԽՌՀԽԞԿԽՆԻՑԼՇԽՋՆՇՌՊՇՍՌՁՆԽՄՑՈԽՊԾՇՊՅՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋ

ՇՆՀՁՋՌՇՈԹՌՀՇՄՇԿՑՇԺՋԽՊՎԹՌՁՇՆՋ

ԟԽԻԹՍՋԽՇԾՌՀԽԹՈՈԹՊԽՆՌԽՐԻԽՋՋՁՎԽԿՊՇՏՌՀՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ ԿՊՇՍՈԼԽՎԽՄՇՈՅԽՆՌԹՄԽՆԼՈՇՁՆՌՋԺԽՌՏԽԽՆ

ՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԹՆԼՌՊԽԹՌԽԼԿՊՇՍՈՋՏԽՊԽԻՇՅՈԹՊԽԼԤԽՆԽՊԹՄ ՄՑԻՇՅՈԹՊՁՆԿՌՀԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՌՇ

ՆԽԿԹՌՁՎԽՇՊՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԼՁԼՆՇՌՅԹՃԽԹԼՁԾԾԽՊԽՆԻԽԥՇՏԽՎԽ ՊՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋ

ԼԫԣՋՌԹԿԽՏԹՋՅԹՊԿՁՆԹՄՄՑՋՌԹՌՁՋՌՁԻԹՄՄՑԼՁԾԾԽՊԽՆՌԾՊՇՅԻՇՆՌՊ ՇՄՋ
ԪԹՆՆԴՀՁՌՆԽՑՈԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋ  ՁՆՌՀԽԞԪԞՏՁՌՀ ĨƌŝĐĂŶůĂǁĞĚ&ƌŽŐ



ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ՅԽԹՋՍՊԽԼ% ԰ՆՇՍՌԳԽՆՌԩԽՆԿՌՀ ԟՇԼՑԴԽՁԿՀՌ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո
ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑ

ՁԾՍՋԽԼ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԡԪԣ        

        

        

    

    

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌԾՇՊ

԰ՁԿՆՁԾՁԻԹՆՌԡՁԾԾԽՊԽՆԻԽՋ ԡՍՆՆԽՌՌ

ՌՏՇՋՁԼԽԼ ԡՍՆՆԽՌՌ

ՌՏՇՋՁԼԽԼ ԡՍՆՆԽՌՌ

ՌՏՇՋՁԼԽԼ ԡՍՆՆԽՌՌ

ՌՏՇՋՁԼԽԼ

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԡՁԾԾ ԡՁԾԾԽՊԽՆԻԽ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ

  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈ ԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ

  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄ ՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ

ԱԹԺՄԽԠՇՅՅԽՆՌՋ

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄՊԽՋՍՄՌՋՏԽՊԽԻՇՅՈԹՊԽԼՌՇՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋՍՋՁՆ ԿԹՌՏՇՋԹՅՈՄԽՌՌԽՋՌԹՋՋՍՅՁՆԿՍՆԽՉՍԹՄ

ՎԹՊՁԹՆԻԽՋ
ԢՐԻԽՄՌՀԽՌՏՇՌԹՁՄԽԼՈՎԹՄՍԽՁՋՊԽՈՇՊՌԽԼ

ԞՌԡԹՑ԰ԳԩԹՆԼԺՇԼՑՏԽՁԿՀՌՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑՄՇՏԽՊՁՆՌՀԽՀ ՁԿՀ
ՅԿԹՁԩՌՊԽԹՌՅԽՆՌՌՀԹՆՁՆ

ՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ՈԠՇՆՎԽՊՋԽՄՑԺՇԼՑՏԽՁԿՀՌՏԹՋՅԹՊ ԿՁՆԹՄՄՑՀՁԿՀԽՊՁՆՌՀԽՄՇՏՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ՅԿԹՁԩՌՀԹՆՁՆՌՀԽԻՇՆՌՊՇՄ
Ո԰ԳԩՏԹՋՅԹՊԿՁՆ ԹՄՄՑՀՁԿՀԽՊՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌՀԹՆ

ՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
Ո

ԞՌԡԹՑ԰ԳԩԹՆԼԺՇԼՑՏԽՁԿՀՌՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑՀՁԿՀԽՊՁՆՌՀԽ ՄՇՏՌՊԽԹՌՅԽՆՌ
ՅԿԹՁԩԺՍՌ

ՄՇՏԽՊՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌ
ՅԿԹՁԩԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽ ԿԹՌՁՎԽԻՇՆՌՊՇՄ
ՈԟՇԼՑՏԽՁԿՀՌ

ՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՀՁԿՀԽՊՌՀԹՆՁՆՌՀԽՆԽԿ ԹՌՁՎԽԻՇՆՌՊՇՄ
Ո

ԟԽԻԹՍՋԽՇԾՌՀԽԹՈՈԹՊԽՆՌԽՐԻԽՋՋՁՎԽԿՊՇՏՌՀՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ ԿՊՇՍՈԿՊՇՏՌՀԽՆԼՈՇՁՆՌՋՏԽՊԽԻՇՅՈԹՊԽԼԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԺԽՌՏԽԽՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԹՆԼՌՊԽԹՌԽԼԿՊՇՍՈՋԴՀԽՆԻՇՅՈԹՊԽԼ ՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌՀԽՊԽՏԽՊԽՆՇ

ԼՁԾԾԽՊԽՆԻԽՋՁՆՌՀԽՄՇՏՌՊԽԹՌՅԽՆՌԿՊՇՍՈԼԹՑ԰Գԩ
ԡՍՆՆԽՌՌՈ ԼԹՑ԰Գԩ
ԡՍՆՆԽՌՌՈ

ԼԹՑՏԽՁԿՀՌ
ԡՍՆՆԽՌՌՈԼԹՑՏԽՁԿՀՌ
ԡՍՆՆԽՌՌՈ ԣՍՊՌՀԽՊՅՇՊԽՌՀԽՄԽՎԽՄՇԾՋՁԿՆՁԾՁԻԹՆԻԽ

ՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՀԹԼԿՊԽԹՌԽՊՋՁԿՆՁԾՁԻԹՆԻԽՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋՁԽ

ՈԱՀԽԼՁԾԾԽՊԽՆԻԽՋՆՇՌԽԼՋՍՈՈՇՊՌՌՀԽՁՆԻՊԽԹՋԽԼԿՊՇՏՌՀԾՊ ՇՅՌՀԽՋՇՄՎԽՆՌԺՍՌԼՇՆՇՌԻՀԹՆԿԽՌՀԽ

ՇՎԽՊԹՄՄԻՇՆԻՄՍՋՁՇՆՌՀԹՌՌՀԽՊԽՏԹՋԹՋՁԿՆՁԾՁԻԹՆՌԼԽԻՊԽԹՋԽՁՆԿՊՇ ՏՌՀՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ԡ ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

ԳԹՄՁԼՁՌՑԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹՏԽՊԽԿԽՆԽՊԹՄՄՑՅԽՌՀՇՏԽՎԽՊՋՇՄՎԽՆՌՁՆՌԽՊԾԽՊԽՆԻԽՏԹՋԹՈՈԹՊԽՆՌԦՆՌՀԽ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋՌՀԽՊԽՏԹՋԹՋՁԿՆՁԾՁԻԹՆՌՁՆԻՊԽԹՋԽՁՆԼԺՇԼՑ ՏԽՁԿՀՌԹՆԼ԰Գԩ
ՋԹՅՈՄԽԱՌԽՋՌՏԹՑ

ԭԹՆԼԼԺՇԼՑՏԽՁԿՀՌ԰ԳԩԥԩԩԹՆԼՆՇՊՅԹՄՁՒԽԼԥԩԩ
 ՋԹՅՈՄԽԱՌԽՋՌՏԹՑԭ

ԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋ

ԱՀԽԾՇՄՄՇՏՁՆԿԹԼԼՁՌՁՇՆԹՄԼԽԾՁԻՁԽՆԻՁԽՋՏԽՊԽՆՇՌԽԼՏՀՁԻՀԼՁԼՆՇՌ ՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌՌՀԽՋԻՁԽՆՌՁԾՁԻ

ՋՇՍՆԼՆԽՋՋՇԾՌՀԽՋՌՍԼՑ
ՁՌՀԽԻՇՅԺՁՆԹՌՁՇՆՇԾՊԽՈՄՁԻԹՌԽՅՇՊՌԹ ՄՁՌՑԹՆԼԽՐԻՄՍՋՁՇՆՋԼՍԽՌՇՄԹՌԽՋՌԹԿԽՌԹԼՈՇՄԽՋ

ԻՇՆՋՁԼԽՊԹԺՄՑՊԽԼՍԻԽԼՌՀԽՆՍՅԺԽՊՇԾՌԹԼՈՇՄԽՋՁՆՋԽՎԽՊԹՄՊԽՈՄՁԻԹՌԽՋ
ՁՁՌՀԽՌԽՅՈԽՊԹՌՍՊԽՊԹՆԿԽՁՆԹ

ԻՇՆՌՁՆՍՇՍՋՄՑՅՇՆՁՌՇՊԽԼՌԹՆՃԽՐԻԽԽԼԽԼՌՀԽՊԹՆԿԽՊԽԻՇՅՅԽՆԼԽԼՁՆՌՀԽԿՍՁԼԽՄՁՆԽՀՇՏԽՎԽՊՈԽՊՁՇԼՁԻԹՄՄՑ

ԼԹՑՅԽԹՋՍՊԽԼՌԽՅՈԽՊԹՌՍՊԽՋՏԽՊԽԹՄՄԻՇՆՋՁՋՌԽՆՌՏՁՌՀՌՀԽԿՍՁԼ ԽՄՁՆԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԹՆԼ
ՁՁՁՋՈՁՆԹՄ

ԻՍՊՎԹՌՍՊԽՏԹՋՇԺՋԽՊՎԽԼՁՆԻՇՆՌՊՇՄՋԹՆԼՁՆԹՄՄՌՊԽԹՌՅԽՆՌՋԽՐԻԽՈՌ ՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏՀԽՊԽԿՊՇՏՌՀ

ԹՆԼԼԽՎԽՄՇՈՅԽՆՌՏԽՊԽՁՆՀՁԺՁՌԽԼ

ԱՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼԹՆԼՌՀԽՊԽՎՁԽՏԽՊՎԽՊՁԾՁԽԼՌՀԹՌՌՀԽ ԾՇՄՄՇՏՁՆԿՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹՏԽՊԽՅԽՌ

ՏՁՌՀՌՀԽՆՇՌԽԼԽՐԻԽՈՌՁՇՆՇԾԹՌՊԹՆՋՁԽՆՌԽԾԾԽԻՌՇՆՌԽՅՈԽՊԹՌՍՊԽՁ ՆԹԻՇՆՌՁՆՍՇՍՋՄՑՅՇՆՁՌՇՊԽԼՌԹՆՃ

ա ԱՀԽԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆԻՇՆԻԽՆՌՊԹՌՁՇՆՏԹՋԹՌՄԽԹՋՌՇԾՌՀԽԹՁՊՋԹՌՍՊԹՌՁՇՆՎԹՄՍԽՌՀՊՇՍԿՀՇՍՌՌՀԽ

ԽՐՈՇՋՍՊԽՈԽՊՁՇԼ

ա ԴԹՌԽՊՌԽՅՈԽՊԹՌՍՊԽԼՁԼՆՇՌԼՁԾԾԽՊԺՑՅՇՊԽՌՀԹՆոԠԺԽՌՏԽԽՆՌԽՋՌ ՎԽՋՋԽՄՋԹՌԹՆՑՇՆԽՌՁՅԽԼՍՊՁՆԿ

ՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԴԹՌԽՊՌԽՅՈԽՊԹՌՍՊԽՏԹՋՅԹՁՆՌԹՁՆԽԼՏՁՌՀՁՆչ ոԠՇԾՌՀԽոԠՌԽՅՈԽՊԹՌՍՊԽ

ՋՈԽԻՁԾՁԽԼՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՇԾԡԹՑՏՀԽՆՌԽՅՈԽՊԹՌՍՊԽՁՆՌՀԽ ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌԹՆՃՏԹՋԹՋ

ՄՇՏԹՋոԠԱՀՁՋՋՄՁԿՀՌԼՁԾԾԽՊԽՆԻԽՁՆՌԽՅՈԽՊԹՌՍՊԽՏԹՋՇԾՋՀՇ ՊՌԼՍՊԹՌՁՇՆԹՆԼՀԹԼՆՇԹԼՎԽՊՋԽ

ՁՅՈԹԻՌՇՆՌՀԽՋՌՍԼՑԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ա ԱՀԽՊԽՏԹՋԹՌՄԽԹՋՌՋՍՊՎՁՎԹՄՇԾԻՇՆՌՊՇՄԹՆՁՅԹՄՋՇՎԽՊՌՀԽԼՍՊ ԹՌՁՇՆՇԾՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԹՆԼ

ՅՇՊՌԹՄՁՌՑՁՆԹՆՑՇՆԽԻՇՆՌՊՇՄՊԽՈՄՁԻԹՌԽԼՁԼՆՇՌԽՐԻԽԽԼՌՏՇՌԹԼՈՇ ՄԽՋ

ա ԱԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽԻՇՆՋՁՋՌԽՆՌՇՎԽՊՌՀԽԻՇՍՊՋԽՇԾՌՀԽՋՌՍԼ Ց
ՁԽԻՇՆՌԹՁՆԽԼԹՌԠԳ

ՎԹՊՁԹԺՁՄՁՌՑՇԾՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇՎԽՊՌՀԽԼԹՑՌԽՋՌ

ա ԱՀԽՈԥՏԹՋՅԹՁՆՌԹՁՆԽԼԺԽՌՏԽԽՆԹՆԼԹՆԼՌՀԽՁՆՌԽՊՊԽՈՄՁԻ ԹՌԽՁՆՌԽՊՌՊԽԹՌՅԽՆՌԼՁԾԾԽՊԽՆՌՁԹՄՋ

ԼՁԼՆՇՌԽՐԻԽԽԼ

ա ԱՀԽՅՁՆՁՅՍՅՅԽԼՁԹՆՋՌԹԿԽՇԾՌՀԽԻՇՆՌՊՇՄՌԹԼՈՇՄԽՋԹՌՌՀԽԽՆԼՇԾ ՌՀԽՌԽՋՌՏԹՋԹՌՄԽԹՋՌ

ա ԱՀԽՌՀԹՆԼՌՀԽՌՀՈԽՊԻԽՆՌՁՄԽՋՇԾՌՀԽԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽԼՁՋՌՊՁԺՍՌՁՇՆԼՁԼՆՇՌԼՁԾԾԽՊԺՑՅՇՊԽ

ՌՀԹՆՋՌԹԿԽՋ
ՋՌԹԿԽԼՁՋՌՊՁԺՍՌՁՇՆՋՏԽՊԽՈՊՇՎՁԼԽԼ

ա ԱՀԽՊԽՏԽՊԽՄԽՋՋՌՀԹՆՌՏՇՆՇՆԻՇՆՌՊՇՄՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏՁՌՀՇ ՎԽՊՌՌՇՐՁԻՁՌՑ

ա ԱՀԽՊԽՏԽՊԽՄԽՋՋՌՀԹՆՌՏՇՊԽՈՄՁԻԹՌԽՋԹԻՊՇՋՋՌՀԽՌԽՋՌՌՀԹՌՏԽՊԽԻ ՇՅՈՊՇՅՁՋԽԼ

Ԣ ԯԽՎՁԽՏԽՊ	ՋԠՇՅՅԽՆՌՋ

ԱՀԽՊԽՎՁԽՏԽՊ	ՋԹՆԹՄՑՋՁՋԹՆԼԻՇՆԻՄՍՋՁՇՆՋՏԽՊԽԿԽՆԽՊԹՄՄՑՁՆԹԿՊԽԽ ՅԽՆՌՏՁՌՀՌՀԽՌՀՇՋԽՇԾՌՀԽՋՌՍԼՑ

ԹՍՌՀՇՊԥՇՏԽՎԽՊՌՀԽՊԽՎՁԽՏԽՊԼՁՋԹԿՊԽԽՋՏՁՌՀՌՀԽՋՌԹՌԽՅԽՆՌՁՆ ՌՀԽԺՇԼՑՇԾՌՀԽՋՌՍԼՑՊԽՈՇՊՌՌՀԹՌՌՀՑՊՇՁԼ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋՏԽՊԽԿԽՆԽՊԹՄՄՑԻՇՆՋՁՋՌԽՆՌՏՁՌՀԽԾԾԽԻՌՋՇՆԿՊՇՏՌՀԞՄՌՀՇՍԿՀՌՀԽԾՁՆԼՁՆԿՋՏԽՊԽ

ԻՇՁՆԻՁԼԽՆՌՏՁՌՀԽԾԾԽԻՌՋՇՆԿՊՇՏՌՀՌՀԽՅՇՊԽԼԽՌԹՁՄԽԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՊԽՈՇՊՌԹՈՈԽԹՊՋՌՇՋՍԿԿԽՋՌՌՀԹՌՌՀԽ

ՀՁՋՌՇՄՇԿՑԾՁՆԼՁՆԿՋԹՊԽԻՇՍՆՌԽՊՌՇՏՀԹՌՅՁԿՀՌԺԽԽՐՈԽԻՌԽԼՁՆԹՈՍՊԽՄՑԿՊՇՏՌՀՅԽԼՁԹՌԽԼԻՇՆՌԽՐՌ

ԱՀԽՋՌՍԼՑՊԽՈՇՊՌԻՇՆՌԹՁՆԽԼՋՇՅԽՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋՆՇՌՊՇՍՌՁՆ ԽՄՑՈԽՊԾՇՊՅԽԼԺՑՌՀԽԞԿԽՆԻՑԹՌՌՀՁՋՌՁՅԽ

ՁՆԻՄՍԼՁՆԿՌՀԽՅՍՄՌՁՉՍԹՆՌՁՄԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌ
ԾՇՊԫԣՋ ՌԹԿԽՋՌԹՌՁՋՌՁԻԹՄԼԽՌԽՊՅՁՆԹՌՁՇՆՇԾ

ՅՇՆՌՇՆՁԻՁՌՑՍՋՁՆԿԹՊԹՆՃԽԼՊԽՋՈՇՆՋԽՐՌՊԽԹՌՅԽՆՌՉՍԹԼՊԹՌՁԻՈՇՄՑՆՇՅՁԹՄՅՇԼԽՄԹՆԼԾՍՊՌՀԽՊՉՍԹՆՌՁՌԹՌՁՎԽ

ԹՆԹՄՑՋԽՋՇԾՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԼՁԹԿՆՇՋԽՋԱՀԽՋԽԻԹՄԻՍՄԹՌՁՇՆՋՏ ԽՊԽՆՇՌՎԽՊՁԾՁԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊ

ԦԦԦ ԯԢԣԢԯԢԫԠԢ԰

ԫՇՆԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR01 ( 7-d wet weight (g) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.927 0.215 1.833 0.195 USE PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 249.00 30.01 15.01 12.05 201.25, 296.75 Dose1 4 284.25 15.63 7.81 5.50 259.38, 309.12 Dose2 4 266.25 13.96 6.98 5.24 244.03, 288.47 Dose3 4 207.25 7.37 3.68 3.55 195.53, 218.97

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 258.00 207.00 273.00 . .

Dose1 278.00 274.00 307.00 114.16 -14.16

Dose2 264.50 252.00 284.00 106.93 -6.93

Dose3 207.50 198.00 216.00 83.23 16.77

******************************************************************************** PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Analysis of Variance (ANOVA) - overall F-test
Numerator df Denominator df F-stat P-value

3 12 12.45 <.001

Dunnett - testing each trt mean signif. different than control Williams - test assumes dose-response relationship, testing negative trend Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC

Level Mean Dunnett Isotonic Williams Tukey p-values p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5

Ctrl 249.00 . 266.63 . . . . . .

Dose1 284.25 0.051 266.63 0.945 . . . . .

Dose2 266.25 0.448 266.25 0.957 0.543 . . . .

Dose3 207.25 0.021 207.25 0.005 <.001 0.004 . . .

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR02 ( 7-d stage (median) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.767 0.001 2.684 0.094 USE NON-PARAMETRIC TESTSԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 54.00 0.00 0.00 0.00 . , . Dose1 4 54.25 0.50 0.25 0.92 53.45, 55.05 Dose2 4 54.00 0.00 0.00 0.00 . , . Dose3 4 53.00 0.82 0.41 1.54 51.70, 54.30

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 54.00 54.00 54.00 . .

Dose1 54.00 54.00 55.00 100.46 -0.46

Dose2 54.00 54.00 54.00 100.00 0.00

Dose3 53.00 52.00 54.00 98.15 1.85

******************************************************************************** NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Kruskal-Wallis test - equality among treatment groups Degrees of Freedom TestStat P-value
3 9.25 0.026

MannWhit - testing each trt median signif. different from control Jonckheere - test assumes dose-response relationship, testing negative trend

Level Median MannWhit p-value Jonckheere p-value

Ctrl 54.00 . .

Dose1 54.00 0.478 0.841

Dose2 54.00 1.000 0.500

Dose3 53.00 0.109 0.011

DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL
Williams Dose3

Jonckheere Dose3

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR03 ( 7-d sn-vent length (mm) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.945 0.408 0.826 0.504 USE PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 15.65 0.55 0.28 3.52 14.77, 16.53 Dose1 4 16.43 0.40 0.20 2.45 15.78, 17.07 Dose2 4 16.10 0.37 0.19 2.32 15.50, 16.70 Dose3 4 14.58 0.38 0.19 2.59 13.97, 15.18

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 15.70 15.00 16.20 . .ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  Dose1 16.40 16.00 16.90 104.95 -4.95

Dose2 16.05 15.70 16.60 102.88 -2.88

Dose3 14.60 14.10 15.00 93.13 6.87

******************************************************************************** PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Analysis of Variance (ANOVA) - overall F-test
Numerator df Denominator df F-stat P-value

3 12 13.92 <.001

Dunnett - testing each trt mean signif. different than control Williams - test assumes dose-response relationship, testing negative trend Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC

Level Mean Dunnett Isotonic Williams Tukey p-values p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5

Ctrl 15.65 . 16.06 . . . . . .

Dose1 16.43 0.065 16.06 0.945 . . . . .

Dose2 16.10 0.359 16.06 0.959 0.717 . . . .

Dose3 14.58 0.011 14.58 0.002 <.001 0.002 . . .

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR04 ( 7-d hind-limb length (mm) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.944 0.396 1.497 0.265 USE PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 2.30 0.16 0.08 7.10 2.04, 2.56 Dose1 4 2.43 0.15 0.07 6.11 2.20, 2.67 Dose2 4 2.45 0.07 0.03 2.71 2.35, 2.56 Dose3 4 1.88 0.18 0.09 9.57 1.59, 2.16

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 2.34 2.10 2.44 . .

Dose1 2.45 2.28 2.56 105.65 -5.65

Dose2 2.47 2.36 2.51 106.51 -6.51

Dose3 1.91 1.63 2.06 81.43 18.57

******************************************************************************** PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Analysis of Variance (ANOVA) - overall F-test
Numerator df Denominator df F-stat P-value

3 12 13.54 <.001

Dunnett - testing each trt mean signif. different than controlԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  Williams - test assumes dose-response relationship, testing negative trend Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC

Level Mean Dunnett Isotonic Williams Tukey p-values p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5

Ctrl 2.30 . 2.40 . . . . . .
Dose1 2.43 0.476 2.40 0.879 . . . . .

Dose2 2.45 0.369 2.40 0.903 0.997 . . . .

Dose3 1.88 0.004 1.88 <.001 <.001 <.001 . . .

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR05 ( 7-d norm hind-limb )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.942 0.379 1.565 0.249 USE PARAMETRIC TESTS (but apparent trend, so move directly to J-T per guideline)

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 0.15 0.01 0.00 6.49 0.13, 0.16 Dose1 4 0.15 0.00 0.00 3.39 0.14, 0.16 Dose2 4 0.15 0.01 0.00 3.28 0.14, 0.16 Dose3 4 0.13 0.01 0.01 10.88 0.11, 0.15

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 0.15 0.14 0.16 . .

Dose1 0.15 0.14 0.15 100.00 0.00

Dose2 0.15 0.15 0.16 103.39 -3.39

Dose3 0.14 0.11 0.14 88.14 11.86

******************************************************************************** NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Kruskal-Wallis test - equality among treatment groups Degrees of Freedom TestStat P-value
3 8.38 0.039

MannWhit - testing each trt median signif. different from control Jonckheere - test assumes dose-response relationship, testing negative trend

Level Median MannWhit p-value Jonckheere p-value

Ctrl 0.15 . .

Dose1 0.15 1.000 0.563

Dose2 0.15 0.461 0.877

Dose3 0.14 0.135 0.082

DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL
Williams Dose3 Jonckheere >highest dose (no sign. differences)ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR06 ( 21-d stage (median) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.951 0.500 3.857 0.038 USE NON-PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 57.00 0.00 0.00 0.00 . , . Dose1 4 58.25 0.96 0.48 1.64 56.73, 59.77 Dose2 4 58.50 1.00 0.50 1.71 56.91, 60.09 Dose3 4 55.75 0.96 0.48 1.72 54.23, 57.27

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 57.00 57.00 57.00 . .

Dose1 58.50 57.00 59.00 102.19 -2.19

Dose2 59.00 57.00 59.00 102.63 -2.63

Dose3 55.50 55.00 57.00 97.81 2.19

******************************************************************************** NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Kruskal-Wallis test - equality among treatment groups Degrees of Freedom TestStat P-value
3 10.52 0.015

MannWhit - testing each trt median signif. different from control Jonckheere - test assumes dose-response relationship, testing negative trend

Level Median MannWhit p-value Jonckheere p-value

Ctrl 57.00 . .

Dose1 58.50 0.109 0.977

Dose2 59.00 0.102 0.986

Dose3 55.50 0.109 0.228

DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL
Williams Dose3 Jonckheere >highest dose (no sign. differences)

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR07 ( 21-d wet weight (g) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.955 0.566 0.279 0.840 USE PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 740.00 45.03 22.52 6.09 668.34, 811.66 Dose1 4 856.50 33.32 16.66 3.89 803.48, 909.52 Dose2 4 797.25 27.10 13.55 3.40 754.13, 840.37 Dose3 4 389.00 40.75 20.38 10.48 324.16, 453.84

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 753.00 679.00 775.00 . .

Dose1 856.00 824.00 890.00 115.74 -15.74

Dose2 795.00 774.00 825.00 107.74 -7.74

Dose3 380.00 350.00 446.00 52.57 47.43

******************************************************************************** PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Analysis of Variance (ANOVA) - overall F-test
Numerator df Denominator df F-stat P-value

3 12 127.42 <.001

Dunnett - testing each trt mean signif. different than control Williams - test assumes dose-response relationship, testing negative trend Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC

Level Mean Dunnett Isotonic Williams Tukey p-values p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5

Ctrl 740.00 . 798.25 . . . . . .

Dose1 856.50 0.002 798.25 0.991 . . . . .

Dose2 797.25 0.120 797.25 0.994 0.164 . . . .

Dose3 389.00 <.001 389.00 <.001 <.001 <.001 . . .

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR08 ( 21-d sn-vent length (mm) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.961 0.687 1.944 0.176 USE PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 22.20 0.42 0.21 1.91 21.52, 22.88 Dose1 4 23.20 0.50 0.25 2.14 22.41, 23.99ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  Dose2 4 22.40 0.08 0.04 0.36 22.27, 22.53 Dose3 4 17.28 0.51 0.26 2.97 16.46, 18.09

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 22.25 21.70 22.60 . .

Dose1 23.20 22.60 23.80 104.50 -4.50

Dose2 22.40 22.30 22.50 100.90 -0.90
Dose3 17.15 16.80 18.00 77.82 22.18

******************************************************************************** PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Analysis of Variance (ANOVA) - overall F-test
Numerator df Denominator df F-stat P-value

3 12 167.29 <.001

Dunnett - testing each trt mean signif. different than control Williams - test assumes dose-response relationship, testing negative trend Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC

Level Mean Dunnett Isotonic Williams Tukey p-values p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5

Ctrl 22.20 . 22.70 . . . . . .

Dose1 23.20 0.014 22.70 0.973 . . . . .

Dose2 22.40 0.838 22.40 0.854 0.077 . . . .

Dose3 17.28 <.001 17.28 <.001 <.001 <.001 . . .

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR09 ( 21-d hind-limb length (mm) )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.968 0.809 0.794 0.520 USE PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 9.99 0.63 0.31 6.27 8.99, 10.99 Dose1 4 11.21 0.71 0.36 6.36 10.07, 12.34 Dose2 4 10.77 1.26 0.63 11.69 8.76, 12.77 Dose3 4 4.95 1.01 0.50 20.37 3.35, 6.55

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 10.06 9.25 10.59 . .

Dose1 11.33 10.23 11.94 112.16 -12.16

Dose2 11.33 8.89 11.51 107.76 -7.76

Dose3 4.50 4.35 6.45 49.55 50.45

******************************************************************************** PARAMETRIC ANALYSES - use alpha-level=0.05 for all testsԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  Analysis of Variance (ANOVA) - overall F-test
Numerator df Denominator df F-stat P-value

3 12 38.32 <.001

Dunnett - testing each trt mean signif. different than control Williams - test assumes dose-response relationship, testing negative trend Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC

Level Mean Dunnett Isotonic Williams Tukey p-values p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5

Ctrl 9.99 . 10.65 . . . . . .

Dose1 11.21 0.209 10.65 0.898 . . . . .

Dose2 10.77 0.528 10.65 0.920 0.908 . . . .

Dose3 4.95 <.001 4.95 <.001 <.001 <.001 . . .

********************************************************************************

TCVP AMA Redo ANALYSIS RESULTS FOR VARIABLE VAR10 ( 21-d norm hind-limb )

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 Use parametric analyses if neither test rejected, otherwise non-parametric analyses. Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion

Test Stat P-value Test Stat P-value
0.972 0.872 1.273 0.328 USE PARAMETRIC TESTS

********************************************************************************

BASIC SUMMARY STATISTICS
Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval Ctrl 4 0.45 0.03 0.01 6.29 0.40, 0.50 Dose1 4 0.48 0.02 0.01 5.10 0.44, 0.52 Dose2 4 0.48 0.06 0.03 11.52 0.39, 0.57 Dose3 4 0.28 0.05 0.02 17.50 0.20, 0.35

Level Median Min Max %of Control(means) %Reduction(means)

Ctrl 0.46 0.41 0.47 . .

Dose1 0.48 0.45 0.51 106.67 -6.67

Dose2 0.51 0.40 0.52 107.22 -7.22

Dose3 0.26 0.25 0.35 61.67 38.33

******************************************************************************** PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests Analysis of Variance (ANOVA) - overall F-test
Numerator df Denominator df F-stat P-value

3 12 22.34 <.001

Dunnett - testing each trt mean signif. different than control Williams - test assumes dose-response relationship, testing negative trend Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC

Level Mean Dunnett Isotonic Williams Tukey p-values p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠ ԳԭՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  Ctrl 0.45 . 0.47 . . . . . .

Dose1 0.48 0.621 0.47 0.834 . . . . .

Dose2 0.48 0.566 0.47 0.863 1.000 . . . .

Dose3 0.28 <.001 0.28 <.001 <.001 <.001 . . .

********************************************************************************

# DATA EVALUATION RECORD

TETRACHLORVINPHOS (TCVP)

Study Type: OCSPP 890.1150, Androgen Recep tor Binding (Rat Prostate Cytosol)

EPA Contract No. EP10H001452 Task Assignment No. 2-59-2012 (MRID 48703101)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation
1910 Sedwick Road Building 100, Suite B

Durham, NC 27713

Primary Reviewer: Signature: Daniel R. Hunt, M.S. Date: 6/13/2012

Secondary Reviewer: Signature: Scott D. Studenberg, Ph.D.,
D.A.B.T. Date: 6/25/2012

Program Manager: Signature: Jack D. Early, M.S. Date: 7/02/2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 7/02/2012

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screenin g Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).TETRACHLORVINPHOS (TCVP) /083702 Androgen Receptor Binding (Rat Prostate Cytosol) (1012) I Page I of 15 OCSPP 890.l ISO/ OECD None



### Primary Reviewer: Linda Taylor, Ph.D. 

### Health Effects Division, Office of Pesticide Programs Secondary Reviewer: Greg Akerman, Ph.D.

# s~:a**~ S1gnatu::~** **Z--~&......d~** ....

# -~...,._.**.__** __ Health Effects Division, Office of Pesticide Programs Date: 

# rB.fa//r

Template version 08/2011 

# I DATAEVALUATIONRECORD

STUDY TYPE: Androgen Receptor Binding (Rat Prostate Cytosol); OCSPP 890.1150



### PC CODE: 083702 

### DP BARCODE: D398849



### TXR#: 0056284 

### CAS No.: 22248- 79-9



### TEST MATERIAL ftURITY): Tetrachlorvinphos (100.05%)



### SYNONYMS: (lZ)-2-chloro-1-(2,4,5-trichlorophenyl)ethenyl dimethyl**phosphate~** 

### TCVP



### CITATION: Rtidig, K. (2012). Endocrine Disruptor Test: Androgen Receptor Binding (Rat

Prostate Cytosol) with Tetrachlorvinphos (TCVP). BSL Bioservice, Scientific
Laboratories GmbH, Planegg, Germany. Laboratory Study No: 114588, January 17, 2012. MRID 48703101. Unpublished.



### SPONSOR: The TCVP Task Force c/o SRA International Inc., 5235 Ragged Pt. Road Cambridge, MD



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In an androgen receptor (AR) binding assay (MRID 48703101),
ventral prostate cytosol from Sprague Dawley rats was used as the source of AR to conduct a saturation binding experiment and a competitive binding experiment. A saturation binding experiment was conducted to demonstrate that the AR in the rat prostate cytosol was present in
reasonable numbers and was functioning with appropriate affinity for the radio-labeled reference androgen (RI 881 ), and the competitive binding experiment measured the binding of a single
concentration of [3H]-R 1881 (1 nM) 

### in the presence of increasing concentrations (logarithmic
increase from 10- 10 

### to 10

- 3 

### M) oftetrachlorvinphos (TCVP; 100.05% purity, Batch #TX 100113). Ethanol was used as a vehicle at a final assay concentration of 3.3%. A total of three

runs were performed for the competitive binding assay, and each run included dexamethasone as

a weak positive control, and Rl 881 as the ligand reference standard.

The saturation binding experiment did not clearly demonstrate that the AR in the rat prostate cytosol was present in reasonable numbers and was functioning with appropriate affmity for
reference ligand (R1881). The maximum binding capacity (Bmax) was 0.4298-0.859 fmol/100 μg protein for the three runs and the dissociation constant 

### (Kd) was 0.5615-1.21 nM. The 

## K-0 was within the range reported in the EPA validation program for Runs 2 and 3 only (the value for
Run 1 was slightly low); however, Bmax 

### values were significantly below the expected range of 10

to 150 fmol/l 00 μg protein for all runs. In addition, specific binding did not reach a plateau in

Run 3, and non-specific binding ranged from 29.2 to 61.7% oftotal binding for Run I and fromAndrogen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 2 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### 13.2 to 32.9% of total binding for Runs 2 and 3 (exc luding one outlier), which is greater than the suggested value of <20% reported in the EPA valida tion program. The Scatchard plot of the data was linear for Runs 2 and 3 only.

In the competitive binding experiment, the estimated mean log IC 50 

### s for R1881 (

− 8.69 M) and the weak positive control, dexamethasone (

− 4.39 M), were within the expected ranges. The mean RBA for the weak positive control was 0.0055% . Confidence in these numbers is high due
to the small variation. The solven t control responses indicated a sl ight drift in the study assay for Run 1 (15%). Performance criteria were not met for top % binding for TCVP (Run 1), top % binding for R1881 (Run 2), bottom % binding for R1881 (all runs), and top % binding for dexamethasone (Run 2).

A log IC 50 

### and RBA for TCVP could not be determined as exposure to TCVP did not result in 50% reduction in [ 3 

### H]-R1881 at any concentration. No pr ecipitation of the test compound was reported.

Based on the results from the three runs, TCVP is classified as Equivocal in the Androgen Receptor Binding Assay.

The assay satisfies the EDSP Tier 1 Test Order require ments for an Androgen Receptor Binding Assay (OCSPP 890.1150).

COMPLIANCE: Signed and dated Data Confiden tiality, GLP Compliance, and Quality Assurance statements were provided. No devia tions from regulatory requirements were noted; however, the saturation binding assay was performed as a non-GLP experiment.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 3 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: BSL Bioservice, Scientif ic Laboratories GmbH

Location: Planegg, Germany Study Director: K. Rödig
Other Personnel: B. K. Bernard, Study Monitor W. Riedel, Management A. Lutterbach, Management U. Hamann, Head of Quality Assurance Unit Study Period: October 25, 2011 to January 17, 2012



### 2. Test substance: Tetrachlorvinphos (TCVP)

Description: Powder
Source: Not reported (NR)
Batch #: TX 100113 Purity: 100.05% Solubility: 11.6 mg/L in water at 20°C; 158 .90 mg/L in acetone at 20°C Volatility: NR Stability: NR Storage conditions: Room temperature, protected from light
CAS #: 22248-79-9 Molecular weight: 365.96 g/mol
Structure:

P O O

H 3 CO OCH 3 Cl

Cl Cl Cl



### 3. Non-labeled ligand: R1881
Supplier: Steraloids Inc. Catalog #:
Batch #: E3164-000

FTB 0485 Purity: 98%
CAS #: 965-93-5



### 4. Radioactive ligand: [ 3 

### H]-R1881
Supplier: Perkin Elmer Catalog and Batch #: NET-590 (679512) Date of production: NR
Date of use: November 22, 2011 to December 13, 2011 Radiochemical purity: ≥ 97% Specific activity: 85.1 Ci/mmol
Concentration of stock: 10 nM



### 5. Positive control: Dexamethasone
Supplier: Sigma Catalog #
Batch #: D4902

NR Purity: NR
CAS # : NR



### 6. Solvent/vehicle control: EthanolAndrogen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 4 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None

Justification for choice of
solvent: None provided

Final Concentration: 3.3%



### B. METHODS

1. Preparation of Rat Ventral Prostate Cytosol: A total of 10 male Sprague Dawley rats from Charles River (France) were castrated at 12 weeks of age and were euthanized on the following day. The prostates were excised immediately after termination, weighed, and
stored at

− 80o C until use. Preparation and storage of the prostate cytosol was not reported.
Protein concentration of the cytosol [Batch # 20072011KG(AR)] was determined to be 7.2 mg/mL using a commercially available prot ein kit compatible with DTT (Uptima BCA Protein Assay Kit).

2. Saturation Radioligand Binding Experiment: A saturation binding experiment measuring total and non-specific binding of [ 3 

### H]-R1881 was performed to demonstrate that the AR was present in reasonabl e concentrations and had the appropriate affinity for the R1881 ligand (Table 1). However, the condition s for the saturation binding were reported separately and not included with the AR binding report (Table 2).

TABLE 1. Summary of Conditions for Saturation Binding Experiment a Source of receptor Not reported Concentration of radioligand (as serial dilutions) Not reported Concentration of non-labeled ligand (100X [radioligand]) Not reported Optimization of receptor co ncentration Not reported Temperature Not reported

Incubation time Not reported Composition of assay buffer (TEDG) Tris Not reported

EDTA Not reported Glycerol Not reported Phenylmethylsulfonyl fluoride Not reported

DTT Not reported a Data were not included in the study report.

TABLE 2. Saturation Binding Experiment Run Total Binding Non-Specific Binding Radioligand alone

Tubes Tubes Tubes [ 3 H]-R1881 Final conc. (nM) [ 3 H]-R1881 Final conc. (nM) R1881 Final conc. (nM) [ 3 H]-R1881 Initial conc. (nM) [ 3 H]-R1881 (μL) No data provided



### 3. Competitive Binding Experiment: A summary of the assay conditions for the competitive binding experiment is included in Table 3.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 5 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None

TABLE 3. Summary of Conditions for Competitive Binding Experiment a Source of receptor Rat ventral prostate cytosol Concentration of radioligand 1 nM Optimization of receptor concentration Sufficient to bind 0.27-0.36% of 1.0 nM radioligand b Concentration of test substance (as serial dilutions) 10

− 10 to 10

− 3 M Incubation Temperature 2-8 oC

Incubation time 16-20 hours Composition of assay buffer Tris 10 mM (pH 7.4)

EDTA 1.5 mM Glycerol 10% Phenylmethylsulfonyl fluoride 1 mM Sodium molybdate (Na 2 MoO 4 ) 1 mM

DTT 15.4 mg Triamcinolone acetonide 60 μM a Data were obtained from pages 17, 21 and 29 of the study report. b The protein concentration used was 300 μg protein/tube (p. 20).



### The competitive binding experiment was performed according to the protocol provided in
the EPA Test Guidelines OCSPP 890.1150. The competitive binding experiment measures the binding of a singl e concentration of [ 3 

### H]-R1881 (specific activity of 85.1 Ci/mmol) to the AR in the presence of increasing concentrations of a test substance.

Ethanol was used as a vehicle. Solubility of TCVP in ethanol a nd assay buffer was not reported. The protein concentration used in the competitive binding experiment (300 μg protein/tube) was sufficient to bind 0.27-0.36% of the [ 3 

### H]-R1881.

Dilutions of the test subs tance, reference standard (R1881), weak positive control (dexamethasone), and solvent control (ethanol) were prepared to achieve the concentrations shown in Table 4. Each assay consisted of th ree independent runs on three different days. Each run included triplicate se ts of the ethanol blank and 1 μ M R1881 (non-specific binding, NSB) at the beginning and end of each run, along with triplicate tubes of the reference standard, the weak pos itive control, and th e test chemical at each concentration, resulting in a total of 81 samples per run.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 6 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None

TABLE 4. Competitor Final Molar (M) Con centrations in Competitive Binding Assay a b

Solvent Control Reference standard We ak positive control Test Chemical None Ethanol R1881 Dexamethasone TCVP

Tubes 1-3 and 70-72 Tubes 4-21 and 73-75 c Tubes 22-45 Tubes 46-69 Tubes 76-81

1×10

− 6 1×10

− 3 1×10

− 3

1×10

− 7 1×10

− 4 1×10

− 4

1×10

− 8 1×10

− 5 1×10

− 5

1×10

− 9 1×10

− 6 1×10

− 6

1×10

− 10 1×10

− 7 1×10

− 7

1×10

− 11 1×10

− 8 1×10

− 8

-- 1×10

− 9 1×10

− 9

-- 1×10

− 10 1×10

− 10 a Data were obtained from pages 26-28, 47, 50, and 53 of the study report. b Each concentration of each chemical was run in triplicat e for a total of 81 tubes per run. Tubes 1-75 contained 50 μL of triamcinolone acetonide and 30 μL [ 3 H]-R1881. Samples were dried, and 300 μl of prostate cytosolwere added. Tubes 1-75 also contained 10 μL of the solvent control, reference standard (non-radiolabeled R1881), weak positive control, or test substance, with the exception of Tube s 4-6 and 73-75 that contained 30 μL of non-radiolabeled R1881 (used to evaluate non-specific binding). Tubes 76-81 contained only 30 μl of [ 3 H]-R1881. c Tubes 4-6 and 73-75 were used to evaluate non-specific binding by adding 100X of cold (non-radiolabeled)
R1881.



### To separate bound from free R1881, hydroxyapatite (HAP) slurry was added to each tube and vortexed once every 5 minutes for 20 minutes . The samples were then centrifuged for 3 minutes at 4°C and 600 x g, and the supernatants were discarded. The samples were washed 3 times in 50 mM TRIS buffer. Following the last wash and decanting of the Tris buffer, the pellets were then extracted by addition of 2-mL portions of ethanol. The samples were vortexed three times at 5 minute intervals, and centrifuged. Supernatants were radioassayed by liquid scintillation counting.

4. Data Analysis: The top and bottom of the curve, Hill Slope and inhibition concentration (IC 50 

### ) were calculated with nonl inear regression analysis by using Graph Pad Prism (GraphPad Software, Inc., San Diego, CA). Log IC 50 

### mean and standard error were
calculated for each run of the co mpetitive binding experiment.

5. Definitions

a. Classification of test material

If the data fit a 4-parameter non linear regression model, the test chemical is classified as:

Binder: The average curve for the test chemical across runs crosses 50% of radioligand bound, and the Hill Slope is between

− 0.6 to

− 1.4.

Equivocal: The average lowest portion of curves across runs is between 50% and 75% radioligand binding ( i.e. radioligand displacement is at le ast 25% but less than 50%), or the Hill slope for the curve falls outside th e range for the weak positive control (

− 0.6 to

− 1.4).Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 7 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### Non-Binder: The average lowest portion of curves acr oss runs is greate r than 75% activity ( i.e. less than 25% displacement of radioliga nd), or the data do not fit the model.

Untestable: If the test compound is not soluble above 1×10

− 6 

### M and the binding curve does not cross 50%, the chemical is judged to be untestable.

b. Descriptors for receptor binding

B max 

### : maximal binding capacity
K d 

### : dissociation constants
IC 50 

### : Concentration of the test substance at which 50% of radioligand is displaced from the AR by the competitor 

### Relative Binding Affinity (RBA): (IC 50 

### of R1881 ÷ IC 50 

### of test substance) × 100 Log RBA: Log 10 

### (IC 50 

### of R1881 ÷ IC 50 

### of test substance)

II. RESULTS

A. SATURATION BINDING EXPERIMENT: Saturation binding experiment parameters are presented in Table 5. The amount of cy tosolic protein added for Run 1 was 300 μg, but Runs 2 and 3 contained 900 μg (no explanati on was included). The dissociation constant (K d 

### ) for [ 3 

### H]-R1881 was 0.8881 ± 0.187 nM, and the estimated B max 

### was 0.6403 ± 0.124
fmol/100 μ g protein for the single batch of prosta te cytosol that was prepared. The K d 

### was within the range reported in the EPA validation program for Runs 2 and 3 (the value for Run 1 was slightly low). Confidence in these numbe rs is moderate due to some variation among runs (goodness of fit values were not reported).

TABLE 5. Saturation Binding Experiment of [ 3 H]R1881 with Androgen R eceptor from Rat Prostate Cytosol a

Parameter Run 1 b Run 2 b Run 3 b Mean ± SE c

R 2 (unweighted?) NR NR NR NA

B max (nM) 0.004298 ± 0.0002153 0.01895 ± 0.001015 0.02578 ± 0.001399 0.01634 ± 0.006

B max (fmol/100 μ g protein) 0.4298 0.632 0.859 0.6403 ± 0.124

K d (nM) 0.5615 ± 0.109 0.8929 ± 0.1558 1.21 ± 0.2063 0.8881 ± 0.187 a Data were obtained from pages 20, 38, 42, and 46 of the study report. b The mean and standard deviation are reported for the concurrent replicates of each run. c Calculated by the study reviewer.
SE Standard Error

R 2 Goodness of fit for curve calculated for specific binding



### Figure 1 depicts the non-specific, specif ic, and total binding curves for [ 3 

### H]-R1881 to the androgen receptor for the 3 Satu ration Experiment runs. The specific binding reached a plateau in Runs 1 and 2 only. Non-specific binding ranged from 13.2 to 32.9% of total binding for Runs 2 and 3, excluding one outli er, and non-specific bi nding ranged from 29.2 to 61.7% of total binding for Run 1; maximum values for all runs we re greater than the suggested value of <20% reported in the EPA validation program. Figure 2 contains theAndrogen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 8 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### Scatchard plots that show the binding of [ 3 

### H]-R1881 to the androgen receptor for the 3 Saturation Experiment runs. The data fits re sulted in linear plots for Runs 2 and 3 only.

FIGURE 1. Binding of [ 3 

### H]-R1881 to the Androgen Receptor during the Saturation Binding Experiment.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 9 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD NoneAndrogen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 10 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### FIGURE 2. Scatchard Pl ots of the Binding of [ 3 

### H]-R1881 to the Androgen Receptor.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 11 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### B. COMPETITIVE BINDING EXPERIMENT: Competitive binding experiment parameters are presented in Table 6 and s hown graphically in Figures 3 through 5.

The estimated average log IC 50 

### was

− 8.69 M for R1881 and

− 4.39 M for the weak positive control (dexamethasone). Compared to R1881, the mean RBA for the positive control was 0.0055%. Confidence in these numbers is high due to the small vari ation. The solvent control responses indicated a slight drift in the study assay for Run 1 (15%).

There were no apparent altera tions in radiolabeled R1881 binding at TCVP concentrations
of 10

− 10 

### to 10

− 8 

### M (81.36-122.94%), with the specific binding of the radiolabeled ligand declining to 72.05-77.95% at a concentration of 10

− 7 

### to 10

− 5 

### M in Run 2, and to 56.34-
64.32% at a concentration of 10

− 3 

### M in Runs 1 and 2. A log IC 50 

### and RBA for TCVP could not be determined as exposure to TCVP did not result in 50% reduction in radiolabeled ligand binding at any concentration. No preci pitation of the test compound was reported. Based on the results of the three valid assays, TCVP is classified as “equivocal” with the androgen receptor under the conditio ns of this assay in Runs 1 and 2, and as a “non-binder”
in Run 3.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 12 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None

TABLE 6. Competitive Binding Assay of T CVP with AR from Rat Prostate Cytosol a

Parameter Run 1 b Run 2 b Run 3 b Mean ± SE c

r 2 (unweighted) R1881 0.9954 0.9978 0.9945 0.9945-0.9978
Dexamethasone 0.9785 0.9775 0.9988 0.9775-0.9988
TCVP NR NR NR NA Log IC 50 (M) R1881

− 8.67 ± 0.11

− 8.84 ± 0.09

− 8.56 ± 0.12

− 8.69 ± 0.08
Dexamethasone

− 4.14 ± 0.11

− 4.74 ± 0.15

− 4.30 ± 0.030

− 4.39 ± 0.18
TCVP NA NA NA NA

IC 50 (M) c R1881 2.16 × 10

− 9 1.43 × 10

− 9 2.74 × 10

− 9 2.11 × 10

− 9 (± 0.38)
Dexamethasone 7.30 × 10

− 5 1.81 × 10

− 5 4.99 × 10

− 5 4.70 × 10

− 5 (± 1.59)

TCVP NA NA NA NA Log RBA c Dexamethasone

− 4.53

− 4.10

− 4.26

− 4.30 ± 0.12
TCVP NA NA NA NA RBA (%) Dexamethasone 0.00296 0.00791 0.00548 0.00545 ± 0.0014

TCVP NA NA NA NA a Data were obtained from pages 26-28 and 56-57 of the study report. b The mean and standard error are reported fo r the concurrent replicates within each run. c Calculated by the study reviewer . For means expressed in scientific notation, the SE values in parentheses are presented in the same order of magnitude as the mean value.
SE Standard Error NA Not applicable. NR Not reported

r 2 Goodness of fit (r 2 is more appropriately expressed as a range, as opposed to a mean). RBA (%) relative binding affinity



### FIGURE 3. Percentage R1881 Bound to th e Androgen Receptor in the Presence of
Radioinert R1881.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 13 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### FIGURE 4. Percentage R1881 Bound to th e Androgen Receptor in the Presence of
Dexamethasone.

FIGURE 5. Percentage R1881 Bound to th e Androgen Receptor in the Presence of
TCVP.

C. PERFORMANCE CRITERIA: To ensure that the competitive binding assay was functioning properly, each run was evaluated using the criteria show n in Table 7.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 14 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None

TABLE 7. Criterion a Tolerance Limit(s) b Value Yes No

Ligand depletion is minimal. The recommended ratio of total binding in the absence of competitor to total amount of [ 3 H]- R1881 added per assay tube. ≤ 15% 0.27 to 0.36 X

Test chemical Top (% binding) c 80 to 115 81.36 to 122.94 X d

R1881 fitted curve parameters Top (% binding) 82 to 114 71.01 to 99.88 X e Bottom (% binding)

− 2.0 to 2.0

− 5.390 to 2.315 X f Hill Slope

− 1.2 to

− 0.8

− 1.187 to

− 0.8887 X Weak positive control (dexamethasone) fitted curve parameters Top (% binding) 87 to 106 83.63 to 92.94 X g Bottom (% binding)

− 12 to 12

− 4.784 to 3.965 X Hill Slope

− 1.4 to

− 0.6

− 1.043 to

− 0.8507 X Saturation Binding Experiment K d (nM) 0.685 to 1.57 0.5615 to 1.21 X h Non-specific binding (%) ≤ 10.0 0.07 to 0.11 i X a Data were obtained from pages 28-29 and 56-57 of the study report. b These values represent ranges from the validation study.
c 10

− 9 to 10

− 10 M. d The top % binding was high (122. 94%) in Run 1, but within the acceptable range in the other two runs. e The top % binding was low (71.01%) in Run 2, but within the acceptab le range in the other two runs. f Values were outside of the tolerance range for all three runs. g The top % binding was low (83.63%) in Run 2, but within the acceptab le range in the other two runs. h Saturation binding K d was low (0.5615) in Run 1, but within the acceptable range in the other two runs. i Calculated by study reviewer.



### In the competitive binding experiment, perfor mance criteria were not met for top % binding for TCVP (Run 1), top % binding for R1881 (Run 2), bottom % binding for R1881 (all runs), and top % binding for dexamethasone (Run 2). However, deviations from the tolerance limits were small and log IC 50 

### values for R1881 and dexamethasone were within the expected ranges.

The curve for the reference material showed that increasing concentrations of unlabeled R1881 displaced [ 3 

### H]-R1881 in a manner consistent with one-site binding, as indicated by a descent from 84.65-102.41% to 11.56-20.19% binding over a 81-fold increase in concentration of R1881 (i.e., covering approxima tely 2 log units) for Runs 1 and 3. For Run 2, percent binding declined from 72.27% to 19.7 7% over 3 log units and to 1.70% over 4 log units. Hill Slopes were close to

− 1.0 for all runs (-1.187 to -0.8887). Examination across
the runs indicated consistenc y of the Hill slope, placement along the X-axis, and top and bottom plateaus.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Within all three runs the test item Tetrachlorvinphos (TCVP) did not fit the 4-parameter nonlinear regression model. Therefore, neither IC 50 

### nor Relative Binding Affi nity (RBA) values could be determined. In this study under the given conditions the test item was classified as a non-binder to the androgen receptor.Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 15 of 15 TETRACHLORVINPHOS (TCVP) /083702 OCSPP 890.1150/ OECD None



### B. AGENCY COMMENTS: The saturation binding experime nt did not clearly demonstrate that the androgen receptor was present in a r easonable concentration and functioning with appropriate affinity for the R1881 liga nd in any of the three runs. The K d 

### values for [ 3 

### H]- R1881 were within the range reported in the EPA validation program for Runs 2 and 3 only (0.8929 and 1.21 nM); however, the reported B max 

### values ranged from 0.4298 to 0.859
fmol/100 μ g protein, which are well below the ex pected range of 10 to 150 fmol/100 μg protein. In addition, specific binding did not reach a plateau in Run 3, and non-specific binding ranged from 29.2 to 61.7% of total binding for Run 1 and from 13.2 to 32.9% of total binding for Runs 2 and 3 (excluding one outlier), which is greater than the suggested value of <20% reported in the EPA validation program. The Scatchard plot was not linear
for Run 1.

In the competitive binding experiment, the estimated mean log IC 50 

### s for R1881 and the weak positive control, dexamethasone, as we ll as the mean RBA for dexamethasone were within the expected ranges. C onfidence in these numbers is high due to the small variation. Performance criteria were not met for top % binding for TCVP (Run 1), top % binding for R1881 (Run 2), bottom % binding for R1881 (all runs), top % binding for dexamethasone (Run 2), and saturation binding K d 

### (Run 1).

No precipitation of the test compound was reported. The specific [ 3 

### H]-R1881 declined to
72.05-77.95% at a concentration of 10

− 7 

### to 10

− 5 

### M TCVP in Run 2, and to 56.34-64.32% at
a concentration of 10

− 3 

### M TCVP in Runs 1 and 2. The mean percent [ 3 

### H]-R1881 AR binding in run 3 was >75%. Based on the resu lts of the three valid assays, TCVP is classified as “equivocal” with the androgen receptor under the conditions of this assay in Runs 1 and 2, and as a “non-binder” in Run 3. Overall TCVP is classified as equivocal in this AR binding assay.

C. STUDY DEFICIENCIES: The following deficiencies were noted that are not considered to have had an adverse impact on the results, interpretation or conclusions of this study:

 Data from the saturation bi nding experiment did not meet the recommended ranges or guidance for K d 

### (Run 1), B max 

### (all runs), non-specific bind ing (all runs), and specific binding (Run 3), and did not produce a linea r Scatchard plot in Run 1. The test guideline recommends that proper saturation bi nding of the reference ligand to the AR
be demonstrated with each batch of rat vent ral prostate cytosol before using the cytosol to conduct competitive binding assays.

 Performance criteria were not me t for all runs (see Table 7).

 Separate curves were not provided for each run and curves of TCVP, the reference standard (R-1881) and weak positive contro l (dexamethasone) were not shown on the same graph.

 Details on the preparation a nd storage of the prostate cytosol were not provided.

 The complete report (including analysis methods) for the saturation binding experiment was not provided; however, pertinent info rmation, data, and graphs were provided allowing the reviewers to evaluate the study.

# DATA EVALUATION RECORD

TETRACHLORVINPHOS (TCVP) Study Type: OCSPP 890.1200, Aromatase Assay

EPA Contract No. EP10H001452 Task Assignment No. 2-59-2012 (MRID 48673801)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer Signature: Joan Harlin, M.S. Date: 6/27/2012

Secondary Reviewer Signature: Scott D. Studenberg, Ph.D., D.A.B.T. Date: 7/05/2012

Program Manager: Signature: Jack D. Early, M.S. Date: 7/09/12

Quality Assurance: Signature: Jack D. Early, M.S. Date: 7/09/12

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).Aromatase (Human Recombinant) Assay (2011) I Page I of 11 TETRACHLORVINPHOS TCVP I 0837010



### Primary Reviewer: Linda Taylor, Ph.D.

Health Effects Division Secondary Reviewer: Greg Akerman, Ph.D.
Health Effects Division



### DATA EVALUATION RECORD OCSPP 890.1100 I OECD None



### STUDY TYPE: Aromatase (Human Recombinant); OCSPP 890.1200



### PC CODE: 083702 

### DP BARCODE: D379676



### TXR#: 0056284 

### CAS No.: 22248- 79-9



### TEST MATERIAL (PURITY): Tetrachlorvinphos (100.05% a.i.)



### SYNONYMS: (lZ)-2-chloro-1-(2,4,5-trichlorophenyl)ethenyl dimethyl phosphate; TCVP



### CITATION: Hofman-Htither, H. (2011). Endocrine Disruptor Test: Aromatase Assay (Human Recombinant) with Tetrachlorvinphos (TCVP). BSL Bioservice,
Scientific Laboratories GmbH, Planegg, Germany. Laboratory Study No.: 114587, December 23, 2011. MRID 48673801. Unpublished.



### SPONSOR: The TCVP Task Force, c/o SRA International Inc., 5235 Ragged Point Road, Cambridge, MD



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In an 

### in vitro aromatase (CYP 19) assay (MRJD 48673801), tetrachlorvinphos (TCVP; 100.05% a.i., Batch# TX 100113) was incubated with human
recombinant aromatase and tritiated androstenedione (1-P [ 3 

### H(N)]-androst-4-ene-3,17-dione;

[ 3 

### H]ASDN) in 1.0% dimethyl sulfoxide (DMSO) at final log concentrations of 10- 10 

### to 10- 3 

### M
for 15 minutes to assess the potential ofTCVP to inhibit aromatase activity.

Aromatase activity was determined by measuring the amount of tritiated water produced at the
end of a 15-minute incubation for each concentration of chemical. Tritiated water was quantified using liquid scintillation counting (LSC). Three runs were conducted and each run included a full activity control, a background activity control, a positive control series (10- 10 

### to 10- 5 

### M) using a known inhibitor ( 4-hydroxyandrostenedione; 4-0H ASDN), and the test chemical series (10- 10 

### to 10- 3 

### M for Run I; 10- 7 

### to 10- 3 

### M for Runs 2 and 3) with three repetitions per concentration. Due to inhibition of aromatase activity observed in Run 1, the concentrations of
the test item used in Runs 2 and 3 were adjusted to include mid-log concentrations.

Aromatase activity in the full activity controls for the three successful runs was 0.181 

### ± 0.024 nmol·mg-protein

- 1 

### ·min- 1 • 

### The response of the full activity controls and background controls was acceptable for each run. Activity in the background controls ranged 1.7-4.4% and averaged 3.03

± 

### 0.93% of the full activity controls.Aromatase (Human Recombinant) A ssay (2011) / Page 2 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### For the positive control substance (4-OH ASDN), aromatase activity results were within the recommended ranges for the performance criteria. The estimated log IC 50 

### for 4-OH ASDN averaged

− 7.3 M and the Hill slope was

− 1.05.

For TCVP, aromatase activity averaged 0.203 ± 0.002 nmol·mg-protein

− 1 

### ·min

− 1 

### at the lowest concentration tested in Run 1 (10

− 10 

### M) and 0.155 ± 0.037 nmol·mg-protein

− 1 

### ·min

− 1 

### at the lowest concentration tested in Runs 2 and 3 (10

− 7 

### M; includes data for Run 1). Aromatase activity was
0.028 ± 0.008 nmol·mg-protein

− 1 

### ·min

− 1 

### at the highest tested c oncentration of TCVP (10

− 3 

### M). The lowest portion of the response curve for TC VP across runs was less than 50% activity. Aromatase activity for TCVP was 10 3.6-105.9% at concentrations from 10

− 10 

### to 10

− 8 

### M (tested in Run 1 only) and 90.0-95.4% at concentrations from 10

− 7 

### to 10

− 5 

### M; activity decreased to
62.6% at 10

− 4 

### M, 33.1% at 3.16 × 10

− 4 

### M, and 17.2% at 10

− 3 

### M. The average log IC 50 

### of TCVP

was

− 3.76 M and the Hill slope was

− 1.01.

Based on the data from the average response curv e, TCVP is classified as an Inhibitor of aromatase activity in this assay.

The assay satisfies the EDSP Tier 1 Test Order requireme nts for an Aromatase assay (OCSPP 890.1200).

COMPLIANCE: Signed and dated Data Confiden tiality, GLP Compliance, and Quality Assurance statements were provided.Aromatase (Human Recombinant) A ssay (2011) / Page 3 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Substance: Tetrachlorvinphos (TCVP)
Description: Powder
Source: The TCVP Task Force, Cambridge, MD Batch# (expiration date): TX 100113 (expiry date to be provided by sponsor) Purity: 100.05% Volatility: Not reported Storage conditions: Room temperature, protected from light Stability: Not reported
Solvent: DMSO Solubility (in test solvent): 11.6 mg/L in water at 20oC; 158. 90 mg/L in acetone at 20oC Highest Concentration Tested: 10

− 3 M Stock Solution Preparation: Not reported Molecular weight: 365.96 g/mol
CAS #: 22248-79-9
Structure:

P O O

H 3 CO OCH 3 Cl

Cl Cl Cl



### 2. Non-Labeled Substrate: Androstenedione (ASDN)

CAS # : 63-05-8
Source: Sigma (Catalog # 46033) Batch # (expiration date): SZB9317XV (November 13, 2014) Purity: 99.1%



### 3. Radiolabeled Substrate: 1- β [ 3 

### H(N)]-Androst-4-ene-3,17-dione; ([ 3 

### H]ASDN)

Source: Perkin Elmer (Catalog #NET-926) Batch # (expiration date): 619344 (expiry not reported) Radiochemical Purity (Supplier): ≥ 97% Specific activity: 26.3 Ci/mmol Radiochemical Purity (In-lab determination): Not determined



### 4. Positive Control: 4-hydroxyandrostenedione (4-OH ASDN)

CAS # 566-48-3
Source: Not reported Batch # (expiration date): Not reported Purity: Not reported



### 5. Solvent (Vehicle Control): Dimethyl sulfoxide (DMSO)

Source: Batch # (expiration date): Not reported Not reported
Justification for choice of solvent Not reported
Concentration (% of total volume in assays) 1%Aromatase (Human Recombinant) A ssay (2011) / Page 4 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### 6. Test Microsomes: Human recombinant aromatase (CYP19) microsomes

Source: BD Biosciences (Catalog # 456260) Lot # (expiration date): 03897 (expiry not reported)

Protein concentration: Not reported Cytochrome C reductase activity: Not reported Aromatase activity: Not reported



### B. METHODS

1. Assay Components and Preparations: A mixture of non-labe led and radiolabeled [ 3 

### H]ASDN was prepared such that the final concentration of ASDN in the assay was approximately 0.1 μM, and the amount of tri tium added to each incubation tube was
0.1 μ Ci.

Test chemical stock solutions were prepared su ch that the total volume of each test chemical formulation used per assay was no more than 1% of the total assay volume to minimize the potential for the solvent to inhibit the enzyme . A rationale for the selection of DMSO was not provided; however, TCVP is soluble in DM SO at the tested concentrations and is a solvent recommended by the EPA guidelines.

A stock solution of the positive control substance, 4-OH ASDN, was formulated in DMSO. Details of the stock solution preparation were not reported. Dilutions were prepared such that the target concentrati ons of the positive control substance (0.1-10,000 nM; Table 4) were achieved by the addition of 10 μL of the dilution for a final assay volume of 1 mL.

Human recombinant microsomes were purchased from BD Biosciences, and stored at

− 80oC (storage interval not reported ). Microsomes were portioned into individual vials based on the protein concentration of the batch ( 0.004 mg/mL microsomal protein per tube) and stored at (storage in terval not reported).

Other assay components sodium phosphate buffer, propylene glycol, and NADPH are reported in Table 1.

TABLE 1. Assay Components and Conditions a Assay Factor Values 0.1M sodium phosphate buffer (pH 7.4)

Microsomal Protein 0.004 mg/mL b

NADPH 0.3 mM [ 3 H]ASDN 100 nM Propylene Glycol 5% Temperature 37 ± 1°C

Incubation Time 15 min a Data were obtained from p. 23 of the study report.



### 2. Suitability Assessments: The protein concentration was determined on each day the aromatase assay was run using a BCA Protein Assay Kit (Uptima). Aromatase activity in each lot of human recombinant microsomes was determined to demonstrate the presence of sufficient activity for analysis of TCVP. The aromatase activityAromatase (Human Recombinant) A ssay (2011) / Page 5 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### was determined to be 0.143-0.204 mol·mg-protein

− 1 

### ·min

− 1 

### , which is greater than the minimum recommended aromatase activity of 0.1 nmol·mg-protein

− 1 

### ·min

− 1



### .

3. Aromatase Assay: Each assay run contained 4 tube s for the full enzyme activity and background activity controls, resp ectively, and a full concentration curve in duplicate for the positive control and in triplicate for the test substance. The aromatase assay was conducted generally according to the procedures described in OCSPP 890.1200 (Section h, pp. 9-10).

The amount of 3 

### H 2 

### O in the aqueous fraction was quantified for each assay tube by LSC, and aromatase activity was reported in units of nmol·mg-protein

− 1 

### ·min

− 1



### .

4. Demonstration of Proficiency: Proficiency data were not provided.

a. Positive Control

(1) Initial Demonstration of Laboratory Proficiency: The positive control data for laboratory met the following criteria:

 Mean aromatase activity in the abse nce of an inhibitor was at least 0.1 nmol·mg-protein

− 1 

### ·min

− 1



### .

 Mean background control activity was ≤ 15% of the full activity control.

 Coefficient of variation (CV) for replicates within each sample type and concentration of 4-OH ASDN was <15% except fo r the highest concentration, 10

− 5 

### M (25.1%).

 Performance criteria (Table 2) were met, with a few minor exceptions, and served as guidance in identifying runs that provided parameters in the preferred ranges.

(2) Demonstration of Proficiency of Ne w Technician for Conducting Assay (when applicable): Assays to classify proficiency chemi cals (econazole, fenarimol, nitrofen, and atrazine) were not performed.

TABLE 2. Performance Criteria for the Positive Control a
Parameter Lower Limit Criteria Upper Limit Crit eria Actual Lower Limit Actual Upper Limit Slope

− 1.2

− 0.8

− 1.27

− 0.5 Top (%) 90 110 82.8 102.5 Bottom (%)

− 5 +6

− 5.0 8.3 Log IC 50 (M)

− 7.3

− 7.0

− 7.4

− 7.2 a Data were obtained from pp. 28, 30, and 32 of the study report.



### b. Proficiency Chemicals: Data for the proficiency ch emicals were not provided.Aromatase (Human Recombinant) A ssay (2011) / Page 6 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None

TABLE 3. Proficiency Chemicals Compound CAS# Class Concentrations
Econazole 24169-02-6 No data No data
Fenarimol 60168-88-9 No data No data
Nitrofen 1836-75-5 No data No data
Atrazine 1912-24-9 No data No data



### 5. Determination of Aromatase Ac tivity with Test Chemical(s): The response of aromatase activity to the presence of eight concentrations of TCVP per run, in triplicate, was tested during three independent runs (Table 4). Because inhibition of aromatase activity was observed in the first run, the test chemical c oncentrations were adjusted in the second and third runs were adjusted to bett er define the response curve.

TABLE 4. Test Chemical Study Design for each Test Run a

Sample Type Repetitions (Tubes) Description Reference or Chemical (M) Full Activity Control 4 All test components b plus solvent vehicle N/A Bkgd Activity Control 4 Same as above without NADPH N/A

4-OH ASDN Conc 1 2 All test components plus 4-OH ASDN 1×10

− 5

4-OH ASDN Conc 2 2 All test components plus 4-OH ASDN 1×10

− 6

4-OH ASDN Conc 3 2 All test components plus 4-OH ASDN 1×10

− 7

4-OH ASDN Conc 4 2 All test components plus 4-OH ASDN 3×10

− 7.5

4-OH ASDN Conc 5 2 All test components plus 4-OH ASDN 1×10

− 8

4-OH ASDN Conc 6 2 All test components plus 4-OH ASDN 3×10

− 8.5

4-OH ASDN Conc 7 2 All test components plus 4-OH ASDN 1×10

− 9

4-OH ASDN Conc 8 2 All test components plus 4-OH ASDN 1×10

− 10

TCVP Conc 1 c, d 3 All test components plus TCVP 1×10

− 3

TCVP Conc 2 c,e 3 All test components plus TCVP 3.16×10

− 4

TCVP Conc 3 c, d 3 All test components plus TCVP 1×10

− 4

TCVP Conc 4 c,e 3 All test components plus TCVP 3.16×10

− 5

TCVP Conc 5 c, d 3 All test components plus TCVP 1×10

− 5

TCVP Conc 6 c,e 3 All test components plus TCVP 3.16×10

− 6

TCVP Conc 7 c, d 3 All test components plus TCVP 1×10

− 6

TCVP Conc 8 c, d 3 All test components plus TCVP 1×10

− 7

TCVP Conc 9 c, f 3 All test components plus TCVP 1×10

− 8

TCVP Conc 10 c, f 3 All test components plus TCVP 1×10

− 9

TCVP Conc 11 c, f 3 All test components plus TCVP 1×10

− 10 a Data were obtained from pp. 20 and 21 of the study report. b The complete assay contained buffer, prop ylene glycol, microsomal protein, ASDN/[ 3 H]ASDN substrate, and NADPH.
c Test chemical.
d Test concentration used in all three runs. e Test concentration used in Runs 2 and 3 only. f Test concentration used in Run 1 only.



### C. DATA ANALYSIS

1. Raw Data: Raw data were converted to aromatase activity (nmol·mg-protein

− 1 

### ·min

− 1 

### ) and percent control for the positive control and test chemical. The following raw data and calculated endpoints for each run were in cluded in the report (Table 5).Aromatase (Human Recombinant) A ssay (2011) / Page 7 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None

TABLE 5. Raw and Calculated Data

Raw/Calculated Data Included (X) DPM/mL for each portion of extract ed aqueous incubation mixture X Average DPM/mL for each aqueous portion (after extraction) X Total DPM for each aqueous portion (after extraction) X The total DPM present in the assay tube at initiation The percentage of substrate converted to product X Total DPM after extraction corrected for background X Aromatase activity expressed in nmol/mg protein/min X Average aromatase activity in the full activity control tubes X Percentage of control activity remaining in the presence of various inhibitor concentrations X DPM Disintegrations per minute



### 2. Statistical Methods: S tatistical analyses performed on the data were means of replicates and standard deviation of the mean. The data were converted to aromatase activity ( 

### nmol·mgprotein

− 1 

### ·min

− 1 

### ). The percent of control activity was calculated by comparison of the respective mean values of the test item or positive control to the full enzyme activity control. The IC 50 

### value was calculated with the software GraphPad Prism.

For each run, the individual and mean concentration of the three test chemical replicates and two positive control replicates were plotted versus the percent of control activity.



### 3. Interpretation of Results: Interpretation of the assay results was based on the average of three runs, using the categor ies presented in Table 6.

TABLE 6. Interpret ation of Results
Criteria Interpretation Data fit 4-parameter nonlinear regression model Average curve across runs crossed 50% a Inhibitor Average lowest portion of curves across runs is between 50% and 75% activity b Equivocal

Average lowest portion of curves across runs is greater than 75% activity b Non-inhibitor

Data do not fit model
--- a Ordinarily, an inhibition curve will fall from 90% to 10% over 2 log units with a slope near

− 1. Unusually steep curves may indicate protein denaturing or solubility issues. If the slope of the curve is steeper than

− 2.0, the result is classified as equivocal. b If the test compound was not soluble above 10

− 6 M and the inhibition curve does not cr oss 50%, the chemical is typically
determined to be untestabl e in the aromatase assay.



### II. RESULTS

A. CONTROL ACTIVITY: Aromatase activity in the full activity controls ranged from 0.143-0.204 nmol·mg-protein

− 1 

### ·min

− 1 

### for the 3 test runs, with a mean and standard deviation of 0.181 ± 0.024 nmol·mg-protein

− 1 

### ·min

− 1 

### . The response of the full activity controls and background controls were acceptable for each run. Activity in the background controls ranged 1.7-4.4% and averaged 3.03 ± 0.93% of the full activity controls.Aromatase (Human Recombinant) A ssay (2011) / Page 8 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### B. POSITIVE CONTROL: For the positive control substance (4-OH ASDN), aromatase activity averaged 0.172 ± 0.035 nmol·mg-protein

− 1 

### ·min

− 1 

### at the lowest tested concentration
of 10

− 10 

### M and 0.007 ± 0.003 nmol·mg-protein

− 1 

### ·min

− 1 

### at the highest tested concentration of
10

− 5 

### M. The mean aromatase activity of the positive control (expressed as % full control activity) for each concentration tested across a ll 3 runs is presented in Table 7, along with the overall standard deviation, SEM, and % CV. As a percent of the control, aromatase activity for 4-OH ASDN was 3.93% at 10

− 5 

### M and 98.50% at 10

− 10 

### M. Inhibition response curves for the positive control replicates from each run are shown in Figures 1-3. These results were generally within the recommende d ranges for the top of the curve, bottom curve, hill slope, and log IC 50 

### . The overall % CV exceeded the recommended 15% at the
10

− 5 

### M test concentration (25.1%).

TABLE 7. Effect of TCVP on Ar omatase Activity (as percent of control) from Independent Runs a
Chemical Concen. (Log M) # Runs Overall Mean b Overall SD b Overall SEM b Overall % CV b

4-OH ASDN (positive control) − 5 3 3.93 0.99 0.57 25.1

− 6 3 10.65 1.31 0.76 12.3

− 6.5 3 18.87 0.89 0.52 4.7

− 7 3 36.90 1.69 0.98 4.6

− 7.5 3 63.95 4.81 2.78 7.5

− 8 3 80.40 10.89 6.28 13.5

− 9 3 94.12 8.67 5.01 9.2

− 10 3 98.50 1.35 0.78 1.4

− 3 3 17.16 3.88 2.24 22.6

− 3.5 2 33.05 6.76 4.78 20.5

− 4 3 62.62 8.48 4.90 13.5

− 4.5 2 78.18 4.17 2.95 5.3

TCVP

− 5 3 90.02 6.07 3.50 6.7

− 5.5 2 91.03 5.33 3.77 5.9

− 6 3 95.44 5.21 3.01 5.5

− 7 3 93.32 11.75 6.78 12.6

− 8 1 104.47 4.17 4.17 4.0

− 9 1 105.93 1.66 1.66 1.6

− 10 1 103.60 1.06 1.06 1.0 a Data were obtained pages 27-32 of the study report b Calculated by the reviewers from data presented in this table.
SD Standard Deviation
SEM Standard error of the mean
CV Coefficient of Variance



### C. TEST SUBSTANCE: For TCVP, aromatase activity averaged 0.203 ± 0.002 nmol·mgprotein

− 1 

### ·min

− 1 

### at the lowest concentra tion tested in Run 1 (10

− 10 

### M), 0.155 ± 0.037 nmol·mg-protein

− 1 

### ·min

− 1 

### at the lowest concentration tested for Runs 2 and 3 (10

− 7 

### M; includes data for Run 1), and 0.028 ± 0.008 nmol·mg-protein

− 1 

### ·min

− 1 

### at the highest tested concentration (10

− 3 

### M). The mean aromatase activity of TCVP (expressed as % full control activity) for each concentration tested across all 3 runs is presented in Table 7 (presented above), along with the overall standard devi ation, SEM, and % CV. Inhibition response curves for TCVP replicates from each run are shown in Figures 1-3. The overall mean aromatase activities compared to the controls was 103.6-105.9% at concentrations from
10

− 10 

### to 10

− 8 

### M (tested in Run 1 only) and 90.0- 95.4% at concentrations from 10

− 7 

### to 10

− 5 

### M. Activity decreased to 62.6% at 10

− 4 

### M, 33.1% at 3.16 × 10

− 4 

### M, and 17.2% at 10

− 3 

### M.Aromatase (Human Recombinant) Assay (2011) / Page 9 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### FIGURE 1. Inhibition Response Curves for 4-OH-ASDN and TCVP From Run 1.

FIGURE 2. Inhibition Response Curves for 4-OH-ASDN and TCVP From Run 2.Aromatase (Human Recombinant) A ssay (2011) / Page 10 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### FIGURE 3. Inhibition Response Curves for 4-OH-ASDN and TCVP From Run 3.

The effect of TCVP on aromatase activity is presented in Table 8. The estimated log IC 50 

### ranged from –3.94 to

− 3.63 M for the test material and averaged

− 3.76 M compared to the positive control 4-OH ASDN, which averaged

− 7.30 M. Confidence in these values is very high due to the small variations. The average slope of the concentration response curve was

− 1.01 for TCVP and

− 1.05 for 4-OH ASDN. Confidence in the Hill slope values is very low due to the large variations (>23% CV).

TABLE 8. Effect of TCVP on Arom atase Activity (as Percent of Cont rol) From Three Independent Runs a

Chemical Run 1 Run 2 Run 3 Mean b SEM b %CV b
Log IC 50 (M)
TCVP

− 3.63

− 3.70

− 3.94

− 3.76 0.09 4.3

4-OH ASDN

− 7.21

− 7.33

− 7.37

− 7.30 0.05 1.15 Hill slope
TCVP

− 0.79

− 0.98

− 1.26

− 1.01 0.14 23.41

4-OH ASDN

− 1.24

− 0.70

− 1.21

− 1.05 0.17 28.55 a Data were obtained pages 27-32 of the study report b Calculated by the reviewers from data presented in this table.
SEM Standard Error of the Mean
CV Coefficient of Variance NA Not applicable



### III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS CONCLUSIONS: In this study under the given conditions, TCVP was determined to inhibit the catalytic activity of aromatase and ther efore, may affect the endocrine system.

B. AGENCY COMMENTS: Aromatase activity in the full activity controls for the three successful runs averaged 0.181 ± 0.024 nmol·mg-protein

− 1 

### ·min

− 1 

### . The response of the full activity controls and background controls were acceptable for each run. Activity in the background controls ranged 1.7-4.4% and av eraged 3.03 ± 0.93% of the full activity
controls.Aromatase (Human Recombinant) A ssay (2011) / Page 11 of 11 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1200 / OECD None



### For the positive control substance (4-OH ASDN) , aromatase results were generally within the recommended ranges for the top of the curve, bottom curve, Hill slope, log IC 50 

### , and %CV for replicates of each concentra tion within runs. The estimated log IC 50 

### for 4-OH ASDN averaged

− 7.3 M and the Hill slope was

− 1.05.

For TCVP, aromatase activity averaged 103.6-105.9% at concentrations from 10

− 10 

### to 10

− 8 

### M (tested in Run 1 only) and 90.0-95. 4% at concentrations from 10

− 7 

### to 10

− 5 

### M; activity
was decreased to 62.6% at 10

− 4 

### M, 33.1% at 3.16 × 10

− 4 

### M, and 17.2% at 10

− 3 

### M. The average estimated log IC 50 

### for TCVP was

− 3.76 M and the Hill slope averaged 1.01. Under
the conditions of this as say, TCVP was an inhibito r of aromatase activity.

C. STUDY DEFICIENCIES: The following deficiencies were noted that are not considered to have had an adverse impact on the results, interpretation or conclusions of this study:

 Although eight test concentrations were employed for each test run, only four of those
test concentrations were used in all thr ee runs. However, for Runs 2 and 3, mid-log concentrations (i.e. 10

− 4.5 

### M) were added in order to obtain the required eight test concentrations, as noted in section (j) of OCSPP 890.1200. The results from this aromatase assay clearly demonstrate that TCVP is an aromatase inhibitor (>50% inhibition).

 Proficiency data were not in cluded in the study report.

 The stability of TCVP was not reported.

 Complete details of the expe rimental design were not repor ted, and CoAs for the test and reference compounds, or a data sheet fo r the microsomes, were not included in the study report. For the human microsomes, the protein concentr ation, cytochrome C reductase activity, and aromatase activity we re not reported. For the positive control and solvent vehicle (DMSO), the source and ba tch/lot numbers were not reported. Also, the purity of the positive control was not reported.

 CVs were > 15% in some cases.

 The bottom of inhibition curves for the pos itive control exceeded the performance limits
in some runs.

# DATA EVALUATION RECORD

TETRACHLORVINPHOS (TCVP)

Study Type: OCSPP 890.1250, Estrogen Receptor Binding Assay

EPA Contract No. EP10H001452 Task Assignment No. 2-62-2012 (MRID 48765001)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer: Signature: Daniel R. Hunt, M.S. Date: 6/14/2012

Secondary Reviewer: Signature: Scott D. Studenberg, Ph.D., D.A.B.T. Date: 6/26/2012

Program Manager: Signature: Jack D. Early, M.S. Date: 6/28/2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 6/28/2012

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screenin g Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).TETRACHLORVINPHOS (TCVP) I 083702 Estrogen Receptor Binding (Rat Uterine CytosoJ) (2011} I Page 1 of 16
OCSPP 890.1250/ OECD None



### Primary Reviewer: Minerva Mercado, Ph.D.


### Health Effects Division Secondary Reviewer: Greg Akerman, Ph.D.


### Health Effects Division Signatur

Date:**___.l.......'ll~~~ -­**  

### Signature:**~~a=:~~~­** 

### Date:

_**___;~-"'=-.J....!.:.~-** Template version 08/2011



### DATA EVALUATION RECORD

STUDY TYPE: Estrogen Receptor Binding Assay Using Rat Uterine Cytosol (ER-RUC);
OCSPP 890.1250



### PC CODE: 083702 

### DP BARCODE: D400718

TXR#: 0056284 

### CAS No.: 22248- 79-9



### TEST MATERIAL (PURITY): Tetrachlorvinphos (100.05%)



### SYNONYMS: (1 Z)-2-chloro-1-(2,4,5-trichlorophenyl)ethenyl dimethyl phosphate; TCVP



### CITATION: Rodig, 

### K. (2012). Endocrine Disruptor Test: Estrogen Receptor Binding (Rat
Uterine Cytosol) with Tetrachlorvinphos (TCVP). BSL Bioservice, Scientific
Laboratories GmbH, Planegg, Germany. Laboratory Study No: 114589, January 18, 2012. MRID 48765001. Unpublished.



### SPONSOR: The TCVP Task Force c/o SRA International Inc., 5235 Ragged Pt. Road, Cambridge, MD

TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In an estrogen receptor (ER) binding assay (MRID 48765001) for tetrachlorvinphos (TCVP), uterine cytosol from Sprague Dawley rats was used as the source of

ER to conduct saturation and competitive binding experiments. The saturation binding experiment was conducted to demonstrate that the ER in the rat uterine cytosol was present in
reasonable numbers and was functioning with appropriate affinity for the radiolabeled reference
estrogen prior to routinely conducting competitive binding experiments. The competitive binding experiment was conducted to measure the binding of a single concentration of 

## [3HJ-17Pestradiol ( 1 nM) 

### in the presence of increasing concentrations (logarithmic increase from 10- 10 

### to 10

- 3 

### M) of TCVP (100.05% purity, Batch #TX 100113). Ethanol was used as the solvent vehicle

at a final concentration of 2%. A total of 3 runs were performed, and each run included 19-
norethindrone as a weak positive control, octyltriethoxysilane as a negative control, and 17-Pestradiol as the natural ligand reference material.

In the saturation binding experiment, the mean maximum binding capacity (Bmax) was 5.464
fmol/l 00 μg protein and the mean dissociation constant (l<-0) 

### was 0.1297 nM. The Bmax value

was lower than the recommended range of 10-150 fmol/l 00 μg protein. The Scatchard plots for
the three Saturation assays were linear. The specific binding reached a plateau in all runs, and non-specific binding was generally less than 20% of total binding.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 2 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### In the competitive binding experiment, the estimated mean log IC 50 

### was

− 9.188 M for 17 β

estradiol and

− 6.484 M for the weak positive control. The mean relative binding affinity (RBA) was 0.1990% for the weak positive control. Conf idence in these numbers is high due to the small variation in the data. All performance criteria were generally met.

TCVP had minimal effect on specific binding of the [ 3 

### H]-ligand; therefore, a log IC 50 

### and RBA could not be calculated for TCVP. Specific [ 3 

### H]-ligand binding to the ER was >75% at all
soluble concentrations of TCVP tested in all runs. Based on the results from the three runs,
TCVP is classified as Not Interactive in the Estrogen Receptor Binding Assay.

The assay satisfies the EDSP Tier 1 Test Order requireme nts for an Estrogen Receptor Binding Assay (OCSPP 890.1250).

COMPLIANCE: Signed and dated Data Confiden tiality, GLP Compliance, and Quality Assurance statements were provided. No devia tions from regulatory requirements were noted; however, the saturation binding assay was performed as a non-GLP experiment.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 3 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: BSL Bioservice, Scientif ic Laboratories GmbH

Location: Planegg, Germany Study Director: K. Rödig

Other Personnel: B. K. Bernard, Study Monitor W. Riedel, Management A. Lutterbach, Management U. Hamann, Head of Qu ality Assurance Unit Study Period: November 9, 2011 to January 18, 2012



### 2. Test substance: Tetrachlorvinphos (TCVP)
Description: Powder

Source: Not reported (NR)

Batch #: TX 100113 Purity: 100.05% Solubility: 11.6 mg/L in water at 20°C; 158 .90 mg/L in acetone at 20°C Volatility: NR Stability: NR Storage conditions: Room temperature, protected from light

CAS #: 22248-79-9 Molecular weight: 365.96 g/mol

Structure:

P O O

H 3 CO OCH 3 Cl

Cl Cl Cl



### 3. Non-labeled ligand (strong positive control): 17 β -estradiol

Supplier: Sigma Catalog #: E8875

Batch #: 079K0131 Purity: 100%

CAS #: 50-28-2



### 4. Radioactive ligand: [ 3 

### H]-17 β -estradiol
Supplier: Perkin Elmer Catalog #: NET-517

Batch#: 650702 Radiochemical purity: ≥ 97% Specific activity: 130.2 Ci/mmol

Concentration of stock: 50 nM



### 5. Weak positive control: 19-Norethindrone
Supplier: Sigma Catalog #: 46525

Lot #: SZB6306XV Purity: NR
CAS #: NR



### 6. Negative control: OctyltriethoxysilaneEstrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 4 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None

Supplier: Sigma Catalog #: 679305

Lot #: 04096BK Purity: NR
CAS #: NR



### 7. Solvent/vehicle control: Ethanol

Justification for choice of
solvent: None provided

Final Concentration: 2%



### B. METHODS

1. Preparation of Rat Uterine Cytosol (RUC): A total of 10 female Sprague Dawley rats from Charles River (France) were ovariectom ized 7 days prior to being euthanized.
Animals were 12-13 weeks old at the time of euthanasia. The uteri were weighed, and
stored at

− 80o C until use. Preparation and storage of the uterine cytoso l was not reported.
Protein concentration of th e cytosol [Batch #20072011KG(ER)] was determined to be 3.6 mg/mL using a protein kit compatible w ith DTT (Uptima BCA Protein Assay Kit).

2. Saturation (radioligand) Binding Experiment: A saturation binding experiment measuring total and non-specific binding of [ 3 

### H]-17 β -estradiol was performed to demonstrate that the ER was present in reason able concentrations and had the appropriate affinity for the native ligand (Table 1). Howe ver, the conditions for the saturation binding
were not included with the ER binding report (Table 2).

TABLE 1. Summary of Conditions for Saturation Binding Experiment Source of receptor Rat uterine cytosol Concentration of radioligand (as serial dilutions) 0.03, 0.06, 0.08, 0.1, 0.3, 0.6, 1.0, 3.0
nM a Concentration of non-labeled ligand (100X [radioligand]) Not reported b Concentration of receptor Not reported b
Temperature Not reported b

Incubation time Not reported b Composition of assay buffer Tris Not reported b

EDTA Not reported b Glycerol Not reported b Phenylmethylsulfonyl fluoride Not reported b

DTT Not reported b a Data included in Appendix 2. b Data were not included in the study report.

TABLE 2. Saturation Binding Experiment Run Not Reported



### 3. Competitive Binding Experiment: A summary of experimental conditions for the competitive binding experiment is included in Table 3.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 5 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None

TABLE 3. Summary of Conditions for Competitive Binding Experiment a Source of receptor Rat Uterine Cytosol Concentration of radioligand 50 nM Concentration of receptor Not Reported b Concentration of test substance (as serial dilutions) 10

− 10 to 10

− 3 M Temperature 2-8 oC

Incubation time 16-20 hours Composition of assay buffer Tris 10 mM (pH 7.4)

EDTA 1.5 mM Glycerol 10% Phenylmethylsulfonyl fluoride 1 mM

DTT 1 mM a Data were obtained from pages 21 of the study report. b The protein concentration was 80 μg protein/tube (p. 20).



### Solubility of TCVP in ethanol or assay buffe r was not evaluated before the final assay, however visually precipitation was noted in the highest test concentration (10

− 3 

### M) during the assay. On the day of the assay, the specific activity of the stock solution [ 3 

### H]-17 β

estradiol was adjusted for decay over time (a djusted specific activity of 125.98 Ci/mmol for Run 1; 125.84 Ci/mmol for Run 2, and 125.70 Ci/mmol for Run 3), and diluted in TEDG
buffer + PMSF to achieve a final concentration of 50 nM. The protein concentration used in the competitive binding experiment was 80 μg /assay tube; percent binding of radioligand was not reported. Serial diluti ons of the test substance, pos itive control (19-norethindrone), negative control (octyltriethoxysilane), and reference material (non-labeled 17 β -estradiol) were prepared to achieve the concentrations shown in Table 4. Each assay consisted of three independent runs on thr ee different days (one run was repeated because the negative control data did not meet the pe rformance criteria). Each run contained three replicates at each concentration plus six replicates of the [ 3 

### H]-17 β -estradiol only control (total radioactivity) and trip licate replicates of the non-sp ecific binding (NSB) and solvent controls, resulting in a to tal of 102 samples per run.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 6 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None

TABLE 4. Molar (M) Concentrations in Competitive Binding Assay Run a b

TCVP Positive control Negative control Reference Chemical 19-Norethindrone Octyltriethoxysilane Non-labeled
17 β -estradiol

Tubes 70-93 c Tubes 25-48 c Tubes 1-24 c Tubes 49-69 and 94-96 c

10

− 10 10

− 8.5 10

− 10 Solvent control d

10

− 9 10

− 7.5 10

− 9 10

− 11

10

− 8 10

− 7 10

− 8 10

− 10

10

− 7 10

− 6.5 10

− 7 10

− 9.5

10

− 6 10

− 6 10

− 6 10

− 9

10

− 5 10

− 5.5 10

− 5 10

− 8.5

10

− 4 10

− 4.5 10

− 4 10

− 8

10

− 3 10

− 4 10

− 3 10

− 7 a Data were obtained from pages 21-22, 26-29, 48, 51, and 54 of the study report. b Each tube contains: 10μL of either the test substance, positive control, negative control, solvent control, or
non-labeled 17 β -estradiol; 390 μL of TEDG + PMSF buffer with [ 3 H]-17 β -estradiol; and 100 μL of uterine cytosol (with ER), for a total of 500 μL.
c Each concentration of each chemical was run in triplicate, for a total of 102 tubes per run. d Solvent is ethanol (2%) in tubes 94-96.



### Tubes were gently vortexed and incubated for 16-20 hours at 2-8  C. To separate bound from free estradiol, hydroxyapatite (HAP) slu rry was added to each tube and vortexed once every 5 minutes for 15 minutes. Subsequently, th e contents of each tube were washed three times as follows: TEDG buffer + PMSF was added, vortexed, centrifuged for 10 min at 4°C
and 1000 × g , and the supernatant decanted and dis carded. Ethanol was added to the HAP pellet remaining in each t ube to extract the bound [ 3 

### H]-17 β -estradiol, followed by vortexing, and centrifugation. Aliquots of the supernatants were radioa ssayed by liquid scintillation counting.

C. DATA ANALYSIS: For the competitive binding expe riment, the top and bottom of the curve, Hill Slope and in hibition concentration (IC 50 

### ) were calculated with nonlinear regression analysis by using GraphPad Prism (GraphPad Software, Inc., San Diego, CA). log IC 50 

### mean and standard error were calculate d for each run of the competitive binding experiment. For parameters reported fr om the saturation binding experiment (K d 

### and B max 

### ),
mean and standard deviation were calculated for each run.

1. Definitions

a. Classification of test material: Classification of the test mate rial is based on the average of
three runs. Each run was first in dividually classified as follows:

Interactive = lowest point on the fitted curve within the range of the data is less than 50% (i.e., >50% of the radiolabeled estrad iol has been displaced from the ER).

Not interactive = there are usable data points at or above 10

− 6 

### M and either the lowest point on the fitted response curve within the range of the da ta is above 75% (i.e., <25% of the radiolabeled estradiol has been displaced from the ER) or a binding curve cannot be fitted and the lowest average percent binding among concentration groups in the data is above 75%.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 7 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### Equivocal up to the limit of concentrations tested = there are no data points at or above a
test chemical concentration of 10

− 6 

### M and either a binding curve can be fit but
≤ 50% of the radiolabeled estradiol has been displaced from the ER or a binding curve cannot be f it and the lowest averag e percent binding among concentration groups in the data is >50%.

Equivocal = A run is classified as equivocal if it does not fall into any of the categories
above.

The categorical classification of each run was assigned a numerical value as follows:

Run Classification Numerical Value
Interactive 2 Equivocal 1
Not interactive 0 Equivocal up to the limit of concentrations tested “missing”



### The values for each run were then averaged acro ss runs and the chemical classified using the following ranges:

Test Material Classifi cation Numerical Range Interactive average ≥ 1.5 Equivocal 0.5 ≥ average <1.5
Not interactive average <0.5 Equivocal up to the limit of concentrations tested “missing”



### b. Descriptors for receptor binding:

B max 

### : maximum specific binding number (fmol ER/1 00 μg cytosol protein) measures the concentration of active receptor sites

K d 

### : dissociation constant (nM), measures the a ffinity of the receptor for its natural ligand
IC 50 

### : concentration of the test substance (M) at which 50% of the radioligand is displaced from the receptor Relative Binding Affinity (RBA %): ( IC 50 

### of 17 β -estradiol ÷ IC 50 

### of test substance) × 100 Log RBA: Log 10 

### ( IC 50 

### of 17 β -estradiol ÷ IC 50 

### of test substance)

II. RESULTS

A. SATURATION BINDING EXPERIMENT

The calculated parameters for the saturation bi nding experiment are presented in Table 5.
The K d 

### for [ 3 

### H]-17 β -estradiol was 0.1297 ± 0.023, and the estimated B max 

### was 5.464 ± 0.494
fmol/100 μ g protein for the prepared ra t uterine cytosol. The K d 

### for each run was within the expected range of 0.03 to 1.5 nM; however, the B max 

### value was lower than the recommended range of 10-150 fmol/100 μg protein (these valu es are not considered strict performance criteria in the Guideline). Figure 1 illustrates the non-specifi c, specific, and total binding curves for [ 3 

### H]-17 β -estradiol to the estrogen receptor. The specific binding reached a plateauEstrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 8 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### in all runs, and non-specific binding was less than 20% of total binding for all [ 3 

### H]-17 β

estradiol concentrations except the highest (3.0 nM). These data produced linear Scatchard plots (Figure 2). Confidence in these numbers is high due to the small variation among runs (goodness of fit was not reported).

TABLE 5. Saturation Bi nding Experiment of [ 3 H]-17 β -estradiol with Estrogen Receptor from Rat Uterine Cytosol a

Parameter Run 1 Run 2 Run 3 Mean ± SE

R 2 (unweighted) NR NR NR NA

B max (nM) 0.01026 ±
0.0002353 0.007603 ±
0.0002048 0.008364 ±
0.0003367 0.008742 ± 0.001

B max (fmol/100 μ g protein) 6.413 4.752 5.228 5.464 ± 0.494

K d (nM) 0.09629 ±
0.008724 0.1733 ±
0.01676 0.1195 ±
0.01827 0.1297 ± 0.023

a Data were obtained from pages 21, 39, 43, and 47 of the study report.

R 2 Goodness of fit for curve calculated for specific binding



### FIGURE 1. Binding of [ 3 

### H]-17 β -estradiol to the Estrogen R eceptor during the Saturation Binding Experiment.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 9 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD NoneEstrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 10 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### FIGURE 2. Scatchard Plot s of the Binding of [ 3 

### H]-17 β -estradiol to the Estrogen Receptor.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 11 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD NoneEstrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 12 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### B. COMPETITIVE BINDING EXPERIMENT: The results from the competitive binding experiments are presented graphically in Figures 3-6. The parameters determined from the competitive binding curves (r 2 

### , IC 50 

### , log IC 50 

### , and RBA) are presented in Table 6.

The three reference chemicals generally perfor med as expected. The estimated mean log
IC 50 

### was

− 9.188 M for 17 β -estradiol and

− 6.484 M for the weak positive control. The mean RBA was 0.1990% for the weak positive control. Octyltriethoxysilane had no effect on specific binding of the [ 3 

### H]-ligand (83.0 to 111.0%). Confidence in these numbers is high
due to the small variation in the data. One run was unacceptable because the negative control did not meet the performance criteria , and the run was repeated. Data from the unacceptable run were not reported.

TABLE 6. Competitive Binding Assay of TCVP with Estrogen Receptor from Rat Uterine Cytosol a

Parameter Run 1 b Run 2 b Run 3 b Mean ± SE c

r 2 (unweighted) 17 β -estradiol 1.000 0.9999 0.9999 0.9999-1.000
19-norethindrone 0.9986 0.9988 0.9974 0.9974-0.9988

TCVP NR NR NR NA Log IC 50 (M) 17 β -estradiol
19-norethindrone
TCVP − 9.134 ± 0.004

− 6.435 ± 0.026
NA − 9.164 ± 0.010

− 6.520 ± 0.024
NA − 9.267 ± 0.009

− 6.497 ± 0.034
NA − 9.188 ± 0.040

− 6.484 ± 0.025
NA

IC 50 (M) d 17 β -estradiol 7.345 × 10

− 10 6.855 × 10

− 10 5.408 × 10

− 10 6.536 × 10

− 10 (± 0.582)
19-norethindrone 3.673× 10

− 7 3.020 × 10

− 7 3.184 × 10

− 7 3.292 × 10

− 7 (± 0.196)

TCVP NA NA NA NA Log RBA d 19-norethindrone

− 2.699

− 2.744

− 2.770

− 2.704 ± 0.047
TCVP NA NA NA NA RBA (%) 19-norethindrone 0.200 0.227 0.170 0.1990 ± 0.0165
TCVP NA NA NA NA a Data were obtained from pages 26-27 and 57-58 of the study report. b The mean is reported for the concu rrent replicates within each run. c The range of r 2 is reported and the mean and SE are reported for the other parameters. Calculated by the study reviewer. For means expressed in scientific nota tion, the SE values in parentheses are presented in the same order of magnitude as the mean value. d Calculated by the study reviewer.

r 2 Goodness of fit RBA (%) Relative binding affinity NA Not applicable. NR Not reported
SE Standard ErrorEstrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 13 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### FIGURE 3. Percentage E2 Bound to the Estrog en Receptor in the Presence of unlabeled
E2.

FIGURE 4. Percentage E2 Bound to the Estrogen Receptor in the Presence of
19-norethindrone.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 14 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### FIGURE 5. Percentage E2 Bound to the Estrogen Receptor in the Presence of Octyltriethoxysilane.

FIGURE 6. Percentage E2 Bound to the Estr ogen Receptor in the Presence of TCVP.Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 15 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### The highest test concentration, 10

− 3 

### M, was excluded from the evaluation due to observed precipitation. As TCVP reduced radiolabeled 17 β -estradiol binding to the ER by <25% at concentrations up to 10

− 4 

### M in all three runs, it is classifi ed as not interactive (0) in this assay (Table 7). There were no appa rent alterations in radiolabeled 17 β -estradiol binding at
TCVP concentrations of 10

− 10 

### to 10

− 4 

### M (98.2-133.4% specific binding).

TABLE 7 Binding Classification of TCVP with Estrogen Receptor a

Run 1 2 3 Mean c Binding Classification d Classification category value b 0 0 0 0 Not interactive a Data were obtained from page 32 of the study report. b Classification category value: Interac tive = 2; Equivocal = 1; Not interactive = 0; Equivocal up to the limit of concentrations tested (“missing”, i.e., not included in calculation of mean). c Mean of three runs expressed to the tenths place
d Interactive = mean ≥ 1.5; Equivocal = 0.5 ≤ mean <1.5; Not inte ractive = mean <0.5



### C. PERFORMANCE CRITERIA: To ensure that the compe titive binding assay functioned properly, each run was evaluated usi ng the criteria shown in Table 8.

TABLE 8. Criterion a Tolerance Limit(s) Value Yes No

17 β -estradiol fitted curve parameters Log e residual SD ≤ 2.35 0.3936 to 0.7552 X Top (% binding) 94 to 111 97.25 to 110.7 X Bottom (% binding)

− 4 to 1

− 2.954 to 7.333 X c Hill Slope (log 10 (M)

− 1 )

− 1.1 to

− 0.7

− 1.527 to

− 0.8290 X d Weak Positive control (19-norethindrone) fitted curve parameters b
Log e residual SD NA 1.843 to 2.740 X Top (% binding) NA 102.1 to 104.9 X Bottom (% binding) NA

− 3.978 to 0.2338 X Hill Slope (log 10 (M)

− 1 ) NA

− 0.9265 to

− 0.8779 X

Solvent concentration

Ethanol ≤ 3% 2% X Negative control (octyltriethoxysilane) does not displace more than 25% of [ 3 H]-17 β -estradiol from the ER on average across
all concentrations ≤ 25% ≤ 17.0 e X

a Data were obtained from pages 28 and 57-58 of the study report.
b The EPA Guideline does not define a set of tolerance li mits for 19-norethindrone. A cceptance criteria were only defined for norethynodrel, which cannot be obtained commercially. The values reported were considered acceptable as they show 19-nor ethindrone to be an accepta ble weak positive control. c The bottom % binding was high in Run 1 (7.333) and Run 2 (1.709). d The Hill Slope was low (

− 1.527) in Run 1, but within the recommended range in the other two runs. e Calculated by the study reviewer. The minimum specific binding of [ 3 H]-17 β -estradiol in the negative control assays was 83.0% (Run 1). NA Not applicable



### The amount of cytosol used in the competitiv e binding assay was 80 ug/tube, however the % binding to the radi oactive ligand ([ 3 

### H]-17 β -estradiol) was not re ported (the guideline requirement is 10-15%).Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 16 of 16 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1250/ OECD None



### Additionally, the curve for the reference material showed that increasing concentrations of
unlabeled 17 β -estradiol displaced [ 3 

### H]-17 β -estradiol in a manner consistent with one-site binding, as indicated by a de scent from 84.7-93.1% to 5.0-8.6% binding over a 81-fold
increase in concentration of the test chemi cal (i.e., covering appr oximately 2 Log units).

TCVP was tested over a concentr ation range that fully defined the top of the curve. The percent binding at this top plateau 100.1-123.1% was within 25 percentage points of the
value for the lowest concentration of the estradiol standard 96.8-107.6%.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: In this study under the given conditions the test item was classified as not-interactive to the estrogen receptor.

B. AGENCY COMMENTS: For the saturation binding experiment, the mean maximum binding capacity (B max 

### ) was 5.464 fmol/100 μg protein and the mean dissociation constant (K d 

### ) was 0.1297 nM. The K d 

### for each run was within the ex pected range of 0.03 to 1.5 nM; however, the B max 

### value was lower the recommended ra nge of 10-150 fmol/100 μg protein. The Scatchard plots for the three saturation assa ys were linear. The specific binding reached a plateau in all runs, and non-specific binding was always less than 20% of total binding.

For the competitive binding experiment, the estimated mean log IC 50s 

### for 17 β -estradiol, the weak positive control, and the mean RBA for the weak positive control were within the expected ranges. All performance criteria were generally met.

TCVP is classified as not interactive in this assay as the mean percent radiolabeled estradiol bound to the ER was >75% at TCVP concentrations up to 10 –4 

### M in all three independent runs (precipitation was observed at 10

− 3 

### M).

C. STUDY DEFICIENCIES: The following deficiencies were noted that are not considered to have had an adverse impact on the results, interpretation or conclusions of this study:

 Separate curves were not provided for each run and curves of TCVP, the reference standard (17 β -estradiol), positive control (19-norethindrone), and negative control (octyltriethoxysilane) were not shown on the same graph.

 The complete report (including analysis methods) for the saturation binding experiment was not provided; however, pertinent info rmation, data, and graphs were provided allowing the reviewers to evaluate the study.

 The purity of the weak positive control (19-norethindrone) and the negative control (octyltriethoxysilane) subs tances were not reported.

# DATA EVALUATION RECORD

TETRACHLOROVINPHOS (TCVP)

Study Type: OCSPP 890.1300, Estrogen Receptor Transcriptional Activation

EPA Contract No. EP10H001452 Task Assignment No. 3-06-2012

(Revisions to MRID 48619501 to include laboratory proficiency data; Main study was originally reviewed under TA 2-59-2012)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer: Signature: Michelle Sharpe-Kass, M.S. Date: 7/16/2012

Secondary Reviewer: Signature: Michael E. Viana, Ph.D., D.A.B.T. Date: 7/19/2012

Program Manager: Signature: Jack D. Early, M.S. Date: 7/25/2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 7/25/2012

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).TETRACHLORVINPHOS (TCVP) I 0837020 Estrogen Receptor Transcriptional Activation (2011) I Page l of 14
OCSPP 890.1300/ OECD 455



### Primary Reviewer: Minerva Mercado, Ph.D.


### Health Effects Division Secondary Reviewer: Greg AkennaP; Ph.D.


### Health Effects Division

# Signatur~~

.

## Date~~**Signature:_~_.._.::;;...;;;;i--~.,,c-~~-** 

### Date: 

# a (<.£(, 

# rTemplate version 0812011



### DATA EVALUATION RECORD

STUDY TYPE: Estrogen Receptor Transcriptional Activation (Human cell Line, HeLa-9903);
OCSPP 890.1300; OECD 455.



### PC CODE: 083702 

### DP BARCODE: D396880



### TXR#: 0056284 

### CAS No.: 22248- 79-9



### TEST MATERIAL (PURITY): Tetrachlorvinphos (100.05% a.i.)



### SYNONYMS: TCVP; (lZ)-2-chloro-1-(2,4,5-trichlorophenyl)ethenyl dimethyl phosphate



### CITATION: Willoughby, J.A. (2011) TCVP: Estrogen Receptor Transcriptional Activation Assay (Human Cell Line (HeLa-9903). CeeTox, Kalamazoo, ML Laboratory Report No.: 9180V-100538ERTA, November 4, 2011. :MR.ID 48609501 Unpublished.

Willoughby, J.A. (2012). Supplemental Information- Laboratory Proficiency

Data for ERT A assays and Saturation Binding Data for AR and ER Binding Assays for Assorted Chemicals. CeeTox, Inc., Kalamazoo, ML July l9 2012.
:MR.ID 48843501. Unpublished.



### SPONSOR: TCVP Task Force c/o SRA International, Inc., 5235 Ragged 

### Pt. Road, Cambridge, l\1D



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In an estrogen receptor transcriptional activation assay (MRID 48619501), hERa.-HeLa-9903 cells cultured 

### in vitro were exposed to tetrachlorvinphos (TCVP,
100.05% a.i., Lot# TXlOOl 13) at logarithmically increasing concentrations from 10- 12 

### to 10- 4 

### M

in 0.1% DMSO for approximately 24 hours in two independent runs. The experiments were perfonned using 96-well plates and each TCVP concentration was tested in 6 wells/plate in each

run. Cells were exposed to the test agent for 24±2 hours at 37±2°C to induce reporter (luciferase) gene products. Luciferase expression in response to activation of the estrogen receptor was measured using a proprietary luciferase assay.

TCVP was tested up to the limit of cytotoxicity, which was observed at 10- 4 

### Min the first run and :::10- 6 

### Min the second run. In the main assays, the responsiveness of the cells to the very weak positive control l 7a-methyltestosterone was lower 

## than the expected values, indicating a decreased sensitivity of the assay to very weak agonists. Although the conditions of this assay

were not optimal to detect very weak activity, TCVP responses were similar to those of theEstrogen Receptor Transc riptional Activation (2011) / Page 2 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### negative control corticosterone and no t comparable to the responses of 17 α -methyltestosterone,
which was able to reach a maximum of 36.5- 46.3% PC. TCVP was only able to reach a maximum of 0.8-2.4% PC when tested up to the highest concentra tion possible based on cytotoxicity (10

− 7 

### M). Because the RPC Max 

### < PC 10 

### in both assay runs, TCVP was considered negative for estrogen receptor transcrip tional activation in this test system.

This assay satisfies the EDSP Tier 1 Test Order requirement for an Estrogen Receptor Transcriptional Activation assay (OCSPP 890.1300).

COMPLIANCE: Signed and dated Data Confiden tiality, GLP Compliance, and Quality Assurance statements were provided.Estrogen Receptor Transc riptional Activation (2011) / Page 3 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: CeeTox, Inc.

Location: Kalamazoo, MI Study Director: J.A. Willoughby
Other Personnel: K. Rutherford (Director Laboratory Operations); D. Blakeman (Senior Scientist); C. Haines (Scientist); S. McColl ey (Scientist); B. Wallace (Lead Cell Culture Scientist); and C. Toole (Director of Project Management) Study Period: August 26, 2011 to November 04, 2011



### 2. Test Substance: TCVP
Description: Technical, white crystalline solid Source (Cat #): Hartz (not reported) Lot/Batch # (Exp date): TX100113 (not reported) Purity: 100.05% Solubility: Not reported (NR) Volatility: NR Stability: NR Storage conditions: Ambient

CAS #: 22248-79-9

Structure:

P O O

H 3 CO OCH 3 Cl

Cl Cl Cl



### 3. Reference substances
17 β -estradiol (strong estrogen; positive control)
Supplier: NR Catalog and Batch #: NR Purity: NR
CAS # : 50-28-2



### 17 α -estradiol (weak estrogen)
Supplier: NR Catalog and Batch #: NR Purity: NR
CAS # : 57-91-0



### Corticosterone (negative compound)
Supplier: NR Catalog and Batch #: NR Purity: NR

CAS # : 50-22-6



### 17 α -methyltestosterone (very weak agonist)
Supplier: NR Catalog and Batch #: NR Purity: NR
CAS # : 58-18-4



### 4. Vehicle(s)

Solvent: DMSO

Solvent control: 0.1% (final concentration)Estrogen Receptor Transc riptional Activation (2011) / Page 4 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### B. METHODS

1. Cell Culture: Stably-transfected hER α -HeLa-9903 cells were obtained from the Japanese
Collection of Research Bioresour ces Cell Bank and were verified to be free of mycoplasma infection by a DNA fluorochrome assay. Cells were maintained in Eagles Minimum Essential Medium without phenol red, supplem ented with 60 mg/L kanamycin and 10%
dextran-coated charcoal-treated fetal bovine serum (source not reported), in an incubator
under 5% CO 2 

### at 37 oC. Upon reaching 75-90% confluen ce, cells were subcultured 27 times prior to exposure to the test material. The cells used in this study were passage 26 (rangefinder), passage 27 and passage 16 (first and seco nd test runs, respectivel y). It was stated that a new batch of cells were brought out of frozen stock for the second run.

2. Transcriptional Activation Assays: For each test, cells were plated in a 96-well plate (estrogenic activity of plastic not reported) at a density of approximately 1×10 4 

### cells/100 μL
medium/well and allowed to attach for 3 hours. The growth media was replaced with media containing serial log dilutions of TCVP in DM SO (0.1% final concentr ation). Cells were incubated for 24±2 hours at 37±2 °C. Cytotoxi city was determined by two-read propidium iodide uptake. The first and second runs fo r the main assay were conducted on September 22 and October 20, 2011, respectively. Transcrip tional activation of th e estrogen receptor was determined as described in CeeTox Standa rd Operating Protocol (SOP) 2041. A list of reagents was provided, but the a ssay reagent was classified as proprietary information, and the SOP was not provided.

a. Preliminary Test: A preliminary test evaluating concentrations ranging from 10

− 6.5 

### to 10

− 3 

### M was conducted to determine the appropri ate concentration range and to determine concentrations resulting in insolu bility and/or cy totoxicity.

b. Proficiency Chemicals: The responsiveness of the test system was tested on March 5, April 12, and April 28, 2011 (MRID 48843501), using cells at passage 15, 25 and 28, respectively. Based on the assay dates and passa ge numbers, it is unlikel y that the cells used for proficiency testing were from the same frozen stock as the cells used in the main assay. The cells were tested using the following set of proficiency chemicals, and each chemical was tested in duplicat e on separate days:Estrogen Receptor Transc riptional Activation (2011) / Page 5 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455

Compound CAS No. Concentration Range (M) Expected Response a Notes

Diethylstilbestrol (DES) 56-53-1 10

− 14 to 10

− 8 Positive
--- 17 α -Ethynyl estradiol (EE) 57-63-6 10

− 14 to 10

− 8 Positive
---

Hexestrol 84-16-2 10

− 13 to 10

− 7 Positive
--- Genistein 446-72-0 10

− 12 to 10

− 5 Positive Cytotoxic at 0.01 b , 0.1, and 1 mM

Estrone 53-16-7 10

− 12 to 10

− 6 Positive
--- Butyl paraben 94-26-8 10

− 11 to 10

− 4 Positive Cytotoxic at 0.1 b and 1 mM 1,3,5-Tris(4- hydroxyphenyl)benzene c 15797-52-
1 10

− 12 to 10

− 5 Positive Cytotoxic at 100 μM. PC Max approx. 50% of PC.
Binds to hER α and has ER antagonistic activity Dibutyl phthalate (DBP) 84-74-2 10

− 11 to 10

− 4 Negative d Cytotoxic at 1 mM

Atrazine 1912-24-9 10

− 11 to 10

− 4 Negative Cytotoxic at 1 mM b

Corticosterone 50-22-6 10

− 10 to 10

− 4 Negative If not cytotoxic at 1 mM, then that should be the highest tested concentration

a Positive = RPC Max ≥ 10% of the response of the positive control in at least 2 of 2 (or 2 of 3) runs Negative = RPC Max fails to achieve at least 10% of the response of the positive control in 2 of 2 (or 2 of 3) runs b Cytotoxicity is expected to be close to 80% at this concentration. c Compound selected to challenge solubility and cytotoxicity. d DBP is negative for ER α mediated transcriptional activation, but may not be negative for non-ER β mediated transcriptional activation. A positive result would indicate that the sy stem is detecting activity other than that due to pure ER α , and is therefore unacceptable.



### c. Reference Chemicals: To ensure the stability of the response from the cell line, eight concentrations of each of the following reference chemicals were included in each plate in the current assay, along w ith the test chemical:

Reference Chemical CAS No. Concentration Range Class

17 β -estradiol 50-28-2 10

− 15 to 10

− 8 Strong estrogen

17 α -estradiol 57-91-0 10

− 13 to 10

− 6 Weak estrogen

Corticosterone 50-22-6 10

− 11 to 10

− 4 Negative compound

17 α -methyltestosterone 58-18-4 10

− 12 to 10

− 5 Very weak agonist



### 3. Data analysis: To obtain the relative transcriptiona l activity to the 1 nM E2 positive control (PC), the luminescence signals from the concur rent plate were analy zed by subtracting the
mean value of the vehicle control from each well value to normalize the data; each normalized value was then divided by the mean value of the normalized PC. The resulting value was multiplied by 100 in order to expres s relative transcriptional activity as a percentage of the PC. The test material was defined as negative for inducing estrogen receptor transcriptional activation if the RPC Max 

### < PC 10 

### in at least 2 of 2 valid runs. Log
EC 50 

### and Hill slope values are calculated onl y if a positive response is observed. Coefficients of variation (CV) were calcula ted for the luminescence data triplicates. Concentrations showing >20% cytotoxicity or evidence of insolubility were excluded from analyses.

4. Definitions

EC 50 

### = concentration of agonist that induces a response ha lfway between the baseline (bottom) and maximum (top) response

PC 10 

### = concentration of a test chemical at which the response is 10% of the response induced by the positive control (E2 at 1 nM) in each plateEstrogen Receptor Transc riptional Activation (2011) / Page 6 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### PC 50 

### = concentration of a test chemical at which the response is 50% of the response induced by the positive control (E2 at 1 nM) in each plate

RPC Max 

### = maximum level of response induced by a test chemical, expressed as a percentage of the response induced by the positive control (1 nM E2) on the same plate

PC Max 

### = concentration of a test chemical inducing the RPC Max



### II. RESULTS

A. PRELIMINARY TEST: Precipitation was observed at 10 –3 

### M TCVP, the results of the cytotoxicity test are presented in Table 1. Concentrations of ≥ 10

− 4 

### M showed cell viability of 66% or less. Based on these results, l ogarithmically increasing concentrations from 10

− 11



### to 10

− 4 

### M were selected for the assay.

TABLE 1. Preliminary Test for Solubility, Cyto toxicity, and Concentration-Selection for TCVP a
Concentration (M) % Viability b Comments

10

− 3 56 Precipitation noted; Cytotoxic

10

− 3.5 58 Cytotoxic

10

− 4 66 Cytotoxic

10

− 4.5 89

10

− 5 97

10

− 5.5 97

10

− 6 99

10

− 6.5 99 a Data were obtained from page 20 of the study report. b If viability is <80%, the concentration is considered cytotoxic.



### B. POSITIVE AND NEGATIVE REFERENCE CHEMICALS

1. Proficiency Chemicals: The laboratory proficiency assa ys to confirm the test system responsiveness were not include d in the original study report , but were provided to the Agency at a later date (MRID 48843501). The re sponsiveness of the cells to proficiency chemicals was tested in duplicate on differe nt days for each chemical. The reported responses are in Tables 2a a nd 2b. The reference chemicals 17 β -estradiol, 17 α -estradiol and
17 α -methyltestosterone were tested concurrently with each run of the assay. In the first run, the responsiveness of 17 β -estradiol indicated diminished se nsitivity to a strong agonist, and the response to 17 α -methyltestosterone showed an elevat ed responsiveness to a very weak agonist when compared to expected log PC values. In the second run the PC 50 

### could not be
calculated for 17 α -methyltestosterone indicating a dimini shed sensitivity to a very weak agonist. In the third run 17 β -estradiol and 17 α -methyltestosterone performed within the expected range, but the Hill Slope for 17 α -estradiol was higher th an expected. The PCinduced activation for 1 nM E2 was within th e Guideline-recommended historical range of 4- to 30-fold in the first and third runs, but induction was 75.1- to 84.7-fold in the second run with no explanation given for th is 3- to 4-fold increase. Re sults of the cytotoxicity assay were not provided for review. Graphs provi ded indicate genistein and butyl paraben had maximum RTAs well above 400% when an approximately 100% maximum is expected. No justifications for the above-menti oned deviations were provided.Estrogen Receptor Transc riptional Activation (2011) / Page 7 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455

TABLE 2a. Proficiency Chemicals
Compound Expected Response Lab Response

Run 1 Run 2 Run 3 Diethylstilbestrol Positive Positive Positive NA

17 α -Ethynyl estradiol Pos itive Positive Positive NA

Hexestrol Positive Positive Positive NA

Genistein Positive Positive Positive NA

Estrone Positive Positive Positive NA Butyl paraben Positive Positive Positive NA 1, 3, 5-Tris(4-hydroxyphenyl)benzene Positive NA Positive Positive Dibutyl phthalate Negativ e Negative Negative NA Atrazine Negative Ne gative NA Negative

Corticosterone Negative Negative NA Negative NA = not applicable. The chemical was not tested at this time.

Table 2b. Performance Criteria for Ref erence Chemicals in the Proficiency test

Reference Chemical
Parameter Acceptable Range Values Acceptable

Run 1 Run 2 Run 3 Yes No

17 β -estradiol Log PC 50 − 11.4 to

− 10.1

− 9.6

− 11.3

− 10.6 Run 1 Log PC 10 <

− 11

− 11.5

− 12.5

− 12.1 X Log EC 50 − 11.3 to

− 10.1

− 9.0

− 11.3

− 10.6 Run 1 Hill Slope 0.7 to 1.5 1.2 0.9 0.8 X Test range (M) 10

− 14 to 10

− 8 10

− 14 to 10

− 8 10

− 14 to 10

− 8 10

− 14 to 10

− 8 X

17 α -estradiol Log PC 50 − 9.6 to

− 8.1

− 8.3

− 9.4

− 8.7 X Log PC 10 − 10.7 to

− 9.3

− 9.3

− 10.5

− 9.9 X Log EC 50 − 9.6 to

− 8.4

− 8.2

− 9.3

− 8.9 Run 1 Hill Slope 0.9 to 2.0 0.9 0.9 2.9 Run 3 Test range (M) 10

− 12 to 10

− 6 10

− 12 to 10

− 6 10

− 12 to 10

− 6 10

− 12 to 10

− 6 X

17 α -methyltestosterone Log PC 50 − 6.0 to

− 5.1

− 6.2 NC

− 5.2 Run 1, 2 Log PC 10 − 8.0 to

− 6.2

− 8.1

− 6.3

− 7.7 Run 1 Test range (M) 10

− 11 to 10

− 5 10

− 11 to 10

− 5 10

− 11 to 10

− 5 10

− 11 to 10

− 5 X

NC = could not be calculated



### 2. Reference Chemicals: The response curves for the th ree estrogenic reference chemicals are shown in Figures 1 – 3, and the values de rived from the concentr ation response curves ( e.g ., log PC 50 

### , log PC 10 

### , log EC 50 

### , Hill slope) for the concurre ntly run reference materials are presented in Table 3. Performan ce criteria were met in both runs for 17 β -estradiol and corticosterone, and all but the Hill slope for 17 α -estradiol, which was slightly higher than the acceptable value. In both assay runs, log PC 50 

### values could not be determined for the very weak agonist, 17 α -methyltestosterone, as it did not reach 50% activation at up to 10

− 5



### M. The PC 10 

### was higher than the acceptable value. For 17 α -methyltestosterone, the mean
RPC Max 

### was 46.3% for the first run and 36.5% for the second run. The performance of 17 α

methyltestosterone as reference chemical in the main assay is compatible with the performance of the same chemical in the labo ratory proficiency assays (see section B1 above).Estrogen Receptor Transc riptional Activation (2011) / Page 8 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455

TABLE 3. Performance Criteria for Reference Chemicals a

Reference Chemical
Parameter Acceptable Range Values Acceptable

Run 1 Run 2 Yes No

17 β -estradiol Log PC 50 − 11.4 to

− 10.1

− 10.4

− 10.6 X Log PC 10 <

− 11

− 11.4

− 11.4 X Log EC 50 − 11.3 to

− 10.1

− 10.3

− 10.5 X Hill Slope 0.7 to 1.5 1.2 1.5 X Test range 10

− 14 to 10

− 8 M 10

− 15 to 10

− 8 M 10

− 15 to 10

− 8 M X

17 α -estradiol Log PC 50 − 9.6 to

− 8.1

− 8.6

− 8.7 X Log PC 10 − 10.7 to

− 9.3

− 9.6

− 9.6 X Log EC 50 − 9.6 to

− 8.4

− 8.6

− 8.8 X Hill Slope 0.9 to 2.0 1.6 2.2 Run 2 Test range 10

− 12 to 10

− 6 M 10

− 13 to 10

− 6 M 10

− 13 to 10

− 6 M X

Corticosterone Test range 10

− 10 to 10

− 4 M 10

− 11 to 10

− 4 M 10

− 11 to 10

− 4 M X

17 α -methyltestosterone Log PC 50 − 6.0 to

− 5.1 NC NC Run 1. 2 Log PC 10 − 8.0 to

− 6.2

− 5.9

− 5.9 Run 1, 2 Test range 10

− 11 to 10

− 5 M 10

− 12 to 10

− 5 M 10

− 12 to 10

− 5 M X a Data were obtained from page 23 of the study report.
NC = could not be calculatedEstrogen Receptor Transcriptional Activation (2011) / Page 9 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### FIGURE 1. Relative Transcription Ac tivation (RTA) of the Natural Ligand,
17 β -estradiol, Compared to the Positive Control, 1 nM 17 β -estradiol.

Mean ± SD are presented (n=6).Estrogen Receptor Transcriptional Activation (2011) / Page 10 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### FIGURE 2. Relative Transcription Ac tivation (RTA) of the Weak Estrogen,
17 α -estradiol, Compared to the Positive Control, 1 nM 17 β -estradiol.

Mean ± SD are presented (n=6).Estrogen Receptor Transcriptional Activation (2011) / Page 11 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### FIGURE 3. Relative Trans cription Activation (RTA) of the Very Weak Estrogen,
17 α -methyltestosterone, Compared to the Positive Control, 1 nM
17 β -estradiol.

Mean ± SD are presented (n=6).



### C. DEFINITIVE ASSAY

1. Vehicle and Positive Controls: Data for the vehicle and positive controls are included in
Table 4. The overall mean TA value for the vehicle control was 16579 for the first run and 8171 for the second, and the overall mean TA value for the positive control was 468167 for
the first run and 1022808 for the second. The in duction for the positive control ranged from
28- to 125-fold. The mean normalized value for the positive control was 451588 for the firstEstrogen Receptor Transc riptional Activation (2011) / Page 12 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### run and 1014637 for the second. The PC 50 

### (50% of the maximum response) for E2 in this assay is 225794 for the first run and 507319 for the second and the PC 10 

### (10% of the maximum response) is 45159 for the first run and 101464 for the second.

TABLE 4. Transcriptional Activation (TA) Response of Vehicle and Positive Control a

Sample Vehicle Control Positive Control b Normalized Positive Control b

Runs Mean SD Mean SD Fold Induction c Mean SD

1 16579 4862 468167 89083 28 451588 89083

2 8171 2781 1022808 322926 125 1014638 322926 a Data were calculated by the reviewer from da ta obtained from pages 31-32 of the study report.
b Positive control was 17 β -estradiol (E2) at 1 nM. c Fold-induction = (mean TA of PC)/(mean TA of VC)



### 2. Test Material: Relative (to the PC) transcriptional ac tivation at each concentration of the test chemical during the two assay runs is pr esented in Table 5. Th e concentration-response curves depicting fold induction of relative tran scriptional activation is presented in Figure 4
below. The mean RPC Max 

### was 2.4% for the first run and 0.8% for the second run, and the
associated PC Max 

### was 10

− 7 

### M for both runs. Because the RPC Max 

### < PC 10 

### in both runs, TCVP was considered negative for estrogen receptor tran scriptional activation in this test system.

TABLE 5. Relative Transcriptional Activation (RTA) of TCVP a

Parameter RTA (mean ± SD); % of Positive Control (PC)

Run 1 Run 2

Conc. (M) Mean SD Mean SD

10

− 4

-- b

-- b NA NA

10

− 5 0.4 1.1 -- b

-- b

10

− 6 1.6 1.2 -- b

-- b

10

− 7 2.4 1.8 0.8 0.3

10

− 8 1.2 1.6 0.7 0.2

10

− 9 1.0 1.6 0.1 0.2

10

− 10 0.7 1.4 0.2 0.3

10

− 11 0.9 1.0 0.1 0.3

10

− 12 NA NA 0.1 0.2 Log EC 50 NA NA Hill Slope NA NA

RPC Max 2.4 0.8

PC Max 10

− 7 10

− 7

PC 50 NA NA

PC 10 NA NA a Data were obtained from pages 21-22 of the study report. b Cytotoxicity observed ( ≤ 77% viability) NA = Not ApplicableEstrogen Receptor Transcriptional Activation (2011) / Page 13 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### FIGURE 4. Fold Induction of Relative Transcription Activation (RTA) of TCVP Compared to the Positive Control.Estrogen Receptor Transc riptional Activation (2011) / Page 14 of 14 TETRACHLORVINPHOS (TCVP) / 0837020 OCSPP 890.1300/ OECD 455



### 3. Performance Criteria: Concurrent results for 17 β -estradiol, 17 α -estradiol, and corticosterone in each experiment fell with in the expected range (Table 3), however results for the concurrent very weak agonist 17 α -methyltestosterone were above the expected range, suggesting diminished sensi tivity of the assay system to detect weak ligands. The fold-induction corresponding to PC 10 

### of concurrent PC was greater than
1+2 standard deviations of the fold-induc tion value of the concurrent VC. The variability among raw data replicates ( i.e ., luminescence intensity data) was higher than desirable per guidance: CV was 20% or more for vehicle control, 1 nM E2 positive control and TCVP in both runs (except for 10 -8 

### M TCVP in second run, CV=13%).

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS’ CONCLUSIONS: The suitable top concentration of TCVP for use in the first independent run was 10

− 5 

### M, based on cytotoxicity at 10

− 4 

### M. In the second run, the suitable top concentration of TCVP was 10

− 7 

### M because of cytotoxicity at 10

− 5 

### and
10

− 6 

### M. Precipitation was only obs erved in the rangefinder at 10

− 3 

### M. In two independent runs of the transcriptional activation assay, TCVP did not result in an increase in luciferase activity at any of the viab le concentrations tested.

TCVP is not an agonist of hu man estrogen receptor alpha (hER α ) in the HeLa-9903 model system.

B. AGENCY COMMENTS: TCVP was tested up to the limit of cytotoxicity, which was
observed at 10

− 4 M in the first run and ≥ 10

− 6 M in the second run. In the main assays, the responsiveness of the cells to the very weak positive control 17 α -methyltestosterone was lower than the expected values, indicating a decr eased sensitivity of the assay to very weak agonists. Although the conditions of this assa y were not optimal to detect very weak activity, TCVP responses were similar to thos e of the negative contro l corticosterone and not comparable to the responses of 17 α -methyltestosterone, which was able to reach a maximum of 36.5-46.3% PC. TCVP was only ab le to reach a maximum of 0.8-2.4% PC when tested up to the highest concentrat ion possible based on cytotoxicity (10

− 7 

### M).
Because the RPC Max 

### < PC 10 

### in both assay runs, TCVP was considered negative for estrogen receptor transcriptional activation in this test system.

C. STUDY DEFICIENCIES: The following deficiencies were noted:

 Excessive variability was not ed in the response of the cells to the test compound, reference compound and the vehicle cont rol in the second run (21-76% CV).

 The cells responded inadequately (<50% RTA) to the very weak estrogen,
17 α -methyltestosterone.

 Certificates of Analyses were not pr ovided for the reference chemicals.

 The source of the fetal bovine serum was not provided.

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԡԹՌԹԯԽՉՍՁՊԽՅԽՆՌ ԢԭԞԡԭԟԹՊԻՇԼԽ 

ԢԭԞԪԯԦԡ 

ԢԭԞԤՍՁԼԽՄՁՆԽ  ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ

ԱԽՋՌՅԹՌԽՊՁԹՄ ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ ԭՍՊՁՌՑ  

ԠՇՅՅՇՆՆԹՅԽԥԹՊՌՒԱԽԻՀՆՁԻԹՄԯԹԺՇՆԦՆՋԽԻՌՁԻՁԼԽ

ԠՀԽՅՁԻԹՄՆԹՅԽԦԲԭԞԠ ՆՇՌՊԽՈՇՊՌԽԼ

ԠԞ԰ՆԹՅԽՆՇՌՊԽՈՇՊՌԽԼ

ԠԞ԰ԫՇՆՇՌՊԽՈՇՊՌԽԼ

԰ՑՆՇՆՑՅՋՆՇՌՊԽՈՇՊՌԽԼ

ԢԭԞԭԠԠՇԼԽ

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԧՇԹՆԤԹՁԼՇՋ ԰ՁԿՆԹՌՍՊԽ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԠԡԪ԰ՅՁՌՀ   ԡԹՌԽ 

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊ ԱԽՊՁ԰ԪՑԽՊՋ ԰ՁԿՆԹՌՍՊԽ

ԭՊՇԿՊԹՅԪԹՆԹԿԽՊԠԡԪ԰ՅՁՌՀ  ԡԹՌԽ 

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԪԹՊՑԠՄՇԻՃԯՍՋՌ

ԟՁՇՄՇԿՁՋՌԢԭԞԬԠ԰ԭԭԬԭԭԢԣԢԡԢԯԟԦԳ ԰ՁԿՆԹՌՍՊԽ

ԡԹՌԽ     

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊ ԯՇԺՁՆ԰ՌԽՊՆԺԽՊԿ ԰ՁԿՆԹՌՍՊԽ

ԴՁՄԼՄՁԾԽԟՁՇՄՇԿՁՋՌԢԭԞԬԠ԰ԭԭԬԭԭԢԣԢԡԢԯԟԦ ԡԹՌԽ 

ԞԼԼՁՌՁՇՆԹՄԯԽՎՁԽՏԽՊ ԠԹՌՀԽՊՁՆԽԞՍԺԽԽ  ԰ՁԿՆԹՌՍՊԽ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԢԭԞԬԠ԰ԭԭԬԭԭԢԣԢԡԢԯԟԦԳ ԡԹՌԽ 

ԡԹՌԽԢՎԹՄՍԹՌՁՇՆԠՇՅՈՄԽՌԽԼ #ԼԼՅՅՑՑՑՑ%

ԠԦԱԞԱԦԬԫ  ԰ԻՀՆԽՁԼԽՊ԰ԷԨԥԪԹՊՌՁՆԱԷԨԽՆԼԹՄՄԹՆԼԥԬԨՊՍԽԿԽՊ ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԣՁՋՀ԰ՀՇՊՌ

ՌԽՊՅ ԯԽՈՊՇԼՍԻՌՁՇՆ ԞՋՋԹՑ ՏՁՌՀ ՌՀԽ ԣԹՌՀԽԹԼ ԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋ ՈՊՇՅԽՄԹՋ   ԭԽՊԾՇՊՅԽԼ ԺՑ ԴՁՄԼՄՁԾԽ ԦՆՌԽՊՆԹՌՁՇՆԹՄ 

### MARY
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### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

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ԭԹԿԽՇԾ ԩՌԼԢԹՋՌՇՆԪԹՊՑՄԹՆԼԯԽՈՇՊՌԫՇԞ ԰ՍԺՅՁՌՌԽԼ ԺՑԱԽՌ ՊԹԻՀՄՇՊՎՁՆՈՀՇՋԱԹՋՃԣՇՊԻԽ 
ԱԠԳԭԱԣԻՇ԰ԯԞ

ԦՆՌԽՊՆԹՌՁՇՆԹՄԠԹՅԺՊՁԼԿԽԪԹՊՑՄԹՆԼԠՇՅՈՄԽՌՁՇՆԼԹՌԽԪԹՑ 



ԫՇՌԽ ԱՀԽԲ԰ԢԭԞԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅ
Ԣԡ԰ԭԱՁԽՊ ՋԻՊԽԽՆՁՆԿԺԹՌՌԽՊՑՁՋԻՇՅՈՊՁՋԽԼՇԾ

ԽՄԽՎԽՆՋԻՊԽԽՆՁՆԿԹՋՋԹՑՋՁՆՌԽՆԼԽԼՌՇՁԼԽՆՌՁԾՑԹԻՀԽՅՁԻԹՄ0ՋՄՁՃԽՄ ՑԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՁԽՁՌՋՈՇՌԽՆՌՁԹՄՌՇ

ՁՆՌԽՊԹԻՌՏՁՌՀՌՀԽԽՋՌՊՇԿԽՆԹՆԼՊՇԿԽՆՇՊՌՀՑՊՇՁԼ
ԢԞՇՊԱՈ ԹՌՀՏԹՑՋԱՀԽՊՇԺՍՋՌՆԽՋՋՇԾՌՀԽԱՁԽՊ

ԺԹՌՌԽՊՑՁՋԺԹՋԽԼՇՆՌՀԽՋՌՊԽՆԿՌՀՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՌՇՁ ԼԽՆՌՁԾՑՈՇՌԽՆՌՁԹՄԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՏՁՌՀ

ԻՇՅՈՄԽՅԽՆՌԹՊՑԽՆԼՈՇՁՆՌՋՏՁՌՀՁՆՌՀԽԹՋՋԹՑՏՀԽՊԽԹՎԹՁՄԹԺՄԽԹՆԼ ՊԽԼՍՆԼԹՆԻՑԹԻՊՇՋՋՌՀԽԺԹՌՌԽՊՑԱՀՍՋ

ՌՀԽՊԽՋՍՄՌՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՋՀՇՍՄԼՆՇՌԺԽԻՇՆՋՁԼԽՊԽԼՁՆՁՋՇՄԹՌՁՇՆԺՍՌՊԹՌՀԽՊՋՀՇՍՄԼԺԽԻՇՆՋՁԼԽՊԽԼ

ՁՆՌՀԽԻՇՆՌԽՐՌՇԾՇՌՀԽՊԹՋՋԹՑՋՁՆՌՀԽԺԹՌՌԽՊՑԹՋՏԽՄՄԹՋԬՌՀԽՊ ԰ԻՁԽՆՌՁԾՁԻԹՄՄՑԯԽՄԽՎԹՆՌԦՆԾՇՊՅԹՌՁՇՆ
Ԭ԰ԯԦ

ԦՆՇՊԼԽՊՌՇԼԽՌԽՊՅՁՆԽՁԾԹԻՀԽՅՁԻԹՄՀԹՋՌՀԽՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹ ԻՌՏՁՌՀՌՀԽԢԞՇՊԱՈԹՌՀՏԹՑՋԹԴԽՁԿՀՌՇԾ

ԢՎՁԼԽՆԻԽ
ԴՇԢԽՎԹՄՍԹՌՁՇՆՇԾԱՁԽՊԹՋՋԹՑՊԽՋՍՄՌՋՁՆԻՇՅԺՁՆԹՌՁ ՇՆՏՁՌՀՌՀԽԾՁՆԼՁՆԿՋՁՆՌՀԽԬ԰ԯԦՋՀՇՍՄԼ

ԺԽՍՆԼԽՊՌԹՃԽՆ
ՊԽԾԽՊՌՇՌՀԽԴՇԢԡՇԻՍՅԽՆՌ

ԢԵԢԠԲԱԦԳԢ԰ԲԪԪԞԯԶ 

ԱՀԽ ԼԹՑ ՋՀՇՊՌՌԽՊՅ ՊԽՈՊՇԼՍԻՌՁՇՆ ԹՋՋԹՑ ՇԾ ՌԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ 
ԱԠԳԭ ՏՁՌՀ ԾԹՌՀԽԹԼ ՅՁՆՆՇՏՋ ԭՁՅԽՈՀԹՄԽՋ

ՈՊՇՅԽՄԹՋ  ՏԹՋ ԻՇՆԼՍԻՌԽԼ ՍՆԼԽՊ ԻՇՆՌՁՆՍՇՍՋ ԾՄՇՏՌՀՊՇՍԿՀ ԻՇՆԼՁՌՁՇՆՋ ԞԼՍՄՌ ԾՁՋՀ 
 ՋՈԹՏՆՁՆԿ ԿՊՇՍՈՋ 

ՅԹՄԽՋ ԹՆԼ  ԾԽՅԹՄԽՋ ՁՆ ԽԹԻՀ ԿՊՇՍՈ  ՅՇՆՌՀՋ ՇՄԼ ՏԽՊԽ ԽՐՈՇՋԽԼ Ռ Շ ԱԠԳԭ 
 ԹՌ ՆՇՅՁՆԹՄ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾ
ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ#ՋՇՄՎԽՆՌԻՇՆՌՊՇՄԼՁՅ ԽՌՀՑՄԾՇՊՅԹՅՁԼԽ
ԡԪԣԹՌԹԾՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆ

ՇԾՅԩԩ%ԹՆԼՅԿԹՁԩՅԽԹՆՅԽԹՋՍՊԽԼ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽ
ԩԬԮ

ՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩ ԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋՅԹՁՆՌԹՁՆԽԼԹՌ

ՌՇ Շ ԠԹՆԼԹՈԥՇԾՌՇ

ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՆՇՌԽԼ ԹՄՄ ՊԽՋՍՄՌՋ ԹՊԽ ՈՊԽՋԽՆՌԽԼ ԺԹՋԽԼ ՇՆ ԻՇՅՈ ԹՊՁՋՇՆ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ  ԫՇ

ՋՁԿՆՁԾՁԻԹՆՌ ԼՁԾԾԽՊԽՆԻԽՋ 
Ո ՏԽՊԽ ԼԽՌԽԻՌԽԼ ԺԽՌՏԽԽՆՌՀԽ ՆԽԿԹ ՌՁՎԽ ԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄ ԿՊՇՍՈՋԾՇՊ ԹՆՑ ՇԾ

ՌՀԽԽՆԼՈՇՁՆՌՋ԰ՍՊՎՁՎԹՄՁՆՅԹՄԽՋԹՆԼԾԽՅԹՄԽՋՏԹՋԾՇՊԹՄՄՌԽ ՋՌՄԽՎԽՄՋՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՇԾՅԹՄԽ

ՋՍՊՎՁՎԹՄ ԹՌ ՌՀԽ  ՅԿ ԹՁԩ ՄԽՎԽՄ ԞԼՍՄՌ ՅԹՄԽ ԹՆԼ ԾԽՅԹՄԽ ՋՍ ՊՎՁՎԹՄ ՏԹՋ ՎՁՋՍԹՄՄՑ ԼԽՌԽՊՅՁՆԽԼ ՌՇ ԺԽ

ՍՆԹԾԾԽԻՌԽԼԺՑՌՊԽԹՌՅԽՆՌ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԣԽԻՍՆԼՁՌՑ ՁՆ ՆԽԿԹՌՁՎԽ ԹՆԼ ՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄ ԿՊՇՍՈՋ ՏԹՋ  ԹՆԼ   ԽԿԿՋԾԽՅԹՄԽԼԹՑՊԽՈՄՁԻԹՌԽ

ՊԽՋՈԽԻՌՁՎԽՄՑ ԾԽՊՌՁՄՁՒԹՌՁՇՆ ՋՍԻԻԽՋՋ ՁՆ ՌՀԽ ՆԽԿԹՌՁՎԽ ԹՆԼ ՋՇՄՎԽՆՌ  ԻՇՆՌՊՇՄ ԿՊՇՍՈՋ ԹՎԽՊԹԿԽԼ  ԹՆԼ 

ՊԽՋՈԽԻՌՁՎԽՄՑ

ԱՀԽՊԽՏԹՋԹՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻՌՁՇՆԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽ ՆՌՄԽՎԽՄՁՆԾԽԻՍՆԼՁՌՑԹՆԼԾԽՊՌՁՄՁՌՑՇԾԹՆԼ

 ՊԽՋՈԽԻՌՁՎԽՄՑ 
Ո ԻՇՅՈԹՊԽԼՌՇՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ  ԱՀԽՊԽՏԹՋ ԹՄՋՇ Թ ՋՁԿՆՁԾՁԻԹՆՌ ԼԽԻՊԽԹՋԽ ՁՆ

ԾԽՅԹՄԽՎՁՌԽՄՄՇԿԽՆՁՆ
ԳԱԤԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՇԾԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ՈԱՀԽՊԽՏԽՊԽՆՇՇՌՀԽՊՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋԺԽՌՏԽԽՆՌ ՀԽՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋԹՆԼՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԾՇՊԹՆՑՇՌՀԽՊԽՆԼՈՇՁՆՌԱՀԽՊԽՏԽՊԽՆՇՆՇՌԹԺՄԽԼՁԾԾԽՊԽՆԻԽՋԺԽՌՏԽ ԽՆՀՁՋՌՇՈԹՌՀՇՄՇԿՑՋԽՎԽՊՁՌՑՋԻՇՊԽՋՇՊԿՇՆԹԼԹՄ

ՋՌԹԿԽՋՁՆՌՊԽԹՌԽԼԿՊՇՍՈՋԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԱՀԽՊԽՏԽՊԽՆՇՆՇՌԹԺՄԽՇԺՋԽՊՎԹՌՁՇՆՋՏՁՌՀՊԽԿԹՊԼՋ

ՌՇ ԺԽՀԹՎՁՇՊ ՇՊ ԻՀԹՆԿԽՋ ՁՆ ԹՈՈԽԹՊԹՆԻԽ ՋՈԽԻՁԾՁԻԹՄՄՑ ԻՇՄՇՊԺԹՆԼՁՆ Կ ՇՎՁՈՇՋՁՌՇՊ ԹՈՈԽԹՊԹՆԻԽ ՇՊ ՋՁՒԽ ՇԾ ԼՇՊՋԹՄ

ՆԹՈԽՈԹԼՁՆՌՀԽԻՇՆՌՊՇՄՇՊՌՊԽԹՌԽԼԿՊՇՍՈՋՇՊԻՄՁՆՁԻԹՄՋՁԿՆՋՇԾ ՌՇՐՁԻՁՌՑԾՇՊԹՆՑՌՊԽԹՌՅԽՆՌԿՊՇՍՈԻՇՅՈԹՊԽԼՌՇՌՀԽ

ԻՇՆՌՊՇՄՋ

ԱՀԽՋՌՍԼՑՅԽՌԹՄՄՇԾՌՀԽՎԹՄՁԼՁՌՑԻՊՁՌԽՊՁԹԪՁՆՇՊԿՍՁԼԽՄՁՆԽԼԽ ՎՁԹՌՁՇՆՋՏԽՊԽՆՇՌԽԼԺՍՌԼՁԼՆՇՌՁՅՈԹԻՌՌՀԽԹԺՁՄՁՌՑ

ՌՇՁՆՌԽՊՈՊԽՌՌՀԽՊԽՋՍՄՌՋՇԾՌՀԽԹՋՋԹՑԱՀՁՋԹՋՋԹՑ ՋԹՌՁՋԾ ՁԽՋՌՀԽԢԡ԰ԭԱՁԽՊԱԽՋՌԬՊԼԽՊՊԽՉՍՁՊԽՅԽՆՌԾՇՊԹԣՁՋՀ

԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌԬՊԿԹՆՁՋՅԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ԻԹ ՅՇՆՌՀՋ

ԪԽԹՆԺՇԼՑՏԽՁԿՀՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՅԽԹՋՍՊԽԼԪԹՄԽԿ ԣԽՅԹՄԽԿ

ԪԽԹՆՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՅԽԹՋՍՊԽԼԫՇՌՊԽՈՇՊՌԽԼ ԱԽՋՌԱՑՈԽ
ԣՄՇՏՌՀՊՇՍԿՀ԰ՌԹՌՁԻ԰ՌԹՌՁԻԯԽՆԽՏԹՄԠՇՆՌՁՆՍՇՍՋԾՄ ՇՏՌՀՊՇՍԿՀԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢԾԾԽԻՌՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԣ԰ԱԯԞՏՁՌՀԱԠԳԭԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԣԽԻՍՆԼՁՌՑԣԽՊՌ԰ՍԻԻԽՋՋԱՍԺԽՊԻՄԽ԰ԻՇՊԽԤ԰ԦԤՇՆԹԼԹՄԥՁՋՌՇԭՄԹՋՅԹԳԱԤԭՄԹՋՅԹԱԭՄԹՋՅԹԢԪԣԪԣԪԣԪԣԪԣԪԣ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫԞ ԫԞ ԫԞ ԫԞ ԫՇԫՇԫՇԫՇԫՇԫՇԫՇԫՇԫՇԫՇԫԞ ԫԞ ԫԞ ԫԞԶԽՋԶԽՋԫՇԫՇԫՇԫՇԫՇԫՇԫՇԶԽՋԫԞ ԫԞ ԫԞ ԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԠՇՆԻԠՇՆԻԽՆՌՊԹՌՁՇՆԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԣԣԽՅԹՄԽԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԪԪԹՄԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ Ԟ՟ՑԽՋՠՁՆԼՁԻԹՌԽՋԹՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄՍՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼ ԱՀԽԻՊՁՌԽՊՁԹԾՇՊՋՁԿՆՁԾՁԻԹՆԻԽԹՊԽԼԽՋԻՊՁԺԽԼՁՆՌՀԽԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼ԰ՌԹՌՁՋՌՁԻԹՄԳԽՊՁԾՁԻԹՌՁՇՆՋԽԻՌՁՇՆՋՇԾՌՀԽԡԢԯԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԦԪԞԱԢԯԦԞԩ԰ԞԫԡԪԢԱԥԬԡ԰

ԤԲԦԡԢԩԦԫԢԣԬԩԩԬԴԢԡ   ԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼԹԻԻՇՊԼՁՆԿՌՇՌՀԽԲ԰ԢԭԞԬԠ԰ԭԭ

՟ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՎԽԞՋՋԹՑՠԹՆԼԬԢԠԡ

ԱՀԽԾՇՄՄՇՏՁՆԿԼԽՎՁԹՌՁՇՆՋՏԽՊԽՆՇՌԽԼ

• ԱՀԽՍՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹԹՆԼ ՊԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽՁՆՌՀԽՌԽՋՌՏԹՌԽՊՏ ԽՊԽՆՇՌ ՊԽՈՇՊՌԽԼԱՀԽ

ԬԠ԰ԭԭՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԽՋՌԹԺՄՁՋՀՅԹՐՁՅՍՅՄԽՎԽՄՋԾՇ ՊՌՀԽՋԽՎԹՄՍԽՋԹՆԼՁՌ

ՁՋՍՆԻՄԽԹՊՁԾՌՀԽՅԹՐՁՅՍՅՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՏԽՊԽԽՐԻԽԽԼԽԼ

• ԱՀԽ ՄՁԿՀՌ ՁՆՌԽՆՋՁՌՑ ՏԹՋ ՊԽՈՇՊՌԽԼ ՌՇ ՊԹՆԿԽ ԾՊՇՅ  ՌՇ  ՄՍՐ ԼՍՊՁՆԿ ԽՐՈՇՋՍՊԽ

ԬԠ԰ԭԭԿՍՁԼԽՄՁՆԽ ՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑՇԾ- ՄՍՐ
ԹՌՏԹՌԽՊ0Ջ

ՋՍՊԾԹԻԽ

• ԦՆԼՁՎՁԼՍԹՄԾՁՋՀՏԽՁԿՀՌՋԹՌՋՌՍԼՑՁՆՁՌՁԹՌՁՇՆՏԽՊԽչՇԾՌՀԽԽ ՋՌՁՅԹՌԽԼՅԽԹՆՋԾՇՊՅԹՄԽՋ

ԹՆԼ ԾԽՅԹՄԽՋ ԬԠ԰ԭԭ  ԿՍՁԼԽՄՁՆԽ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ՋՍԺՋԹ ՅՈՄԽ ՇԾ ԾՁՋՀ

ՏԽՁԿՀԽԼԺԽԾՇՊԽՌՀԽՌԽՋՌԺԽՏՁՌՀՁՆչՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԾՇ ՊԽԹԻՀՋԽՐ

ԱՀԽՋԽԼԽՎՁԹՌՁՇՆՋԼՇՆՇՌՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌՌՀԽՊԽՋՍՄՌՋՇՊՁՆՌ ԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀՁՋՋՌՍԼՑ

 ԠԬԪԭԩԦԞԫԠԢ    ԰ՁԿՆԽԼԹՆԼԼԹՌԽԼԫՇԡԹՌԹԠՇՆԾՁԼԽՆՌՁԹՄՁՌՑԤԩԭԹՆԼԮՍԹՄՁՌՑԞ ՋՋՍՊԹՆԻԽ

ՋՌԹՌԽՅԽՆՌՋՏԽՊԽՈՊՇՎՁԼԽԼԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼՁՆԻՇՅՈՄՁԹՆԻ ԽՏՁՌՀԹՄՄ

ՈԽՊՌՁՆԽՆՌԲ԰ԢԭԞԤՇՇԼԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽՊԽԿՍՄԹՌՁՇՆՋՏՁՌՀՌՀ ԽԾՇՄՄՇՏՁՆԿ

ԽՐԻԽՈՌՁՇՆՋՈԽՊՁՇԼՁԻԹՆԹՄՑՋԽՋՇԾՏԹՌԽՊԾՇՊՈՇՌԽՆՌՁԹՄԻՇՆՌԹՅՁՆԹՆ ՌՋՏԽՊԽՆՇՌ

ՈԽՊԾՇՊՅԽԼԹԻԻՇՊԼՁՆԿՌՇԤՇՇԼԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽ԰ՌԹՆԼԹՊԼՋԺՍՌ ՏԽՊԽ

ՈԽՊԾՇՊՅԽԼՍՋՁՆԿԹԻԽՊՌՁԾՁԽԼՄԹԺՇՊԹՌՇՊՑԹՆԼՋՌԹՆԼԹՊԼԲ԰ԢԭԞԹՆԹՄ ՑՌՁԻԹՄՅԽՌՀՇԼՋ

ԱՀԽԻՀԹՊԹԻՌԽՊՁՒԹՌՁՇՆՇԾՌՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽՋԹՆԼՌՀԽՋՌԹԺՁՄՁՌՑՇ ԾՌՀԽՌԽՋՌ

ՋՍԺՋՌԹՆԻԽՋՍՆԼԽՊԻՇՆԼՁՌՁՇՆՋՇԾՋՌՇՊԹԿԽԹՌՌՀԽՌԽՋՌՋՁՌԽՏԽՊԽՆՇ ՌԼԽՌԽՊՅՁՆԽԼ

ԹԻԻՇՊԼՁՆԿՌՇԤԩԭՋՌԹՆԼԹՊԼՋ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԞԱԢ԰ԱԪԞԱԢԯԦԞԩ  ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԠԞ԰ՆՇՌՊԽՈՇՊՌԽԼ

ԡԽՋԻՊՁՈՌՁՇՆ   ԰ՇՄՁԼ

ԩՇՌԫՇԟԹՌԻՀԫՇ  ԱԵԹՆԼԱԵ

ԭՍՊՁՌՑ     

ԦՅՈՍՊՁՌՁԽՋ    ԫՇՆԽՊԽՈՇՊՌԽԼ

԰ՌԹԺՁՄՁՌՑՇԾԠՇՅՈՇՍՆԼ ԞՆԹՄՑՌՁԻԹՄՎԽՊՁԾՁԻԹՌՁՇՆՇԾՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄԾՊՇՅՌՁՅԽ ԹՆԼԼԹՑՋ

ՑՁԽՄԼԽԼՊԽԻՇՎԽՊՁԽՋՇԾՌՇՇԾՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԰ՌՇԻՃՋՇՄՍՌՁՇՆԾՇՊՌՁԾՁԽԼՏՁՌՀԱԠԳԭ

ԹՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՇԾ   ԹՆԼ  ՅԿ ԹՁԩ ՑՁԽՄԼԽԼ ՊԽԻՇՎԽՊՁԽՋ ՇԾ   ԮՍԹՄՁՌՑ

ԻՇՆՌՊՇՄՋԹՅՈՄԽՋՇԾԱԠԳԭՁՆԾՊԽՋՀՏԹՌԽՊԾՇՊՌՁԾՁԽԼԹՌԻՇՆԻԽՆՌՊԹՌՁՇ ՆՋՇԾԹՆԼՅԿԹՁԩ

ՀԹԼԹՅԽԹՆ ՊԽԻՇՎԽՊՑՇԾ ± ԭՊԽՌԽՋՌԼՁՄՍՌԽՊՎԽՊՁԾՁԻԹՌՁՇՆՋԹՅՈՄԽՋԻՇՄՄԽԻՌԽԼԹՆԼ ԼԹՑՋ

ՈՊՁՇՊՌՇՌԽՋՌ ՁՆՁՌՁԹՌՁՇՆՑՁԽՄԼ ՊԽԻՇՎԽՊՁԽՋ ՇԾ ՇԾՆՇՅՁՆԹՄ ԹՌՌՀԽ ԹՆԼՅԿ

ԹՁԩՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԱՀԽՌԽՋՌՅԹՌԽՊՁԹՄԹՈՈԽԹՊՋՌՇԺԽՋՌԹԺՄԽՍՆԼԽՊՌՀԽՌԽՋՌԻՇՆԼՁՌՁՇՆՋԹՌՌՀԽՋԽ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾԱԽՋՌԠՀԽՅՁԻԹՄՋ ԰ՌՇՊԽԼՍՆԼԽՊԹՅԺՁԽՆՌԻՇՆԼՁՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԟԱԽՋՌՇՊԿԹՆՁՋՅԱԹԺՄԽԤԽՆԽՊԹՄԦՆԾՇՊՅԹՌՁՇՆԞԺՇՍՌՌՀԽԱԽՋՌ԰ՈԽԻՁԽՋԹՆԼԞԻԻՄՁՅԹՌՁՇՆԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՈԽԻՁԽՋԻՇՅՅՇՆՆԹՅԽ ԣԹՌՀԽԹԼԪՁՆՆՇՏ ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԹՌՀԽԹԼՅՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼԴԽՊԽԾՁՋՀՇԺՌԹՁՆԽԼԾՊՇՅԹՋՁՆԿՄԽՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃ!ԶԽՋ ԩԹԺՇՊԹՌՇՊՑՊԹՁՋԽԼԾՁՋՀՇԺՌԹՁՆԽԼԾՊՇՅԬՋԹԿԽԠԹՌԾՁՋՀԽՊՁԽՋԦՆԻՇԾԬՋԹԿԽԟԽԹԻՀԪՁՋՋՇՍՊՁ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԾՊՇՅԹՋՁՆԿՄԽ
ՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃԴԽՊԽԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԹԻԻՄՁՅԹՌԽԼ ՍՆԼԽՊՏԹՌԽՊՉՍԹՄՁՌՑԹՆԼՁՄՄՍՅՁՆԹՌՁՇՆ ԻՇՆԼՁՌՁՇՆՋՌՀԹՌԹՊԽՋՁՅՁՄԹՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽ

ՌԽՋՌԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼՅՇՆՌՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՌՏՇՏԽԽՃ ԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԫՇՌԽՌՀԹՌՌՀԽ ԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼՁՋԼՁԾԾԽՊԽՆՌԾՊՇՅՌՀԽ ՋՍԺՋԽՉՍԽՆՌՁՆՋՁՌՍՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՀԽԹՄՌՀԪՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽԼԹՑՋՈՊՁՇՊՌՇՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼՏԹՋԣՁՋՀԼՁԼՆՇՌՊԽԻԽՁՎԽԹՆՑՌՊԽԹՌՅԽՆՌԾՇՊԼՁՋԽԹՋԽԼՍՊՁՆԿԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԟԽՀԹՎՁՇՊԹՄԹԺՆՇՊՅԹՄՁՌՁԽՋՇՊԻՄՁՆՁԻԹՄՋՁԿՆՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽ ԼԹՑՋՈՊՁՇՊՌՇՌՀԽՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽԺԽ ՄԽՋՋՌՀԹՆՇԾՌՀԽԻՍՄՌՍՊԽՈՇՈՍՄԹՌՁՇՆԦԾ ՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽՋԽԼԹՑՋՁՋԿՊԽԹՌԽՊՌՀԹՆ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԾՁՋՀԺԽ ՊԽՂԽԻՌԽԼԦԾՅՇՊՌԹՄՁՌՑՁՋԺԽՌՏԽԽՆ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽՀԽՄԼԹՆՇՌՀԽՊ ԼԹՑՋԦԾՅՇՊՌԹՄՁՌՁԽՋԿՊԽԹՌԽՊՌՀԹՆՇԻԻՍՊ ԼՍՊՁՆԿՌՀՁՋԽՐՌԽՆԼԽԼԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԾՁՋՀՆՇՌԺԽՍՋԽԼԱՑՈԽՇԾԾՇՇԼ԰ԽՊԹԳՁՈԹՆԹՆԼԺՊՁՆԽՋՀՊՁՅՈՆԹՍՈՄՁՁ ԞՊՌԽՅՁԹ

ՋԹՄՁՆԹ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԾԽԼԾՊՇՒԽՆ ԺՊՁՆԽՋՀՊՁՅՈՌՏՁԻԽՈԽՊԼԹՑՌՇՈՊՇՅՇՌԽ ԹԻՌՁՎԽՊԽՈՊՇԼՍԻՌՁՇՆԹՆԼՅԹՁՆՌԹՁՆԺՇԼՑ

ԻՇՆԼՁՌՁՇՆ԰ՇՍՊԻԽՇԾԾՇՇԼ԰ԽՊԹԫՇՊՌՀԞՅԽՊՁԻԹՆԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿ+ՌՁՅԽՋԼԹՑ ԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿԣՁՋՀՆՇՌԾԽԼԹՌՄԽԹՋՌՀՇՍՊՋՈՊՁՇՊՌՇՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԣՁՋՀ԰ԽՄԽԻՌՁՇՆԹՆԼԭՊԽԢՐՈՇՋՍՊԽԭԽՊԾՇՊՅԹՆԻԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՅՇՆՌՀՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՊՇԼՍԻՌՁՎԽՄՑՅԹՌՍՊԽ ՋԽՐՍԹՄՄՑԼՁՅՇՊՈՀՁԻԾՁՋՀՅՇՆՌՀՋ

ՇՄԼԪԽԹՆՏԽՁԿՀՌՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԿ ԟԹՋԽԼՇՆՅԹՄԽՋՍՋԽԼՌՇՋՌՇԻՃԹՉՍԹՊՁԹԾՇՊՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԹՋՍԺՋԹՅՈՄԽ ՇԾԾՁՋՀԺԽՏԽՁԿՀԽԼԺԽԾՇՊԽՌՀԽՌԽՋՌՌՇ ԽՋՌՁՅԹՌԽՌՀԽՅԽԹՆՏԽՁԿՀՌԾՇՊԽԹԻՀՋԽՐԦՌ ՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌՀԽՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌ ՇԾԽԹԻՀԾՁՋՀՋԽՄԽԻՌԽԼԾՇՊՌՀԽՌԽՋՌԺԽՏՁՌՀՁՆ չՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԾՇՊԽԹԻՀՋԽՐԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼ ԦՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋՏՁՌՀՁՆչՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԪԽԹՆՏԽՁԿՀՌՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԿ ԟԹՋԽԼՇՆԾԽՅԹՄԽՋՍՋԽԼՌՇՋՌՇԻՃԹՉՍԹՊՁԹԾՇՊՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼ ԦՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋՏՁՌՀՁՆչՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԪԽԹՆՄԽՆԿՌՀՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼԪԽԹՆՄԽՆԿՌՀՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡՍՊԹՌՁՇՆՇԾՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ ԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾԼԹՑՋԴԽՊԽՈՊԽԽՐՈՇՋՍՊԽԻՇՆԼՁՌՁՇՆՋՁԼԽՆՌՁԻԹՄՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽ ԻՇՆԼՁՌՁՇՆՋՁՆԻՄՍԼՁՆԿՌԽՅՈԽՊԹՌՍՊԽ ՈՀՇՌՇՈԽՊՁՇԼԾԽԽԼՁՆԿԽՌԻԺԽՁԼԽՆՌՁԻԹՄՌՇ ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԻՇՆԼՁՌՁՇՆՋԫՍՅԺԽՊՇԾՈՊԽԽՐՈՇՋՍՊԽՌԹՆՃՋ ԞԼԼՁՌՁՇՆԹՄԺՊԽԽԼՁՆԿԿՊՇՍՈՋՏԽՊԽՅԹՁՆՌԹՁՆԽԼՋՇԺՊԽԽԼՁՆԿԿՊՇՍՈՋՏՁՌՀԹՈՊՇՎԽՆՀՁՋՌՇՊՑՇԾՋՈԹՏՆՁՆԿԻՇՍՄԼԺԽՋԽՄԽԻՌԽԼԾՇՊՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹԼԼՁՌՁՇՆԹՄՌԹՆՃՋՋԽՌ ՍՈԹՌՌՀԽԺԽԿՁՆՆՁՆԿՇԾՈՊԽԽՐՈՇՋՍՊԽՏՁՄՄ ԽՆՋՍՊԽՌՀԹՌՋՍԾԾՁԻՁԽՆՌՊԽՈՄՁԻԹՌԽՋՏՁՌՀՌՀԽ ԻՇՊՊԽԻՌՋԽՐՊԹՌՁՇԹՊԽԹՎԹՁՄԹԺՄԽԾՇՊՌՀԽ
ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԫՍՅԺԽՊՇԾՅԹՄԽՋՈԽՊՌԹՆՃ ԫՍՅԺԽՊՇԾԾԽՅԹՄԽՋՈԽՊՌԹՆՃ ԭՊԽԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑ ԫՇՌՊԽՈՇՊՌԽԼԱՀԽՌՇՈՋՈԹՏՆՁՆԿԿՊՇՍՈՋԾՊՇՅՌՀԽՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼՏԽՊԽՋԽՄԽԻՌԽԼԾՇՊՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽ ԾԽԻՍՆԼՁՌՑՁՆԽԹԻՀՊԽՈՄՁԻԹՌԽ
ՌԹՆՃՋԽՄԽԻՌԽԼ ԾՇՊՍՋԽՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԹՌՄԽԹՋՌ ԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՊԽՈՄՁԻԹՌԽ ԼՍՊՁՆԿՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԫՍՅԺԽՊՇԾՋՈԹՏՆՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽՌՏՇՌՁՅԽՋՁՆԼԹՑՋԹՆԼԹՌՄԽԹՋՌԽԿԿՋԾԽՅԹՄԽԼԹՑԞՊԽՈՄՁԻԹՌԽԹՉՍԹՊՁՍՅՏԹՋԻՇՆՋՁԼԽՊԽԼՋՍՁՌԹԺՄԽԾՇՊՍՋԽՁՆՌՀԽՌԽՋՌՁԾՋՈԹՏՆՁՆԿՁՆՌՀԹՌԹՉՍԹՊՁՍՅՇԻԻՍՊՊԽԼԹՌՄԽԹՋՌՌՏՁԻԽԼՍՊՁՆԿՌՀԽԼԹՑՈԽՊՁՇԼՁՅՅԽԼՁԹՌԽՈՊԽԻԽԼՁՆԿՌԽՋՌՁՆՁՌՁԹՌՁՇՆԹՆԼՁԾՌՀԽՊԽՏԽՊԽԹՌՄԽԹՋՌԽԿԿՋՈԽՊԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՁՆՌՀԹՌԹՉՍԹՊՁՍՅ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՈԹՏՆՁՆԿՇԻԻՍՊԹՌ ՄԽԹՋՌՌՏՁԻԽՁՆՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽ
ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԡԽՌԹՁՄՋՇՆՈՊԽԽՐՈՇՋՍՊԽ ԫՇՆԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԠԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱՑՈԽՇԾԽՐՈՇՋՍՊԽԣՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏ ՌՀՊՇՍԿՀՋՑՋՌԽՅԞՋՆՇՌԽԼՁՆՌՀԽ ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋԼՇԻՍՅԽՆՌ   ՌՀԽՍՋԽՇԾԹՋՌԹՌՁԻՊԽՆԽՏԹՄՋՑՋՌԽՅՁՋՆՇՌ ՊԽԻՇՅՅԽՆԼԽԼԾՇՊՌՀՁՋԹՋՋԹՑԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅԠՇՆՌՁՆՍՇՍՋ ԫՇՌԾՍՊՌՀԽՊԼԽՋԻՊՁԺԽԼ ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ ՊԽԻՇՅՅԽՆԼԽԼ ԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽՎՇՄՍՅԽԹԼԼՁՌՁՇՆՋՌԽՋՌՎԽՋՋԽՄԼԹՑԱՀԽՌԽՋՌՋՇՄՍՌՁՇՆՋՏԽՊԽՈՍՅՈԽԼԾՊՇՅՌՀԽՅՁՐՁՆԿԻՀԹՅԺԽՊՋՁՆՌՇՌՀԽՌԽՋՌԻՀԹՅԺԽՊՋԹՌԹՌԹՊԿԽՌՊԹՌԽՇԾՅԩՅՁՆ ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋ ՅԩՅՁՆ
ԩՀՊՇՊԹՌՄԽԹՋՌՌՇՌԹՄ ՎՇՄՍՅԽԽՐԻՀԹՆԿԽՋՈԽՊԼԹՑԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅԱՁԽՊԞՋՋԹՑՋ
ԬԠ԰ԭԭԱԽՋՌԤՍՁԼԽՄՁՆԽ԰ԽՊՁԽՋԪԹՊԻՀԬԾԾՁԻԽՇԾԠՀԽՅՁԻԹՄ԰ԹԾԽՌՑԹՆԼԭՇՄՄՍՌՁՇՆԭՊԽՎԽՆՌՁՇՆԬԠ԰ԭԭԴԹՋՀՁՆԿՌՇՆԡԠՀՌՌՈՏՏՏԽՈԹԿՇՎԽՆԼՇՈՍԺՋԹՋՋԹՑՎԹՄՁԼԹՌՁՇՆԻՄԹՊՁԾՁԻԹՌՁՇՆԼՇԻՈԼԾԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋԱՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋՇՊՋՇՄՎԽՆՌՏԽՊԽԼՁՄՍՌԽԼՏՁՌՀՏԽՄՄՏԹՌԽՊՁՆՌՀԽՅՁՐՁՆԿԻՀԹՅԺԽՊՋՁՆՇՊԼԽՊՌՇՇԺՌԹՁՆՌՀԽԼԽՋՁՊԽԼՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՈՊՁՇՊՌՇԼԽՄՁՎԽՊՑՌՇՌՀԽՌԽՋՌԻՀԹՅԺԽՊՋԱՀԽԾՄՇՏՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊՁՆՌՇԽԹԻՀՅՁՐՁՆԿԻՀԹՅԺԽՊՏԹՋԻՇՆՌՊՇՄՄԽԼՍՋՁՆԿՊՇՌԹՅԽՌԽՊՋԞԾՌԽՊՅՁՐՁՆԿՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՁՆԽԹԻՀՅՁՐՁՆԿԻՀԹՅԺԽՊՏԹՋՈՍՅՈԽԼՁՆՌՇՌՀԽԹՈՈՊՇՈՊՁԹՌԽՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊՍՋՁՆԿԹՈԽՊՁՋՌԹՄՌՁԻՈՍՅՈԱՊԽԹՌՅԽՆՌՊԽԻՇՎԽՊՁԽՋՈՊՁՇՊՌՇՌԽՋՌՁՆՁՌՁԹՌՁՇՆԼԹՑՏԽՊԽԣՄՇՏՊԹՌԽՋՎԹՊՁԽԼԺՑՆՇՅՇՊԽՌՀԹՆչ ԯԽԻՇՅՅԽՆԼԽԼՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏ ՌՀՊՇՍԿՀՋՑՋՌԽՅՋԪՁՐՁՆԿԻՀԹՅԺԽՊՁՋ ՊԽԻՇՅՅԽՆԼԽԼԺՍՌՆՇՌՊԽՉՍՁՊԽԼ ԞԽՊԹՌՁՇՆՁՋՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՅՁՐՁՆԿ ԞԼԽՅՇՆՋՌՊԹՌՁՇՆՌՀԹՌՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆ ՁՋԻՇՅՈՄԽՌԽՄՑՅՁՐԽԼԺԽԾՇՊԽՁՆՌՊՇԼՍԻԽԼ ՁՆՌՇՌՀԽՌԽՋՌՋՑՋՌԽՅՁՋՊԽԻՇՅՅԽՆԼԽԼ ԱՀԽՊԽԻՇՅՅԽՆԼԽԼԾՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑ

ՁՋՏՁՌՀՁՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԽՊԹՌՁՇՆ!ԫՇ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹԽՊԹՌՁՇՆՁԾԼՁՋՋՇՄՎԽԼ ՇՐՑԿԽՆՊԽԹԻՀԽՋ ՅԿԩ
 

ՋԹՌՍՊԹՌՁՇՆ԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ ԴԽՄՄՏԹՌԽՊԱՀԽՏԽՄՄՏԹՌԽՊՏԹՋՈԹՋՋԽԼՌՀՊՇՍԿՀԹՋԹՆԼԾՁՄՌԽՊՌՇՊԽՅՇՎԽՈԹՊՌՁԻՄԽՋԿՊԽԹՌԽՊՌՀԹՆԹՈՈՊՇՐՁՅԹՌԽՄՑսՅԹՆԼՈՍՅՈԽԼՁՆՌՇԹԩՋՌՇՊԹԿԽՌԹՆՃՏՀԽՊԽՌՀԽՏԹՌԽՊՏԹՋԹԽՊԹՌԽԼՏՁՌՀՋՈՊԹՑՆՇՒՒՄԽՋԭՊՁՇՊՌՇՍՋԽՌՀԽՏԹՌԽՊՏԹՋԾՁՄՌԽՊԽԼՌՇսՅՌՇՊԽՅՇՎԽԾՁՆԽՈԹՊՌՁԻՄԽՋԹՆԼՏԹՋՈԹՋՋԽԼՌՀՊՇՍԿՀԹՆՍՄՌՊԹՎՁՇՄԽՌ
ԲԳՋՌԽՊՁՄՁՒԽՊԱՀԽՏԽՄՄՏԹՌԽՊՁՋԻՀԹՊԹԻՌԽՊՁՒԽԼԹՋՅՇԼԽՊԹՌԽՄՑՀԹՊԼՏԹՌԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼ ՏԹՌԽՊՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄ ՏԹՌԽՊԺԽՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊ ՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊ ՈՇՋՋՁԺՄԽԻՇՆՌԹՅՁՆԹՆՌՋԬԢԠԡԹԻԻԽՈՌՋ ԹՆՑՏԹՌԽՊՁՆՏՀՁԻՀՌՀԽՌԽՋՌՋՈԽԻՁԽՋՋՀՇՏ ԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋ ՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!ԶԽՋ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՋՌՎԽՋՋԽՄՌՑՈԽՅԹՌԽՊՁԹՄՋ ԤՄԹՋՋԹՉՍԹՊՁԹ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՏԹՌԽՊ ԻՇՆՌԹԻՌՈՇՊՌՁՇՆՋՇԾՌՀԽՋՑՋՌԽՅՆՇՌ ԻՇՅՈՊՇՅՁՋԽՌՀԽՋՌՍԼՑ
ԽԿ ԹՄՄԿՄԹՋՋ ՎԽՋՋԽՄՋՇՊԿՄԹՋՋՎԽՋՋԽՄՋՏՁՌՀՋՌԹՁՆՄԽՋՋ ՋՌԽԽՄԾՊԹՅԽՋԹՊԽԹԻԻԽՈՌԹԺՄԽԽՐԹՅՈՄԽՋԱԽՋՌՎԽՋՋԽՄՋՁՒԽԩ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԩՌԽՋՌ ԻՀԹՅԺԽՊՋ
ԽԿՐՐԻՅԣՁՄՄՎՇՄՍՅԽԩԻՅԼԽՈՌՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋԩՋՇՄՍՌՁՇՆՈԽՊՌԹՆՃ԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՅԹՌԽՊՁԹՄ ԱՀՊԽԽՁՆՎԽՊՌԽԼՋԽՅՁԻՁՊԻՍՄԹՊԭԳԠՈՁՈԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԽԹԻՀՌԹՆՃԻՇՆՌԹՁՆ ՌՀՊԽԽՋԽՅՁԻՁՊԻՍՄԹՊՋՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋ ԽԿԹԿԽԼԭԳԠՈՁՈԽԻՅՁՆ ՄԽՆԿՌՀՋՈՄՁՌՄԽՆԿՌՀՏՁՋԽ԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋՁՒԽ ԠԹԻՅՄԽՆԿՌՀԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽՋՑՋՌԽՅ ԞՈՈՊՇՐՁՅԹՌԽՄՑՏԽԽՃՄՑԼՍՊՁՆԿՌՀԽՌԽՋՌՌՀԽՌԽՋՌԾՁՋՀՏԽՊԽՌՊԹՆՋԾԽՊՊԽԼՌՇԻՄԽԹՆՌԽՋՌԻՀԹՅԺԽՊՋՌՇՈՊԽՎԽՆՌՌՀԽԺՍՁՄԼՍՈՇԾՅՁԻՊՇԺՁԹՄԿՊՇՏՌՀԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՅՈԽՊԹՌՍՊԽ
ոԠ   ԴԽԽՃՄՑՁՆԽԹԻՀՌԽՋՌԻՀԹՅԺԽՊԻՇՆՌՁՆՍՇՍՋՄՑՁՆՇՆԽՌԽՋՌԻՀԹՅԺԽՊԼՍՊՁՆԿՌՀԽՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԹՆԼՁՆՇՆԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՊԽՈՄՁԻԹՌԽԼՍՊՁՆԿՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչ Շ Ԡ ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼ Շ ԠՈԥ   ԴԽԽՃՄՑՁՆԽԹԻՀՌԽՋՌԻՀԹՅԺԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥՌՇԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆՅԿԩ   ԴԽԽՃՄՑՁՆԽԹԻՀՌԽՋՌԻՀԹՅԺԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ

ԡԬ ՅԿԩ
 ԹՁՊՋԹՌՍՊԹՌՁՇՆԱՇՌԹՄԹՄՃԹՄՁՆՁՌՑՅԿԩԹՋԠԹԠԬ  ԴԽԽՃՄՑՁՆՇՆԽՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊՇԾՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՌՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈՏՁՌՀՅԽԹՋՍՊԽՅԽՆՌՋՌՑՈՁԻԹՄՄՑԹՄՌԽՊՆԹՌՁՆԿԺԽՌՏԽԽՆՊԽՈՄՁԻԹՌԽՋԹՌԽԹԻՀՅԽԹՋՍՊԽՅԽՆՌՁՆՌԽՊՎԹՄ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՇՌԹՄԹՄՃԹՄՁՆՁՌՑ  ՅԿԩԹՋԠԹԠԬ ԥԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬ  ԱՇՌԹՄՇՊԿԹՆՁԻԻԹՊԺՇՆՅԿԠԩԫՇՌՊԽՈՇՊՌԽԼԫՇՌՊԽՈՇՊՌԽԼԬՆԻԽԼՁՄՍՌՁՇՆՏԹՌԽՊՅԽԹՋՍՊԽԼԼՍՊՁՆԿՌՀԽՏԽԽՃՈԽՊՁՇԼՁՅՅԽԼՁԹՌԽՄՑՈՊԽԻԽԼՁՆԿՌՀԽՌԽՋՌ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՇՌԹՄՇՊԿԹՆՁԻ ԻԹՊԺՇՆՁՆԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ ՅԿԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԲՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹμԿԩԫՇՌՊԽՈՇՊՌԽԼԫՇՌՊԽՈՇՊՌԽԼԫՇՌՊԽՈՇՊՌԽԼ ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՍՆՁՇՆՁՒԽԼ ԹՅՅՇՆՁԹՁՆՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ 

μ ԿԩԯԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽμԿԩԫՇՌՊԽՈՇՊՌԽԼԫՇՌՊԽՈՇՊՌԽԼԫՇՌՊԽՈՇՊՌԽԼ ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽ ՁՆԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ μ ԿԩԠՇՆԼՍԻՌՁՎՁՌՑμ԰ԻՅ  ԴԽԽՃՄՑՁՆՇՆԽՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊՇԾՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՌՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈՏՁՌՀՅԽԹՋՍՊԽՅԽՆՌՋՌՑՈՁԻԹՄՄՑԹՄՌԽՊՆԹՌՁՆԿԺԽՌՏԽԽՆՊԽՈՄՁԻԹՌԽՋԹՌԽԹԻՀՅԽԹՋՍՊԽՅԽՆՌՁՆՌԽՊՎԹՄ ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑ ՇԾՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ՌԽՅՈԽՊԹՌՍՊԽՈԥԹՆԼԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ ԺԽՅԽԹՋՍՊԽԼՁՆԹՄՄՌԽՋՌՌԹՆՃՋԹՌՄԽԹՋՌ ՏԽԽՃՄՑԹՆԼՌՀԹՌՀԹՊԼՆԽՋՋԹՆԼԹՄՃԹՄՁՆՁՌՑ ԺԽՅԽԹՋՍՊԽԼՁՆԻՇՆՌՊՇՄՋԹՆԼՁՆՇՆԽՌԹՆՃ ԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՄԽԹՋՌ ՏԽԽՃՄՑԦՆԹԼԼՁՌՁՇՆԻՇՆՌՁՆՍՇՍՋ ՌԽՅՈԽՊԹՌՍՊԽՅՇՆՁՌՇՊՁՆԿՇԾԹՌՄԽԹՋՌՇՆԽ ՌԹՆՃՁՋԽՆԻՇՍՊԹԿԽԼԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ ԪԽԹՆՋՏԽՊԽԻԹՄԻՍՄԹՌԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊԹՋՌՀԽԹՎԽՊԹԿԽՇԾՌՀԽՅՁՆՁՅԹԹՆԼՅԹՐՁՅԹԾՇՊՌՀԽՊԹՆԿԽՋՈՊՇՎՁԼԽԼԹԻՊՇՋՋԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌԽԼՄԽՎԽՄՋԞԻԻՇՊԼՁՆԿՌՇՌՀԽՋՌՍԼՑՊԽՈՇՊՌ՟ԱԽՅՈԽՊԹՌՍՊԽՅՇՆՁՌՇՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑՁՆՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՊԽՈՄՁԻԹՌԽԞՊԽՅԹՁՆԽԼՏՁՌՀՁՆՌՀԽՌԹՊԿԽՌՊԹՆԿԽՌՀՊՇՍԿՀՇՍՌՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՇԾԡԹՑՋԹՆԼՏՀԽՆՌՀԽՅՁՆՁՅՍՅՌԽՅՈԽՊԹՌՍՊԽՏԹՋՊԽԻՇՊԼԽԼԹՋՄՇՏԹՋոԠԱՀԽԼՁԾԾԽՊԽՆԻԽՁՆՌԽՅՈԽՊԹՌՍՊԽՏԹՋՋՄՁԿՀՌԹՆԼՀԹԼՆՇԹԼՎԽՊՋԽՁՅՈԹԻՌՇՆՌՀԽՋՌՍԼՑՊԽՋՍՄՌՋՠԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԡ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ!ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊ

ՁԾՀՇՍՊԩԠ  ԼԹՌԹԾՇՊՌՀԽԾԹՌՀԽԹԼՅՁՆՆՇՏ
ԹՊԽՍՆԹՎԹՁՄԹԺՄԽԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!ԱՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊՏԹՋՋԽՄԽԻՌԽԼԺԹՋԽԼՇՆՋՇՄՍԺՁՄՁՌՑՌՊՁԹՄՋՌՀԹՌՁՆԼՁԻԹՌԽԼԹԾՍՆԻՌՁՇՆԹՄՋՇՄՍԺՁՄՁՌՑՁՆՏԽՄՄՏԹՌԽՊՇԾԹՈՈՊՇՐՁՅԹՌԽՄՑՅԿԹՁԩ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽՋԽՄԽԻՌԽԼԺԹՋԽԼՇՆՌՇՐՁԻՁՌՑ ԼԹՌԹԾՇՊՇՌՀԽՊԾՁՋՀՋՌՍԼՁԽՋՇՊՋՈԽԻՁԽՋՁԾ ԹՎԹՁՄԹԺՄԽԬՌՀԽՊՏՁՋԽԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑ ՄՁՅՁՌՇԾՌՀԽՌԽՋՌԻՇՅՈՇՍՆԼՇՊՅԿԩ ՏՀՁԻՀԽՎԽՊՁՋՄՇՏԽՊՁՋԹՈՈՊՇՈՊՁԹՌԽ԰ՈԽԻՁԽՋԫՇՌՊԽՈՇՊՌԽԼ ԩՁԾԽՋՌԹԿԽԫՇՌՊԽՈՇՊՌԽԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԹՆԿԽԾՁՆԼՁՆԿՌԽՋՌՋ ԺԽՈԽՊԾՇՊՅԽԼՏՁՌՀԾՁՋՀՇԾՋՁՅՁՄԹՊԹԿԽԹՆԼ ՋՁՒԽՌՇՌՀՇՋԽՌՀԹՌՏՇՍՄԼԺԽՍՌՁՄՁՒԽԼՁՆՌՀԽ

ՌԽՋՌԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՀՇՍՊԽՐՈՇՋՍՊԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԫՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩԱՀԽՊԹՆԿԽԾՁՆԼԽՊՏԹՋԻՇՆԼՍԻՌԽԼՏՁՌՀՌՀԽՍՋԽՇԾԹՋՇՄՎԽՆՌԹՆԼԹՏՀՁՌԽՈՊԽԻՁՈՁՌԹՌԽՏԹՋՆՇՌԽԼՁՆՌՀԽՅՁՐՁՆԿԻՀԹՅԺԽՊԹՌՅԿԹՁԩԞՆԹՄՑՌՁԻԹՄՊԽԻՇՎԽՊՁԽՋՊԹՆԿԽԼԾՊՇՅՌՇՇԾՆՇՅՁՆԹՄԱՀԽՊԽՏԹՋՅՇՊՌԹՄՁՌՑՁՆՌՀԽՅԿԹՁԩՏՁՌՀՆՇՇՌՀԽՊՅՇՊՌԹՄՁՌՁԽՋՇԻԻՍՊՊՁՆԿՁՆԹՆՑԻՇՆՌՊՇՄՇՊՌՊԽԹՌՅԽՆՌԿՊՇՍՈԴՀՁՄԽՆՇՅՇՊՌԹՄՁՌՁԽՋՇԻԻՍՊՊԽԼՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑՁՆԻՄՍԼՁՆԿՄԽՌՀԹՊԿՑՄՑՁՆԿՇՆՌՀԽԺՇՌՌՇՅՇԾՌՀԽՌԹՆՃԹՆԼՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅՏԽՊԽՇԺՋԽՊՎԽԼՁՆԹՄՄԾՁՋՀՁՆՌՀԽԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՌԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊ ՏՁՌՀԾՁՎԽՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՈՄՍՋԹԻՇՆՌՊՇՄ ՋՁՐՌՇՌԹՄՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՏՁՌՀԾՇՍՊ ԾԽՅԹՄԽՋԹՆԼՌՏՇՅԹՄԽՋՈԽՊԽՐՈՇՋՍՊԽՌԹՆՃ ԾՁՋՀՌՇՌԹՄԱՀԽՆՍՅԺԽՊՇԾՅՇՊՌԹՄՁՌՁԽՋ ՌՀԹՌՇԻԻՍՊՅԹՑԺԽՍՋԽԼՌՇԼԽՎԽՄՇՈԹ ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԻՍՊՎԽ ԟԹՋԽԼՍՈՇՆՌՀԽՊԽՋՍՄՌՋՌՀԽՀՁԿՀԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՌՀԹՌԼՇԽՋՆՇՌՊԽՋՍՄՌՁՆ ՁՆԻՊԽԹՋԽԼՅՇՊՌԹՄՁՌՑՇՊՋՁԿՆՋՇԾՇՎԽՊՌ ՅՇՊԺՁԼՁՌՑԻՇՅՈԹՊԽԼՌՇԻՇՆՌՊՇՄՋՇՊՌՀԽ ԼԽՊՁՎԽԼՀՊԩԠ  ՅԹՑԺԽՋԽՄԽԻՌԽԼԹՋՌՀԽ ՀՁԿՀԽՋՌԽՐՈՇՋՍՊԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽ

ԼԹՑՌԽՋՌԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ԼՍՊԹՌՁՇՆ ՇԾ ՌՀԽ ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԼԹՑՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԪԹՐՁՅՍՅԻՇՆԻԽՆՌՊԹՌՁՇՆԺԹՋԽԼՇՆՇԾՌՀԽԻՇՆԻԽՆՌՊԹՌՁՇՆՌՀԹՌԻԹՍՋԽԼՅՇՊՌԹՄՁՌՑՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ ՁԽՅԿԹՁԩԞՋՈԹԻՁՆԿԾԹԻՌՇՊՇԾՏԹՋՋԽՄԽԻՌԽԼԾՇՊՌՀԽՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾ ՌՀԽՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊ ԼԽՅՇՆՋՌՊԹՌԽՋԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ ԽԿՌՀԽՀՇՍՊԩԠ  ՏՀՁԻՀԽՎԽՊ ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽԫՇՌՊԽՈՇՊՌԽԼ԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ
ՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԹՆԼՅԿԹՁԩ ԢԭԞՋՍԿԿԽՋՌՋՌՀԹՌԹԻՇՆԻԽՆՌՊԹՌՁՇՆ ՋԽՈԹՊԹՌՁՇՆՇԾԺԽՌՏԽԽՆ
ՇՊՌՀՊԽԽԾՇՄԼ ԹՆԼ
ՇՊՌԽՆԾՇՄԼՁՋՋԻՁԽՆՌՁԾՁԻԹՄՄՑ

ԹԻԻԽՈՌԹԺՄԽ  ԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄՁԾԹՈՈՊՇՈՊՁԹՌԽԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!ԶԽՋ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋԪԽԹՆՅԽԹՋՍՊԽԼ ԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿԹՁԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡ ԫՇՌՊԽՈՇՊՌԽԼԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԹՆԼԼԹՑՋ  ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅ ԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽՅԽԹՋՍՊԽԼՈՊՁՇՊՌՇՌՀԽ ԹԼԼՁՌՁՇՆՇԾԾՁՋՀՁՆԹՄՄՌԹՆՃՋԹՆԼԹՌՄԽԹՋՌ ՏԽԽՃՄՑՌՀԽՊԽԹԾՌԽՊՁՆՌՏՇՊԽՈՄՁԻԹՌԽՋՈԽՊ ՌՊԽԹՌՅԽՆՌՄԽՎԽՄԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋՌՀԽՊԹՆԼՇՅՁՒԽԼԻՇՅՈՄԽՌԽԺՄՇԻՃԼԽՋՁԿՆՍՋԽԼ!ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹՄՄԾՁՋՀԺԽՊԹՆԼՇՅՄՑ ԹՋՋՁԿՆԽԼՌՇՌԹՆՃՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽ ԱԹՆՃՋԹՊԽՌՀԽՆՊԹՆՃԽԼԹԻԻՇՊԼՁՆԿՌՇՈՊԽ ԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑԹՆԼՌՀԽՌԹՆՃՋՏՁՌՀՌՀԽ ՀՁԿՀԽՋՌԾԽԻՍՆԼՁՌՑԹՊԽՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇ ԹԼԽԾՁՆՁՌՁՎԽՌԽՋՌՌՊԽԹՌՅԽՆՌԹՆԼԺՄՇԻՃԾՁՊՋՌ ԢԹԻՀԺՄՇԻՃԻՇՆՌԹՁՆՋՇՆԽՊԽՈՄՁԻԹՌԽՇԾԽԹԻՀ ՌՊԽԹՌՅԽՆՌՁՆԻՄՍԼՁՆԿԻՇՆՌՊՇՄՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԻՇՆԻՍՊՊԽՆՌ ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿԹԿԽՆՌՁՋ ՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽ ԫՍՅԺԽՊՇԾԾԽՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԽՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ!ԶԽՋ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԡԪԣԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁԾԹՈՈՄՁԻԹԺՄԽμԩԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌ ԽՐԻԽԽԼՅՄԩ ԬԢԠԡՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌՋՇՄՎԽՆՌՀԹՎԽՆՇԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊ ՈՊՇԼՍԻԽԹՆՑՇՌՀԽՊԹԼՎԽՊՋԽԽԾԾԽԻՌՋԹՆԼՌՀԹՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՆՇՌԺԽԿՊԽԹՌԽՊՌՀԹՆՅՄԩ ԴԹՋԹՈՇՋՁՌՁՎԽԻՇՆՌՊՇՄՍՋԽԼ! ԫՇԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՋՁԾԹՈՈՄՁԻԹԺՄԽԫԞ ԭՀՇՌՇՈԽՊՁՇԼՀՊՋՄՁԿՀՌՀՊՋԼԹՊՃՅՁՆՍՌԽՌՊԹՆՋՁՌՁՇՆՈԽՊՁՇԼՇԾՄՇՏՄՁԿՀՌՁՆՌԽՆՋՁՌՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ

ՄՁԿՀՌԼԹՊՃԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏԞՉՍԹՌՁԻԱՇՐՁԻՇՄՇԿՑՈՈ-ԬԢԠԡ
ԤՍՁԼԹՆԻԽԡՇԻՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋՇՆԱԽՋՌՁՆԿԹՆԼԞՋՋԽՋՋՅԽՆՌԫՇԭԹՊՁՋԣՊԹՆԻԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԩՁԿՀՌՁՆՌԽՆՋՁՌՑԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽՄՍՐ ԣՄՍՇՊԽՋԻԽՆՌՄՁԿՀՌԺՍՄԺՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑ- ՄՍՐ
ԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԱՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋՏԽՊԽՅՁՐԽԼԺՑՁՆՎԽՊՋՁՇՆԹՆԼՊԹՆԿԽԼՁՆԹՈՈԽԹՊԹՆԻԽԾՊՇՅԻՄԽԹՊԹՆԼՋՄՁԿՀՌՄՑՄՁԿՀՌՑԽՄՄՇՏՌՇԻՄԽԹՊԹՆԼՑԽՄՄՇՏՏՁՌՀՆՇՎՁՋՁԺՄԽՈՊԽԻՁՈՁՌԹՌԽՋԱՀԽ ՌԽՋՌ ՋՇՄՍՌՁՇՆՋ ՁՆ ՌՀԽ ԼՁՄՍՌԽՊ ՅՁՐՁՆԿԻՀԹՅԺԽՊՋ ԹՆԼ ՌԽՋՌ ԻՀԹՅԺԽՊՋ ԹՈՈԽԹՊԽԼԻՄԽԹՊԹՆԼԻՇՄՇՊՄԽՋՋԼՍՊՁՆԿՌՀԽՌԽՋՌՏՁՌՀՆՇԽՎՁԼԽՆԻԽՇԾՈՊԽԻՁՈՁՌԹՌՁՇՆՇԺՋԽՊՎԽԼՁՆԹՆՑԻՇՆՌՊՇՄՇՊՌՊԽԹՌՅԽՆՌՋՇՄՍՌՁՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱՊԽԹՌՅԽՆՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԠԳԭԱՊԽԹՌՅԽՆՌԦԡԫՇՅՁՆԹՄԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԪԽԹՆԪԽԹՋՍՊԽԼԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԪԽԹՆԠԳ
ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑԩԬԮԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌԽՋՌՁՌԽՅ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՅԹՁՆՌԹՁՆԽԼԹՌԹԻՇԽԾԾՁԻՁԽՆՌ ՇԾՎԹՊՁԹՌՁՇՆ
ԠԳ ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԩԬԮ ԫԞԱՊԽԹՌՅԽՆՌ չԱՊԽԹՌՅԽՆՌչԱՊԽԹՌՅԽՆՌչԡՁՄՍՌԽՊ԰ՌՇԻՃԫԞԫԞԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ ԩԬԮՅԿԹՁԩԬՆԽՇԾՌՀԽԼՍՈՄՁԻԹՌԽՋԹՅՈՄԽՋԾՇՊԡԹՑՀԹԼԹՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՅԿԹՁԩԞԻԻՇՊԼՁՆԿՌՇՌՀԽՋՌՍԼՑՊԽՈՇՊՌ՟ԪԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏԹՋՆՇՌԽՎՁԼԽՆՌՁՆԼՍՈՄՁԻԹՌԽՋԹՅՈՄԽՌԹՃԽՆՇՆԡԹՑՇՊԹՌԹՆՑՇՌՀԽՊՁՆՌԽՊՎԹՄԹՆԼՁՋԹՌՌՊՁԺՍՌԽԼՌՇՈՇՋՋՁԺՄԽՋԹՅՈՄԽԻՇՆՌԹՅՁՆԹՌՁՇՆՠ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԢԬԺՋԽՊՎԹՌՁՇՆՋ  ԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋ ԰ՍՊՎՁՎԹՄԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽ ՋՋԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋՏԽՊԽՇԺՋԽՊՎԽԼ

ԼԹՁՄՑԞՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ
ԡԹՑՋԽԻՇՆԼԹՊՑՋԽՐԻՀԹՊԹԻՌԽՊՁՒ ԹՌՁՇՆ
ԺՇԼՑ

ԻՇՄՇՊՈԹՌՌԽՊՆԺՇԼՑՋՀԹՈԽԺՇԼՑՏԽՁԿՀՌՄԽՆԿՌՀՌՍԺԽՊԻՄԽՋԻՇՊ ԽԿՇՆԹԼԹՄ

ՋՌԹԿՁՆԿԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑԹՆԼՈՄԹՋՅԹՎՁՌԽՄՄՇԿԽՆՁՆՏԽՊԽԽՎԹՄՍԹ ՌԽԼ  ԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ! ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՋՍՊՎՁՎԹՄԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄ ՁՒԹՌՁՇՆՋՍԻԻԽՋՋՋԽԻՇՆԼԹՊՑՋԽՐԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋ

ԹՆԼՇՌՀԽՊԻՄՁՆՁԻԹՄՋՁԿՆՋՇԻԻՍՊԹՌՄԽԹՋՌԼԹՁՄՑԞՌՌԽՋՌՌԽՊՅՁՆԹ ՌՁՇՆ
ԡԹՑԹԼԼՁՌՁՇՆԹՄՇԺՋԽՊՎԹՌՁՇՆՋՁՆԻՄՍԼԽ

ԺՇԼՑՏԽՁԿՀՌԹՆԼՄԽՆԿՌՀՆՍՈՌՁԹՄՌՍԺԽՊԻՄԽՋԻՇՊԽԿՇՆԹԼԹՄՋՌԹԿՁՆԿԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՈՄԹՋՅԹՎՁՌԽՄՄՇԿԽՆՁՆԹՆԼ

ՈՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋ
ՌԽՋՌՇՋՌԽՊՇՆԽԹՆԼ ȕ ԽՋՌՊԹԼՁՇՄՁԾՅԽԹՋՍՊԽԼԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
Ԥ԰ԦՁՋ

ԻԹՄԻՍՄԹՌԽԼՍՋՁՆԿԹՊԹՌՁՇՇԾԿՇՆԹԼՏԽՁԿՀՌՌՇԺՇԼՑՏԽՁԿՀՌ
ԿՇՆԹԼՏԽՁԿՀՌՌՇՌՀԽՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌ

ՁՆՅԿՐԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ

ԠՄՁՆՁԻԹՄՋՁԿՆՋՇԾՇՎԽՊՌՌՇՐՁԻՁՌՑՅԹՑՁՆԻՄՍԼԽ
ԺՍՌԹՊԽՆՇՌՄՁՅՁՌ ԽԼՌՇՀԽՅՇՊՊՀԹԿԽԻԽՋՋԹՌՁՇՆՇԾԾԽԽԼՁՆԿԹՆԼ

ՇՌՀԽՊԹԺՆՇՊՅԹՄԺԽՀԹՎՁՇՊԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԦԦԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫԞԯԽՋՍՄՌՋԪԹՄԽ ՋՍՊՎՁՎԹՄՏԹՋ     ԹՆԼ  ՁՆ ՌՀԽ ՅԽԹՆՅԽԹՋՍՊԽԼ  
ԻՇՆՌՊՇՄ  
ՋՇՄՎԽՆՌ   ԹՆԼ  ՅԿ ԹՁԩ ՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑԹՆԼԾԽՅԹՄԽՋՍՊՎՁՎԹՄՎԹՄՍԽՋՏԽՊԽԹՌԹՄՄՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ
ԱԹԺՄԽԱԹԺՄԽԞԼՍՄՌԣՁՋՀ԰ՍՊՎՁՎԹՄՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԪԹՄԽՋԣԽՅԹՄԽՋԫ԰ՍՊՎՁՎՁՆԿ԰ՍՊՎՁՎԹՄԫ԰ՍՊՎՁՎՁՆԿ԰ՍՊՎՁՎԹՄԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ ԱՇՌԹՄՆՍՅԺԽՊՇԾԾՁՋՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԪԽԹՆՅԹՄԽԺՇԼՑՏԽՁԿՀՌՎԹՄՍԽՋՏԽՊԽԹՆԼԿԹՆԼՅԽԹՆԾԽՅԹՄԽԺՇԼՑՏԽՁԿՀՌՎԹՄՍԽՋՏԽՊԽԹՆԼԿՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄ
ՋՇՄՎԽՆՌԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ ՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽԪԽԹՆՅԹՄԽԺՇԼՑՄԽՆԿՌՀՎԹՄՍԽՋՏԽՊԽԹՆԼՅՅԹՆԼԾԽՅԹՄԽԺՇԼՑՄԽՆԿՌՀՎԹՄՍԽՋՏԽՊԽԹՆԼՅՅՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄ
ՋՇՄՎԽՆՌԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑԱԹԺՄԽ԰ՁՒԽԹՌԱԽՋՌԱԽՊՅՁՆԹՌՁՇՆՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԟՇԼՑԴԽՁԿՀՌԩԽՆԿՌՀԪԹՄԽՋԣԽՅԹՄԽՋԪԹՄԽՋԣԽՅԹՄԽՋՆԪԽԹՆԿչ԰ԡՆԪԽԹՆԿչ԰ԡՆԪԽԹՆՅՅչ԰ԡՆԪԽԹՆՅՅչ԰ԡԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ            ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ                                            ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆԩԬԮՅԿԹՁԩ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԪԽԹՆԾԽԻՍՆԼՁՌՑՎԹՄՍԽՋՏԽՊԽԹՆԼԽԿԿՋ ԾԽՅԹՄԽԼԹՑԹՆԼԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋ

ՏԹՋ     ԹՆԼ  ՁՆ ՌՀԽ  
ԻՇՆՌՊՇՄ  
ՋՇՄՎԽՆՌ   ԹՆԼ  ՅԿ

ԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

ԱԹԺՄԽԣԽԻՍՆԼՁՌՑԹՆԼԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ  ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ



ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ% ԣԽԻՍՆԼՁՌՑ 

ԪԽԹՆչ԰ՌԹՆԼԹՊԼԡԽՎՁԹՌՁՇՆ ԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋ
 

ԪԽԹՆչ԰ՌԹՆԼԹՊԼԡԽՎՁԹՌՁՇՆ

ԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ չ չ

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ չ չ

 չ չ

 չ չ

 չ չ

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԫԡ ԫՇՌԼԽՌԽՊՅՁՆԽԼ

  ԣԽԻՍՆԼՁՌՑՁՋԻԹՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋՈԽՊՋՍՊՎՁՎՁՆԿԾԽ ՅԹՄԽՈԽՊՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՈԽՊՊԽՈՄՁԻԹՌԽ

  ԣԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋ
ՁՋԻԹՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽՅԺՊՑ ՇՋԼՁՎՁԼԽԼԺՑՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋ

ՅՍՄՌՁՈՄՁԽԼԺՑ

ԩԬԮՅԿԹՁԩ 

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԪԽԼՁԹՆ ՅԹՄԽ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽՋ ՏԽՊԽ     ԹՆԼ  ՁՆ ՌՀԽ ՅԽԹՆՅԽԹՋՍՊԽԼ ՌՀԽ 

ԻՇՆՌՊՇՄ
ՋՇՄՎԽՆՌԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽ ՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽԫՇՆԽ

ՇԾՌՀԽՋՍՊՎՁՎՁՆԿԾԽՅԹՄԽՋՏԽՊԽԾՇՍՆԼՌՇՀԹՎԽՌՍԺԽՊԻՄԽՋ

ԪԽԼՁԹՆՅԹՄԽԾԹՌՈԹԼՋԻՇՊԽՋՏԽՊԽԹՆԼՁՆՌՀԽՅԽԹՆՅԽԹ ՋՍՊԽԼՌՀԽ
ԻՇՆՌՊՇՄ
ՋՇՄՎԽՆՌ

ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ ՊԽՋՈԽԻՌՁՎԽՄՑԫՇԾԽՅԹՄԽՋՏԽՊԽՆՇՌԽԼՏՁՌՀԹԾԹՌՈԹԼ

ՋԻՇՊԽՆՇԾԹՌՈԹԼՎՁՋՁԺՄԽ

ԱԹԺՄԽԫՍՈՌՁԹՄԱՍԺԽՊԻՄԽ԰ԻՇՊԽՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ



ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ% ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆ

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ Ն ԪԽԼՁԹՆ

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ

ԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ    

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ    

    

    

    

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԫԡ ԫՇՌԼԽՌԽՊՅՁՆԽԼ ԰ԡ ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

ԩԬԮՅԿԹՁԩ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԪԽԹՆՅԹՄԽԤ԰ԦՏԹՋ ԹՆԼԹՆԼՅԽԹՆԾԽ ՅԹՄԽԤ԰ԦՏԹՋ

ԹՆԼՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄ
ՋՇՄՎԽՆՌԹՆԼՅԿԹՁԩ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

ԱԹԺՄԽԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐ
Ԥ԰ԦՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ



ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ% ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԹՆԤ԰Ԧ 

 չ԰ԡ Ն ԪԽԹՆԤ԰Ԧ 

 չ԰ԡ

ԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ      

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ      

      

      

      

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ

  ԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
ՁՋԻԹՄԻՍՄԹՌԽԼԹՋԿՇՆԹԼՏԽՁԿՀՌ
ՌՇՌՀԽՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌ
ՅԿՐ



ԩԬԮՅԿԹՁԩ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԪԽԼՁԹՆՅԹՄԽԿՇՆԹԼԹՄՋՌԹԿԽՋՏԽՊԽԹՆԼԹՆԼԾԽՅԹՄԽԿՇՆԹԼԹՄՋՌԹԿԽՋՏԽՊԽ

ԹՆԼՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄ
ՋՇՄՎԽՆՌ ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ

ՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

ԱԹԺՄԽԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ



ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ% ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆ԰ՌԹԿԽ  Ն ԪԽԼՁԹՆ԰ՌԹԿԽ 

ԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ    

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ    

    

    

    

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԧ ԧՍՎԽՆՁՄԽ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԫԡ ԫՇՌԼԽՌԽՊՅՁՆԽԼ ԲԱ԰ ԲՆԹԺՄԽՌՇՋՌԹԿԽ

  ԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼՋՌՀԽԾՇՄՄՇՏՁՆԿԿՇՆԹԼԹՄՋՌԹԿՁՆԿՋԻԹՄԽԾ ՇՊՅԹՄԽԾԹՌՀԽԹԼՅՁՆՆՇՏՍՆԼԽՎԽՄՇՈԽԼԽԹՊՄՑՋՈԽՊՅԹՌՇԿԽՆՁԻ

ՅՁԼՋՈԽՊՅԹՌՇԿԽՆՁԻՄԹՌԽՋՈԽՊՅԹՌՇԿԽՆՁԻՋՈԽՆՌ

  ԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼՋՌՀԽԾՇՄՄՇՏՁՆԿԿՇՆԹԼԹՄՋՌԹԿՁՆԿՋԻԹՄԽԾ ՇՊԾԽՅԹՄԽԾԹՌՀԽԹԼՅՁՆՆՇՏՍՆԼԽՎԽՄՇՈԽԼԽԹՊՄՑԼԽՎԽՄՇՈՅԽՆՌ

ՅՁԼԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՀՑԼՊԹՌԽԼՈՇՋՌՇՎՍՄԹՌՇՊՑ

ԩԬԮՅԿԹՁԩ

ԦՆՅԹՄԽԾՁՋՀՌՀԽՊԽՏԹՋՇՆԽՁՆԻՁԼԽՆԻԽՇԾՅՁՄԼՇՊՅՇԼԽՊԹՌԽՁՆԻՊԽ ԹՋԽՁՆՈՊՇՈՇՊՌՁՇՆՇԾՋՈԽՊՅԹՌՇԿՇՆՁԹԹՄՌԽՊԽԼ

ՈՊՇՈՇՊՌՁՇՆՋՇԾՋՈԽՊՅԹՌՇԻՑՌԽՋՇՊՋՈԽՊՅԹՌՁԼՋԹՆԼՇՊԿՊԹՆՍՄՇՅԹՌՇՍՋՁՆԾՄԹՅՅԹՌՁՇՆՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ԱԹԺՄԽՋ ԦՆԾԽՅԹՄԽԾՁՋՀՌՀԽՊԽՏԹՋՇՆԽ

ՁՆԻՁԼԽՆԻԽՇԾՅՁՄԼՇՊՅՇԼԽՊԹՌԽՁՆԻՊԽԹՋԽՁՆՇՇԻՑՌԽԹՌՊԽՋՁԹՁՆՌՀԽ ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼ

ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋԹՆԼՇՆԽՁՆԻՁԼԽՆԻԽՇԾՋԽՎԽՊԽՇՇԻՑՌԽԹՌՊԽՋՁԹՁՆՌՀԽՅԿԹՁԩ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ԱԹԺՄԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԦՆԻՊԽԹՋԽԼԭՊՇՈՇՊՌՁՇՆՇԾ԰ՈԽՊՅԹՌՇԿՇՆՁԹԭՊԽՋԽՆԻԽՇԾԱԽՋՌՁՋԬՎԹԦՆԻՊԽԹՋԽԼԱԽՋՌՁԻՍՄԹՊԡԽԿԽՆԽՊԹՌՁՇՆԡՍԻՌԪՁՆԽՊԹՄՁՒԹՌՁՇՆԦՆՌԽՊՋՌՁՌՁԹՄԻԽՄՄԩԽՑԼՁԿՀՑՈԽՊՌՊՇՈՀՑՀՑՈԽՊՈՄԹՋՁԹՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄԩԬԮ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄԩԬԮ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԦՆԻՊԽԹՋԽԼԭՊՇՈՇՊՌՁՇՆՇԾ԰ՈԽՊՅԹՌՇԿՇՆՁԹԭՊԽՋԽՆԻԽՇԾԱԽՋՌՁՋԬՎԹԦՆԻՊԽԹՋԽԼԱԽՋՌՁԻՍՄԹՊԡԽԿԽՆԽՊԹՌՁՇՆԡՍԻՌԪՁՆԽՊԹՄՁՒԹՌՁՇՆԦՆՌԽՊՋՌՁՌՁԹՄԻԽՄՄԩԽՑԼՁԿՀՑՈԽՊՌՊՇՈՀՑՀՑՈԽՊՈՄԹՋՁԹՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԡԽԻՊԽԹՋԽԼԭՊՇՈՇՊՌՁՇՆՇԾ԰ՈԽՊՅԹՌՇԿՇՆՁԹԦՆԻՊԽԹՋԽԼԳԹՋԻՍՄԹՊՇՊԦՆՌԽՊՋՌՁՌՁԹՄԭՊՇՌԽՁՆԹԻԽՇՍՋԣՄՍՁԼԞՋՑՆԻՀՊՇՆՇՍՋԤՇՆԹԼԡԽՎԽՄՇՈՅԽՆՌԞՄՌԽՊԽԼԭՊՇՈՇՊՌՁՇՆՋՇԾ԰ՈԽՊՅԹՌՇԻՑՌԽՋՇՊ԰ՈԽՊՅԹՌՁԼՋԤՊԹՆՍՄՇՅԹՌՇՍՋԦՆԾՄԹՅՅԹՌՁՇՆՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄԩԬԮԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄԩԬԮԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ  ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
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ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾ ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽԩԬԮՅԿԹՁԩԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԦՆԻՊԽԹՋԽԼԬՇԻՑՌԽԞՌՊԽՋՁԹԭԽՊՁԾՇՄՄՁԻՍՄԹՊԠԽՄՄԥՑՈԽՊՈՄԹՋՁԹԥՑՈԽՊՌՊՇՈՀՑԡԽԻՊԽԹՋԽԼԶՇՄՃԣՇՊՅԹՌՁՇՆԞԿԿՊԽԿԹՌԽՋՇԾՅԹԻՊՇՈՀԹԿԽՋՅՍՄՌՁԾՇԻԹՄՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ  ԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԦՆԻՊԽԹՋԽԼԬՇԻՑՌԽԞՌՊԽՋՁԹԭԽՊՁԾՇՄՄՁԻՍՄԹՊԠԽՄՄԥՑՈԽՊՈՄԹՋՁԹԥՑՈԽՊՌՊՇՈՀՑԡԽԻՊԽԹՋԽԼԶՇՄՃԣՇՊՅԹՌՁՇՆԞԿԿՊԽԿԹՌԽՋՇԾՅԹԻՊՇՈՀԹԿԽՋՅՍՄՌՁԾՇԻԹՄՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞ ԫԞԫԞ ԫԞԫԞԫԞԫԞԫԞԫԞԫԞԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾ ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽԩԬԮՅԿԹՁԩԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԦՆՌԽՊՋՌՁՌՁՍՅՅՍՄՌՁԾՇԻԹՄՁՆԾՄԹՅՅԹՌՁՇՆԢԿԿԡԽԺՊՁՋՁՆԬՎՁԼՍԻՌԤՊԹՆՍՄՇՅԹՌՇՍՋԦՆԾՄԹՅՅԹՌՁՇՆԡԽԻՊԽԹՋԽԼԭՇՋՌԬՎՍՄԹՌՇՊՑԣՇՄՄՁԻՄԽՋՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ  ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ  ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԦՆՌԽՊՋՌՁՌՁՍՅՅՍՄՌՁԾՇԻԹՄՁՆԾՄԹՅՅԹՌՁՇՆԢԿԿԡԽԺՊՁՋՁՆԬՎՁԼՍԻՌԤՊԹՆՍՄՇՅԹՌՇՍՋԦՆԾՄԹՅՅԹՌՁՇՆԡԽԻՊԽԹՋԽԼԭՇՋՌԬՎՍՄԹՌՇՊՑԣՇՄՄՁԻՄԽՋՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽ ԢՆԼՈՇՁՆՌՋԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏԽՊԽՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՀՁԿՀՅՇՊՌԹՄՁՌՑԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԩԬԮՅԿԹՁԩ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԪԽԹՆՅԹՄԽԳԱԤՏԹՋԹՆԼՆԿՅԩԹՆԼՅԽԹՆԾ ԽՅԹՄԽԳԱԤՏԹՋՐ 



Ր  Ր  Ր  ԹՆԼՐ  ՆԿՅԩՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄ
ՋՇՄՎԽՆՌ

ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ ԱԹԺՄԽ

ԱԹԺՄԽԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ



ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ% ԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆ
ԳԱԤ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԹՆ

ՆԿՅԩՈՄԹՋՅԹ չ԰ԡ Ն ԪԽԹՆ

ՆԿՅԩՈՄԹՋՅԹ չ԰ԡ

ԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ     Ր   Ր 

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ     Ր   Ր 

     Ր   Ր 

     Ր   Ր 

     Ր   Ր 

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԫԡ ԫՇՌԼԽՌԽՊՅՁՆԽԼ ԰ԡ ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

ԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԪԽԹՆՈՄԹՋՅԹՌԽՋՌՇՋՌԽՊՇՆԽԹՆԼՈՄԹՋՅԹȕԽՋՌՊԹԼՁՇՄՁՆՅԹՄԽԹՆԼԾԽՅԹՄԽՋՏԹՋՆՇՌՅԽԹՋՍՊԽԼ
ԱԹԺՄԽԱԹԺՄԽԭՄԹՋՅԹ԰ԽՐ԰ՌԽՊՇՁԼՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԫՇՌՅԽԹՋՍՊԽԼԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԭՄԹՋՅԹԱԽՋՌՇՋՌԽՊՇՆԽ
ԱԭՄԹՋՅԹȕԽՋՌՊԹԼՁՇՄ
ԢԪԹՄԽՋԣԽՅԹՄԽՋԪԹՄԽՋԣԽՅԹՄԽՋՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՀԽՊԽՏԽՊԽՆՇՆՇՌԹԺՄԽՇԺՋԽՊՎԹՌՁՇՆՋՏՁՌՀՊԽԿԹՊԼՋՌՇԺԽՀԹՎՁՇՊՇՊԻՀԹՆԿԽՋՁՆԹՈՈԽԹՊԹՆԻԽՋՈԽԻՁԾՁԻԹՄՄՑԻՇՄՇՊԺԹՆԼՁՆԿՇՎՁՈՇՋՁՌՇՊԹՈՈԽԹՊԹՆԻԽՇՊՋՁՒԽՇԾԼՇՊՋԹՄՆԹՈԽՈԹԼՁՆՌՀԽԻՇՆՌՊՇՄՇՊՌՊԽԹՌԽԼԿՊՇՍՈՋ
ԱԹԺՄԽԱՀԽՊԽՏԹՋՇՆԽՅԹՄԽՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՌՀԹՌԼՁԽԼԞՄՄՇՌՀԽՊԾՁՋՀՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋԹՆԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԹՈՈԽԹՊԽԼՆՇՊՅԹՄԹՆԼՆՇՇՎԽՊՌՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑՏԽՊԽՇԺՋԽՊՎԽԼԼՍՊՁՆԿՌՀԽՌԽՋՌՈԽՊՁՇԼԱԹԺՄԽ԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋԪԹՄԽՋԣԽՅԹՄԽՋԱՑՈԽՆԦՆԻՁԼԽՆԻԽԱՑՈԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮԫՇՆԽԫԞԫԞԫՇՆԽԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮԫՇՆԽԫԞԫԞԫՇՆԽԫԞ ԫԞԫՇՆԽԫԞԫԞԫՇՆԽԫԞ ԫԞԫՇՆԽԫԞԫԞԫՇՆԽԫԞ ԫԞԫՇՆԽԫԞԫԞԫՇՆԽԫԞ ԫԞԩԬԮՅԿԹՁԩ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԟ ԰ՌՍԼՑԞՍՌՀՇՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

ԱՀԽ ՋՌՍԼՑ ԹՍՌՀՇՊ ԹՆԹՄՑՒԽԼ ՋՍՊՎՁՎԹՄՏԽՌՏԽՁԿՀՌՌՇՌԹՄ ՄԽՆԿՌՀՌ ՍԺԽՊԻՄԽ ՋԻՇՊԽ ԿՇՆԹԼԹՄ ԼԽՎԽՄՇՈՅԽՆՌ

Ԥ԰ԦԾԽՊՌՁՄՁՌՑԾԽԻՍՆԼՁՌՑԳԱԤԹՆԼՁՆԻՁԼԽՆԻԽԹՆԼՋԽՎԽՊՁՌՑՇԾԿՇՆԹԼԹԺՆՇՊՅԹՄՁՌՁԽՋԡԹՌԹՏԽՊԽԿԽՆԼԽՊ

ՋՈԽԻՁԾՁԻ ԹՆԼ ԹՆԹՄՑՒԽԼ ՁՆ ԻՇՅՈԹՊՁՋՇՆ ՌՇ ՌՀԽ ՈՇՇՄԽԼ ԻՇՆՌՊՇՄ ՋՁՆԻԽ ՆՇ ԼՁԾԾԽՊԽՆԻԽՋ ՏԽՊԽ ԼԽՌԽԻՌԽԼ

ԺԽՌՏԽԽՆՌՀԽՌՏՇԻՇՆՌՊՇՄԿՊՇՍՈՋ
Ո ԾՇՊԹՆՑՈԹՊԹՅԽՌԽՊ

ԡԽՋԻՊՁՈՌՁՎԽՋՌԹՌՁՋՌՁԻՋ
ՅԽԹՆՋՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆԽՌԻՏԽՊԽԼԽ ՌԽՊՅՁՆԽԼԾՇՊԽԹԻՀԽՆԼՈՇՁՆՌ԰ՁԿՆՁԾՁԻԹՆՌ

ԽԾԾԽԻՌՋՏԽՊԽԼԽՌԽՊՅՁՆԽԼԹՌՈ ≤ 
԰Ԟ԰ՎԽՊՋՁՇՆ԰ՍՊՎՁՎԹՄԼԹՌԹՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿԣՁՋ ՀԽՊՋ

ԢՐԹԻՌ ՌԽՋՌ ԹՆԼ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ ՋԻՇՊԽՋ ԹՆԼ ՋՌԹԿԽՋ ՏԽՊԽ ԹՆԹՄՑՒԽԼ ՍՋՁՆԿ ՋՌԽՈԼՇՏՆ ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ ՌՊԽՆԼ ՌԽՋՌ  ԣՇՊ ՌՀԽ ՇՌՀԽՊ ԽՆԼՈՇՁՆՌՋ ՁԾ ՌՀԽ ՊԽՋՍՄՌՋ Տ ԽՊԽ ԻՇՆՋՁՋՌԽՆՌ ՏՁՌՀ Թ ՅՇՆՇՌՇՆՁԻ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ՌԽՋՌ ՏԹՋ ՍՋԽԼ  ԞՄՄ  ԽՆԼՈՇՁՆՌՋ ԽՐԻԽՈՌ ՋՍՊՎՁՎԹՄ ԹՆԼ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ ՋԽՎԽՊՁՌՑ ՋԻՇՊԽՋՏԽՊԽ ԹՆԹՄՑՒԽԼ ԺՑ ՈԽՊԾՇՊՅՁՆԿ ՈԹՁՊ ՏՁՋԽ ԻՇՅՈԹՊՁՋՇՆՋ ՍՋՁՆԿԡՍՆՆԽՌՌ0Ջ

ԪՍՄՌՁՈՄԽԠՇՅՈԹՊՁՋՇՆՌԽՋՌՌՇԼԽՌԽՊՅՁՆԽՏՀՁԻՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԼՁ ԾԾԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑԾՊՇՅՌՀԽԻՇՆՌՊՇՄ

ԭՊՁՇՊՌՇԡՍՆՆԽՌՌ0ՋԼԹՌԹՏԽՊԽԹՆԹՄՑՒԽԼԺՑ԰ՀԹՈՁՊՇԴՁՄՃ0ՋՌԽՋՌԹՆԼԩԽՎԽՆԽ0ՋՌՇՌԽՋՌԾՇՊՆՇՊՅԹՄՁՌՑԹՆԼ

ՀՇՅՇԿԽՆԽՁՌՑ ՇԾ ՎԹՊՁԹՆԻԽՋ ՊԽՋՈԽԻՌՁՎԽՄՑ α     ԦԾ ՆՇՊՅԹՄՁՌՑ ԹՆԼ ՀՇՅՇԿԽՆԽՁՌՑ ՌԽՋՌՋ ՈԹՋՋԽԼ

Ո  Թ ՈԹՊԹՅԽՌՊՁԻ ԹՆԹՄՑՋՁՋ ՏԹՋ ՈԽՊԾՇՊՅԽԼ ՍՋՁՆԿ ՌՀԽ ՌՊԹՆՋԾՇ ՊՅԽԼ ԼԹՌԹ  ԦԾ ՆՇՆՆՇՊՅԹՄՁՌՑ ՇՊ

ՍՆԽՉՍԹՄ ՎԹՊՁԹՆԻԽ ՏԽՊԽ ՁՆԼՁԻԹՌԽԼ 
Ո Թ ՆՇՆՈԹՊԹՅԽՌՊՁԻ ԹՆԹՄ ՑՋՁՋ ՏԹՋ ՈԽՊԾՇՊՅԽԼ 
ԴՁՄԻՇՐՇՆ

ՊԹՆՃՋՍՅՌԽՋՌՇՆՌՀԽ ՊԹՆՃՋՇԾՌՀԽԼԹՌԹԪԽԹՋՍՊԽՅԽՆՌՋՇԾՎՁՌԽՄՄՇԿԽՆՁՆԹՊԽՁՆՀԽՊԽՆՌՄՑՎԹՊՁԹԺՄԽԹՆԼ

ԺՇՐՈՄՇՌՋՏԽՊԽՄՇԿՌՊԹՆՋԾՇՊՅԽԼԳԱԤՎԹՄՍԽՋՏԽՊԽՍՋԽԼՌՇՁԼԽՆՌՁԾՑ ՈՇՌԽՆՌՁԹՄՇՍՌՄՁԽՊՋ
ԱՍՃԽՑ0ՋՅԽՌՀՇԼ

ԱՀԽՋԽՅԽՌՀՇԼՋԹՈՈԽԹՊՌՇԺԽԻՇՆՋՁՋՌԽՆՌՏՁՌՀՌՀԽՅԽՌՀՇԼՋՊԽԻՇՅՅԽՆ ԼԽԼՁՆՌՀԽԿՍՁԼԽՄՁՆԽ

ԱՀԽՊԽՏԽՊԽՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼԽԻՊԽԹՋԽՋՁՆՋՍՊՎՁՎԹՄՁ ՆԹՆՑՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՆԻՇՅՈԹՊՁՋՇՆՌՇ

ՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄԼՍՊՁՆԿՌՀԽՌԽՋՌ
Ո ԱՀԽՊԽՏԽՊԽՆՇՋ ՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋՇՆՌՇՌԹՄ

ՄԽՆԿՌՀՇՊՏԽՌՏԽՁԿՀՌԹՅՇՆԿՅԹՄԽՋՇՊԾԽՅԹՄԽՋՁՆԹՆՑՌՊԽԹՌՅԽՆՌԿՊ ՇՍՈՁՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՈՇՇՄԽԼ

ԻՇՆՌՊՇՄ
Ո ԱՀԽՊԽՏԹՋԹՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՌՊԽ ԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՇՆՊԽՈՊՇԼՍԻՌՁՇՆՁՆ

ՌՀԽՀՁԿՀ
ՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ
ՈԱՀԽՊԽՏԽՊ ԽՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋ

ՇՆՌՍԺԽՊԻՄԽՋԻՇՊԽՋԹՅՇՆԿՅԹՄԽՋՁՆԹՆՑՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՆԻՇՅՈԹՊ ՁՋՇՆՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ
Ո 

 ԞՄՄ ԾԽՅԹՄԽՋ ՁՆ ՌՀԽ ՌԽՋՌ ՀԹԼ Թ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽ ՇԾ  
ՆՇ ՌՍ ԺԽՊԻՄԽՋ ՈՊԽՋԽՆՌ  ԱՀԽՊԽՏԽՊԽ ՆՇ

ԹՈՈԹՊԽՆՌՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԻՀԹՆԿԽՋՁՆՋՁՒԽՇՊՋՀԹՈԽՇԾՌՀԽԾԹՌՈԹԼՁՆՅԹՄԽՋՁՆԹՆՑՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ՁՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽԻՇՆՌՊՇՄԹՆԼՆՇԾԽՅԹՄԽՋՁՆԹՆՑԿՊՇՍՈՏԽՊԽՆՇՌԽԼՏՁՌՀԹԾԹՌՈԹԼԱՀԽՊԽԾՇՊԽՁՌ

ԻԹՆ ԺԽ ԻՇՆԻՄՍԼԽԼ ՌՀԹՌ ՌՀԽՊԽ ՏԽՊԽ ՆՇ ՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼ ԽԾԾԽԻՌՋ Շ Ն ՋԽԻՇՆԼԹՊՑ ՋԽՐ ԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋ

ԹՅՇՆԿՅԹՄԽՋՇՊԾԽՅԹՄԽՋԹՌԹՆՑԻՇՆԻԽՆՌՊԹՌՁՇՆՌԽՋՌԽԼԱՀԽՊԽՏԽՊԽ ՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋ

ՇՆԤ԰ԦԹՅՇՆԿՅԹՄԽՋՇՊԾԽՅԹՄԽՋՁՆԹՆՑՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՆԻՇՅՈԹՊՁ ՋՇՆՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ
Ո 

ԱՀԽՊԽՏԽՊԽՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՇՊՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՇՆԳԱԤ ԹՅՇՆԿՅԹՄԽՋ ՁՆ

ԹՆՑ ՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈ ՁՆ ԻՇՅՈԹՊՁՋՇՆ ՌՇ ՌՀԽ ՈՇՇՄԽԼ ԻՇՆՌՊՇՄ 
Ո    ՀՇՏԽՎԽՊ ՌՀԽՊԽ ՏԹՋ 

ՊԽԼՍԻՌՁՇՆՁՆԳԱԤՇԾՅԹՄԽՋՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ ԱՀՁՋՊԽԼՍԻՌՁՇՆՁՋԻՇՆՋՁՋՌԽՆՌՏՁՌՀ

ԾՁՋՀՌՀԹՌ ՀԹՎԽ ՁՅՈԹՁՊԽԼ ՊԽՈՊՇԼՍԻՌՁՇՆ ԱՀԽ ԼԽԻՊԽԹՋԽ ՁՆԳԱԤ ԹՅՇՆԿԾԽՅԹՄԽՋ ՁՆՌՀԽՅԿ

ԹՁԩՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈ ՁՆ ԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽ ՈՇՇՄԽԼԻՇՆՌՊՇՄՏԹՋ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌ 
Ո

ԹՆԼ ԻՇՆՋՁԼԽՊԽԼ ՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼ ԱՀՁՋ ՊԽԼՍԻՌՁՇՆ ՁՋ ԻՇՆՋՁՋՌԽՆՌ ՏՁՌՀ ԾՁՋՀ ՌՀԹՌ ՀԹՎԽ ՁՅՈԹՁՊԽԼ

ՊԽՈՊՇԼՍԻՌՁՇՆ  ԴՁՌՀ ՊԽԿԹՊԼՋ ՌՇ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ ՆԽՁՌՀԽՊ ՌՀԽ ՇՎԹՊ ՁԽՋ ՆՇՊ ՌՀԽ ՌԽՋՌԽՋ ԾՊՇՅ ՌՀԽ ՌՀՊԽԽ

ՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈՋ ՋՀՇՏԽԼ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌ ԼՁԾԾԽՊԽՆԻԽՋ Ծ ՊՇՅ ՌՀԽ ՆԽԿԹՌՁՎԽ ՇՊ ՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄ

ԿՊՇՍՈՋԹՆԼՆՇՆԽՇԾՌՀԽՇԺՋԽՊՎԽԼԹԺՆՇՊՅԹՄՁՌՁԽՋԹՈՈԽԹՊԽԼՌՇԺԽՊ ԽՄԹՌԽԼՌՇԽՐՈՇՋՍՊԽՌՇԱԠԳԭ

ԬՎԽՊԹՄՄՌՀԽՊԽՏԽՊԽ ՆՇ ԹՈՈԹՊԽՆՌ ԽԾԾԽԻՌՋ ՇՆՋՍՊՎՁՎԹՄ ԿՊՇՏՌՀՋԽ ԻՇՆԼԹՊՑՋԽՐ ԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋԤ԰Ԧ ՇՊ

ԿՇՆԹԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԾՁՋՀԽՐՈՇՋԽԼՌՇՌԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋԾՇՊ ԼԹՑՋԱՀԽՊԽՏԹՋԹՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼ

ԽԾԾԽԻՌ ՁՆ ՊԽՈՊՇԼՍԻՌՁՇՆ ՁՆՌՀԽՅԿ ԹՁԩՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈՏՀ ԽՊԽՌՀԽՊԽՏԹՋ Թ ԼԽԻՊԽԹՋԽ ՁՆ

ԽԿԿՈՊՇԼՍԻՌՁՇՆԹՆԼԹՋՄՁԿՀՌԽԾԾԽԻՌՇՆԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋԞԼ ԼՁՌՁՇՆԹՄՄՑՌՀԽՊԽՏԽՊԽԼԽԻՊԽԹՋԽՋՁՆԺՇՌՀ

ՅԹՄԽԹՆԼԾԽՅԹՄԽԳԱԤՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՌՀԹՌ ՏԽՊԽԹՌՌՊՁԺՍՌԽԼՌՇՌՀԽԼԽԻՊԽԹՋԽՁՆ

ՊԽՈՊՇԼՍԻՌՁՇՆ ԱՀԽ ԹԺՋԽՆԻԽ ՇԾ ԽԾԾԽԻՌՋ ՇՆ ՀՁՋՌՇՄՇԿՁԻԹՄ ԽՆԼՈՇՁՆՌՋ ԹՆԼ ՋԽԻՇՆԼԹՊՑ ՋԽՐ ԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋ

ՋՍԿԿԽՋՌՌՀԹՌՌՀԽՋԽԽԾԾԽԻՌՋՏԽՊԽՌՀԽՊԽՋՍՄՌՇԾԾՊԹՆՃՌՇՐՁԻՁՌՑԹԾ ԾԽԻՌՁՆԿՊԽՈՊՇԼՍԻՌՁՇՆ

ԠԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋ  ԱՀԽ ՊԽՎՁԽՏԽՊ ԹՋՋԽՋՋԽԼՋՍՊՎՁՎԹՄ 
ՅՇՊՌԹՄՁՌՑ ԼԹՌԹ ԺԹՋԽԼ ՇՆՎՁՋՍ ԹՄ ՇԺՋԽՊՎԹՌՁՇՆ

ԣԽՅԹՄԽ ԹՆԼ ՅԹՄԽ ԺՇԼՑ ՏԽՁԿՀՌ ՅԹՄԽ ԹՆԼ ԾԽՅԹՄԽ ԺՇԼՑ ՄԽՆԿՌՀ ՅԹՄԽ ԹՆԼ ԾԽՅԹՄԽ Ԥ԰Ԧ ԹՆԼ ՅԹՄԽ

ՌՍԺԽՊԻՄԽ ՋԻՇՊԽ ԼԹՌԹ ՏԽՊԽ ՆՇՌ ԻՇՆՋՁՋՌԽՆՌ ՏՁՌՀ Թ ՅՇՆՇՌՇՆՁԻ ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ ԺՍՌ ԹՄՄ ԼԹՌԹ

ՋԹՌՁՋԾՁԽԼ ՌՀԽ ՈԹՊԹՅԽՌՊՁԻ ԹՋՋՍՅՈՌՁՇՆՋ ՇԾ ՆՇՊՅԹՄՁՌՑ ՍՋՁՆԿ ԰ՀԹՈՁՊՇ ԴՁՄՃՋ ՌԽՋՌ ԹՆԼ ՀՇՅՇԿԽՆԽՁՌՑ ՇԾ

ՎԹՊՁԹՆԻԽՋՍՋՁՆԿԩԽՎԽՆԽ0ՋՌԽՋՌԱՀԽՋԽԽՆԼՈՇՁՆՌՋՏԽՊԽԹՆԹՄՑՒԽԼՍՋ ՁՆԿԡՍՆՆԽՌՌ0ՋՌԽՋՌԪԹՄԽԳԱԤԼՁԼ

ՆՇՌ ԽՐՀՁԺՁՌ Թ ՅՇՆՇՌՇՆՁԻ ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ ԺՍՌ ՌՀԽՋԽ ԼԹՌԹ ԼՁԼ ՆՇՌ ՋԹՌՁՋԾՑ ՈԹՊԹՅԽՌՊՁԻ

ԹՋՋՍՅՈՌՁՇՆՋՋՇՌՀԽՑՏԽՊԽ ԹՆԹՄՑՒԽԼ ՍՋՁՆԿՌՀԽ ՆՇՆՈԹՊԹՅԽՌՊՁԻԪԹՆՆ ԴՀՁՌՆԽՑԲՌԽՋՌԣԽԻՍՆԼՁՌՑ ԹՆԼ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԾԽՅԹՄԽ ԳԱԤ ԼԹՌԹ ԽՐՀՁԺՁՌԽԼ Թ ՅՇՆՇՌՇՆՁԻԹՄՄՑԼԽԻՊԽԹՋՁՆԿ ՌՊԽՆԼ ԹՆԼ  ՌՀԽՋԽ ԼԹՌԹ ՋԹՌՁՋԾՁԽԼ ՈԹՊԹՅԽՌՊՁԻ

ԹՋՋՍՅՈՌՁՇՆՋ ՌՀԽՑ ՏԽՊԽ ԹՆԹՄՑՒԽԼ ՍՋՁՆԿ ՌՀԽ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ Ռ ԽՋՌ ԣԽՊՌՁՄՁՒԹՌՁՇՆ ՋՍԻԻԽՋՋ ԼԹՌԹ

ԽՐՀՁԺՁՌԽԼ Թ ՅՇՆՇՌՇՆՁԻԹՄՄՑԼԽԻՊԽԹՋՁՆԿ ՌՊԽՆԼ ԺՍՌ ՌՀԽՋԽ ԼԹՌԹ ԼՁԼ ՆՇՌ ՋԹՌՁՋԾՑ ՈԹՊԹՅԽՌՊՁԻ ԹՋՋՍՅՈՌՁՇՆՋ

ՌՀԽՑՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԫՇՆԽՇԾ ՌՀԽՋՍՊՎՁՎՁՆԿԾԽՅԹՄԽՋՏԽՊԽԾՇՍՆԼ

ՌՇ ՀԹՎԽ ՌՍԺԽՊԻՄԽՋ  ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՁՆԼՁԻԹՌԽԼ ԽԾԾԽԻՌՋ ՏԽՊԽ ԻՇ ՆՋՁԼԽՊԽԼ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌ ԹՌ

Ո ԱՀԽՋԽ ԹՆԹՄՑՋԽՋ ՏԽՊԽ ԻՇՆԼՍԻՌԽԼ ՍՋՁՆԿ ԠԢԱԦ԰ ՎԽՊՋՁՇՆ  ԹՆԼ ԺԹԻՃԽՆԼ ՋԽՌՌՁՆԿՋ

ԹՈՈՊՇՎԽԼ ԾՇՊ ՍՋԽ ԺՑ ԢԣԢԡ ՇՆ  ԱՊԽԹՌԽԼ ԿՊՇՍՈՋ ՏԽՊԽ ԻՇՅՈԹՊ ԽԼ ՌՇ ՇՆՄՑ ՌՀԽ ՆԽԿԹՌՁՎԽ

ԻՇՆՌՊՇՄՆՇՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋ
Ո ՏԽՊԽԼԽՌԽԻՌԽԼԺԽՌՏ ԽԽՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ԿՊՇՍՈՋՍՋՁՆԿԹՌՏՇՋՁԼԽԼ԰ՌՍԼԽՆՌ0ՋՌՌԽՋՌԹՋՋՍՅՁՆԿԽՉՍԹՄՎԹՊՁԹՆ ԻԽՋԪԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ՏԽՊԽՍՋԽԼՌՇԼՁՋԻՍՋՋԽԾԾԽԻՌՋՁՆՌՀՁՋՋՌՍԼՑ

 ԠՇՆԻՄՍՋՁՇՆՋ

ԞԼՍՄՌ ՅԹՄԽ ԹՆԼ ԾԽՅԹՄԽ ՋՍՊՎՁՎԹՄ ՏԽՊԽ ՍՆԹԾԾԽԻՌԽԼ ԺՑ ՌՊԽԹՌՅԽՆՌ ՏՁՌ Հ ԱԠԳԭ ՋՍՊՎՁՎԹՄ ՁՆ ԾԽՅԹՄԽՋ ԹՆԼ

ՅԹՄԽՋՏԹՋԾՇՊԹՄՄՌԽՋՌՄԽՎԽՄՋՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆ ՇԾՋ ՍՊՎՁՎԹՄՇԾՅԹՄԽՋԹՌՌՀԽՅԿ

ԹՁԩՄԽՎԽՄ

ԱՀԽՊԽ ՏԹՋ Թ ՋՁԿՆՁԾՁԻԹՆՌ ՊԽԼՍԻՌՁՇՆ ԹՌ ՌՀԽ  ՅԿ ԹՁԩ ՌՊԽԹՌՅԽ ՆՌ ՄԽՎԽՄ ՁՆ ԾԽԻՍՆԼՁՌՑ ԹՆԼ ԾԽՊՌՁՄՁՌՑ

ԻՇՅՈԹՊԽԼ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ ՇԾ  ԹՆԼ  ՊԽՋՈԽԻՌՁՎԽՄ Ց 
Ո ԧՇՆԻՃՀԽԽՊԽ  ԱՀԽՊԽ

ՏԹՋ ԹՄՋՇ Թ ՋՁԿՆՁԾՁԻԹՆՌ ԼԽԻՊԽԹՋԽ ՁՆ ԾԽՅԹՄԽ ԳԱԤ ԹՌ ՌՀԽ  ՅԿ Թ Ձԩ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ ՇԾ 

ԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ՈԧՇՆԻՃՀԽԽՊԽԱՀԽՊԽՏ ԽՊԽՆՇՇՌՀԽՊՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋ

ԺԽՌՏԽԽՆՌՀԽՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄՋ ԹՆԼ ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԾՇՊ ԹՆՑ ՇՌՀԽՊ  ԽՆԼՈՇՁՆՌ ԱՀԽՊԽՏԽՊԽ ՆՇ ՆՇՌԹԺՄԽ

ԼՁԾԾԽՊԽՆԻԽՋ ՁՆ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ ՋԽՎԽՊՁՌՑ ՋԻՇՊԽՋ ՇՊ ԿՇՆԹԼԹՄ ՋՌԹԿԽՋ  ՁՆ ՌՊԽԹՌԽԼ ԿՊՇՍՈՋ ԻՇՅՈԹՊԽԼ ՌՇ ՌՀԽ

ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄՋ  ԱՀԽՊԽ ՏԽՊԽ ՆՇ ՆՇՌԹԺՄԽ ՇԺՋԽՊՎԹՌՁՇՆՋ ՏՁՌՀ ՊԽԿ ԹՊԼՋ ՌՇ ԺԽՀԹՎՁՇՊ ՇՊ ԻՀԹՆԿԽՋ ՁՆ

ԹՈՈԽԹՊԹՆԻԽ ՋՈԽԻՁԾՁԻԹՄՄՑ ԻՇՄՇՊԺԹՆԼՁՆԿ ՇՎՁՈՇՋՁՌՇՊ ԹՈՈԽԹՊԹՆԻԽ ՇՊ ՋՁՒԽ ՇԾ ԼՇՊՋԹՄ ՆԹՈԽ ՈԹԼ ՁՆ ՌՀԽ

ԻՇՆՌՊՇՄ ՇՊ ՌՊԽԹՌԽԼ ԿՊՇՍՈՋ ՇՊ ԻՄՁՆՁԻԹՄ ՋՁԿՆՋ ՇԾ ՌՇՐՁԻՁՌՑ ԾՇՊ ԹՆՑ  ՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈ ԻՇՅՈԹՊԽԼ ՌՇ ՌՀԽ

ԻՇՆՌՊՇՄՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԱԠԳԭԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԱՍԺԽՊԻՄԽ԰ԻՇՊԽԤ԰ԦԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿԹՆԼԥՁՋՌՇԭՄԹՋՅԹԳԱԤԭՄԹՋՅԹԱԭՄԹՋՅԹԢԪԽԼՁԹՆՈԡՁԾԾՈԢԾԾԽԻՌ!ԶԽՋԫՇԡՁԾԾԭԡՁԾԾՈԡՁԾԾՈԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԩԬԮ  ԫԞ ԫԞԫՇ ԫԞԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ     ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌԡՍՆՆԽՌՌ0ՋԡՍՆՆԽՌՌ0ՋԫԞ ԪԹՆՆԴՀՁՌՆԽՑԲ ԫԞԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԠՇՆԻԠՇՆԻԽՆՌՊԹՌՁՇՆԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՁՆԼՁԻԹՌԽԼ ԽԾԾԽԻՌՋ ԹՆԼ ՈԽՊԻԽՆՌ 
 ԼՁԾԾԽՊԽՆԻԽՋ ԹՊԽ ՊԽՈՇՊՌԽԼ ԺԹՋԽԼ ՇՆ ԻՇՅՈԹՊՁՋՇՆ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ 
ԻՄԽԹՆ ՏԹՌԽՊ ԻՇՆՌՊՇՄ  ԠՇՆԻՄՍՋՁՇՆՋ ՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԞՄՌՀՇՍԿՀ Թ ՆՇՆՈԹՊԹՅԽՌՊՁԻ ՌԽՋՌ ՏՇՍՄԼ ԺԽ ԹՈՈՊՇՈՊՁԹՌԽ ՌՇ ԹՋՋԽՋՋ ՅԽԼՁԹՆ ՎԹՄՍԽՋ ԾՇՊ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽ ՁՆ ՌՀՁՋ ԻԹՋԽ ՁՌ ՏՇՍՄԼ ՆՇՌ ԺԽ ԽՐՈԽԻՌԽԼ ՌՇ ՑՁԽՄԼ ԼՁԾԾԽՊԽՆՌ ՇՎԽՊԹՄՄԻՇՆԻՄՍՋՁՇՆՋԹՋԻՇՅՈԹՊԽԼՌՇԡՍՆՆԽՌՌ0ՋՌԽՋՌԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԱԠԳԭԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%ԣԽԻՍՆԼՁՌՑԣԽՊՌ԰ՍԻԻԽՋՋԱՍԺԽՊԻՄԽ԰ԻՇՊԽԤ԰ԦԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿԹՆԼԥՁՋՌՇԭՄԹՋՅԹԳԱԤԭՄԹՋՅԹԱԭՄԹՋՅԹԢԡՁԾԾՈԡՁԾԾԭԪԽԼՁԹՆՈԡՁԾԾՈԢԾԾԽԻՌ!ԶԽՋԫՇԡՁԾԾՈԡՁԾԾՈԡՁԾԾՈԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄԩԬԮ ԫԞ  ԫԞ  ԫԞ  ԫԞ ԫՇ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄԩԬԮ     ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ     ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ     ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ    ԫԞ   ԫՇ ԫԞ ԫԞ ԫԞ ԫԞ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌԧՇՆԻՃՀԽԽՊԽԧՇՆԻՃՀԽԽՊԽԫԞ ԡՍՆՆԽՌՌ0Ջ ԫԞ ԧՇՆԻՃՀԽԽՊԽ ԫԞ ԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԠՇՆԻԠՇՆԻԽՆՌՊԹՌՁՇՆԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՁՆԼՁԻԹՌԽԼ ԽԾԾԽԻՌՋ ԹՆԼ ՈԽՊԻԽՆՌ 
 ԼՁԾԾԽՊԽՆԻԽՋ ԹՊԽ ՊԽՈՇՊՌԽԼ ԺԹՋԽԼ ՇՆ ԻՇՅՈԹՊՁՋՇՆ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ 
ԻՄԽԹՆ ՏԹՌԽՊ ԻՇՆՌՊՇՄ  ԠՇՆԻՄՍՋՁՇՆՋ ՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈԩԬԮՅԿԹՁԩ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋ  ՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԣ԰ԱԯԞՏՁՌՀԱԠԳԭ

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ% ԟՇԼՑԴԽՁԿՀՌ ԩԽՆԿՌՀ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ ԪԹՄԽՋ ԣԽՅԹՄԽՋ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԫԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԩԬԮ  ԫԞ  ԫԞ  ԫԞ  ԫԞ

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ 
ԩԬԮ        

        

        

        

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԡՁԾԾ ԡՁԾԾԽՊԽՆԻԽ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ

  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽՊԽՈՇՊՌ ԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊ

ԻՇՆՌՊՇՄ

  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄ ՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌ#Ո%

 ԩԬԮՅԿԹՁԩ

Ԣ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

ԱՀԽՊԽՏԽՊԽՋՇՅԽՅՁՆՇՊԼԽՎՁԹՌՁՇՆՋԼԽՋԻՊՁԺԽԼՁՆ԰ԽԻՌՁՇՆԦԪԹՌԽՊՁ ԹՄՋԹՆԼԪԽՌՀՇԼՋՇԾՌՀՁՋԡԢԯՊԽԿԹՊԼՁՆԿ

ԾԹՁՄՍՊԽՌՇՊԽՈՇՊՌԻԽՊՌԹՁՆՏԹՌԽՊԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼՅԽԽՌԽՆՎՁՊՇ ՆՅԽՆՌԹՄԻՊՁՌԽՊՁԹ

• ԱՀԽՍՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹԹՆԼՊԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽՁՆՌՀԽՌԽՋՌՏԹՌԽՊՏ ԽՊԽՆՇՌՊԽՈՇՊՌԽԼԱՀԽԬԠ԰ԭԭ

ՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԽՋՌԹԺՄՁՋՀՅԹՐՁՅՍՅՄԽՎԽՄՋԾՇՊՌՀԽՋ ԽՎԹՄՍԽՋԹՆԼՁՌՁՋՍՆԻՄԽԹՊՁԾՌՀԽ

ՅԹՐՁՅՍՅՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՏԽՊԽԽՐԻԽԽԼԽԼ

• ԱՀԽ ՄՁԿՀՌ ՁՆՌԽՆՋՁՌՑ ՏԹՋ ՊԽՈՇՊՌԽԼ ՌՇ ՊԹՆԿԽ ԾՊՇՅ  ՌՇ  ՄՍՐ ԼՍՊՁՆԿ ԽՐՈՇՋՍՊԽ ԬԠ԰ԭԭ

 ԿՍՁԼԽՄՁՆԽ ՊԽՉՍՁՊԽՅԽՆՌՋ ՊԽԻՇՅՅԽՆԼ ՄՁԿՀՌ ՁՆՌԽՆՋՁՌՑ ՇԾ   -  ՄՍՐ 
ԹՌ ՏԹՌԽՊ0Ջ

ՋՍՊԾԹԻԽ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ • ԦՆԼՁՎՁԼՍԹՄ ԾՁՋՀ ՏԽՁԿՀՌՋ ԹՌ ՋՌՍԼՑ ՁՆՁՌՁԹՌՁՇՆ ՏԽՊԽ չ  ՌՀԽ ԽՋՌՁ ՅԹՌԽԼ ՅԽԹՆՋ ԾՇՊ ՅԹՄԽՋ ԹՆԼ

ԾԽՅԹՄԽՋԢԭԞ ՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՍԺՋԹՅՈՄԽՇԾԾՁՋՀՏԽՁԿՀԽԼԺԽԾՇ ՊԽՌՀԽՌԽՋՌԺԽՏՁՌՀՁՆչ

ՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԾՇՊԽԹԻՀՋԽՐ

   ԱՀԽՊԽՅԹՁՆՁՆԿՎԹՄՁԼՁՌՑ ԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԾՇՊԬԠ԰ԭԭՏԽՊԽՅԽՌ

ԣԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋ

ԱՀԽՊԽՎՁԽՏԽՊ0ՋԹՆԼՌՀԽՋՌՍԼՑԹՍՌՀՇՊՋ0ՊԽՋՍՄՌՋՏԽՊԽՁՆԹԿՊԽԽՅԽՆՌ ԟՇՌՀՌՀԽՋՌՍԼՑԹՍՌՀՇՊ0ՋԹՆԼՊԽՎՁԽՏԽՊ0Ջ

ԹՆԹՄՑՋՁՋԼԽՌԽԻՌԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻՌՁՇՆՋ
Ո ՁՆԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՌՑԹՆԼԾԽՅԹՄԽԳԱԤԹՌՌՀԽ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄԻՇՅՈԹՊԽԼՌՇՌՀԽԻՇՆՌՊՇՄԫՇՇՌՀ ԽՊՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽ

ՆՇՌԽԼԾՇՊՌՀԽՇՌՀԽՊԽՆԼՈՇՁՆՌՋԱՀԽՊԽՎՁԽՏԽՊ0ՋԻՇՆԻՄՍՋՁՇՆՋԺԹՋԽ ԼՇՆՌՀԽԬԠ԰ԭԭԾՄՇՏԻՀԹՊՌԹՊԽ

ՈՊԽՋԽՆՌԽԼՁՆՌՀԽԢՐԽԻՍՌՁՎԽ԰ՍՅՅԹՊՑԹՆԼԠՇՆԻՄՍՋՁՇՆՋՋԽԻՌՁՇՆՋՇԾ ՌՀՁՋԡԢԯ

ԱՀԽ ՊԹՆԿԽԾՁՆԼԽՊ ՏԹՋ ԻՇՆԼՍԻՌԽԼ ՍՋՁՆԿ Թ ՋՇՄՎԽՆՌ ԹՆԼ Թ ՏՀՁՌԽ ՈՊԽԻ ՁՈՁՌԹՌԽ ՏԹՋ ՆՇՌԽԼ ՁՆ ՌՀԽ ՅՁՐՁՆԿ

ԻՀԹՅԺԽՊԹՌՅԿԹՁԩԞՆԹՄՑՌՁԻԹՄ ՊԽԻՇՎԽՊՁԽՋ ՊԹՆԿԽԼԾՊՇՅ ՌՇՇԾՆՇՅՁՆԹՄԭՊԽՄՁՅՁՆԹՊՑՌՊՁԹՄՋ

ՏԽՊԽԻՇՆԼՍԻՌԽԼՌՇԼԽՌԽՊՅՁՆԽՁԾՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՋԻՇՍՄԼԺԽԼԽՄՁ ՎԽՊԽԼՏՁՌՀՇՍՌՋՇՄՎԽՆՌՀՇՏԽՎԽՊԼՍԽՌՇՌՀԽ

ՁՅՈՊԹԻՌՁԻԹՄՁՌՑ ՇԾ ՈՊԽՈԹՊՁՆԿ ՋՌՇԻՃ ՋՇՄՍՌՁՇՆ ՁՆՏԹՌԽՊ ԹՌ Թ ՀՁԿՀ Խ ՆՇՍԿՀ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՌՇ ԹԻՀՁԽՎԽ  ՅԿ

ԹՁԩ ՁՆ ՌՀԽ ԾՄՇՏՌՀՊՇՍԿՀ ՋՑՋՌԽՅ ՌՀԽ ՋՌՇԻՃ ՋՇՄՍՌՁՇՆՋ ՍՋԽԼ ՁՆ ՌՀԽ ԼԽԾՁՆՁՌՁՎԽ ՌԽՋՌ ՏԽՊԽ ՈՊԽՈԹՊԽԼ ՁՆ

ԼՁՅԽՌՀՑՄԾՇՊՅԹՅՁԼԽ
ԡԪԣ

ԦԦԦ ԯԢԣԢԯԢԫԠԢ԰

Բ԰ ԢՆՎՁՊՇՆՅԽՆՌԹՄ ԭՊՇՌԽԻՌՁՇՆ ԞԿԽՆԻՑ  ԰ԽՊՁԽՋ ԢՆԼՇԻՊՁՆԽ ԡՁՋՊՍՈՌՇՊ ԰ԻՊԽԽՆՁՆԿ ԭՊՇԿՊԹՅ

ԱԽՋՌԤՍՁԼԽՄՁՆԽՋԬԠ԰ԭԭԫՍՅԺԽՊԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍ ԻՌՁՇՆԞՋՋԹՑ

ԬՊԿԹՆՁՒԹՌՁՇՆ ԾՇՊ ԢԻՇՆՇՅՁԻ ԠՇՇՈԽՊԹՌՁՇՆ ԹՆԼ ԡԽՎԽՄՇՈՅԽՆՌ  ԬԢ Ԡԡ ԤՍՁԼԽՄՁՆԽՋ ԾՇՊ ԱԽՋՌՁՆԿ ՇԾ

ԠՀԽՅՁԻԹՄՋԤՍՁԼԽՄՁՆԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑԞ ԼՇՈՌԽԼ԰ԽՈՌԽՅԺԽՊ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀ

ԱԽՌՊԹԻՀՄՇՊՎՁՆՈՀՇՋ
ԱԠԳԭ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ ԞԭԥԞԞԴԴԞԴԢԣ԰ՌԹՆԼԹՊԼԪԽՌՀՇԼՋԾՇՊՌՀԽԢՐԹՅՁՆԹՌՁՇՆՇԾ ԴԹՌԽՊԹՆԼԴԹՋՌԽՏԹՌԽՊՌՀ

ԢԼՁՌՁՇՆԞՅԽՊՁԻԹՆԭՍԺՄՁԻԥԽԹՄՌՀԞՋՋՇԻՁԹՌՁՇՆԞՅԽՊՁԻԹՆԴԹՌԽՊԴՇՊ ՃՋԞՋՋՇԻՁԹՌՁՇՆԴԹՌԽՊԢՆՎՁՊՇՆՅԽՆՌ

ԣԽԼԽՊԹՌՁՇՆԴԹՋՀՁՆԿՌՇՆԡԠ

ԬՊԿԹՆՁՒԹՌՁՇՆ ԾՇՊ ԢԻՇՆՇՅՁԻ ԠՇՇՈԽՊԹՌՁՇՆ ԹՆԼ ԡԽՎԽՄՇՈՅԽՆՌ  ԠՍՊՊԽՆՌ ԞՈՈՊՇԹԻՀԽՋ ՁՆ ՌՀԽ

԰ՌԹՌՁՋՌՁԻԹՄ ԞՆԹՄՑՋՁՋ ՇԾ ԢԻՇՌՇՐՁԻՁՌՑ ԡԹՌԹ Ԟ ԤՍՁԼԹՆԻԽ ՌՇ ԞՈՈՄՁԻԹ ՌՁՇՆ ԬԢԠԡ

ԢԫԳԧԪԪԬԫԬ


ԱՀԽ԰Ԟ԰԰ՑՋՌԽՅԾՇՊԴՁՆԼՇՏՋԳԽՊՋՁՇՆ԰Ԟ԰ԦՆՋՌՁ ՌՍՌԽԦՆԻԠԹՊՑԫՇՊՌՀԠԹՊՇՄՁՆԹ

### CETIS Summary Report Report Date: 18 Mar-13 13:28 (p 1 of 1)

Test Code: 083702 48838201 | 01-6831-5405

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Batch ID: 20-5322-7121

Start Date: 13 Sep-11
Ending Date: 19 Oct-11 Test Type: EDSP FSTRA Tier 1

Duration: 36d 0h Protocol: OCSPP 890.1350 Tier I FSTRA Diluent: Well Water

Brine: Not Applicable Species: Pimephales promelas

Source: Osage Catfisheries, Osage Beach, MI Analyst:

Age: 5mo

Sample ID: 00-1835-0742 Sample Date: 13 Sep-11

Receive Date: 19 Oct-11 Code: 48838201

Sample Age: NA Source: TCVP Task Force c/o SRA Intl, Inc.

Station: Client: CDM Smith
Project: Insecticide Material: Tetrachlorvinphos (#961-11-5)

083702 48838201

083702 48838201 Batch Note:
Sample Note:

Comparison Summary

NOEL LOEL TOEL Endpoint Analysis ID Method PMSD TU

0 >0 13-1921-5189 Equal Variance t Two-Sample Test 26.1% MaleMedianTubercleScore

0.57 >0.57 NA 14-1552-8224 Dunnett Multiple Comparison Test 36.6% MaleMedianTubercleScore

Control Type Mean Min Max Std Dev Count CV% Std Err C-mg ai/L MaleMedianTubercleScore Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 20.4 17 25 3.5 4 17.2% 1.75 14.8 25.9 0.0%

0 Negative Control 21.4 18 25 2.93 4 13.7% 1.46 16.7 26 -4.91%

0.006 25.1 18.5 32.5 6.02 4 24.0% 3.01 15.5 34.7 -23.3%

0.055 19.5 16 22.5 2.86 4 14.7% 1.43 15 24 4.29%

0.57 23.8 19 28 3.88 4 16.4% 1.94 17.6 29.9 -16.6%

Control Type C-mg ai/L MaleMedianTubercleScore Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 17 21 25 18.5

0 Negative Control 18 20.5 25 22

0.006 32.5 18.5 27 22.5

0.055 22.5 16 18.5 21

0.57 19 22.5 28 25.5

CETISTM v1.8.7.4 000-503-186-3 QA:________ Analyst:________

### CETIS Summary Report Report Date: 05 Mar-13 14:35 (p 1 of 5)

Test Code: 083702 48838201 | 20-5135-7040

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Batch ID: 09-8173-2666

Start Date: 13 Sep-11
Ending Date: Test Type: EDSP FSTRA Tier 1

Duration: NA Protocol: OCSPP 890.1350 Tier I FSTRA Diluent:

Brine: Species: Pimephales promelas

Source: Osage Catfisheries, Osage Beach, MI Analyst:

Age:

Sample ID: 09-5521-0244 Sample Date: 13 Sep-11

Receive Date: Code: 48838201

Sample Age: NA Source: Tetrachlorvinphos Task Force c/o SRA Inter

Station: Client: CDMSmith
Project: Material: Tetrachlorvinphos (#961-11-5)

TCVP, 98.7%, continuous flow-through
TCVP, 98.7%, continuous flow-through, 083702 Batch Note:
Sample Note:

Comparison Summary

NOEL LOEL TOEL Endpoint Analysis ID Method PMSD TU

0 >0 07-6304-9958 Equal Variance t Two-Sample Test 32.4% Fecundity

0.055 0.57 0.1771 05-9773-6663 Jonckheere-Terpstra Step-Down Test NA Fecundity

0.055 0.57 0.1771 17-4754-6361 Dunnett Multiple Comparison Test 28.1% Fecundity

0 >0 11-4179-8296 Equal Variance t Two-Sample Test 13.0% FemaleBodyWt

0.57 >0.57 NA 17-5834-2739 Jonckheere-Terpstra Step-Down Test NA FemaleBodyWt

0.57 >0.57 NA 16-1728-7098 Dunnett Multiple Comparison Test 13.1% FemaleBodyWt

0 >0 05-0252-3123 Equal Variance t Two-Sample Test 18.6% FemaleGSI

0.57 >0.57 NA 15-7829-9169 Dunnett Multiple Comparison Test 23.4% FemaleGSI

0 >0 00-6459-7368 Equal Variance t Two-Sample Test 3.26% FemaleLength

0.57 >0.57 NA 13-9141-8861 Dunnett Multiple Comparison Test 3.05% FemaleLength

0 >0 10-6993-6392 Equal Variance t Two-Sample Test 27.9% FemaleVTG

0.055 0.57 0.1771 01-8759-1834 Jonckheere-Terpstra Step-Down Test NA FemaleVTG

0.57 >0.57 NA 03-0499-0230 Dunnett Multiple Comparison Test 36.2% FemaleVTG

0 >0 16-2325-0042 Equal Variance t Two-Sample Test 1.74% Fertility

0.055 0.57 0.1771 20-0294-5573 Jonckheere-Terpstra Step-Down Test NA Fertility

0.055 0.57 0.1771 20-2783-7361 Mann-Whitney U Two-Sample Test 7.88% Fertility

0 >0 13-5583-0568 Equal Variance t Two-Sample Test 18.5% MaleBodyWt

0.57 >0.57 NA 15-5808-2690 Jonckheere-Terpstra Step-Down Test NA MaleBodyWt

0.57 >0.57 NA 00-1968-9681 Dunnett Multiple Comparison Test 17.3% MaleBodyWt

0 >0 02-8944-9180 Equal Variance t Two-Sample Test 25.8% MaleGSI

0.57 >0.57 NA 09-1868-6263 Dunnett Multiple Comparison Test 31.1% MaleGSI

0 >0 19-8012-0331 Equal Variance t Two-Sample Test 5.21% MaleLength

0.57 >0.57 NA 17-6084-4440 Dunnett Multiple Comparison Test 4.91% MaleLength

0 >0 13-2354-2119 Equal Variance t Two-Sample Test 286.0% MaleVTG

0.57 >0.57 NA 07-4245-1728 Jonckheere-Terpstra Step-Down Test NA MaleVTG

0.57 >0.57 NA 06-0627-9472 Mann-Whitney U Two-Sample Test 159.0% MaleVTG

CETISTM v1.8.7.4 000-503-186-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 05 Mar-13 14:35 (p 2 of 5)

Test Code: 083702 48838201 | 20-5135-7040

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type Mean Min Max Std Dev Count CV% Std Err Group Fecundity Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 24.5 18 31.5 5.58 4 22.7% 2.79 15.6 33.4 0.0%

0 Negative Control 26.6 20.4 29.8 4.31 4 16.2% 2.15 19.7 33.5 -8.46%

0.006 28.3 26.8 31.7 2.31 4 8.19% 1.16 24.6 31.9 -15.2%

0.055 20.8 12.6 30.8 7.53 4 36.2% 3.77 8.84 32.8 15.1%

0.57 10.3 7.9 13.3 2.27 4 22.1% 1.13 6.67 13.9 58.1%

Control Type Mean Min Max Std Dev Count CV% Std Err Group FemaleBodyWt Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 1.25 1.16 1.37 0.0998 4 7.97% 0.0499 1.09 1.41 0.0%

0 Negative Control 1.2 1.11 1.3 0.0785 4 6.55% 0.0392 1.07 1.32 4.39%

0.006 1.34 1.21 1.49 0.123 4 9.18% 0.0613 1.14 1.53 -6.59%

0.055 1.29 1.14 1.4 0.113 4 8.74% 0.0565 1.11 1.47 -3.19%

0.57 1.23 1.2 1.32 0.0585 4 4.75% 0.0293 1.14 1.33 1.6%

Control Type Mean Min Max Std Dev Count CV% Std Err Group FemaleGSI Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 15.9 14.5 17.4 1.19 4 7.49% 0.596 14 17.8 0.0%

0 Negative Control 14 12.2 16.4 1.76 4 12.6% 0.88 11.2 16.8 12.1%

0.006 14.6 12.5 15.7 1.49 4 10.2% 0.743 12.3 17 8.02%

0.055 16.7 12.9 19.8 2.92 4 17.5% 1.46 12 21.3 -4.87%

0.57 15.3 13.5 17.1 1.61 4 10.5% 0.804 12.7 17.9 3.77%

Control Type Mean Min Max Std Dev Count CV% Std Err Group FemaleLength Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 48 47 49 0.816 4 1.7% 0.408 46.7 49.3 0.0%

0 Negative Control 47.3 46 48 0.957 4 2.03% 0.479 45.7 48.8 1.56%

0.006 48.8 48 50 0.957 4 1.96% 0.479 47.2 50.3 -1.56%

0.055 48 47 49 0.816 4 1.7% 0.408 46.7 49.3 0.0%

0.57 47 46 48 0.816 4 1.74% 0.408 45.7 48.3 2.08%

Control Type Mean Min Max Std Dev Count CV% Std Err Group FemaleVTG Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 1.97E+6 1.56E+6 2.44E+6 3.62E+5 4 18.4% 1.81E+5 1.39E+6 2.54E+6 0.0%

0 Negative Control 1.79E+6 1.58E+6 2.03E+6 1.89E+5 4 10.6% 9.44E+4 1.49E+6 2.09E+6 9.2%

0.006 1.62E+6 1.05E+6 2.33E+6 5.36E+5 4 33.0% 2.68E+5 7.71E+5 2.48E+6 17.5%

0.055 1.34E+6 1.00E+6 2.07E+6 4.96E+5 4 37.1% 2.48E+5 5.48E+5 2.13E+6 32.1%

0.57 1.25E+6 9.91E+5 1.63E+6 2.70E+5 4 21.6% 1.35E+5 8.22E+5 1.68E+6 36.4%

Control Type Mean Min Max Std Dev Count CV% Std Err Group Fertility Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 98.1 97.1 98.5 0.64 4 0.65% 0.32 97 99.1 0.0%

0 Negative Control 98.6 96.8 99.5 1.24 4 1.26% 0.622 96.7 101 -0.61%

0.006 98.5 97.7 99.1 0.589 4 0.6% 0.294 97.6 99.4 -0.46%

0.055 98.4 96.8 99.7 1.45 4 1.48% 0.726 96.1 101 -0.38%

0.57 89.6 73 96.7 11.1 4 12.4% 5.57 71.9 107 8.59%

Control Type Mean Min Max Std Dev Count CV% Std Err Group MaleBodyWt Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 2.54 2.08 2.77 0.325 4 12.8% 0.163 2.03 3.06 0.0%

0 Negative Control 2.59 2.41 2.89 0.218 4 8.42% 0.109 2.25 2.94 -1.87%

0.006 2.65 2.5 3 0.238 4 8.98% 0.119 2.27 3.03 -4.13%

0.055 2.65 2.3 3.1 0.342 4 12.9% 0.171 2.11 3.19 -4.13%

0.57 2.4 2 2.7 0.294 4 12.3% 0.147 1.93 2.87 5.7%

CETISTM v1.8.7.4 000-503-186-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 05 Mar-13 14:35 (p 3 of 5)

Test Code: 083702 48838201 | 20-5135-7040

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type Mean Min Max Std Dev Count CV% Std Err Group MaleGSI Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 1.75 1.51 2.03 0.25 4 14.2% 0.125 1.36 2.15 0.0%

0 Negative Control 1.78 1.43 2.11 0.281 4 15.7% 0.141 1.34 2.23 -1.71%

0.006 1.69 1.19 1.91 0.335 4 19.9% 0.168 1.15 2.22 3.99%

0.055 1.95 1.56 2.24 0.286 4 14.6% 0.143 1.5 2.41 -11.4%

0.57 1.88 1.39 2.34 0.445 4 23.6% 0.222 1.18 2.59 -7.41%

Control Type Mean Min Max Std Dev Count CV% Std Err Group MaleLength Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 57.5 55 60 2.38 4 4.14% 1.19 53.7 61.3 0.0%

0 Negative Control 57.5 57 58 0.577 4 1.0% 0.289 56.6 58.4 0.0%

0.006 59.3 58 60 0.957 4 1.62% 0.479 57.7 60.8 -3.04%

0.055 58 56 60 1.63 4 2.82% 0.816 55.4 60.6 -0.87%

0.57 58.3 54 60 2.87 4 4.93% 1.44 53.7 62.8 -1.3%

Control Type Mean Min Max Std Dev Count CV% Std Err Group MaleVTG Summary

95% LCL 95% UCL %Effect

0 Solvent Blank 420 20 1500 721 4 172.0% 360 -727 1570 0.0%

0 Negative Control 450 20 1600 767 4 171.0% 384 -771 1670 -7.14%

0.006 343 70 970 421 4 123.0% 210 -327 1010 18.5%

0.055 480 80 1300 559 4 116.0% 279 -409 1370 -14.3%

0.57 94.8 37 160 50.9 4 53.8% 25.5 13.7 176 77.4%

CETISTM v1.8.7.4 000-503-186-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 05 Mar-13 14:35 (p 4 of 5)

Test Code: 083702 48838201 | 20-5135-7040

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type Group Fecundity Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 23.3 25.3 31.5 18

0 Negative Control 27 20.4 29.8 29.2

0.006 26.8 27.1 31.7 27.4

0.055 30.8 19.1 20.8 12.6

0.57 10.4 7.9 9.5 13.3

Control Type Group FemaleBodyWt Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 1.16 1.37 1.18 1.3

0 Negative Control 1.2 1.3 1.18 1.11

0.006 1.21 1.27 1.37 1.49

0.055 1.14 1.28 1.35 1.4

0.57 1.32 1.21 1.2 1.2

Control Type Group FemaleGSI Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 15.7 17.4 16 14.5

0 Negative Control 13.5 16.4 12.2 13.8

0.006 14.7 12.5 15.7 15.6

0.055 12.9 19.8 16.2 17.8

0.57 17.1 14.5 13.5 16.1

Control Type Group FemaleLength Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 48 49 47 48

0 Negative Control 47 48 48 46

0.006 48 48 49 50

0.055 47 48 48 49

0.57 48 47 47 46

Control Type Group FemaleVTG Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 1.98E+6 1.91E+6 1.56E+6 2.44E+6

0 Negative Control 1.58E+6 1.74E+6 1.80E+6 2.03E+6

0.006 2.33E+6 1.05E+6 1.44E+6 1.67E+6

0.055 2.07E+6 1.00E+6 1.06E+6 1.22E+6

0.57 1.63E+6 9.91E+5 1.21E+6 1.17E+6

Control Type Group Fertility Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 97.1 98.3 98.5 98.3

0 Negative Control 99.2 96.8 99.1 99.5

0.006 98.7 98.5 99.1 97.7

0.055 96.8 97.6 99.7 99.6

0.57 73 94.1 96.7 94.7

Control Type Group MaleBodyWt Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 2.08 2.77 2.56 2.77

0 Negative Control 2.45 2.41 2.89 2.62

0.006 3 2.5 2.5 2.6

0.055 3.1 2.3 2.5 2.7

0.57 2.5 2 2.7 2.4

CETISTM v1.8.7.4 000-503-186-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 05 Mar-13 14:35 (p 5 of 5)

Test Code: 083702 48838201 | 20-5135-7040

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type Group MaleGSI Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 1.51 1.9 1.58 2.03

0 Negative Control 1.43 1.75 1.85 2.11

0.006 1.91 1.19 1.87 1.77

0.055 1.56 2.04 1.98 2.24

0.57 2.34 1.64 2.17 1.39

Control Type Group MaleLength Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 55 60 56 59

0 Negative Control 57 57 58 58

0.006 60 59 58 60

0.055 60 56 58 58

0.57 60 54 59 60

Control Type Group MaleVTG Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Solvent Blank 70 20 90 1500

0 Negative Control 100 20 80 1600

0.006 970 170 160 70

0.055 360 80 180 1300

0.57 160 100 82 37

CETISTM v1.8.7.4 000-503-186-1 QA:________ Analyst:________

# DATA EVALUATION RECORD

TETRACHLORVINPHOS (TCVP)

Study Type: OCSPP 890.1400, In vivo Hershberger Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-32-2012 (MRID 48946701)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer Signature: Rebecca L. Bryan, B.S. Date: 11/13/2012

Secondary Reviewer Signature: Michael E. Viana, Ph.D., D.A.B.T. Date: 11/14/2012

Program Manager: Signature: Jack D. Early, M.S. Date: 12/11/2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 12/11/2012

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screenin g Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).

# . ..

TETRACHLORVINPHOS (TCVP} I 083701



### Primary Reviewer: Linda Taylor, Ph.D.


### Health Effects Division Secondary Reviewer: Greg Akerman, Ph.D.


### Health Effects Division In vivo Hershberger Assay (2012)/ Page 1 of 14
OCSPP 890.1400/0ECD 441

# S'.gna:**~ S1gnatu** **~ ~** 

.....

# --'-"**~~ ..,,_.-~~-** **=-=---** Date:**~1/1** 

## her
Template version 10/2011



### DAT A EVALUATION RECORD

STUDY TYPE: 

## In Vivo Hershberger Assay (Rat); OCSPP 890.1400; OECD 441



### PC CODE: 083702 

### DP BARCODE: D406501



### TXR#: 0056284 

### CAS#: 22248- 79-9



### TEST MATERIAL (PURITY): Tetrachlorvinphos (100.05% a.i.)



### SYNONYMS: 2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate (Z-isomer); TCVP



### CITATION: Boulet, 

### J. (2012) Hershberger Bioassay in Rats: A Short-Term Screening Assay
for Androgenic and Anti-Androgenic Properties ofTetrachlorvinphos. Product Safety Labs, Dayton, NJ. Laboratory Report No.: 33549, August 31, 2012.

MRlD 48946701. Unpublished.



### SPONSOR: The Tetrachlorvinphos (TCVP) Task Force, c/o 

### SRA International Inc., 5235 Ragged Point Road, Cambridge, MD



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In a Hershberger assay (MRlD 48946701) screening for androgenic activity, tetrachlorvinphos (TCVP, 100.05% a.i., Lot# TX 10113) in aqueous 0.1% (w/v) methylcellulose was administered daily by oral gavage to groups of 57-day old, castrated
male Sprague Dawley (Crl:CD[SD]) rats (6/group) at dose levels of 0 (vehicle), 50, 150, or 350 mg/kg/day. The androgenic assay included a positive control group consisting of six
castrated rats exposed to 0.4 mg/kg/day of testosterone propionate (TP) by subcutaneous (s.c.) injection.

To screen for potential anti-androgenic activity, TCVP in aqueous 0.1 % (w/v) methylcellulose

was administered daily via oral gavage to 57-day old, castrated male Sprague Dawley rats (6/group) at dose levels of 50, 150, or 350 mg/kg/day in conjunction with a daily dose of
reference androgen TP at 0.4 mg/kg/day by s.c. injection. The control group for the antiandrogenic assay consisted of six castrated male rats dosed daily with TP (0.4 mg/kg/day) by s.c. injection, and the positive control group consisted of six castrated male rats dosed orally with
flutamide (FT) at 3 mg/kg/day in conjugation with a daily s.c. dose ofTP (0.4 mg/kg/day).

For both components of the assay, the animals were dosed for ten consecutive days and necropsied approximately 24 hours after the final dose administration to determine weights of
the five androgen-dependent tissues.In vivo Hershberger Assay (2012)/ Page 2 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### In the androgen agonist assa y, body weights and body weight gain s for each TCVP-treatment group were comparable to controls throughout the assay. Food consumption was initially decreased (p<0.05) by 8% for Days 1-3 in the 350 mg/kg/day group, but was then increased for Days 3-10. For Days 3-10, food consumption in the 150 mg/kg/day group was increased (p<0.001) by 10%. Overall food consumption on Days 1-10 was increased (p<0.001) by 27% in the 150 mg/kg/day group, and increased 3% in both the 50 and 350 mg/kg/day groups. No effects on food efficiency were observed for the TCVP treatment groups. For the positive control group (TP), food consumption was incr eased (p<0.01) by 11% and food efficiency was increased (p<0.01) by 50% for Days 1-10.

Liver weights in the agonist assay were increased by 6, 13 and 30% in the 50, 150, and 350 mg/kg/day group, respectively, but th e increase was only significant (p ≤ 0.01) at the highest dose. Adrenal gland weights we re also increased (p ≤ 0.01) by 39, 47, and 44% in the 50, 150, and 350 mg/kg/day groups, respectively. Except for a 32% increase (p ≤ 0.01) in the levator anibulbocavernosus (LABC) weight of the 50 mg/k g/day group, there were no significant changes in accessory sex organ weights of the TCVP-t reated groups. Animals in the TP group had increases (p ≤ 0.01) in unadjusted accessory sex organ weights as follows: 370% in ventral prostate, 295% in seminal vesicles, 179% in LA BC, 205% in Cowper’s gland, and 72% in glans penis.

In the anti-androgen assay, body weights for each TCVP-treated group were comparable to controls throughout the assay. At 350 mg/kg/day, there was a mean daily body weight loss (p ≤ 0.05) on Days 1-2 and body weight gains on Days 2-3 were decr eased (NS) by 46%, resulting in an overall reduction (Days 1-10) of 23% (NS) in body weight gains. In the 150 mg/kg/day group, body weight gains were decreased (p<0.05) on Days 2-3 but increased (p<0.05) on Days 6-7. Overall body weight gains (Days 1-10) fo r the 50 and 150 mg/kg/day groups were similar to controls. For the positive control group (TP + FT), overall mean daily body weight gains were decreased (p ≤ 0.05) by 14%. Food consumption in the 150 and 350 mg/kg/day groups were decreased (p<0.01) by 14-16% for Days 1-3. For Days 3-10, food consumption in the 50 mg/kg/day group was decreased (p<0.01) by 3%. Compared to the TP-c ontrol, overall food consumption (Days 1-10) was decreased (p<0.01) by 5% in the 350 mg/kg/day group, but there was no effect in the 50 and 150 mg/kg/day groups. For the positive control group (TP+FT), food consumption was increased (p<0.01) by 7-8%. Ther e was an initial decrea se (p<0.01) of 96% in food efficiency in the 350 mg/kg/day group, but ot herwise food efficiency in the TCVP-treated and positive control group were si milar to the TP control.

Liver weights in the anti-androge n assay were increased by 17% (p ≤ 0.05) at 350 mg/kg/day, but were comparable to the control at the two lower doses. There were no decreases in accessory sex organ weights of TCVP-treated animals. However, non-dose-dependent increases (p ≤ 0.01) in the following accessory sex organ weights were observed in all TCVP -treated groups: 85-139% in ventral prostate, 143-203% in seminal vesicl es, and 47-60% in the Cowper’s gland. In addition, there was a 24% increase (p ≤ 0.01) in LABC weights in the 50 mg/kg/day group. Animals dosed with FT + TP (positive control) had the following decreases in accessory sex organ weights: 61% in ventral prostate; 67 % in seminal vesicles; 44% in LABC; 56% in Cowper’s glands; and 27% in glans penis.In vivo Hershberger Assay (2012)/ Page 3 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### The high dose of TCVP selected for this study (350 mg/kg/day) was considered adequate based on decreased overall body weight gains and incr eased liver weights observed in the current

assay.

TCVP was negative for androgenic activity in the Hershberger assa y as statistically significant increases in organ weights were not seen in two or more of the fi ve androgen sensitive tissues in the androgen agonist assay. TCVP was also ne gative for anti-androgenicity in the Hershberger assay as no statistically significan t decreases in organ weights were seen in two or more of the five androgen sensitive tissues in the androgen antagonist assay. The biological significance of the increases in accessory sex organ weights of TCVP-treated rats in the anti-androgen assay is unclear. The accessory sex organ weight increase s were not dose dependent, and TCVP did not give a positive response in the agonist assay. However, the da ta suggest that TCVP may be affecting the metabolism of the testosterone, whic h would not have been evident in the agonist assay as the castrated rats were already testosterone de ficient. Testosterone concentrations were not determined in this assay.

The assay satisfies the EDSP Tier 1 Test Order requireme nts for a Hershberger assay (OCSPP 890.1400).

COMPLIANCE: Signed and dated GLP Compliance a nd Quality Assurance statements were provided.In vivo Hershberger Assay (2012)/ Page 4 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Product Safety Labs

Location: Dayton, New Jersey Study Director: J. Boulet
Other Personnel: J. John (Primary Scientist), D. Knox (Test Substance Analysis) Study Period: March 14, 2012 to August 31, 2012



### 2. Test Substance: Tetrachlorvinphos
Description: Off-white to tan powder
Source: The Hartz Mountain Corporation (Secaucus, NJ)
Lot #: TX 10113 (expiration date 6/16/12) Purity: 100.05% a.i. Stability: Stable for up to 14 days at ambient temperature
CAS #: 22248-79-9
Structure:



### P O O Cl

Cl Cl Cl O CH

3

O CH

3



### 3. Reference Androgen: Testosterone propionate (TP)
Supplier: Sigma-Aldrich (St. Louis, MO)
Lot #: 051M1803V (expires July 7, 2012) Purity: 102%
CAS # : 57-85-2



### 4. Reference Anti-androgen: Flutamide (FT)
Supplier: Sigma-Aldrich (St. Louis, MO)
Lot #: 019K1556V (expires July 7, 2012) Purity: >99%
CAS # : 13311-84-7



### 5. Solvent/Vehicle Control : Methylcellulose
Supplier: Sigma-Aldrich (St. Louis, MO)
Lot #: 021M0067 (expires August 9, 2014) Rationale (if other than water) : Not reported
Final concentration: 0.1% in reverse-osmo sis deionized waterIn vivo Hershberger Assay (2012)/ Page 5 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### 6. Test Animals:

Species: Rat (castrated males)

Strain: Sprague Dawley (Crl:CD[SD] IGS) Age/weight at dose initiation: Post-natal day (PND) 57; 211-269 g

Source: Charles River Laboratories (Stone Ridge, NY) Housing: Three per polycarbonate shoe box cage with Sani-Chips ® hardwood contact bedding and wire-mesh lids.

Diet: 2016C Harlan Teklad Global Rodent Diet ®

, ad libitum ; minimal phytoestrogen content (not specified).

Water: Deionized water , ad libitum

Environmental conditions: Temperature: Humidity: Air changes: Photoperiod: 19-22oC
40-57% Not reported 12 hrs light/12 hrs dark Acclimation period: Eight days



### B. STUDY DESIGN

1. In-life dates: Start: 3/22/2012 End: 4/2/2012

2. Study Design: This Hershberger Assay was conduc ted to screen for both potential androgenic and anti-androgenic activity. In the test for androgeni c activity, TCVP was administered daily via oral gavage to groups of castrated male rats. Positive androgenic activity is defined as a significant increase in tw o or more target organ weights compared to the vehicle control group. The positive cont rol group for androgenic activity consisted of castrated male rats dosed by s.c. injection with TP at 0.4 mg/kg/day. In the test for antiandrogenic activity, TCVP was admi nistered daily via oral gavage to groups of castrated male rats in conjunction with TP at 0.4 mg/kg/day by s.c. injection. Anti-androgenic activity is indicated by a statistically signifi cant decrease in two or more target organ weights of the treated groups (test substance + TP) compared to the TP-only control group. The positive control group for anti-androgenic activity consiste d of castrated male rats dosed by s.c. injection with TP (0.4 mg/kg/day) in conjunction with an oral dose of FT (3.0 mg/kg/day). For both assays, the animals were dosed for ten consecutive days and necropsied approximately 24 hours after the fi nal dose administration for measurement of target organ weights.

3. Study Schedule: Following the initial 8-day acclimati on period, castrated rats (surgical manipulation performed by the Supplier at PND 42) were administered the test substance
from PND 57 to PND 66. Rats were euth anized on PND 67, approximately 24 hours after the last dose and necropsied for organ weight measurements.

4. Animal Assignment: Animals were randomly assigned, stratified by body weight, to the test groups noted in Table 1. The body weight of each animal was within 20% of the overall mean on the day of randomization.In vivo Hershberger Assay (2012)/ Page 6 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441

TABLE 1. Study design a
Test group Dose (mg/kg/day) # of Males
Androgen Agonist Assay Vehicle control (negative control) 0 6 Low (TCVP) 50 6 Mid (TCVP) 150 6 High (TCVP) 350 6 Testosterone propionate (TP) (s.c.), positive control b 0.4 6 Anti-Androgen Assay 0.1% methycellulose + TP (vehicle control) b 0 + 0.4 6 Low (TCVP +TP) 50 + 0.4 6 Mid (TCVP +TP) 150 + 0.4 6 High (TCVP +TP) 350 + 0.4 6 Flutamide (oral gavage) + TP (s.c.), positive control 3 + 0.4 6 a Data were obtained from page 18 of the study report. b The positive control group for the androgen agonist was used as the vehicle control group for the anti-androgen assay. This did not affect the outcome or conclusions of this study.



### 5. Dose Selection Rationale: The dose levels were reportedl y selected in consultation with the Study Director and based on a preliminary range-finding study 1 

### ; however, no results of the range-finding study were provided.

6. (a) Dose Preparation: Dose formulations were prep ared daily prior to treatment by mixing the TCVP in aqueous 0.1% (w/v) methylcellulose

. FT and TP were prepared daily prior to dosing by mixing in 0.1% aqueous met hylcellulose. As the dose formulation for the test substance was prepared daily, its st ability over the 10-day dosing period was not determined. However, purity of the neat te st compound was verified on Study Days -3 and 11. Homogeneity was determined by collecti ng samples from the top, middle, and bottom of each test concentration prio r to test initiation. Concentrations were determined from homogeneity assessment on Day -3 and near the end of the study (Day 9).

( b) Dose Analysis

Results

Homogeneity (%RSD): 3.17-4.09%

Stability (% of nominal): not applicable

Concentration (% of nominal): 98.5-109.0% The analytical data indicated that the mixing procedure was ad equate and that the variation between nominal and actual dosage to the animals was acceptable.

7. Dosage administration: Test formulations of TCVP we re administered to the animals daily via oral gavage (5 mL/kg bw) for 10 da ys. TP was given vi a s.c. injection at

1 Barnett, J. Oral (Gavage) Repeated Dose Range-Findi ng Study of Tetrachlorvinphos in Rats. Testing Facility Study No. 20012366. Charles River Laboratories, Horsham, PA.In vivo Hershberger Assay (2012)/ Page 7 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### 0.5 mL/kg bw, and FT was administered via or al gavage at 5 mL/ kg bw. Dose volumes were adjusted daily based on the concurrent body weight measurement.

8. Statistics: Body weights, body weight gains, organ weights (adrenals, kidneys, and liver), and accessory sex organ weights were subjected to statistical analyses. Data were analyzed for homogeneity of variance and normality using Bartlett’s test. When the Bartlett’s test indicated homogeneous varian ces, means were compared using One-Way Analysis of Variance (ANOVA). When the ANOVA was significant, group means were compared using Dunnett’s test for multiple comparisons. When variances were significantly different using Bartlett’s test, means were compared us ing the non-parametric Kruskal-Wallis test. When the Kruskal-Wallis test was significan t, group means were compared using Dunn’s test. Significance was denoted at p<0.05. St atistical analyses we re conducted using ProvantisTM version 8.4.2.0 and GraphPad soft ware. The statistical analyses were considered adequate.

C. METHODS

1. Clinical Examinations: All animals were checked for viability at least twice daily. Cage-side observations includi ng (but not limited to) change s in skin, fur, eyes, and mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g., lacrimation, piloerection, pupil si ze, unusual respiratory patter n), changes in gait, posture and response to handling, as well as the pr esence of clonic or tonic movements, stereotypies (e.g., excessive grooming, repetitive circling), or bizarre behavior (e.g., selfmutilation, walking backwards) were recorded daily.

2. Body Weight: Animals were weighed at rando mization, daily thr oughout the dosing period, and prior to necropsy. Mean body weight gain was determined daily and for Days
1-10.

3. Food Consumption: Food consumption (g/animal/day) was measured weekly. Mean daily food consumption and mean food efficien cy was determined for Days 1-3, Days 3-10, and Days 1-10.

4. Serum Hormone Measurements (Optional): Serum hormone measurements were not
conducted.

5. Dissection and Measurement of Tissue and Organ Weights: On PND 67 approximately
24 hours after the final administration of the te st substance, all anim als (fasted overnight) were anesthetized by isoflurane inhalation, euthanized by ex sanguination, and subjected to a gross necropsy. The five mandatory andr ogen-dependent organs (ventral prostate, seminal vesicles, LABC, Cowper’s gland, and gl ans penis) were excised, trimmed free of adhering tissue, and weighed fresh (unfix ed) according to the standard operating procedures detailed in the U.S. EPA Guideline (OCSPP 890.1400). Additionally, the liver, kidneys, and adrenals were collected and wei ghed. Blood sample were collected by cardiac puncture and processed into serum for poten tial measurement of luteinizing hormone, follicular stimulating hormone, testosterone, t hyroxine, and thyroid stimulating hormone. It was stated that the serum samples were discarded unanalyzed at study completion.In vivo Hershberger Assay (2012)/ Page 8 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### II. RESULTS

A. OBSERVATIONS

1. Mortality: All animals survived until scheduled termination.

2. Clinical signs of toxicity: No treatment-related clinical si gns of toxicity were observed in animals from any dose groups.

Alopecia was observed in one animal from th e 50 mg/kg/day group in the androgen agonist assay, and one animal from each of the 50, 150, 350 mg/kg/day and positive control groups in the anti-androgen assay.

B. BODY WEIGHT AND WEIGHT GAIN: Selected body weight and body weight gains for the androgen agonist assay are presente d in Table 2. No adverse effects on body weights or body weight ga ins were observed for any TCVP dose groups.

TABLE 2. Selected Group Mean (±SD ) Body Weights and Mean Daily Body Weight Gains (g) in the Androgen Agonist Assay a

Study Day # Dose (mg/kg/day)

Vehicle Control Positive Control Vehicle + TP (0.4) b TCVP (50) TCVP (150) TCVP (350)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 6 290.1 15.1 6 294.8 13.1 6 292. 6 13.7 6 296.4 15.0 6 293.2 11.0

4 6 299.8 15.1 6 317.8 17.9 6 307. 5 14.9 6 309.0 17.5 6 303.1 13.4

7 6 316.8 19.7 6 338.2 20.3 6 324. 9 16.3 6 327.4 18.9 6 323.0 18.1

10 6 333.6 20.6 6 365.6 21.0 6 344. 3 18.7 6 347.0 18.6 6 341.4 19.4

B WG (Days 1- 10) 6 4.83 0.94 6 7.86 1.08 6 5.74 0.80 6 5.62 0.57 6 5.36 1.07

a Data were obtained from Tables 3 and 4 on pages 36-37 and 40-41 of the study report. b The positive control group for the androgen agonist assay was used as the vehicle control group for the anti-androgen assay. This did not affect the outc ome or conclusions of this study. N Number of animals in the group
SD Standard Deviation



### Selected body weight and body weight gain da ta for the anti-androgen assay are presented in Table 3. Body weights in all dose groups were comparable to controls throughout the duration of the assay. At 350 mg /kg/day, mean body weight loss (p ≤ 0.05) was observed on Days 1-2 and mean body weight gains were decreased (NS) by 46% on Days 2-3, resulting in a 23% decrease (NS) for overall (Days 1-10) body weight gains. Mean body weight gains were decreased (p<0.05) on Days 2- 3 in the 150 mg/kg/day group; however, body weight gains were increased (p<0.05) on Da ys 6-7 and overall body weight gains were
similar to controls. No other adverse effect s on body weight gains were observed. For the positive control group (TP + FT), mean daily body weight gains were decreased (p<0.05) on Days 5-6 and 9-10, and overall mean da ily body weight gains were decreased (p ≤ 0.05) by 14%.In vivo Hershberger Assay (2012)/ Page 9 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441

TABLE 3. Selected Group Mean (±SD) Body Weights and Mean Daily Body Weight Gains (g) in the AntiAndrogen Assay a

Study Day # Dose (mg/kg/day)

Vehicle Control

+ TP (0.4) b Positive Control
TP + FT (0.4 + 3.0) TCVP +TP (50 + 0.4) TCVP +TP (150 + 0.4) TCVP +TP (350 + 0.4)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 6 294.8 13.1 6 289.6 22.8 6 290.8 16.0 6 295.3 13.3 6 292.2 6.74

4 6 317.8 17.9 6 306.4 21.6 6 307.9 18.2 6 311.8 13.9 6 302.3 9.95

7 6 338.2 20.3 6 327.0 21.7 6 331. 5 19.1 6 335.9 19.0 6 325.2 11.9

10 6 365.6 21.0 6 350.2 21.7 6 351. 0 21.4 6 358.9 23.9 6 346.5 14.0

B WG (days 1-10) 6 7.86 1.08 6 6.74* ( ↓ 14) 0.20 6 6.69 ( ↓ 15) 0.75 6 7.07 ( ↓ 10) 1.58 6 6.04 ( ↓ 23) 0.91

a Data were obtained from Tables 3 and 4 on pages 38-39 and 42- 43 of the study report. Percent differences from controls, calculated by the reviewers, are included in parentheses. b The vehicle control group for the anti-androgen assay was the same as the positive control group for the androgen agonist assay. This did not affect the outc ome or conclusions of this study. N Number of animals in the group
SD Standard Deviation * Significantly different from controls at p ≤ 0.05



### C. FOOD CONSUMPTION AND EFFICIENCY: Food consumption data for the androgen agonist assay are presented in Table 4. F ood consumption in the 350 mg/kg/day group was decreased (p<0.05) by 8% for Days 1-3 compared to the control, but was then increased (p<0.01) by 7% for Days 3-10. For Days 3-10, food consumption in the 150 mg/kg/day group was increased (p<0.001) by 10%. Over all food consumption on Days 1-10 was increased (p<0.001) by 27% in the 150 mg/kg/day group, and in creased 3% in both the 50 and 350 mg/kg/day groups. No effects on f ood efficiency were observed for the TCVP treatment groups.

For the positive control group (TP), food cons umption was increased (p<0.01) by 11% and food efficiency was increased (p <0.01) by 50% for Days 1-10.In vivo Hershberger Assay (2012)/ Page 10 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441

TABLE 4. Food Consumption (g/animal/d ay) In the Androgen Agonist Assay a

Study Day

Interval Dose (mg/kg/day)

Vehicle Control Positive Control Vehicle + TP (0.4) b TCVP (50) TCVP (150) TCVP (350)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1-3 6 28.0 1.46 6 30.3 1.55 6 26.6 0.82 6 33.0 0.00 6 25.8* ( ↓ 8) 0.27

3-10 6 26.1 0.21 6 29.1** ( ↑ 11) 0.05 6 27.7 0.39 6 28.8*** ( ↑ 10) 0.21 6 27.9** ( ↑ 7) 1.46

Overall (1-10) 6 26.6 0.16 6 29.4** ( ↑ 11) 0.39 6 27.4 ( ↑ 3) 0.12 6 33.8*** ( ↑ 27) 4.34 6 27.4 ( ↑ 3) 1.20

a Data were obtained from Table 5 on page 44 of the study report. Percent differences from controls, calculated by the reviewers, are included in parentheses. b The positive control group for the androgen agonist assay was used as the vehicle control group for the anti-androgen assay. This did not affect the outc ome or conclusions of this study. N Number of animals in the group
SD Standard Deviation * Significantly different from controls at p ≤ 0.05 ** Significantly different from controls at p ≤ 0.01 *** Significantly different from controls at p ≤ 0.001



### Food consumption data for the anti-androge n assay are presented in Table 5. Food consumption in the 150 and 350 mg/kg/day grou ps were decreased (p<0.01) by 14-16% for Days 1-3. For Days 3-10, food consumpti on in the 50 mg/kg/day group was decreased (p<0.01) by 3%. Overall food consumption on Days 1-10 was decreased (p<0.01) by 5% in the 350 mg/kg/day group, and no effects we re observed in the 50 and 150 mg/kg/day groups. Food efficiency was decreased (p <0.01) by 96% in the 350 mg/kg/day group for Days 1-3. No other effects on food efficien cy were observed for the TCVP treatment groups or positive control group.

For the positive control group (TP+FT), food consumption was decreased (p<0.01) by 7-
8%.

TABLE 5. Food Consumption (g/anima l/day) In the Anti-Androgen Assay a

Study Day

Interval Dose (mg/kg/day)

Vehicle Control

+ TP (0.4) b Positive Control
TP + FT (0.4 + 3.0) TCVP +TP (50 + 0.4) TCVP +TP (150 + 0.4) TCVP +TP (350 + 0.4)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1-3 6 30.3 1.55 6 28.3** ( ↓ 7) 0.27 6 29.1 1.37 6 26.0** ( ↓ 14) 1.64 6 25.4** ( ↓ 16) 0.82

3-10 6 29.1 0.05 6 26.9** ( ↓ 8) 0.05 6 28.3** ( ↓ 3) 0.21 6 29.1 0.81 6 28.8 0.13

Overall (1-10) 6 29.4 0.39 6 27.2** ( ↓ 7) 0.02 6 28.5 0.47 6 28.4 0.99 6 28.0** ( ↓ 5) 0.08

a Data were obtained from Table 5 on page 45 of the study report. Percent differences from controls, calculated by the reviewers, are included in parentheses. b The vehicle control group for the anti-androgen assay was the same as the positive control group for the androgen agonist assay. This did not affect the outc ome or conclusions of this study. N Number of animals in the group
SD Standard Deviation ** Significantly different from controls at p ≤ 0.01In vivo Hershberger Assay (2012)/ Page 11 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### D. SERUM HORMONE CONCE NTRATIONS (OPTIONAL): Serum hormone
concentrations were not determined.

E. ORGAN WEIGHTS: Accessory sex organ weights fo r the androgen agonist assay are presented in Table 6. At 50 mg/kg/day, the absolute LA BC weights were increased (p ≤ 0.01) by 32%, but no other accessory sex organ weight increases were observed in any TCVP treatment groups. A dose dependent incr ease in liver weights was noted for TCVP, with the increase attaining significant (p ≤ 0.01) at the 350 mg/kg/day dose (30%). Adrenal gland weights were increased (p ≤ 0.01) by 39, 47, and 44% in the 50, 150, and 350 mg/kg/day groups, respectively. Animal s in the TP group had increases (p ≤ 0.01) in unadjusted accessory sex organ weights as follows: 370% in ventral prostate, 295% in seminal vesicles, 179% in LABC, 205% in Co wper’s gland, and 72% in glans penis.

The maximum guideline-specified %CV was ex ceeded for the Cowper’s gland (64.57% vs. 55%) and glans penis (27.61% vs. 22%) in the c ontrol. All other %CV values were less
than the maximum recommended values.

TABLE 6. Accessory Sex Organ Weights from A ndrogen Agonist Assay in Sprague-Dawley Rats a

Organ Dose (mg/kg/day)

Vehicle control TCVP (50) TCVP (150) TCVP (350) Positive Control Vehicle + TP (0.4) b

N Mean SD CV (%) N Mean SD N Mean SD N Mean SD CV (%) N Mean SD

Ventral
Prostate (mg) 6 16.22 2.98 18.3 6 17.53 3.43 6 19. 18 5.05 6 16.07 2.85 17.7 6 76.30** ( ↑ 370) 33.4

Seminal
Vesicles (mg) 6 36.97 8.78 23.7 6 44.65 7.58 6 40. 47 6.52 6 36.65 9.06 24.7 6 146.18** ( ↑ 295) 74.5

LABC (mg) 6 171.7 27.1 15.8 6 225.9** ( ↑ 32) 27.6 6 181.7 24.2 6 193.9 30.9 15.9 6 478.78** ( ↑ 179) 39.7

Cowper’s glands (mg) 6 7.65 4.94 64.6 6 7.55 2.25 6 6 .40 3.27 6 7.03 1.55 22.0 6 23.33*** ( ↑ 205) 4.97

Glans penis (mg) 6 42.67 11.8 27.6 6 46.43 7.93 6 50. 53 11.8 6 48.10 7.02 14.6 6 72.90*** ( ↑ 72) 9.58

Adrenal
Glands (mg) 6 61.73 7.08 NA 6 85.98** ( ↑ 39) 19.3 6 90.52** ( ↑ 47) 9.20 6 88.75** ( ↑ 44) 10.7 NA 6 71.48 10.7

Kidneys (mg) 6 1946.8 239 NA 6 2017.8 138 6 2105. 8 143 6 2174.9 254 NA 6 2174.1 118

Liver (g) 6 9.10 1.83 NA 6 9.67 ( ↑ 6) 0.54 6 10.30 ( ↑ 13) 0.70 6 11.82** ( ↑ 30) 1.56 NA 6 9.92 0.73

a Data were obtained from page 30 and Table 8 pages 49 and 50 of the study report. Percent differences from controls were calculated by the reviewers and included in parentheses. b The positive control group for the androgen agonist assay was used as the vehicle control group for the anti-androgen assay. This did not affect the outc ome or conclusions of this study. N Number of animals in the group
SD Standard Deviation
CV Coefficient of Variation NA Not applicable ** Significantly different from controls at p ≤ 0.01 *** Significantly different from controls at p ≤ 0.001In vivo Hershberger Assay (2012)/ Page 12 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### Accessory sex organ weights for the anti-andr ogen assay are presented in Table 7. There were no treatment-related weight decreases in any of the acce ssory sex organs of animals dosed with TCVP. However, the following increases (p ≤ 0.01) in accessory sex organ weights were observed in all TCVP treatment groups: 85-139% in ve ntral prostate, 143- 203% in seminal vesicles, and 47-60% in th e Cowper’s gland. The LABC weights were increased by 24% (p ≤ 0.01) at 50 mg/kg/day. The unadjus ted liver weights were increased by 17% (p ≤ 0.05) at 350 mg/kg/day.

Rats in the positive control (FT + TP) group had accessory sex organ weight decreases (p<0.05) as follows: 61% in ventral prostate ; 67% in seminal vesicles; 44% in LABC; 56% in Cowper’s glands; a nd 27% in glans penis.

The maximum guideline-specified %CV was exceed ed for the ventral prostate (43.74% vs. 40%) and seminal vesicles (50.98% vs. 40%) in the control. All other %CV values were
less than the maximum recommended values.

TABLE 7. Accessory Sex Organ Weights from Anti -Androgen Agonist Assay in Sprague-Dawley Rats a

Organ Dose (mg/kg/day)

Vehicle Control

+ TP (0.4) b TCVP +TP (50 + 0.4) TCVP +TP (150 + 0.4) TCVP +TP (350 + 0.4) Positive Control
TP + FT (0.4 + 3.0)

N Mean SD CV (%) N Mean SD N Mean SD N Mean SD CV (%) N Mean SD

Adrenal
Glands (mg) 6 71.48 10.7 NA 6 76.68 18.9 6 84.85 10.7 6 76.57 19.7 NA 6 73.35 8.51

Kidneys (mg) 6 2174.1 118 NA 6 2091.4 210 6 2166.5 166 6 2197.1 257 NA 6 2009.9 169.3

Liver (g) 6 9.92 0.73 NA 6 9.88 1.11 6 10.90 ( ↑ 10) 1.21 6 11.57* ( ↑ 17) 1.26 NA 6 9.23 1.29

Ventral
Prostate (mg) 6 76.30 33.4 43.7 6 182.0
*** ( ↑ 139) 37.8 6 141.3** ( ↑ 85) 26.8 6 154.4** ( ↑ 102) 29.3 19.0 6 29.75 ( ↓ 61) 8.18

Seminal
Vesicles (mg) 6 146.2 74.5 51.0 6 442.9
*** ( ↑ 203) 64.4 6 355.9** ( ↑ 143) 88.7 6 383.0
*** ( ↑ 162) 117 30.5 6 47.87 ( ↓ 67) 13.0

LABC (mg) 6 478.8 39.7 8.28 6 593.1** ( ↑ 24) 48.2 6 548.6 68.3 6 542.6 46.2 8.52 6 267.5 ( ↓ 44) 74.3

Cowper’s glands (mg) 6 23.33 4.97 21.3 6 37.28** ( ↑ 60) 8.25 6 34.40* ( ↑ 47) 4.86 6 34.27* ( ↑ 47) 6.50 19.0 6 10.2 ( ↓ 56) 3.33

Glans penis (mg) 6 72.90 9.58 13.1 6 84.42 13.2 6 84. 10 10.8 6 86.15 8.61 10.0 6 53.38 ( ↓ 27) 11.4

a Data were obtained from page 30 and Table 8 pages 51 and 52 of the study report. Percent differences from controls were calculated by the reviewers and included in parentheses. b The vehicle control group for the anti-androgen assay was the same as the positive control group for the androgen agonist assay. This did not affect the outc ome or conclusions of this study. N Number of animals in the group
SD Standard Deviation
CV Coefficient of Variation NA Not applicable * Significantly different from controls at p ≤ 0.05 ** Significantly different from controls at p ≤ 0.01 *** Significantly different from controls at p ≤ 0.001In vivo Hershberger Assay (2012)/ Page 13 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: There were no clinical, body weight, body weight gain, food consumption, food efficiency or macroscopic changes associated with the administration of TCVP under the parameters of the present study. Although TCVP showed no clear sign of androgenic or anti-a ndrogenic activity, as defined by the testing guidelines, the significant incr eases in weights of androgen sensitive tissues in the antiandrogen assay may indicate the potential for TCVP to interact with the endocrine system in the presence of artificially elevated testosterone levels in this test system.

B. AGENCY COMMENTS: All animals survived until scheduled termination. There were
no treatment-related clini cal signs of toxicity.

In the androgen agonist assay, body weight s and body weight gains for each TCVPtreatment group were comparable to controls throughout the assay. Food consumption was initially decreased in the 350 mg/kg/day gr oup, but was then increased for Days 3-10. Food consumption was also increased for Days 3-10 in the 150 mg/ kg/day group. Overall food consumption (Days 1-10) was increase d (p<0.001) by 27% in the 150 mg/kg/day group, and by 3% (NS) in both the 50 and 350 mg/kg/day groups. No effects on food efficiency were observed for the TCVP treatment groups. For the TP-control group, food consumption was increased (p<0.01) by 11% an d food efficiency was increased (p<0.01) by 50% for Days 1-10.

Liver weights in the agonist assay were increased by 6, 13 and 30% in the 50, 150, and 350 mg/kg/day group, respectively, but th e increase was only significant (p ≤ 0.01) at the highest dose. Adrenal gland weights were also increased (p ≤ 0.01) by 39, 47, and 44% in the 50, 150, and 350 mg/kg/day groups, respectively. Except for a 32% increase (p ≤ 0.01) in the LABC weight of the 50 mg/kg/day group, there were no significant ch anges in accessory sex organ weights of the TCVP-treated groups . Animals in the positive TP-control group showed the expected increases (p ≤ 0.05) in accessory sex organ weights.

In the anti-androgen assay, body weights for each TCVP-treated group were comparable to controls throughout the assay. At 350 mg/kg/day, there was a mean daily body weight loss (p ≤ 0.05) on Days 1-2 and body weight gains on Days 2-3 were decreased (NS) by 46%, resulting in an overall reduction (Days 1-10) of 23% (NS) in body weight gains. In the 150 mg/kg/day group, body weight gains were decr eased (p<0.05) on Days 2-3 but increased (p<0.05) on Days 6-7. Overall body weight gains (Days 1-10) for the 50 and 150 mg/kg/day groups were similar to controls. For the positive control group (TP + FT), overall mean daily body weight gains were decreased (p ≤ 0.05) by 14%. Food consumption in the 150 and 350 mg/kg/day groups were decr eased (p<0.01) by 14-16% for Days 1-3. For Days 3-10, food consumption in the 50 mg/kg/day group was decreased (p<0.01) by 3%. Compared to the TP-control, overall food consumption (Days 1-10) was decreased (p<0.01) by 5% in the 350 mg/kg/day group, but there was no effects in the 50 and 150 mg/kg/day groups. For the positive contro l group (TP+FT), food consumption was increased (p<0.01) by 7-8%. There was an initial decrease (p< 0.01) of 96% in foodIn vivo Hershberger Assay (2012)/ Page 14 of 14 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1400/ OECD 441



### efficiency in the 350 mg/kg/day group, but othe rwise food efficiency in the TCVP-treated and positive control group were similar to the TP-control.

Liver weights in the anti-androge n assay were increased by 17% (p ≤ 0.05) at 350 mg/kg/day, but were comparable to the cont rol at the two lower doses. There were no decreases in accessory sex organ weights of TC VP-treated animals. However, increases (p ≤ 0.01) in the following accessory sex organ wei ghts were observed in all TCVP-treated groups: 85-139% in ventral prostate, 143-203% in seminal vesicles, and 47-60% in the Cowper’s gland. In additi on, there was a 24% increase (p ≤ 0.01) in LABC weights in the 50 mg/kg/day group. The biological significance of these increases is unclear as they were not dose dependent, and TCVP did not give a positive response in the androgen assay. However, these data suggest that TCVP may be affecting the metabolism of testosterone.
Such an effect would not have been evident in the agonist assay as th e castrated rats were already testosterone deficient. Animals dosed with FT + TP (positive control) showed the expected decreases in accesso ry sex organ weights.

The high dose of TCVP selected for this st udy (350 mg/kg/day) was considered adequate based on decreased overall body weight gains an d increased liver weights observed in the current assay. No androgenic or anti-androgenic effects were observed for TCVP at doses up to 350 mg/kg/day under the conditions of this assay.

C. STUDY DEFICIENCIES: The following deficiencies were noted that did not have an adverse effect on the results, interpreta tion or conclusions of this study:

 In the androgen agonist assay, the maxi mum guideline-specified %CV was exceeded for the Cowper’s gland (64.6% vs. 55%) and glans penis (27.6% vs. 22%) in the
control.

 In the anti-androgen assay, the maximum guideline-specified %CV was exceeded for the ventral prostate (43.7% vs. 40%) and se minal vesicles (51.0% vs. 40%) in the
control.

# DATA EVALUATION RECORD

TETRACHLORVINPHOS (TCVP)

Study Type: OCSPP 890.1450, Female Pubertal Assay

EPA Contract No. EP10H001452 Task Assignment No. 4-05-2013 (MRID 49186901)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer: Signature: Kelly Luck, M.S. Date: 9/9/2013

Secondary Reviewer: Signature: Michael E. Viana, Ph.D., D.A.B.T. Date: 9/12/2013

Program Manager: Signature: Jack D. Early, M.S. Date: 09/23/2013

Quality Assurance: Signature: Jack D. Early, M.S. Date: 09/23/2013

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screenin g Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).Female Pubertal Assay (1013) I Page 1 of 19 TETRACHLORVINPHOS (fCVP) I 083702 OCSPP 890.1450/ OECD None



### Primary Reviewer: Ronnie J. Bever Jr

.. Ph.D., DABT 

### Signature:

# ~ 

# </·**~.** Risk Assessment Branch VII, Health Effects Division (7509P) Date:**9.?!(~** 

### Secondary Reviewer: Elizabeth Mendez, Ph.D. 

### Signature:

. ..i

....,

### _....,1r.-lfili(il9i~..,.!..--~ 

### Health Effects Division Date: 

## '!'
Templa e ersion 08/1011



### DATA EV ALU A TI ON RECORD

STUDY TYPE: Female Pubertal Assay; OCSPP 890.1450; OECD None.



### PC CODE: 083702 DP 

### BARCODE: D413982

TXR#: 0056284 

### CAS No.: 22248- 79-9



### TEST MATERIAL (PURITY): Tetrachlorvinphos (99.52%)



### SYNONYMS: (1Z)-2-chloro·1 ·(2,4,S·trichlorophenyl)ethenyl dimethyl phosphate; TCVP



### CITATION: Boulet, J. (2013). Pubertal development and thyroid function in intact juvenile/peripubertal male and female rats exposed to tetrachlorvinphos.
Product Safety Labs, Dayton, NJ. Laboratory Study No.: 33547, July 26, 2013.
MRID 49186901. Unpublished.



### SPONSOR: The Tetrachlorvinphos (TCVP) Task Force, c/o SRA Consulting Inc., 5235 Ragged Point Road, Cambridge, MD



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In a Female Pubertal Assay (MR.ID 49186901 ), 15 Sprague Dawley [SD® !GS] rats/dose group were treated daily by oral gavage with tetrachlorvinphos (TCVP) (99.52% ai; Lot# TX 100113) in aqueous 0.1% (w/v) methylcellulose at doses 

## ofO (vehicle), 50, or 350 mg/kg/day from post-natal day (PND) 22 to 42/43. In addition, a reference

group of 15 females dosed with 17a·ethynylestradiol (EE), by subcutaneous injection, at 0.003 mg/kg/day was included in the study. Animals were examined for vaginal opening (VO) daily beginning on PND 22, and age and weight at day of attainment were recorded. After sacrifice on PND 42 or 43, blood was collected for clinical chemistry analyses, and total thyroxine (T4) and thyroid stimulating hormone (TSH) levels were determined using a radioimmunoassay (RIA). Adrenal, liver, kidney, pituitary, thyroid, and urogenital organs were weighed, and microscopic
examinations were performed on the ovaries, uterus, thyroid, liver, and kidneys.

There were no adverse, treatment-related effects on mortality, clinical signs of toxicity, body weights, body weight gains, food consumption, clinical chemistry, or macroscopic pathology.

Serum T4 levels were decreased by18% (not statistically significant [NS]) and 65% (p<0.05) at 50 and 350 mg/kg/day, respectively, but serum TSH concentrations at 50 and 350 mg/kg/day

were comparable to control. Follicular cell height was slightly increased and follicular colloid

area was slightly decreased in a dose-dependent manner in the 50 and 350 mg/kg/day treatmentFemale Pubertal Assay (2013) / Page 2 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### groups; it was reported that the differences we re only statistically si gnificant in the 350 mg/kg/day group.

There were no effects of treatment on age and bo dy weight at attainment of VO. All females achieved complete VO. There were no effects of treatment on mean age at first vaginal estrus, mean cycle length (a slight increase was cons idered non-adverse), % cycling or regularly cycling, or cycle status at necr opsy. Corpora lutea were present in the ovary of all individuals,
and no atretic follicles were noted in controls or TCVP-treated groups.

Compared to the control group, relative (to body weight) liver weights we re increased (p<0.001) by 8%, and absolute and relative adrenal weig hts were increased (p<0.001) by 30-31% at 50 mg/kg/day. At 350 mg/kg/day, ab solute and relative liver we ights were increased (p<0.001) by 21-25%, and absolute and re lative adrenal weights were increased (p<0.001) by 37-42%. There were increased incidence and severity of chronic progressive nephropathy in the 350 mg/kg/day group compared to the control.

The high dose (350 mg/kg/day) was considered to be adequate, based on increased liver and adrenal weights and increased incidence and seve rity of chronic progressive nephropathy. Mean adrenal glands weight was 37.6 mg, but the acceptable range is 38.34-48.84 mg.

For animals in the positive control group (EE gr oup), food consumption over the course of the study was decreased (p<0.05, ↓ 9%), leading to decreased ov erall body weight gain (p<0.05, ↓ 14%). The mean age at attainment of VO wa s decreased (p<0.01) by 8 days (PND 25.6 treated vs. PND 33.6 controls) and body weight at atta inment of VO was decr eased (p<0.01) by 39%. All EE-treated females were non-cycling in cons tant estrus from PND 26 through the entire observation period. Absolute ovaries weights were decreased (p<0.001, ↓ 48%) and relative pituitary weights were increased (p<0.05, ↑ 21%). The following clinical chemistry parameters were increased (p<0.05) compared to controls: bilirubin ( ↑ 18%), total protein ( ↑ 9%), albumin ( ↑ 10%), globulin ( ↑ 8%), and calcium ( ↑ 4%). Many of these changes were as expected for an estrogen agonist.

The assay satisfies the EDSP Tier 1 Test Order require ments for a Female Pubertal Assay (OCSPP 890.1450).

COMPLIANCE: Signed and dated Data Confiden tiality, GLP Compliance, and Quality Assurance statements were provided.Female Pubertal Assay (2013) / Page 3 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Product Safety Labs

Location: Dayton, NJ Study Director: J. Boulet

Other Personnel: J. D. John (Primary Scientist) D. J. Merkel (Laboratory Director) R. S. Krick (Director of Quality Assurance) C. Dunn (Technical Writing Supervisor) Study Period: July 12, 2012 to July 26, 2013



### 2. Test Substance: Tetrachlorvinphos (TCVP)
Description: Off-white to tan powder

Source: Hartz Mountain Corporation

Lot/Batch #: TX 100113 (expiration date 4/11/2013) Purity: 99.52% Stability: No data provided

CAS #: 22248-79-9

Structure:



### 3. Vehicle: 0.1% (w/v) Methylcellulose (expira tion date 8/9/2014) in reverse
osmosis deionized water

4. Test Animals:
Species: Rat
Strain: Sprague Dawley [SD® CD® IGS] Age/Weight at Study Initiation: PND 22/ 44.7 – 60.1 g

Source: Charles River Laboratories, Inc. (Raleigh, NC) Housing: Dams were individually housed in polysulfone shoebox cages with wi re-mesh lids containing bedding material (Certified Harlan Sani Chips®). Female wean lings were housed in the same type cage at 3/cage, avoiding same-sex littermates.

Diet: Harlan Teklad 2016C diet free of alfalfa and soybean meal, ad libitum Isoflavone (genistein + daidzein aglycone equivalents) ≤ 300 μg/g

Water: Deionized (on-site) tap water , ad libitum

Environmental
Conditions: Temperature: Humidity: Air changes: Photoperiod: 23  3 °C
30-70% Not reported 14 h light/10 h dark



### B. STUDY DESIGN

1. In-Life Dates: Start: August 17, 2012 End: September 18, 2012

2. Mating: Time-mated pregnant dams were received from the supplier between gestation days (GD) 7-10 and allowed to litter normally. On PND 4, litters were culled to 8-10 pups; all litters within the study were culled to the same number of pups where possible. The male offspring were used in a concu rrent male pubertal assay (MRID 49186901b). P O O Cl

Cl Cl Cl O CH

3

O CH

3Female Pubertal Assay (2013) / Page 4 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### 3. Animal Assignment: Offspring were weaned on PND 21 and weighed. Female pups having a body weight within ±20% of the m ean were selected and distributed by body weight using a stratified randomization procedure to the test groups noted in Table 1. No littermates were assigned to the same dose group. A reference group dosed with 17 α

ethynylestradiol (EE) was included in the study.

TABLE 1. Study Design a Test group Dose (mg/kg/day) # of Females

Control 0 15
17 α -Ethynylestradiol (EE) 0.003 15 Low (TCVP) 50 15 High (TCVP) 350 15 a Data were obtained from page 19 of the study report.



### 4. Dose Selection Rationale: It was stated that the dose levels were selected based on a preliminary range-finding study 1 

### ; however, no results of th is study were provided.

5. Dose Preparation and Analysis: Dose formulations were prepared daily by mixing appropriate amounts of test substance with 0.1% (w/v) MC in deionized water. Stirring was continuous during dose administration, and formul ations were used within approximately two hours of preparation. Homogeneity was tested in the current study in both TCVP formulations by collecting samples from the top, middle, and bottom of the mixture. Samples of dose formulations from both TCVP groups were analyzed at the beginning (PND 22) and end (PND 54; male study) of the dosing period to evaluate achieved
concentration.

Results of Dose Analysis

Homogeneity (% CV): 1.4 and 5.2%

Stability: Not tested because formulations were used within two hours of preparation

Concentration (% of nominal): 91.0-100.9%

The analytical data indicated that the mixing procedure was ad equate and that the variation between nominal and actual dosage to the animals was acceptable.

6. Dosage Administration: All doses of TCVP were admini stered once daily by gavage, from PND 22 through PND 42/43, in a volume of 5.0 mL /kg of body weight. Doses of EE were administered once daily via subcutaneous injection in a volume of 0.5 mL/kg of body weight. Dosing was performed in the morning at approximately the same time each day ± 2 hours with exception of the final day of ad ministration, when dosing occurred between approximately 7:00-9:00 am.

1 Charles River Laboratories (2011). Oral (gavage) repe ated dose range-finding study of tetrachlorvinphos in rats.
CRL No. 20021366.Female Pubertal Assay (2013) / Page 5 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### 7. Statistics: The following parameters were subjected to statistical analysis: body weights, body weight gains, food consumption, age and b ody weight at attainment of VO, clinical chemistry, hormone levels, and organ weight s. If warranted by su fficient group sizes, untransformed data within groups were evalua ted for homogeneity of variances by Bartlett's
test. When the Bartlett’s test indicated homogeneous variances, means were compared using a One-Way Analysis of Variance ( ANOVA). When the ANOVA was significant, group means were compared using Dunnett’s test for multiple comparisons. When variances were significantly different using Ba rtlett’s test, means were compared using the non-parametric Kruskal-Wallis test. When th e Kruskal-Wallis test was significant, group means were compared using Dunn’s test. Age and body weight at VO, and all organ weights were also analyzed by Analysis of Covariance (ANCOVA) us ing the body weight at PND 21 as the covariate. If the Shapiro-Wilk test is not significant but Levene's test is significant, a robust version of Dunnett's test was used.

Clinical pathology data were analyzed for homogeneity using Levene’s test and for normality using Shapiro-Wilk test. If these tests did not indicate significance, an ANOVA test followed by a Dunnett’s test were conducted. If data were found to be non-normal or heterogeneous, so that non-parametric tests were done, then the analyses were re-run after changing the group significan ce level to 0.05 and selecti ng Dunn as the subtest.

Incidences of follicular cell hypertrophy and associ ated colloid area decrease in the thyroid were analyzed using a chi-squared test of a ssociation, followed by a Fisher Exact probability test using independent contingency tables. Severity scores for follicular cell hypertrophy
and associated colloid area decrease were co mpared using a Kruskal-Wallis non-parametric ANOVA, followed by a paired t-te st (Dunn’s) where appropriate.

Significance was denoted at p ≤ 0.05. The statistical analyses were considered adequate.

C. METHODS

1. Mortality and Clin ical Examinations: All animals were examined at least twice daily for mortality and moribundity. Cage -size observations we re conducted at least once daily and
detailed clinical examinati ons were conducted weekly.

2. Body Weight: Animals were weighed prior to ra ndomization, daily during the dosing period, and on the day of necropsy. Mean body weight gains were calculated for PND 22-29, 29-36, and 36-41, and for PND 22-41.

3. Food Consumption: Food consumption was measured at least weekly; the method of measuring food consumption was not reporte d. Food consumption was reported for the same intervals as body weight gains.

4. Vaginal Opening (VO): Beginning on PND 22, all animals were examined daily for onset of VO; observations were perfor med at approximately the same time each day. The initial and subsequent appearance of pa rtial and/or complete VO, incl uding a persistent small "pin hole" or a vaginal thread was r ecorded as applicable. The presence of a "pin hole" or thread indicated incomplete vaginal opening. Age and weight on the day of completion of vaginal opening were recorded.Female Pubertal Assay (2013) / Page 6 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### 5. Estrous Cyclicity: Beginning on the day of complete VO, up to and including the day of necropsy, daily vaginal smears were obtaine d and evaluated for estrus cyclicity. Observations were performed at approximately the same time each day, and cycle length was determined as the first day of diestrus to the first day of the next diestrus. The age at first vaginal estrus was recorded, and the av erage cycle length was calculated and reported for complete cycles. Additionally, the percenta ge of females cycling and regularly cycling was calculated and reported.

6. Sacrifice and Pathology: All animals were euthanized by decapitation without anesthesia on PND 42 (8 animals in each group) or 43 (7 animals in each group) at least two hours post-dosing; animals were fasted overnight prior to sacrifice. All term inal procedures were completed by 1300 hours. Blood was collected at necropsy from the abdominal aorta and centrifuged for 30 min at 4 °C to obtain se rum. Serum samples were stored at <

− 20 °C and shipped on dry ice to DuPont Haskell Globa l Centers for Health and Environmental Sciences (Newark, DE) for subsequent horm one and clinical chemistry evaluations.

a. Hormone Analysis: Total T 4 

### and TSH levels were determined at an external laboratory (DuPont) using RIA kits.

b. Clinical Chemistry: The following CHECKED (X) parameters were examined.

ELECTROLYTES OTHER

X Calcium X Albumin

X Chloride X Creatinine* Magnesium X Urea nitrogen* X Inorganic phosphorus X Total cholesterol

X Potassium X Globulins

X Sodium X Glucose

ENZYMES X Total bilirubin
X Alkaline phosphatase (ALP) X Total protein Cholinesterase (ChE) X Triglycerides Creatine phosphokinase Se rum protein electrophoresis Lactic acid dehydrogenase (LDH) X Alanine aminotransferase (ALT) X Aspartate aminotransferase (AST) X Sorbitol dehydrogenase (SDH) Gamma glutamyl transferase (GGT) Glutamate dehydrogenase * Recommended for the pubertal assay in fe male rats based on Guideline 890.1450.



### c. Organ Weights and Histopathology: The following CHECKED (X) tissues were collected and weighed. The (XX) organs, in addition, were subject ed to histological
examination.Female Pubertal Assay (2013) / Page 7 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None

UROGENITAL OTHER XX Ovaries (paired, without oviducts)*+ XX Thyroid*+

XX Uterus*+ XX Liver* XX Kidneys (paired)*+ X Adrenals (paired)* X Pituitary* * Weights required based on Guideline 890.1450 + Histopathological examination re quired based on Guideline 890.1450



### All organs collected except the thyroid were weighed prior to fixa tion. Paired organs (kidneys, adrenals, and ovaries) were weighe d together. The uterus and cervix were separated from the vagina and weighed. The uterus was weighed again following removal of the fluid in the lumen (blotted weight).

The ovaries and uterus were fi xed in 10% neutral buffered fo rmalin prior to embedding. The thyroid (with parathyroid), adrenals, liver, pituitary, a nd kidneys were fixed in 10%
buffered formalin for at least 48 hrs. Followi ng fixation, the thyroid wa s dissected from the trachea. All collected tissues were routinely processed into paraffin blocks, sectioned, and stained with hematoxylin and eosin. The followi ng tissues were examined microscopically: left kidney, thyroid, left ovary, and uterus from all animals in the study; livers from the vehicle control and high dose group; right kidney in the ve hicle control and TCVP dose groups; and any gross lesions of potential toxi cological significance including the liver of two control group females and the uterus of two EE group females.

Histological assessment was performed by Hi sto-Scientific Research Laboratories (Frederick, MD). It was stat ed that histological evaluations were conducted in compliance with the requirements of the OCSPP 890.1450 guideli nes; however, detailed descriptions of the procedures used to evaluate tissues were not provided. Thyroid/pa rathyroid glands were subjectively graded based on the ratio of follicular epithelial cell height to colloid area using a five point grading scale, with 1 = shortest epithelium or least a bundant colloid, and 5 = tallest epithelium or most abundant colloid. In addition, based on the reported results, ovaries were evaluated for the presence of atretic follicles and changes in corpus luteus development. Other histological findings we re graded as minimal, slight, moderate, marked, or present.

II. RESULTS

A. MORTALITY: All animals survived until scheduled termination.

B. CLINICAL SIGNS OF TOXICITY: No clinical signs of toxicity were observed in animals for any dose groups.

C. GENERAL GROWTH AND VAGINAL OPENING: Body weights, body weight gains, and age and body weight at attainment of VO are presented in Table 2. There were no effects of TCVP treatment on body weights, bod y weight gains, or age or body weight at
attainment of VO. All females achieved co mplete VO. Mean daily body weights (not shown in Table 2) for female rats receiving TC VP were comparable with the vehicle control group throughout the study, with the exception of rats in the high dose group on PND 23, forFemale Pubertal Assay (2013) / Page 8 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### which mean body weight was decreased (p<0.05, ↓ 6%); mean body weights for subsequent days were comparable to controls.

During PND 22-29, food consumption in the TC VP dose groups was decreased (p<0.001) by 10% at 350 mg/kg/day compared to the co ntrol. However, food consumption rebounded
and was similar to controls fo r the remainder of the study.

For rats in the group receiving EE at 0.003 mg/kg/day, mean daily body weights were decreased compared to vehicl e control values after PND 26, with statistical significance (p<0.05) attained on PND 36 ( ↓ 7%), 38 ( ↓ 11%), 40 ( ↓ 9%), and 41 ( ↓ 8%), leading to decreased (p<0.01) overall (PND 22-41) body weight gain of 13%. Food consumption over the course of the study (PND 22-41) was also decreased (p<0.001) by 9%. In addition, the mean age at attainment of VO was decreased (p<0.01) by 8 days (PND 25.6 treated vs. PND 33.6 controls), and body weight at attainme nt of VO was decreased (p<0.01) by 39%.

The means and %CV for age and body weight at VO and final body weight in the control group were within the recommended range of th e performance criteria provided in the Guideline (890.1450).Female Pubertal Assay (2013) / Page 9 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None

TABLE 2. General Growth and Vaginal Opening (VO) a

Parameter
Evaluated Vehicle Control EE (0.003 mg/kg/day) TCVP (50 mg/kg/day) TCVP (350 mg/kg/day)

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%) Initial body weight (PND 22; g) U 15 51.1 2.9 5.68 15 52.05 3.49 NR 15 52.3 3.08 5.89 15 50.6 3.54 6.99

A 15 51.1 -- -- NR NR -- -- 15 52.3 -- -- 15 50.6 -- --

Body weight at vaginal opening (g) U 15 111.5 8.14 7.3 15 67.8** ( ↓ 39) 4.12 NR 15 105.9 11.6 11.0 15 99.1 11.3 11.4

A 15 111.5 -- -- NR NR -- -- 15 105.9 -- -- 15 99.1 -- -- Final body weight (PND 41, unfasted; g) U 15 152.7 9.96 6.52 15 140.1* ( ↓ 8) 6.93 NR 15 154.5 16.6 10.74 15 149.5 14.36 9.61

A NR NR -- -- NR NR -- -- NR NR -- -- NR NR -- --

Final body weight (% of control) U -- NA -- -- 15 91.7 -- -- 15 100.6 -- -- 15 97.3 -- --

A -- NA -- -- NR NR -- -- NR NR -- -- NR NR -- --

Body weight gain (final – initial; g) U 15 101.6 9.41 9.26 15 88.0** b ( ↓ 14) NR NR 15 102.2 14.1 13.8 15 98.8 12.2 12.4

A 15 101.6 -- -- NR NR -- -- 15 102.2 -- -- 15 98.8 -- --

Age at vaginal opening (PND) U 15 33.6 1.99 5.92 15 25.6** ( ↓ 8 d) 0.63 NR 15 32.3 1.53 4.74 15 31.9 1.22 3.82

A 15 33.6 -- -- NR NR -- -- 15 32.3 -- -- 15 31.9 -- -- Proportion unopened (#/N) 0/15 0/15 0/15 0/15

a Data were obtained from Table 4 on page s 57-60 and Table 17 on page 95 of the study report. Percent differences from vehicle controls, calculated by the study reviewer, are included in parentheses. b Calculated by the study reviewer based on reported mean daily body weight gain over the course of the study (Table 5, page 62). U Unadjusted for body weight on PND 21 A Adjusted for body weight on PND 21
N Number of animals examined
SD Standard Deviation CV Coefficient of Variation; %CV wa s not reported for the EE group. NA Not applicable NR Not reported ** Significantly different from controls at p<0.01



### D. ORGAN WEIGHTS: Organ weights at necropsy are presented in Table 3. At 50 mg/mg/day, relative (to body weight) liver we ights were increased (p<0.001) by 8% and absolute and relative adrenal weights were increased (p<0.001) by 30-31% compared to controls. At 350 mg/kg/day, abso lute and relative liver weig hts were increased (p<0.001) by 21-25%, relative kidney weights were in creased (p<0.001) by 10%, and absolute and relative adrenal weights were increased (p<0.001) by 37-42%. There were no effects of TCVP treatment on the weights of pitu itary, ovaries, uter us, or thyroid.

For rats in the group receiving EE at 0.003 mg/kg/day, absolute ovary weights were decreased (p<0.001, ↓ 48%) and relative pituitary we ights were increased (p<0.05, ↑ 20%) compared to the controls. There were no e ffects on the weights of liver, kidney, adrenals, uterus, or thyroid.

The unadjusted values for all organ weights in the control group were within the acceptable range of the performance criteria provided in the Guideline (8 90.1450), with the exception of mean adrenal glands weight ( 37.62 mg; acceptable range 38.34-48.84 mg).Female Pubertal Assay (2013) / Page 10 of 19TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1450/ OECD NoneTABLE 3. Organ Weights at NecropsyaOrganVehicle ControlEE(0.003 mg/kg/day)TCVP(50mg/kg/day)TCVP(350mg/kg/day)N Mean SD CV (%) N Mean SDCV(%) N Mean SD CV (%) N Mean SD CV (%)Liver(g)U 15 4.951 0.46 9.39 15 4.681 0.41 NR 15 5.423 0.64 11.73 155.990***(↑21)0.73 12.17A 15 4.951 -- -- NR NR -- -- 15 5.423 -- -- 15 5.990 -- --R 15 3.397 0.178 5.25 15 3.473 0.201 NR 153.667***(↑8)0.129 3.52 154.239***(↑25)0.208 4.91Kidneys(g)U 15 1.211 0.11 8.84 15 1.163 0.097 NR15 1.237 0.12 10.02 15 1.29 0.14 10.87A 15 1.211 -- -- NR NR -- -- 15 1.237 -- -- 15 1.29 -- --R 15 0.832 0.041 4.94 15 0.863 0.056 NR 15 0.838 0.042 5.04 150.913***(↑10)0.055 6.00Pituitary(mg)U 15 8.01 1.93 24.09 15 8.93 1.87 NR15 7.65 2.24 29.28 15 7.29 1.51 20.71A 15 8.01 -- -- NR NR -- -- 15 7.65 -- -- 15 7.29 -- --R 15 0.0055 0.0013 23.32 150.0066*(↑20)0.0013 NR 15 0.0052 0.001427.47 15 0.0052 0.0010 19.69Adrenals(mg)U 15 37.62 4.26 11.32 15 37.67 6.33 NR 1549.34***(↑31)7.05 14.29 1551.57***(↑37)7.90 15.32A 15 37.62 -- -- NR NR -- -- 15 49.34 -- -- 15 51.57 -- --R 15 0.0258 0.0027 10.39 15 0.0280 0.0047 NR 150.0335***(↑30)0.0042 12.64 150.0367***(↑42)0.0055 14.97Ovaries(mg)U 15 50.04 8.51 17.01 1526.00***(↓48)6.88 NR 15 50.75 10.97 21.62 15 50.06 8.31 16.60A 15 50.04 -- -- NR NR -- -- 15 50.75 -- -- 15 50.06 -- --Uterus, wet(mg)U 15 260.23 86.05 33.07 15 268.92 21.71 NR15 290.29 94.30 32.48 15 290.31 91.71 31.59A 15 260.23 -- -- NR NR -- -- 15 290.29 -- -- 15 290.31 -- --Uterus,blotted(mg)U 15 246.07 71.35 29.00 15 261.13 21.03 NR15 269.44 70.78 26.27 15 267.96 65.35 24.39A 15 246.07 -- -- NR NR -- -- 15 269.44 -- -- 15 267.96 -- --Thyroid,fixed(mg)U 15 12.38 1.01 8.18 15 12.33 1.42 NR15 12.47 1.84 14.79 15 11.91 1.72 14.41A 15 12.38 -- -- NR NR -- -- 15 12.47 -- -- 15 11.91 -- --a Data were obtained from Table 14 on pages 87 and 88, Table 15 onpage 90, and Table 17 on page 97 of the study report. Percent differences from vehicle controls,calculated by the study reviewer, are included in parentheses.U Unadjusted for body weight on PND 21A Adjusted for body weight on PND 21N Number of animals examinedSD Standard DeviationCV Coefficient of Variation; %CV was not reported for the EE group.R Organ-to-body weight ratio (relative to body weight); reported results were corrected by the study reviewer to reflect ratioas percent.NR Not reported* Significantly different from controls at p<0.05Female Pubertal Assay (2013) / Page 11 of 19TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1450/ OECD None** Significantly different from controls at p<0.01*** Significantly different from controls at p<0.001Female Pubertal Assay (2013) / Page 12 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### E. ESTROUS CYCLICITY: Estrous cycle data are provi ded in Table 4. There were no effects of treatment on mean age at first vagi nal estrus, mean cycle length, % cycling or regularly cycling, or cycle status at necropsy. The slight increase (NS) in mean cycle length
with TCVP administration was c onsidered to be non-adverse.

It was noted that 2/15 females the vehicle c ontrol group (13%), 3/15 females in the low dose group (20%), and 2/15 females in the high dose group (13%) had diestrus stages longer than 3 days. In addition, 1/15 females the vehicle control group (7%), 1/15 females in the low dose group (7%), and 2/15 females in the high dose group (13%) displayed >2-day estrus cornification. The one additional animal in the high dose group in extended estrus corresponds with the slig htly reduced age and body weight at vaginal opening in this group. These findings were considered to be inci dental and toxicologically insignificant.

Limited estrous cyclicity data were provided for the EE group. It was reported that all EEtreated females were non-cycling in consta nt estrus from PND 26 through the entire observation period.

TABLE 4. Estrous Cyclicity a

Treatment Groups N Mean Age at First Vaginal Estrus (PND) Mean Cycle Length (days) Cycling (%) Regularly Cycling

(%) Cycle Status at Necropsy (# Females)

Diestrus b Proestrus Estrus Not Cycling

Vehicle 15 32.5 3.1 73.3 73.3 8 3 4 4

EE (0.003 mg/kg/day) 15 Not reported 0 0 0 Not reported for individual animals

TCVP (50 mg/kg/day) 15 33.0 3.4 66.7 66.7 9 2 4 5

TCVP (350 mg/kg/day) 15 32.3 3.8 66.7 66.7 7 2 6 5

a Data were obtained from page 35, Table 10 on page 69, and Table 17 on page 96 of the study report. b Including metestrus.
N Number of animals



### F. CLINICAL CHEMISTRY AND HORMONE LEVELS: Mean hormone and clinical chemistry levels are presented in Table 5. Serum T 4 

### levels were decreased by 18% (NS) and 65% (p<0.05) at 50 and 350 mg/kg/day, respec tively. Serum TSH levels at 50 and 350 mg/kg/day were comparable to controls. The following changes in clinical chemistry parameters were observed at 350 mg/kg/day: cholesterol was increased (p<0.05) by 22%; albumin was decreased (p<0.05) by 7%; and po tassium was decreased (p<0.05) by 8%. All clinical chemistry parameters in the 50 mg /kg/day group were comparable to controls.

For rats in the group receiving EE at 0.003 mg /kg/day, the following clinical chemistry parameters were increased (p<0.05) co mpared to controls: bilirubin ( ↑ 18%), total protein ( ↑ 9%), albumin ( ↑ 10%), globulin ( ↑ 8%), and calcium ( ↑ 4%).

The results for serum T 4 

### in the control group were with in the acceptable range of the performance criteria provided in the Guide line (890.1450). Historical control data were provided for the following parameters: in males – globulin (2.0-2.6 g/dL), aspartate aminotransferase (103-245 U/L) , and bilirubin (0.1-0.16 mg/dL); females – cholesterol (72-Female Pubertal Assay (2013) / Page 13 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### 128 mg/dL), bilirubin (0.08-0.15 mg/dL), total protein (5.1-5.8 g/dL ), albumin (3.2-3.7 g/dL), globulin (1.9-2.3 g/dL), and calcium (10.8-12.0 mg/dL). The mean results for the control and TCVP dose groups were within the historical data ranges. Historical data for
hormone levels and the other clinical chemistry parameters were not provided.Female Pubertal Assay (2013) / Page 14 of 19TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1450/ OECD NoneTABLE 5. Hormone Levelsand Clinical ChemistryaParameterEvaluatedVehicle ControlEE(0.003 mg/kg/day)TCVP(50 mg/kg/day)TCVP(350mg/kg/day)N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%)HormonesSerum T4, Total(μg/dL)15 3.310 0.705 21.3 15 2.858 0.937 32.8 15 2.721(↓18)0.870 32.0 4b1.152*(↓65)0.181 15.7Serum TSH (ng/mL) 15 4.511 1.73938.6 15 5.467 2.418 44.2 15 3.9640.977 24.7 15 3.946 0.985 25.0Clinical ChemistryAST (U/L) 15 151 54 36 15 166 48 29 15 170 54 32 15 130 40 31ALT (U/L) 15 49 11 22 15 53 9 17 15 53 8 15 15 49 9 18SDH (U/L) 15 6.7 2.5 37 15 5.7 2.6 46 15 6.9 4.2 61 15 6.2 2.7 44ALP (U/L) 15 216 45 21 15 194 54 28 15 230 39 17 15 192 32 17Bilirubin (mg/dL) 15 0.11 0.02 18 15 0.13*(↑18)0.02 15 15 0.11 0.02 18 15 0.11 0.01 9Blood urea nitrogen(mg/dL)15 13 2 15 15 13 2 15 15 13 2 15 15 15 3 20Creatinine (mg/dL) 15 0.20 0.02 10 15 0.210.03 14 15 0.21 0.04 19 15 0.20 0.04 20Cholesterol (mg/dL) 15 107 19 18 15 113 25 22 15 121 25 21 15 131*(↑22)27 21Triglycerides(mg/dL)15 88 33 38 15 95 35 37 14c78 26 33 15 70 27 39Glucose (mg/dL) 15 109 10 9 15 112 8 7 15 107 15 14 15 102 12 12Total protein (g/dL) 15 5.5 0.2 4 15 6.0*(↑9)0.3 5 15 5.5 0.3 5 15 5.5 0.4 7Albumin (g/dL) 15 3.5 0.2 6 15 3.8*(↑10)0.2 5 15 3.3 0.2 6 15 3.2*(↓7)0.2 6Globulin (g/dL) 15 2.1 0.1 5 15 2.3*(↑8)0.1 4 15 2.1 0.2 10 15 2.2 0.2 9Calcium (mg/dL) 15 11.3 0.4 4 15 11.7*(↑4)0.3 3 15 11.3 0.3 3 15 11.1 0.5 5Inorganicphosphorus (mg/dL)15 9.7 0.7 7 15 9.6 0.8 8 15 9.8 0.8 8 15 10.1 0.8 8Sodium (mmol/L) 15 137.9 1.7 1.2 15 139.02.4 1.7 15 138.9 2.1 1.5 15 138.6 3.1 2.2Potassium (mmol/L) 15 6.85 0.38 5.5 156.85 0.69 10 15 7.01 0.45 6.4 15 6.31*(↓8)0.67 11Chloride (mmol/L) 15 98.8 1.7 1.7 15 99.42.1 2.1 15 100.0 1.9 1.9 15 99.2 2.4 2.4a Data were obtained from Table 11 on page71, Table 12 on pages 77-81, and Table 17 onpage 98 of the study report. Percent differences from controls are included inparentheses.b For 11 of the 15 animals in this group, serum T4was found to be below the limit of quantitation, which wasnot defined. These 11 results were not included in thecalculation of mean, SD, and CV.c For one animal in this group, there was insufficient quantity to determine triglycerides.Female Pubertal Assay (2013) / Page 15 of 19TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1450/ OECD NoneN Number of animals examinedSD Standard DeviationCV Coefficient of Variation; calculated by the study reviewerfor all results for the EE dose group and for clinical chemistryparameters, except creatinine and blood ureanitrogen, for the control and TCVP dose groups.* Significantly different from controls at p<0.05.Female Pubertal Assay (2013) / Page 16 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### G. MACROSCOPIC EXAMINATIONS: There were no treatment-related macroscopic findings at necropsy. Fluid-fill ed uterus was observed in 2/15 females in the control groups, 2/15 females in the EE group, 3/15 females in the 50 mg/kg/day, and 2/15 females in the 350 mg/kg/day group. These findings were found to be attributable to normal variation in the estrus cycle.

H. HISTOPATHOLOGY: The incidences of histopathologi cal findings of the thyroid gland are presented in Table 6. Follicular cell height was increased and follicular colloid area was decreased in a dose-dependent manner at 50 and 350 mg/kg/day; it was reported that the differences were only statistically si gnificant in the 350 mg/kg/day group.

TABLE 6. Thyroid Gland Follicular Cell Height and Colloid Area a

Findings Vehicle Control EE (0.003 mg/kg/day) TCVP (50 mg/kg/day) TCVP (350 mg/kg/day)
Number of animals
examined 15 15 15 15

Follicular cell height b

1 15 14 12 9

2 0 1 3 6

3 0 0 0 0

4 0 0 0 0

5 0 0 0 0

Follicular colloid area b

1 0 0 0 0

2 0 0 0 0

3 0 0 0 0

4 0 1 3 6

5 15 14 12 9 a Data were obtained from pages 635, 638, 640, and 642 of the study report. b A five-point grading scale (1 = shortest / smallest; 5 = tallest / largest) was used.



### The incidences of histopathological findings of the ovaries, uterus, and kidneys are presented in Table 7. There was increased in cidence and severity of chronic progressive nephropathy in the 350 mg/kg/day group compared to the control. In the liver, minimal to slight hepatocellular hypertrophy, unaccompanied by hepatocellular hyperplasia, degeneration, necrosis or inflammation, wa s characterized by increased size of the hepatocytes of the centrilobul ar zone, often extending in to the midlobular/midzonal hepatocytes, in 10/15 females in the 350 mg/kg/day TCVP group.

Microscopic findings attributed to EE administration include d reduction of the number of corpora lutea and atrophy of the follicles (13-14/14 treated females compared to 0/15 controls). In addition, microsc opic findings consistent with uter us in estrus were observed. All changes were as expected for an estrogen agonist.Female Pubertal Assay (2013) / Page 17 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None

TABLE 7. Incidence of Histopathological Lesion s of the Liver, Kidne y, Ovary, and Uterus a

Findings Dose Level (# mg/kg/day)

Vehicle Control EE (0.003 mg/kg/day) TCVP (50 mg/kg/day) TCVP (350 mg/kg/day)

Liver 15 0 0 15 Centrilobular hepatocellular hypertrophy; total 0 0 0 10

Minimal 0 NA NA 9 Slight 0 NA NA 1 Kidney, left 15 15 15 15

Mononuclear cell infiltration
Minimal 0 0 1 0 Chronic progressive nephropathy;
total 4 4 3 7

Minimal 4 4 3 5 Slight 0 0 0 1

Moderate 0 0 0 1 Kidney, right 15 0 15 15 Chronic progressive nephropathy;
total 3 NA 2 3

Minimal 3 NA 2 2 Slight 0 NA 0 0

Moderate 0 NA 0 1 Ovary 15 14 b 15 15 Decreased corpora lutea; total 0 13 0 0

Minimal 0 1 0 0 Slight 0 4 0 0

Moderate 0 2 0 0

Marked 0 6 0 0 Atretic follicles; total 0 14 0 0

Slight 0 7 0 0

Moderate 0 4 0 0

Marked 0 3 0 0

Proestrus 4 1 4 3

Estrus 2 0 3 6

Metestrus 3 0 2 0

Diestrus 6 0 6 6

Uterus 15 15 15 15

Estrus 4 15 7 5

Metestrus 2 0 0 0

Proestrus 5 0 3 5

Diestrus 4 0 5 5 a Data were obtained from pages 470 and 471 of the study report. b This organ was missing for one animal. NA Not applicable



### III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS’ CONCLUSIONS: There were no mortalitie s, clinical signs, body weight, body weight gain, food consumption, food efficiency or macroscopic changes
associated with the administration of TCVP under the parameters of the present study. There were no changes in the incidence of or age and weight or VO attainment in females
attributable to the administration of TCVP. There were no significant changes in the mean estrus cycle length or number of cycles resu lting from the administration of TCVP. Oral administration of TCVP up to 350 mg/kg/day di d not induce organ weig ht or histologicFemale Pubertal Assay (2013) / Page 18 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### changes in the ovary or uterus of peripubertal rats. Expected changes in reference control values support the validity of this assay. Th ere were no macroscopic changes resu lting from the administration of TCVP in peripubertal females. Considered influences on the feedback loop of the thyroid-reproductive endocrine axis resulting from the administration of TCVP included statistically significant decreases in serum thyroxine concentr ation in female rats administered 350 mg/kg/day. These changes, without alteration in thyroid-stimulating hormone levels and reductions in thyroid we ight, were histological ly correlated with increased follicular cell height and decreased colloid area of th e thyroid. Without changes in serum thyroid stimulating hormone, the microsc opic changes in thyroid follicular cells were
considered the non-adverse resu lt of enzymatic induction resu lting from administration of the test substance. Adrenal weight was also significantly increased in females (50 and 350 mg/kg/day). These findings, commen surate with a lack of change in pituitary weight or TSH levels are of unknown biological significance at this time. Increased liver weights were statistically significant at the highest dose level in females and increased relative kidney weights combined with confirmed histologi c liver hepatic cell hypertrophy and kidney changes in the form of increased chr onic progressing nephrop athy (350 mg/kg/day), respectively, are considered the result of i nduction of hepatic microsomal enzymes resulting from metabolic activation by the test substan ce. Chronic progressi ve nephropathy is a common spontaneous age-related finding in adult Sprague-Dawley rats. Histologic changes in the ovaries of females administered EE, we re as expected for these substances. TCVP showed no clear clinical signs of estrogenic or anti-estrogenic ac tivity in female peripubertal rats, as defined by the testing guidelines.

B. AGENCY COMMENTS: There was no treatment-rela ted mortality, and no treatmentrelated clinical signs of toxi city were observed during the da ily examinations. There were no effects of TCVP treatment on body weight s or body weight gains. There were no treatment-related macroscopic findings at necropsy. During PND 22-29, food consumption was decreased (p<0.001) by 10% at 350 mg /kg/day. However, food consumption
rebounded and was similar to controls for the remainder of the study. This effect on food consumption did not result in an effect on body weight and was not considered to be of toxicological significance.

Relative (to body weight) liver weights were in creased (p<0.001) by 8% and absolute and relative adrenal weights were increased (p<0.001) by 30-31% at 50 mg/kg/day. At 350 mg/kg/day, absolute and relative liver weights were increased (p<0.001) by 21-25%, relative kidney weights were increased (p<0.001) by 10% , and absolute and re lative adrenal weights were increased (p<0.001) by 37-42%. The effect on adjusted kidney weight ( ↓ 7%) was minor and not statistically significant; the effect on relative kidney weight was not considered toxicologically relevant. However, there were increased incidence and severity of chronic progressive nephropat hy in the 350 mg/kg/day group compared to the control. In the liver, minimal to slight hepatocellular hypertrophy was obser ved in 10/15 females in the 350 mg/kg/day group and was considered an adaptive effect

The following changes in clinical chemistry pa rameters were observed at 350 mg/kg/day: cholesterol was increased (p<0.05) by 22%; albumin was decreased (p<0.05) by 7%; and potassium was decreased (p<0.05) by 8%. This effects were considered minor and without toxicological significance. All clinical chem istry parameters in the 50 mg/kg/day group were comparable to controls.Female Pubertal Assay (2013) / Page 19 of 19 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1450/ OECD None



### There were no effects of treatment on age a nd body weight at atta inment of VO. All females achieved complete VO. There were no effects of treatment on mean age at first vaginal estrus, mean cycle length, % cycling or regularly cycling, or cycle status at necropsy. There was a slight (NS) increase in mean cycle length with TCVP administration which was considered to be non-adverse. Corp ora lutea were present in the ovary of all individuals, and no atretic follicles were noted in controls or TCVP-treated groups.

Serum T 4 

### levels were decreased by 18% (NS) an d 65% (p<0.05) at 50 and 350 mg/kg/day, respectively. Serum TSH levels at 50 and 350 mg/kg/day were comparable to controls.Follicular cell height was increased and follicular colloid area was decreased in a dosedependent manner at 50 and 350 mg/kg/day, although the differen ces were reported to be statistically significant only in the 350 mg/kg/day group.

For animals dosed with EE, food consumption over the course of th e study was decreased (p<0.05, ↓ 9%), leading to d ecreased overall body weight gain (p<0.05, ↓ 14%). The mean age at attainment of VO was decreased (p<0.01) by 8 days (PND 25.6 treated vs. PND 33.6 controls) and body weight at attainment of VO was decreased(p<0.01) by 39%. All EEtreated females were non-cycling in consta nt estrus from PND 26 through the entire observation period. Absolute ovaries weights were decreased (p<0.001, ↓ 48%) and relative pituitary weights were increased (p<0.05, ↑ 20%). The following clinical chemistry parameters were increased (p<0.05) co mpared to controls: bilirubin ( ↑ 18%), total protein ( ↑ 9%), albumin ( ↑ 10%), globulin ( ↑ 8%), and calcium ( ↑ 4%). Many of these changes were as expected for an estrogen agonist.

C. STUDY DEFICIENCIES: The following minor deficienci es were noted that are not considered to have had an adverse impact on the results, interpretati ons or conclusions of this study:

 Performance criteria data were not reporte d, but were determined by the reviewers. Control mean adrenal glands weight ( 37.6 mg) was below the acceptable range of 38.34-48.84 mg.

# DATA EVALUATION RECORD

Tetrachlorvinphos (TCVP)

Study Type: OCSPP 890.1500, Male Pubertal Assay

EPA Contract No. EP10H001452 Task Assignment No. 4-05-2013 (MRID 49186901)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer: Signature: Kelly Luck, M.S. Date: 9/9/2013

Secondary Reviewer: Signature: Michael E. Viana, Ph.D., D.A.B.T. Date: 9/16/2013

Program Manager: Signature: Jack D. Early, M.S. Date: 09/24/2013

Quality Assurance: Signature: Jack D. Early, M.S. Date: 09/24/2013

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screenin g Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).Male Pubertal Assay (2013) I Page 1 ofll TETRACHLORVINPHOS (TCVP) I 083702 OCSPP 890.1500 I OECD None



### Primary Reviewer: Ronnie J. Bever Jr., Ph.D., DABT

# Signature:~#·~, Risk Assessment Branch VII, Health Effects Division (7509P) Date:

## ~ 

# =: Secondary Reviewer: John 

### Liccione, Ph.D. Signature: · 

# fu>

Health Effects Division Date: ://
Templat version 08/2011



### DATA EVALUATION RECORD

STUDY TYPE: Male Pubertal Assay; OCSPP 890.1500



### PC CODE: 083702 

### DP BARCODE: D413983

TXR#: 0056284 

### CAS No.: 22248- 79-9



### TEST MATERIAL fl!URITX): Tetrachlorvinphos (99.52%)



### SYNONYMS: (lZ)-2-chloro-1-(2,4,5-trichlorophenyl)ethenyl dimethyl phosphate; TCVP



### CITATION: Boulet, J. (2013). Pubertal development and thyroid function in intact juvenile/peripubertal male and female rats exposed to tetrachlorvinphos.
Product Safety Labs, Dayton, NJ. Laboratory Study No.: 33547, July 26, 2013.
MRlD 49186901. Unpublished.



### SPONSOR: The Tetrachlorvinphos (TCVP) Task Force, c/o SRA Consulting Inc., 5235 Ragged Point Road, Cambridge, MD



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In a Male Pubertal Assay (MRID 49186901), 15 Sprague Dawley [SD® IGS] rats/dose group were treated daily via oral gavage with tetrachlorvinphos (TCVP) (99.52% 

### ai; Lot# TX 100113) in aqueous 0.1% (w/v) methylcellulose at doses of 0 (vehicle), 50,

or 350 mg/kg/day from post-natal day (PND) 23 to 53/54. In addition, two separate positive
control reference groups of 15 males were dosed with either testosterone propionate (TP), via
subcutaneous injection, at 1.0 mg/kg/day, or with the androgen antagonist, flutamide (FT) via
oral gavage at 3.0 mg/kg/day. Animals from each group were examined for preputial separation (PPS) daily beginning on PND 30, and age and weight at day of attainment were recorded. Following sacrifice on PND 53 or 54, blood was collected for clinical chemistry analyses, and
total serum testosterone, thyroxine (T 

### 4), and thyroid stimulating hormone (TSH) levels were determined using a radioimmunoassay (RIA). Adrenal, liver, pituitary, thyroid, and urogenital

organs were weighed, and microscopic examinations were performed on the testes, epididymides, thyroid, liver, and kidneys.

There was no TCVP-related mortality, clinical signs of toxicity, body weights, body weight gains, food conswnption, or macroscopic pathology. There were no effects of TCVP treatment

on age and body weight at attainment of PPS. In the control group and two TCVP dose groups, 14/15 males achieved complete PPS.Male Pubertal Assay (2013) / Page 2 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### Thyroid weight was unaffected by TCVP treatment . Follicular cell heig ht was increased and colloid area was decreased in a dose-dependent manner in the 50 and 350 mg/kg/day treatment groups, with the differences being signifi cant in the 350 mg/kg/day group. Serum T 4 

### levels were decreased by 15% (not statistically significan t [NS]) and 68% (p<0.05) at 50 and 350 mg/kg/day, respectively, and serum TSH levels were in creased (NS) by 8% and 31% at 50 and 350 mg/kg/day.

There were no effects of TCVP treatment on the weights of pituitary, adrenals, seminal vesicle plus coagulating gland (with or without fluid), ventral prostate, dorsolateral prostate, levator anibulbocavernosus (LABC) muscle complex, epidid ymides, testes, or thyroid. There were no treatment-related microscopic findings in the male reproductive tissues. Serum testosterone levels were unaffected by treatment.

At 350 mg/kg/day, absolute and re lative liver weights were also increased (p<0.001) by 23-27% and absolute and relative kidney weights we re increased (p<0.05) by 11-15%. There was increased incidence (9/15) of chronic progressive nephropat hy in the 350 mg/kg/day group compared to the control (1/15). In the liver, slight to modera te hepatocellular hypertrophy was also observed in all males in the 350 mg/kg/day group.

The high dose (350 mg/kg/day) was considered to be marginally adequate based on increased liver and kidney weights and increased inci dence of chronic progressive nephropathy.

Groups receiving either with the androgen agoni st (TP) or the antagon ist (FT) showed the expected effects on sexual deve lopment and reproductive tissues. For rats receiving TP, age at attainment of PPS was decreased (p<0.01) by 5.6 days (PND 43.4 treated vs. PND 49.0 controls) and body weight at attainment of PPS was decr eased (p<0.01) by 20%. The weights of seminal vesicle plus coagulating gland (with fluid), ventral prostate, dorsolateral prostate, and LABC were increased (p<0.001, incr 77%, 50%, 29%, and 27%, respectively) and the weights of epididymides and testes were decreased (p<0.001, decr 15-16% and 48%, respectively) compared to the controls. Serum testoster one was increased (p<0.05) by 617% compared to controls. Microscopic findings attributed to TP administration included testicular degeneration and/or depletion of the round sper matids and spermatocytes, degene ration and/or depletion of the elongating spermatids, atrophy of the Leydig cells, re duction in testicular si ze, and effects in the epididymis (ductular epithelium cribiform change, sloughed germ cells, and reduced sperm) in
13-14/14 males.

For rats receiving FT, age at attainment of PPS was increased (p<0.01) by 4.7 days (PND 53.7 vs. PND 49.0). The weights of the following or gans were decreased (p<0.01) compared to controls: seminal vesicle plus coagulating gla nd with fluid (decr 52%), ventral prostate (decr 27%), dorsolateral prostate (decr 35%), LABC (decr 29%), and epididymides (decr 23-25%). Microscopic findings attributed to FT administration included hype rplasia of the Leydig cells in
the testis in 14/15 males.

The assay satisfies the EDSP Tier 1 Test Order requirement s for a Male Pubertal Assay (OCSPP 890.1500).

COMPLIANCE: Signed and dated Data Confiden tiality, GLP Compliance, and Quality Assurance statements were provided.Male Pubertal Assay (2013) / Page 3 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Product Safety Labs

Location: Dayton, NJ Study Director: J. Boulet
Other Personnel: J. D. John (Primary Scientist) D. J. Merkel (Laboratory Director) R. S. Krick (Director of Quality Assurance) C. Dunn (Technical Writing Supervisor) Study Period: July 12, 2012 to July 26, 2013



### 2. Test Substance: Tetrachlorvinphos (TCVP)
Description: Off-white to tan powder
Source: Hartz Mountain Corporation
Lot/Batch #: TX 100113 (expiration date 4/11/2013) Purity: 99.52% Stability: No data provided
CAS #: 22248-79-9
Structure:



### 3. Vehicle: 0.1% (w/v) Methylcellulose (expira tion date 8/9/2014) in reverse
osmosis deionized water

4. Test Animals:
Species: Rat
Strain: Sprague Dawley [SD® CD® IGS] Age/Weight at Study Initiation: PND 23/ 50.0 – 64.9 g

Source: Charles River Laboratories, Inc. (Raleigh, NC) Housing: Dams were individually housed in polysulfone shoebox cages with wire-mesh lids containing bedding material (Cer tified Harlan Sani Chips®). Male weanlings were housed in the same type cage at 3/cage.
Diet: Harlan Teklad 2016C diet free of alfalfa and soybean meal, ad libitum Isoflavone (genistein + daidzein aglycone equivalents) ≤ 300 μg/g

Water: Deionized (on-site) tap water , ad libitum
Environmental
Conditions: Temperature: Humidity: Air changes: Photoperiod: 23  3 °C
30-70% Not reported 14 h light/10 h dark



### B. STUDY DESIGN

1. In-Life Dates: Start: August 18, 2012 End: September 18, 2012

2. Mating: Time-mated pregnant dams were receiv ed from the supplier on gestation day (GD) 7-10 and allowed to litter normally. On PND 4, litters were culled to 8-10 pups; all litters within the study were cu lled to the same number of pups where possible. The female offspring were used in a concurrent female pubertal assay (MRID 49186901a). P O O Cl

Cl Cl Cl O CH

3

O CH

3Male Pubertal Assay (2013) / Page 4 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### 3. Animal Assignment: Offspring were weaned on P ND 21 and weighed. Male pups having a body weight within ±20% of the mean were selected and distribu ted by body weight using a stratified randomization procedure to the test groups noted in Table 1. No littermates were assigned to the same dose group. Two refere nce groups, one dosed with testosterone propionate (TP) and one dosed with flut amide (FT), were included in the study.

TABLE 1. Study Design a Test group Dose (mg/kg/day) # of Males

Control 0 15 Testosterone propionate (TP) 1.0 15 Flutamide (FT) 3.0 15 Low (TCVP) 50 15 High (TCVP) 350 15 a Data were obtained from page 19 of the study report.



### 4. Dose Selection Rationale: It was stated that the dose le vels were selected based on a preliminary range-finding study 1 

### ; however, no results of th is study were provided.

5. Dose Preparation and Analysis: Dose formulations were prepared daily by mixing appropriate amounts of test substance with 0.1% (w/v) MC in deionized water. Stirring was continuous during dose administration and formul ations were used within approximately two hours of preparation. Homogeneity was tested in the current study in both TCVP formulations by collecting samples from the top, middle, and bottom of the mixture. Samples of dose formulations from both TCVP groups were analyzed at the beginning and end of the study to evaluate achieved concentration.

Results

Homogeneity (% CV): 1.4 and 5.2%

Stability: Not tested because formulations used within two hours of preparation

Concentration (% of nominal): 91.0-100.9%

The analytical data indicated that the mixing procedure was ad equate and that the variation between nominal and actual dosage to the animals was acceptable.

6. Dosage Administration: All doses of TCVP and FT were administered once daily by gavage from PND 23 through PND 53/54, in a volume of 5.0 mL/kg of body weight. Doses
of TP were administered once daily via subcutaneous injecti on in a volume of 0.5 mL/kg of body weight. Dosing was performed in the morn ing at approximately the same time each day ± 2 hours with exception of the final da y of administration, when dosing occurred between approximately 7:00-9:00 am.

1 Charles River Laboratories (2011). Oral (gavage) repe ated dose range-finding study of tetrachlorvinphos in rats.
CRL No. 20021366.Male Pubertal Assay (2013) / Page 5 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### 7. Statistics: The following parameters were subjected to statistical analysis: body weights, body weight gains, food consumption, age and body weight at attainment of PPS, clinical chemistry, hormone levels, and organ weight s. If warranted by su fficient group sizes, untransformed data within groups were evalua ted for homogeneity of variances by Bartlett's
test. When the Bartlett’s test indicated homogeneous variances, means were compared using a One-Way Analysis of Variance ( ANOVA). When the ANOVA was significant, group means were compared using Dunnett’s test for multiple comparisons. When variances were significantly different using Ba rtlett’s test, means were compared using the non-parametric Kruskal-Wallis test. When th e Kruskal-Wallis test was significant, group means were compared using Dunn’s test. Age and body weight at PPS, and all organ weights were also analyzed by Analysis of Covariance (ANCOVA) us ing the body weight at PND 21 as the covariate. If the Shapiro-Wilk test is not significant but Levene's test is significant, a robust version of Dunnett's test was used.

Although not stated in the study re port, it appears that in ca ses where preputial separation had not occurred prior to necrops y, the last day of observation +1 was used as the age at PPS when determining the mean for each group.

Clinical pathology data were analyzed for homogeneity using Levene’s test and for normality using Shapiro-Wilk test. If these tests did not indicate significance, an ANOVA test followed by a Dunnett’s test were conducted. If data were found to be non-normal or heterogeneous, so that non-parametric tests were done, then the analyses were re-run after changing the group significan ce level to 0.05 and selecti ng Dunn as the subtest.

Incidences of follicular cell hypertrophy and asso ciated colloid area decrease in the thyroid were analyzed using a chi-squared test of a ssociation, followed by a Fisher Exact probability test using independent contingency tables. Severity scores for follicular cell hypertrophy
and associated colloid area decrease were co mpared using a Kruskal-Wallis non-parametric ANOVA, followed by a paired t-te st (Dunn’s) where appropriate.

Significance was denoted at p ≤ 0.05. The statistical analyses were considered adequate.

C. METHODS

1. Mortality and Clin ical Examinations: All animals were examined at least twice daily for mortality and moribundity. Cage -size observations we re conducted at least once daily and
detailed clinical examinati ons were conducted weekly.

2. Body Weight: Animals were weighed prior to ra ndomization, daily during the dosing period, and on the day of necropsy. Mean body weight gains were calculated for PND 23-29, 29-36, 36-43, 43-50, and for PND 23-50.

3. Food Consumption: Food consumption was measured at least weekly; the method of measuring food consumption was not reporte d. Food consumption was reported for the same intervals as body weight gains.

4. Preputial Separation (PPS): Beginning on PND 30, all animals were examined daily forMale Pubertal Assay (2013) / Page 6 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### onset of PPS. The initial and subsequent appearance of partial and/or complete PPS or the presence of persistent threads of tissue between the glans and prepuce was recorded as applicable. PPS observations were performed at approximately the same time each day. Age and weight at on the day of completion of PPS were recorded. Any animal exhibiting incomplete separation (including persistent thr eads) for greater than three days was reported and underwent a separate group analysis using the age at which partial separation was first
observed.

5. Sacrifice and Pathology: All animals were euthanized by decapitation without anesthesia on PND 53 (8 animals in each group) or 54 (7 animals in each group) at least two hours post-dosing; animals were fasted overnight prior to sacrifice. All term inal procedures were completed by 1300 hours. Blood was collected at necropsy from the abdominal aorta and centrifuged for 30 min at 4 °C to obtain se rum. Serum samples were stored at <

− 20 °C and shipped on dry ice to DuPont Haskell Globa l Centers for Health and Environmental Sciences (Newark, DE) for subsequent horm one and clinical chemistry evaluations.

a. Hormone Analysis: Total testosterone, T 4 

### , and TSH levels were dete rmined at an external laboratory (DuPont) using ra dioimmunoassay (RIA) kits.

b. Clinical Chemistry: The following CHECKED (X) parameters were examined.

ELECTROLYTES OTHER

X Calcium X Albumin
X Chloride X Creatinine* Magnesium X Urea nitrogen* X Inorganic phosphorus X Total cholesterol
X Potassium X Globulins
X Sodium X Glucose

ENZYMES X Total bilirubin X Alkaline phosphatase (ALP) X Total protein Cholinesterase (ChE) X Triglycerides Creatine phosphokinase Se rum protein electrophoresis Lactic acid dehydrogenase (LDH) X Alanine aminotransferase (ALT) X Aspartate aminotransferase (AST) X Sorbitol dehydrogenase (SDH) Gamma glutamyl transferase (GGT) Glutamate dehydrogenase

* Recommended based on Guideline 890.1500.



### c. Organ Weights and Histopathology: The following CHECKED (X) tissues were collected and weighed. The (XX) organs, in addition, were subject ed to histological
examination.Male Pubertal Assay (2013) / Page 7 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None

UROGENITAL OTHER XX Testes (left and right separately)* + XX Thyroid* + XX Epididymides (left and right separately)* + XX Liver* X Seminal vesicle plus coagulating glands (w ith and without fluid)* X Adrenals (paired)* X Ventral prostate* X Pituitary* X Dorsolateral prostate* X Levator ani-bulbocavernosus (LABC) muscle complex* XX Kidneys (paired)* + * Weights required based on Guideline 890.1500 + Histopathological examination re quired based on Guideline 890.1500



### All organs collected, except th e thyroid/trachea, were weighe d prior to fixation. Kidneys and adrenals were weighed together, and th e epididymides and testes were weighed separately. Following weighing, th e left testis and left epid idymis of all animals were preserved in modified Davidson’s fixative fo r approximately 24 hours and then transferred
to 10% neutral buffered formalin until trimmi ng/embedding. All other weighed tissues were preserved in 10% buffered formalin for at leas t 48 hrs. Following fixation, the thyroid was
dissected from the trachea. All collected ti ssues were routinely processed into paraffin blocks, sectioned, and stained with hematoxy lin and eosin. The following tissues were examined microscopically: left kidney, thyroid, left epididym is, and left testis from all animals in the study; livers from the vehicle control and high dose gr oup; and right kidney in the vehicle control and TCVP dose groups.

Histological assessment was performed by Hi sto-Scientific Research Laboratories (Frederick, MD). It was stat ed that histological evaluations were conducted in compliance with the requirements of the OCSPP 890.1450 guideli nes; however, detailed descriptions of the procedures used to evaluate tissues were not provided. Thyroid/pa rathyroid glands were subjectively graded based on the ratio of follicular epithelial cell height to colloid area using a five point grading scale, with 1 = shortest epithelium or least a bundant colloid, and 5 = tallest epithelium or most abunda nt colloid. Other histologic al findings were graded as minimal, slight, moderate, marked, or present.

II. RESULTS

A. MORTALITY: One animal in the TP dose gr oup (#7037) was found dead on PND 38 following an accidental injury during handli ng. One animal in the 350 mg/kg/day TCVP group (#7118) was euthanized for humane reas ons on PND 53, due to a suspected gavage error; prior to euthanasia, this animal was not ed as having bilateral black ocular discharge, black nasal discharge, and a firm, visible sw elling on the left forelimb severe enough to disable its use when walking. Macroscopic a nd microscopic examinations of this animal confirmed gavage error. All other ra ts survived until scheduled sacrifice.

B. CLINICAL SIGNS OF TOXICITY: No treatment-related clini cal signs of toxicity were observed during daily examinations in animal s for any dose group. The only findings noted were slight to moderate alopecia on the back of two animals in the TP dose group during PND 35-37 (#7037) a nd PND 35-45 (#7039).

C. GENERAL GROWTH AND PREPUTIAL SEPARATION: Body weights, body weight gains, age of attainment of PPS and weight at day of PPS are presented in Table 2. ThereMale Pubertal Assay (2013) / Page 8 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### were no effects of TCVP treatment on body wei ghts, overall body weight gains, or age and body weight at attainment of PPS. In the control group and two TCVP dose groups, 14/15 males achieved complete PPS. Mean daily body weight gain (not s hown in Table 2) was decreased (p<0.05) by 11% compared to c ontrols during PND 36-43; this finding was
considered to be incidental because it was a singular occurrence. Food consumption in the TCVP dose groups was comparable to cont rols over the course of the study.

For rats receiving TP, age at attainment of PPS was decreased (p<0.001) by 5.6 days (PND 43.4 treated vs. PND 49.0 controls), and body weight at attain ment of PPS was decreased (p<0.01) by 20%. Body weights and body weight gains in this group were comparable to controls throughout the study. M ean daily food consumption in this group was increased (p<0.001) by 15% on PND 23-29 and by 9% on PND 29-36, and decreased (p<0.01) by 12% on PND 43-50; mean daily food consum ption over the course of the study was comparable to controls.

For rats receiving FT, age at attainment of PPS was increased (p<0.01) by 4.7 days (PND 53.7 vs. PND 49.0). Body weights, body weight ga ins, body weight at attainment of PPS, and food consumption in this group were compar able to controls th roughout the study.

The mean age at PPS, body weight at PPS, wean ing weight, and final body weight in the control group were within the acceptable range of the performance criteria provided in the Guideline (890.1500), with the exception of mean age at PPS (49.0; acceptable range 39.781-46.513) and the %CV for body weight at PPS (8.12%; maximum of 7.57%).Male Pubertal Assay (2013) / Page 9 of 20TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1500 / OECD NoneTABLE 2. General Growth and Preputial Separation (PPS)aParameterEvaluatedVehicle ControlTP(1.0mg/kg/day)FT(3.0mg/kg/day)TCVP(50mg/kg/day)TCVP(350mg/kg/day)N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%)Initial body weight(PND 23; g)U 15 58.0 4.21 7.26 15 57.6 4.08NR 15 56.8 4.43 NR 15 57.3 4.58 7.99 15 56.9 4.88 8.58A 15 58.0 -- -- NR NR -- -- NR NR -- -- 15 57.3 -- -- 15 56.9 -- --Body weight atPPS(g)U14 252.1 20.48 8.12 14 201.7**(↓20)26.4 NR 6 270.2 36.0 NR 14 247.9 27.47 11.08 14 239.9 25.38 10.58A 14 252.1 -- -- NR NR -- -- NR NR -- -- 14 247.9 -- -- 14 239.9 -- --Final body weight(unfasted; g)U 15 285.8 17.87 6.25 14 282.7 15.3 NR 15 272.829.9 NR 15 288.6 29.07 10.07 14 274.2 18.05 6.58A 15 285.8 -- -- NR NR -- -- NR NR -- -- 15 288.6 -- -- 14 274.2 -- --Final body weight(% of control)U -- NA -- -- 14 98.9 -- -- 15 95.5 -- -- 15 101.5 -- -- 14 95.2 -- --A -- NA -- -- NR NR -- -- NR NR -- -- NR NR -- -- NR NR -- --Body weight gain(final – initial; g)U 15 227.8 17.61 7.73 NR NR -- -- NR NR-- -- 15 231.3 26.39 11.41 15 216.9 15.38 7.09A 15 227.8 -- -- NR NR -- -- NR NR -- -- 15 231.3 -- -- 15 216.9 -- --Age at PPS(PND)U 1549.0 2.59 5.29 1543.4*** 4.84 NR 15 53.7** 1.29 NR 1548.9 2.69 5.50 14 48.5 2.67 5.28A 15 49.0 -- -- NR NR -- -- NR NR -- -- 15 48.9 -- -- 14 48.5 -- --Proportionunseparated (#/N)1/15 1/15 9/15 1/15 1/15a Data were obtained from page 37, Table 4 on pages 51-56, Table 8on page 67, and Table 16 on page 91 of the study report. Percent differences from controls, calculated bythe reviewers, are included in parentheses.U Unadjusted for body weight on PND 21A Adjusted for body weight on PND 21N Number of animals examinedSD Standard DeviationCV Coefficient of VariationNA Not applicableNR Not reported** Significantly different from controls at p<0.01.*** Significantly different from controls at p<0.001.Male Pubertal Assay (2013) / Page 10 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### D. ORGAN WEIGHTS: Organ weights at necropsy are presented in Table 3. At 50 mg/mg/day, relative (to body weight) liver weights were increased (p<0.05) by 6% compared to controls. At 350 mg/kg/day, abso lute and relative liver and kidney weights were increased (p<0.05) by 23-27% and 11-15%, respectively. There were no effects of TCVP treatment on the weights of pituitary, adrenals, seminal vesicle plus coagulating gland (with or without fluid), ventral prostate, dorsolateral prostate, LABC, epididymides, testes, or thyroid.

For rats in the group receiving TP, the weight s of seminal vesicle plus coagulating gland with fluid, ventral prostate , dorsolateral prostate, and LABC were increased (p<0.001, ↑ 77%, 50%, 29%, and 27%, respectiv ely), and the weights of epididymides and testes were decreased (p<0.001, ↓ 15-16% and 48%, respectively) compar ed to the controls. There were no effects on the weights of liver, kidne y, pituitary, adrenals, or thyroid.

For rats in the group receiving FT, the wei ghts of the following organs were decreased (p<0.01) compared to controls: seminal ve sicle plus coagulating gland with fluid ( ↓ 52%), ventral prostate ( ↓ 27%), dorsolateral prostate ( ↓ 35%), LABC ( ↓ 29%), and epididymides ( ↓ 23-25%). There were no effects on the weights of liver, kidney, pituitary, adrenals, testes, or thyroid.

The unadjusted values for all organ weights in the control group were within the acceptable range of the performance criteria provided in the Guideline (890.1500) , with the exception of mean liver weight (8.845 g; acceptabl e range 9.990-15.350 g), mean kidneys weight (2.024 g; acceptable range 2.242-3.050 g), and % CV for mean pituitary weight (16.57%; maximum of 15.98%).Male Pubertal Assay (2013) / Page 11 of 20TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1500 / OECD NoneTABLE 3. Organ Weights at NecropsyaOrganVehicle ControlTP(1.0mg/kg/day)FT(3.0mg/kg/day)TCVP(50mg/kg/day)TCVP(350mg/kg/day)N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%)Liver(g)U15 8.845 0.939 10.62 14 8.556 0.771 NR 15 8.595 1.410 NR 15 9.525(↑8)1.07 11.23 14 10.859***(↑23)0.681 6.27A 15 8.845 -- -- NR NR -- -- NR NR -- -- 15 9.525 -- -- 14 10.859 -- --R15 3.248 0.215 6.61 14 3.1530.200 NR 15 3.273 0.172 NR 15 3.438*(↑6)0.126 3.65 14 4.133***(↑27)0.126 3.04Kidneys(g)U15 2.024 0.209 10.33 14 2.061 0.131 NR 151.906 0.218 NR 15 2.084 0.217 10.41 14 2.248*(↑11)0.213 9.48A 15 2.024 -- -- NR NR -- -- NR NR -- -- 15 2.084 -- -- 14 2.248 -- --R15 0.744 0.053 7.08 14 0.760 0.039 NR 150.730 0.045 NR 15 0.754 0.046 6.16 14 0.854***(↑15)0.043 5.05Pituitary(mg)U 15 10.32 1.71 16.57 14 9.95 1.88 NR 14b10.91 1.22 NR 15 10.40 2.0719.90 14 9.62 1.43 14.86A 15 10.32 -- -- NR NR -- -- NR NR -- -- 15 10.40 -- -- 14 9.62 -- --R 15 0.0038 0.0007 19.4 14 0.0037 0.001 NR 14 0.00410.0004 NR 15 0.0038 0.001 26.5 14 0.0037 0.0005 13.6Adrenals(mg)U 14 47.21 6.72 14.23 14 50.363.87 NR 15 45.81 8.61 NR 14c52.47 10.84 20.66 13c48.96 6.87 14.03A 14 47.21 -- -- NR NR -- -- NR NR -- -- 14 52.47 -- -- 13 48.96 -- --R 14 0.0172 0.0022 12.62 14 0.0186 0.002 NR 15 0.01750.002 NR 14 0.0190 0.0033 17.24 13 0.0188 0.0027 14.24Seminal vesicle +coagulating gland,with fluid (mg)U15 498.89 130.81 26.22 14 881.5***(↑77)181.9 NR 15 238.2***(↓52)92.62 NR 15 483.49 123.53 25.55 14 454.45 111.41 24.52A 15 498.89 -- -- NR NR -- -- NR NR -- -- 15 483.49 -- -- 14 454.45 -- --Seminal vesicle +coagulating gland,without fluid (mg)U15 281.79 48.99 17.39 13c383.13***(↑36)58.72 NR 15 155.49***(↓45)42.80 NR 15 271.14 55.66 20.53 14 257.37 67.14 26.09A 15 281.79 -- -- NR NR -- -- NR NR -- -- 15 271.14 -- -- 14 257.37 -- --Ventral prostate(mg)U15 235.59 52.20 22.16 14 353.23***(↑50)77.32 15 15 172.05**(↓27)38.47 NR 15 230.13 43.98 19.11 14 209.81 40.37 19.24A 15 235.59 -- -- NR NR -- -- NR NR -- -- 15 230.13 -- -- 14 209.81 -- --Dorsolateralprostate(mg)U15 161.53 31.88 19.74 14 209.0***(↑29)39.07 NR 15 104.8***(↓35)26.72 NR 15 156.59 27.93 17.84 14 146.41 33.05 22.57A 15 161.53 -- -- NR NR -- -- NR NR -- -- 15 156.59 -- -- 14 146.41 -- --LABC(mg)U15 593.95 97.26 16.38 14 755.3***(↑27)64.08 NR 15 420.57***(↓29)58.02 NR 15 567.85 81.64 14.38 14 546.04 50.19 9.19A 15 593.95 -- -- NR NR -- -- NR NR -- -- 15 567.85 -- -- 14 546.04 -- --Epididymis, left(mg)U15 217.25 20.13 9.27 14 182.02***(↓16)12.18 NR 15 166.57***(↓23)23.94 NR 15 214.68 19.52 9.0914 209.95 18.25 8.69A 15 217.25 -- -- NR NR -- -- NR NR -- -- 15 214.68 -- -- 14 209.95 -- --Male Pubertal Assay (2013) / Page 12 of 20TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1500 / OECD NoneTABLE 3. Organ Weights at NecropsyaOrganVehicle ControlTP(1.0mg/kg/day)FT(3.0mg/kg/day)TCVP(50mg/kg/day)TCVP(350mg/kg/day)N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%)Epididymis, right(mg)U15 218.81 25.2 11.52 14 186.86***(↓15)17.46 NR 15 164.73***(↓25)23.69 NR 15 213.72 20.02 9.37 14 211.59 21.48 10.15A 15 218.81 -- -- NR NR -- -- NR NR -- -- 15 213.72 -- -- 14 211.59 -- --Testis, left(mg)U15 1373.3 116.82 8.51 14 720.7***(↓48)119.6 NR 15 1297.78 258.5 NR 15 1388.8 115.16 8.29 14 1389.75 105.32 7.58A 15 1373.3 -- -- NR NR -- -- NR NR -- -- 15 1388.8 -- -- 14 1389.75 -- --Testis, right(mg)U15 1370.1 115.31 8.42 14 709.7***(↓48)119.7 NR 15 1301.14 264.8 NR 15 1375.4 99.31 7.22 14 1399.77 106.31 7.59A 15 1370.1 -- -- NR NR -- -- NR NR -- -- 15 1375.4 -- -- 14 1399.77 -- --Thyroid, fixed(mg)U 15 14.733 1.186 8.05 14 14.0340.791 NR 15 14.721 0.819 NR 14b14.258 1.412 9.90 13b14.607 0.966 6.61A 15 14.733 -- -- NR NR -- -- NR NR -- -- 14 14.258 -- -- 13 14.607 -- --a Data were obtained from Table 14 on pages84-86, Table 15 on page 89, and Table 17 onpages 92 and 93 of the study report. Percent differences from vehicle controls,calculated by the study reviewer, are included in parentheses.b The weight for this organ in one animal was reported to be “Not Taken” without explanation.c The weight for the organ in oneanimal was excluded because itwas damaged during procurement orincluded extraneous tissue or fluid.U Unadjusted for body weight on PND 21A Adjusted for body weight on PND 21R Organ-to-body weight ratio (relative to body weight); reported results were corrected by the study reviewer to reflect ratioas percent.N Number of animals examinedSD Standard DeviationCV Coefficient of Variation* Significantly different from controls at p<0.05.** Significantly different from controls at p<0.01.*** Significantly different from controls at p<0.001.Male Pubertal Assay (2013) / Page 13 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### E. CLINICAL CHEMISTRY AND HORMONE LEVELS: Mean hormone and clinical chemistry levels are presented in Table 4. Serum testosterone leve ls were unaffected by
TCVP treatment. Serum T 4 

### levels were decreased by 15% (NS) and 68% (p<0.05) at 50 and 350 mg/kg/day, respectively, and there were non- significant increases in TSH levels at 50 ( ↑ 8%) and 350 ( ↑ 31%) mg/kg/day. The following changes in clinical chemistry parameters were observed at 50 and 350 mg/kg/day: AS T was decreased (p<0.05) by 23% and 21%, respectively; and globulin was increased (p<0.05) by 9% at both doses. All other clinical chemistry parameters in the 50 and 350 mg/kg/ day groups were comparable to controls.

For rats receiving TP, serum testosterone wa s increased (p<0.05) by 617% compared to
controls. Serum T 4 

### and TSH levels and all clinical ch emistry parameters were comparable to controls. For rats receiving FT , bilirubin was increased (p<0.05; ↑ 18%) compared to controls; all other clinical chemistry paramete rs and hormone levels were comparable to
controls.

The results for serum T 4 

### , TSH, and testosterone in th e control group were within the acceptable range of the performance criter ia provided in the Guideline (890.1500).
Historical control data were provided for the following parameters: AST (103-245 U/L), bilirubin (0.1-0.16 mg/dL), and gl obulin (2.0-2.6 g/dL). The mean results for the control and all dose groups were within the historical data ranges.Male Pubertal Assay (2013) / Page 14 of 20TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1500 / OECD NoneTABLE 4. Hormone Levelsand Clinical ChemistryaParameterEvaluatedVehicle ControlTP(1.0mg/kg/day)FT(3.0mg/kg/day)TCVP(50mg/kg/day)TCVP(350mg/kg/day)N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%)HormonesSerum T4, Total(μg/dL)15 5.718 0.837 14.6 14 4.846 0.66016.2 15 5.563 1.229 22.1 15 4.836(↓15)1.279 26.5 14 1.836*(↓68)0.467 25.4Serum TSH(ng/mL)15 8.982 3.45 38.4 14 7.848 3.442 43.9 15 10.949 13.922 127 15 9.669(↑8)4.626 47.8 14 11.801(↑31)5.646 47.8Serumtestosterone(ng/mL)12b1.394 1.126 80.8 13c9.995*(↑617)2.578 25.8 15 3.495 4.064 116 13d1.061 0.648 61.1 12d1.228 0.693 56.4Clinical ChemistryAST (U/L) 15 159 37 23 14 132 31 23 15 149 50 34 15 123*(↓23)37 30 14 126*(↓21)50 39ALT (U/L) 15 50 6 12 14 46 7 15 15 53 9 17 15 48 7 15 14 51 9 18SDH (U/L) 15 7.0 2.1 30 14 7.1 2.8 39 157.9 5.6 71 15 6.6 1.9 29 14 6.2 2.5 40ALP (U/L) 15 242 47 19 14 247 53 21 15 287 53 18 15 265 65 25 14 238 53 22Bilirubin (mg/dL) 15 0.12 0.02 17 14 0.13 0.02 15 15 0.15*(↑18)0.03 20 15 0.12 0.02 17 14 0.11 0.01 9Blood ureanitrogen (mg/dL)15 12 2 17 14 12 2 17 15 13 3 23 15 13 2 15 14 14 2 14Cholesterol(mg/dL)15 99 21 21 14 101 23 23 15 111 18 16 15 115 20 17 14 112 16 14Creatinine(mg/dL)15 0.24 0.04 17 14 0.24 0.03 13 15 0.26 0.05 19 15 0.23 0.03 13 14 0.25 0.02 8Triglycerides(mg/dL)15 94 32 34 14 73 32 44 15 91 34 37 15 113 39 35 14 85 43 51Glucose (mg/dL) 15 111 16 14 14 105 11 10 15 111 14 13 15 100 12 12 14 102 12 12Total protein(g/dL)15 5.5 0.3 5 14 5.5 0.3 5 15 5.70.3 5 15 5.7 0.2 4 14 5.7 0.3 5Albumin (g/dL) 15 3.2 0.2 6 14 3.2 0.26 15 3.3 0.1 3 15 3.2 0.1 3 14 3.2 0.2 6Globulin (g/dL) 15 2.3 0.2 9 14 2.4 0.1 4 15 2.4 0.2 8 15 2.5*(↑9)0.2 8 14 2.5*(↑9)0.2 8Calcium (mg/dL) 15 11.0 0.4 4 14 10.9 0.33 15 11.1 0.4 4 15 11.1 0.4 4 14 11.1 0.2 2Inorganicphosphorus(mg/dL)15 10.2 0.4 4 14 9.8 0.4 4 15 10.20.4 4 15 10.2 0.6 6 14 10.8 0.5 5Sodium (mmol/L) 15 138.5 2.8 2.014 138.7 1.8 1.3 15 137.9 2.0 1.515 139.0 2.2 1.6 14 137.7 1.3 0.9Male Pubertal Assay (2013) / Page 15 of 20TETRACHLORVINPHOS (TCVP) / 083702OCSPP 890.1500 / OECD NoneTABLE 4. Hormone Levelsand Clinical ChemistryaParameterEvaluatedVehicle ControlTP(1.0mg/kg/day)FT(3.0mg/kg/day)TCVP(50mg/kg/day)TCVP(350mg/kg/day)N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%) N Mean SDCV(%)Potassium(mmol/L)15 7.05 0.50 7.1 14 6.93 0.41 5.9 15 7.03 0.32 4.6 15 6.80 0.51 7.5 14 6.73 0.35 5.2Chloride(mmol/L)15 98.7 2.0 2.0 14 99.5 1.2 1.2 15 98.7 1.9 1.9 15 99.6 2.2 2.2 14 98.3 1.4 1.4a Data were obtained from Table 11 on page70, Table 12 on pages 72-76, and Table 16 onpage 94 of the study report. Percent differences from controls are included inparentheses.b For 3 of the animals in this group, serum testosterone was found to be below the lower limit of quantitation, which was not defined. These results were not included in thecalculation of mean, SD, and CV.c For 1 of the animals in this group, serum testosterone was found to be above the upper limit of quantitation, which was not defined. This result was not included in thecalculation of mean, SD, and CVd For 2 of the animals in this group, serum testosterone was found to be below the lower limit of quantitation, which was not defined. These results were not included in thecalculation of mean, SD, and CV.N Number of animals examinedSD Standard DeviationCV Coefficient of Variation; calculated by the study reviewerfor all results for the EE dose group and for clinical chemistryparameters, except creatinine and blood ureanitrogen, for the control and TCVP dose groups.* Significantly different from controls at p<0.05.** Significantly different from controls at p<0.01.Male Pubertal Assay (2013) / Page 16 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### F. MACROSCOPIC EXAMINATIONS: There were no treatment-related macroscopic findings at necropsy.

G. HISTOPATHOLOGY: The incidences of histopathologi cal findings of the thyroid gland are presented in Table 5. Follicular cell height was increased and follicular colloid area was decreased in the 50 and 350 mg/kg/day treatment groups; it was reported that the differences were only statistically significan t in the 350 mg/kg/day group.

TABLE 5. Thyroid Gland Follicular Cell Height and Colloid Area a

Findings Vehicle Control TP (1.0 mg/kg/day) FT (3.0 mg/kg/day) TCVP (50 mg/kg/day) TCVP (350 mg/kg/day)

Number of
animals
examined 15 14 15 14 c 14 c

Follicular cell height b

1 11 10 12 8 4

2 4 3 3 3 8

3 0 1 0 2 1

4 0 0 0 1 1

5 0 0 0 0 0

Follicular colloid area b

1 0 0 0 0 0

2 0 0 0 1 1

3 0 1 0 2 1

4 4 3 3 3 8

5 11 10 12 8 4 a Data were obtained from pages 634, 636, 637, 639, 640, and 641 of the study report. b A five-point grading scale (1 = shortest / smallest; 5 = tallest / largest) was used. c The results for one animal were reported to be missing.



### The incidences of histopathological findings of the liver, testes, epididymides and kidneys are presented in Table 6. There was increase d incidence of chronic progressive nephropathy in the 350 mg/kg/day group (9/15 rats) compared to the control (1/15 rats). In the liver, slight to moderate hepatocellular hypertrophy, unaccompanied by hepatocellular hyperplasia, necrosis, or in flammation, was characterized by increased size of the hepatocytes of the centrilobul ar zone, often extending in to the midlobular/midzonal hepatocytes, in all males in the 350 mg/ kg/day TCVP group (15/15 rats) compared to controls (0/15 rats).

Microscopic findings attributed to TP administration included te sticular degeneration and/or depletion of the round spermatids and sperma tocytes (affecting early stage tubules), degeneration and/or depletion of the elongating spermatids (affecting early and late stage tubules), and atrophy of the Leydi g cells in all males. Epididymal changes were secondary to the testicular changes and included the presence of lumi nal sloughed germ cells/cellular debris, reduced sperm, and cribriform change of the ductular epithelium in 13-14/14 males. These changes were as expect ed for an androgen agonist.Male Pubertal Assay (2013) / Page 17 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### Microscopic findings attributed to FT administration incl uded hyperplasia of the Leydig cells in the testis in 14/15 males, expect ed for an androgen an tagonist. In addition, epididymal changes included the presence of luminal sloughed germ cells/cellular debris, reduced sperm, and cribriform change of the ductular epithelium in 1/15 males.

TABLE 6. Incidence of Histopatho logical Lesions of the Liver, Testes, Epididymides, and Kidney a

Findings Dose Level (# mg/kg/day)

Vehicle
Control TP (1.0 mg/kg/day) FT (3.0 mg/kg/day) TCVP (50 mg/kg/day) TCVP (350 mg/kg/day)

Liver 15 0 0 0 15 Vacuolation; Tota l 1 NA NA NA 3

Minimal 1 NA NA NA 2 Slight 0 NA NA NA 1
Centrilobular hepatocellular hypertrophy; Total 0 NA NA NA 15 Slight 0 NA NA NA 9

Moderate 0 NA NA NA 6 Mononuclear infiltration;
Minimal 4 NA NA NA 0 Kidney, left 15 14 15 15 15

Mononuclear cell infiltration; Minimal 0 1 0 1 0 Chronic progressive nephropathy; Total 1 5 4 5 9

Minimal 1 5 4 4 9 Slight 0 0 0 1 0 Kidney, right 15 0 0 15 15

Mononuclear cell infiltration; Minimal 1 NA NA 1 1 Chronic progressive nephropathy; Total 5 NA NA 6 8

Minimal 5 NA NA 6 5 Slight 0 NA NA 0 3 Epididymis (left) 15 14 15 15 15 Ductular epithelium: cribriform change; Total 0 13 1 0 0

Minimal 0 1 0 0 0 Slight 0 10 1 0 0

Moderate 0 2 0 0 0 Sloughed germ cells; Total 0 14 1 0 0

Minimal 0 2 1 0 0 Slight 0 11 0 0 0

Moderate 0 1 0 0 0 Reduced sperm; Total 0 14 1 0 0

Minimal 0 1 0 0 0 Slight 0 1 0 0 0

Moderate 0 6 0 0 0

Marked 0 6 1 0 0 Testis (left) 15 14 15 15 15 Tubular atrophy
Marked 0 0 1 0 0 Leydig cell: hyperplasia;
Total 0 0 14 0 0

Minimal 0 0 12 0 0 Slight 0 0 2 0 0Male Pubertal Assay (2013) / Page 18 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None

TABLE 6. Incidence of Histopatho logical Lesions of the Liver, Testes, Epididymides, and Kidney a

Findings Dose Level (# mg/kg/day)

Vehicle
Control TP (1.0 mg/kg/day) FT (3.0 mg/kg/day) TCVP (50 mg/kg/day) TCVP (350 mg/kg/day) Degeneration/depletion round spermatids and spermatocytes; Total 0 14 0 0 0 Slight 0 11 0 0 0

Moderate 0 3 0 0 0 Degeneration/depletion elongating spermatids;
Total 0 14 0 0 0 Slight 0 4 0 0 0

Moderate 0 8 0 0 0

Marked 0 2 0 0 0 Leydig cell atrophy; Total 0 14 0 0 0 Slight 0 1 0 0 0

Moderate 0 7 0 0 0

Marked 0 6 0 0 0 Reduced size; Total 0 14 0 0 0

Minimal 0 1 0 0 0 Slight 0 11 0 0 0

Moderate 0 2 1 0 0 a Data were obtained from pages 468 and 469 of the study report. NA Not applicable



### III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: There were no mortalitie s, clinical signs, body weight, body weight gain, food consumption, food efficiency or macroscopic changes
associated with the administration of TCVP under the parameters of the present study. There were no changes in the incidence of or age and weight at PPS attainment in males
attributable to the administration of TCVP . Oral administration of TCVP up to 350 mg/kg/day did not induce organ we ight or histologic changes in the testis or epididymis of peripubertal rats. Expected changes in refere nce control values suppor t the validity of this assay. There were no macroscopic changes resulting from the administration of TCVP in peripubertal males. Considered influences on the feedback loop of th e thyroid-reproductive endocrine axis resulting from the administrati on of TCVP included stat istically significant
decreases in serum T 4 

### concentration in male rats administered 350 mg/kg/day. These changes, without alteration in TSH levels a nd non-statistically si gnificant reductions in thyroid weight, were histologically correlated with increased follicular cell height and decreased colloid area of the thyroid. Wit hout changes in serum TSH, the microscopic changes in thyroid follicular cells were c onsidered the non-adverse result of enzymatic induction resulting from administration of the test substance. Increased liver weights were statistically significant at th e highest dose level in males and increased kidney weights combined with confirmed histologic liver hepatic cell hypertrophy and kidney changes in
the form of increased chroni c progressing nephropathy (350 mg /kg/day), respectively, are considered the result of induction of hepati c microsomal enzymes resulting from metabolic
activation of the test substance. Chronic progressive nephropathy is a common spontaneous age-related finding in adult Spra gue-Dawley rats. Histologic changes in the testes and epididymis in males administered TP and FT were as expected for these substances. TCVPMale Pubertal Assay (2013) / Page 19 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### showed no clear clinical signs of androgenic or anti-androgenic activity in male peripubertal rats, as defined by the testing guidelines.

B. AGENCY COMMENTS: There was no TCVP-related mort ality, and no treatment-related clinical signs of toxicity were observed during the daily examinations. There were no effects of TCVP treatment on body weights, body weight gains, or food consumption. There were no treatment-related macroscopic fi ndings at necropsy, and there were no effects of TCVP treatment on age and body weight at atta inment of PPS. In the control group and two TCVP dose groups, 14/15 males achieved complete PPS.

For the TCVP treated groups, there was no e ffect on the weights of male reproductive tissues, pituitary, adrenals, or thyroid. However, relative (to body weight) liver weights were increased (p<0.05) by 6% at 50 mg/kg/day (a minor effect ), and absolute and relative liver weights were increased (p<0.001) by 23- 27% at 350 mg/kg/day. In addition, absolute and relative kidney weights were increased (p<0.05) by 11-15% at the high dose. There was increased incidence of chronic progressi ve nephropathy in the 350 mg/kg/day group compared to the control. In the liver, sli ght to moderate hepatocellular hypertrophy was observed in all males in the 350 mg/kg/day group.

Serum testosterone levels were una ffected by TCVP treatment. Serum T 4 

### levels were decreased by 15% (NS) and 68% (p<0.05) at 50 and 350 mg/kg/day, re spectively, and there were non-significant increases in in serum TSH levels of 8% and 31% at 50 and 350 mg/kg/day, respectively. Although thyroid weig hts were unaffected by TCVP treatment, follicular cell height was increased and colloid area was decreased in a dose-dependent manner in the 50 and 350 mg/kg/day treatment groups, with the changes reportedly being statistically significant in the 350 mg/kg/day group.

The following changes in clinical chemistr y parameters were observed at 50 and 350 mg/kg/day: AST was decreased (p<0.05) by 23 and 21%, respectively; and globulin was increased (p<0.05) by 9% at both doses. Thes e changes were not considered adverse. All other clinical chemistry parameters in the 50 and 350 mg/kg/day groups were comparable to
controls.

The high dose (350 mg/kg/day) was consider ed to be marginally adequate based on increased liver and kidney weights and in creased incidence of chronic progressive nephropathy.

For rats receiving TP, age at attainment of PPS was decreased (p<0.01) by 5.6 days (PND 43.4 treated vs. PND 49.0 controls) and body wei ght at attainment of PPS was decreased (p<0.01) by 20%. The weights of seminal vesi cle plus coagulating gland (with fluid), ventral prostate, dorsolateral prosta te, and LABC were increased (p<0.001, ↑ 77%, 50%, 29%, and 27%, respectively), and the weights of epididymides and testes were decreased (p<0.001, ↓ 15-16% and 48%, respectively) compared to the controls. Serum testosterone was increased (p<0.05) by 617% compared to co ntrols. Microscopic fi ndings attributed to
TP administration included tes ticular degeneration and/or de pletion of the round spermatids and spermatocytes, degeneration and/or deplet ion of the elongating sp ermatids, atrophy of the Leydig cells, reduction in testicular size, and effects in the epididymis (ductularMale Pubertal Assay (2013) / Page 20 of 20 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1500 / OECD None



### epithelium cribiform change, sloughed germ cells , and reduced sperm) in 13-14/14 males. These changes were as expect ed for an androgen agonist.

For rats receiving FT, age at attainment of PPS was increased (p<0.01) by 4.7 days (PND 53.7 vs. PND 49.0). The weights of the follo wing organs were decreased (p<0.01) compared to controls: seminal vesicl e plus coagulating gland with fluid ( ↓ 52%), ventral prostate ( ↓ 27%), dorsolateral prostate ( ↓ 35%), LABC ( ↓ 29%), and epididymides ( ↓ 23-25%). Microscopic findings attributed to FT administration incl uded hyperplasia of the Leydig
cells in the testis in 14/15 males. Thes e changes were as expected for an androgen antagonist.

C. STUDY DEFICIENCIES: The following deficiencies were noted that are not considered to have had an adverse impact on the results, interpretation or conclusions of this study:

The following parameters did not satisfy the Guideline performance criteria for controls:

 Mean age at PPS was 49.0 (acceptable range 39.781-46.513)

 %CV for body weight at PPS was 8.12% (maximum 7.57%)

 Mean liver weight was 8.845 g (acceptable range 9.990-15.350 g)

 Mean kidneys weight was 2.024 g (acceptable range 2.242-3.050 g)

 % CV for mean pituita ry weight was 16.57% (maximum of 15.98%)

# DATA EVALUATION RECORD

TETRACHLORVINPHOS (TCVP)

Study Type: OCSPP 890.1550, Steroidogenesis Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-42-2013 (MRID 48805201)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer: Signature: Scott D. Studenberg, Ph.D., D.A.B.T. Date: 2/08/2013

Secondary Reviewer: Signature: Michelle J. Sharpe-Kass, M.S. Date: 2/15/2013

Program Manager: Signature: Jack D. Early, M.S. Date: 2/20/2013

Quality Assurance: Signature: Jack D. Early, M.S. Date: 2/20/2013

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel

.

### The US EPA Endocrine Disruptor Screenin g Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).TETRACHLORVINPHOS TCVP I 083702



## Primary Reviewer: Linda Tavlor. Ph.D. 

## Health Effects Division 

## Secondary Reviewer: John Liccione. Ph.D.
Health Effects Division Steroidogenesis Assay (2012) I Page 1 of 15
OCSPP 890. 550/ OECD 456

# Signatur;;e:~;2~~;~-- Date:**---¥-4:......A-~...L....-**



### DATA EVALUATION RECORD

STUDY TYPE: Steroidogenesis Assay (H295R Cells); OCSPP 890.1550



### PC CODE: 083702 

### DP BARCODE: D4016 l 9

TXR#: 0056284 

### CAS No.: 22248- 79-9



### TEST MATERIAL <PURITY): Tetrachlorvinphos (100.05%)



### SYNONYMS: (lZ)-2-chloro-1-(2,4,5-trichlorophenyl) ethenyl phosphate; TCVP



### CITATION: Hofman-Huther, H. (2012). Endocrine Disruptor Test: 

### In vitro Steroidogenesis Assay with Tetrachlorvinphos (TCVP). BSL Bioservice, Scientific Laboratories GmbH, Planegg, Germany. Laboratory Study No.: 114586, April 04, 2012.

MRID 48805201. Unpublished.



### SPONSOR: The Tetrachlorvinphos (TCVP) Task Force, c/o SRA International Inc., 5235 Ragged Point Road, Cambridge, MD



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In a steroidogenesis assay (MRJD 48805201 ), H295R cells
cultured 

### in vitro in 24-well plates were incubated with TCVP (100.05% purity, Batch# TX 100113) at serial log concentrations from 0.0000001to100 μMin triplicate for 48 hours. Dimethyl sulfoxide (DMSO) was used as a vehicle, at a final assay concentration of 0.1 %. Only

two independent experiments were performed, rather than the Guideline recommended three



## runs.

Testosterone and estradiol concentrations were measured using an enzyme-linked
immunosorbent assay (ELISA) method. A Quality Control (QC) plate was run concurrently with
each independent run of a test chemical plate to demonstrate that the assay responded properly to positive control agents at two concentration levels; positive controls included the known
inhibitor (prochloraz) and inducer (forskolin) of estradiol and testosterone production. The highest concentration of TCVP suitable for evaluation was 10 μM due to cytotoxicity observed

at 100 μM TCVP in both runs; half log or intermediate concentrations were not investigated.

Minimum basal hormone production for testosterone**(~500** 

### pg/mL) was not met in any blank or solvent control (SC) wells (mean testosterone values were :5180 pg/mL), but minimum basal production of estradiol**(~40** 

### pg/mL) was achieved. The reviewers could not determine if basal
hormone production met the fold-increase criteria in the SC wells of2::5-fold for testosterone andSteroidogenesis Assay (2012) / Page 2 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### ≥ 2.5-fold for estradiol above the minimum determ ination limit (MDL) of the assay because the MDLs for the ELISA were not reported.

On the QC plates, exposure to 10 μM fo rskolin induced testosterone production ≥ 2-fold and estradiol production ≥ 7.5-fold over SC. Exposure to 1 μM prochloraz inhibited synthesis of testosterone by 2.22% and 84.62%, and inhibited estradiol sy nthesis by 47.96% and 56.69%, relative to the SC (Guideline recommendation is ≥ 50% inhibition). The mean fold-change data did not meet the performance criteria recomm ended by the Guideline, and there was a high degree of variability in testoste rone induction (forskolin) and i nhibition (prochloraz) responses between the two assay runs. In Run 1, the induction of testoster one in the presence of 1 μM forskolin was approximately 7-fold greater than the induction achieved at 10 μM forskolin. The
testosterone induction at 1 μ M forskolin in Run 1 was also approximately 7-fold greater than the response to 1 μM forskolin in Run 2. Inhibiti on of testosterone synthe sis in the presence of 0.1 μM prochloraz varied approximately 18-fold be tween the two assay runs (fold differences of 7.27 versus 0.43). This variability may be associated with poor analytical performance of the ELISA or poor cell response; howev er, the reviewer’s assessment was hampered by the lack of methodological details and pr oficiency testing data.

Only a single hormone concentration value for te stosterone and estradiol, respectively, was reported for the SC replicates for each assay run; no distinction between SC values for the test or QC plates was provided. The % CVs for absolu te testosterone concentrations for the SC replicates within the test pl ates were 50% and 26%; theref ore, only the second run met the ≤ 30% performance criteria recommended in the Test Gu ideline. The % CVs for absolute estradiol concentrations for the SC replicates within the test plates were 17% and 9%, with both values meeting the recommended performance criteria. The between-plate % CVs for the absolute hormone concentrations in the SC, which were 58% for testosterone and 38% for estradiol, were greater than the recommende d performance criteria of ≤ 30%. All % CV determinations were calculated by the reviewers.

With regards to the effects of TCVP, the results fr om the two runs were vari able for testosterone. In Run 1, there was a 22.4-fold induction in te stosterone production at 10 μM TCVP, but no induction ( ≤ 0.70-fold) was observed at the other reporte d TCVP concentrations, and there was a
marked inhibition in testosterone production (0.26-fold) at the lowest concentration of TCVP (0.000001 μ M). In Run 2, no induction or inhibition of testosterone pr oduction (0.87- to 1.24- fold) was observed at 0.000001 to 10 μ M TCVP, but there was again a marked reduction in testosterone (0.32-fold) at the lowest TCVP concentration tested (0.0000001 μ M). For estradiol production, there was no consiste nt induction or inhibition in either run at 0.000001 to 10 μ M TCVP, with fold-change values ranging from 0.8 0- to 1.70-fold in Run 1 and 0.83- to 1.14-fold in Run 2. Although the results of the assay do not indicate a role for TCVP as an inhibitor or inducer of testosterone or estradiol producti on, the num erous deficiencies noted in the study preclude making a definitive conclusion with re gards to the effects of TCVP on hormone production in this assay.

The assay does not satisfy the EDSP Tier 1 Test Order requir ements for a Steroidogenesis assay (OCSPP 890.1550) because only two of the three experimental runs were conducted and a number of performance criteria were not met.Steroidogenesis Assay (2012) / Page 3 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### COMPLIANCE: Signed and dated Data Confidentia lity, GLP Compliance, Flagging and Quality Assurance statements were provided.Steroidogenesis Assay (2012) / Page 4 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: BSL Bioservice, Scientif ic Laboratories GmbH

Location: 

### Planegg, Germany
Study Director: H. Hofman-Hüther Study Period: October 25, 2011 to April 04, 2012



### 2. Test Substance: Tetrachlorvinphos (TCVP)
Description: Powder
Source: TCVP Task Force
Lot #: Purity: TX 10113 (expiry date not provided; expiration date 6/16/12?)
100.05% Solubility (in Solvent): Soluble in DMSO up to 100 mM Stability: Stability in test preparations was not conducted. Storage conditions: Room temperature, protected from light.
CAS #: 22248-79-9 Molecular weight: 365.96
Structure:

P O O Cl

Cl Cl Cl O CH

3

O CH

3



### 3. Positive Control (Inducer): Forskolin
Description: Not reported (NR)
Source: Sigma Aldrich (F6886) Lot #: (Expiration Date): NR Purity: 98% Solubility (in Solvent): Soluble in DMSO up to 100 mM Storage conditions: NR CAS #: 66575-29-9



### 4. Positive Control (Inhibitor): Prochloraz
Description: NR
Source: Sigma Aldrich (45631) Lot #: (Expiration Date) NR Purity: 99% Solubility (in Solvent): Soluble in DMSO up to 100 mM Storage conditions: NR CAS #: 67747-09-5



### 5. Solvent/Vehicle Control: Dimethyl Sulfoxide (DMSO)
Description: NR
Source: NR Lot #: (Expiration Date) NR Purity: NR Storage conditions: NR
Justification for choice of solvent: NR (TCVP, forskolin, and prochloraz soluble at test concentrations)
Final concentration: (% volume in assay) 0.1% (v/v)Steroidogenesis Assay (2012) / Page 5 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### 6. Stock Medium: Dulbecco’s modified Eagle’s medium/Ham’s F12 nutrient mixture (DMEM/Ham-F12)
Description: Without phenol red
Source: Invitrogen Lot / Batch #: (Expiration Date) NR

Sodium bicarbonate: NR
Nu-Serum: Source NR; testing for background hormone concentrations NR. ITS+ premix: Becton Dickinson.



### 7. Test Cells: H295R human adrenocortical carcinom a cells (ATCC, CLR-2128; Lot # not reported). Cells were maintained in DM EM/Ham-F12, ITS+Premix, and Nu-Serum in a
5.0% CO 2 

### incubator at 37±1oC. The background horm one concentrations present in the NuSerum for testosterone and estr adiol were not reported. The initial number of cell passages prior to being frozen in liquid nitrogen was not reported. After thawing, cells were cultured for three passages prior to use in the steroidoge nesis assay. Cells were plated into wells of 24-well culture plates at a de nsity of approximately 3 × 10 5 

### cells/mL. Plates were incubated
in a 5% CO 2 

### atmosphere at 37oC for approximately 24 hours prior to exposure to the test chemical or the positive controls.

The following performance criteria were met (indicated by an “x”):
NR Cell passage identifier. Cell Passage #: NR NR Cells frozen down at passage 5 NR Frozen cells cultured for 4 additional passages X Total number of passages does not exceed 10



### B. METHODS

1. Pre-Test Information

a. Hormone Assay Interference Test: Hormone cross-reactivity or interference tests were not conducted. It was reported th at samples were extracted w ith ether to remove potential
interference from medium constituents.

b. Hormone Extraction: Testosterone and estradiol were extracted from H295Rsupplemented medium by liquid/liquid extract ion with water:ether, mixed thoroughly, the water fraction frozen, and the ether supernatant decanted. This extraction was repeated, and the ether fractions were combined and evapor ated under nitrogen at 33oC. The resultant
extracts were reconstituted in ELISA buffe r and analyzed by ELISA methods. The method
MDLs for testosterone and es tradiol were not provided.

c. Laboratory Proficiency Test: Laboratory proficiency testing was not reported for the current study.

2. Test Solutions: A 100 mM stock of TCVP was prepar ed in DMSO, followed by serial dilutions (1:10) in DMSO. Forskolin and proc hloraz solutions were also prepared (details were not provided in the study report). Fina l concentrations after addition to the 24-well culture plates were 1 and 10 μM for forsko lin, 0.1 and 1 μM for prochloraz, and 0.0001 to 100 μM for TCVP. The final concentra tion of DMSO in the medium was 0.1%.Steroidogenesis Assay (2012) / Page 6 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### 3. Cell Plating and Preincubation: H295R cells (ATCC CLR-2128) we re frozen (the initial number of passages prior to freezing was not re ported). After thawing, cells were cultured additionally for three passages prior to use. Cells were grown to 90% confluency, washed and trypsinized, and the tryps inization was stopp ed with fresh, supplemented DMEM-F12 medium. Cells (1 mL) were seeded into well s of 24-well culture plates at a density of approximately 3 × 10 5 

### cells/mL. Plates were incubated in a 5% CO 2 

### atmosphere at 37±1oC for approximately 24 hours prior to exposure to the test chemical or the positive controls. The percent confluency after 24- hour incubation was not reported.

4. Exposure: After incubation for 24 hours, the medium was removed and replaced with 1 mL of supplemented medium. The cells were exposed to identical volumes of either each serial dilution of the test compound or DMSO (SC) in triplicate. It was reported that 24- well plates were used, but a dosing schematic for the test chemical plate(s), with ten concentrations of TCVP, was not provided.

A concurrent quality control (QC) plate was in cluded with each of the two independent runs of the test chemical plates to demonstrate th e assay’s response to forskolin (an inducer of testosterone and estradiol pr oduction) and prochloraz (an inhi bitor of testosterone and estradiol production). The QC plate was repor tedly prepared and dosed in the same manner with either forskolin or prochloraz; however, a dosing schematic for the QC plate was not provided.

Following dosing, the plates were incubated for 48 hours under the conditions described previously. Cell viability was determin ed after media removal was completed.

5. Cell Viability/Cytotoxicity Assay: Cell viability was determined with the MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] test described by Mosman (1983) 1 

### immediately on removal of the culture medium after the 48-hour inc ubation. The QC plate wells designated to receive methanol (MeOH) were rinsed with phosphate-buffered saline (PBS), followed by incubation with MeOH (inc ubation time was not specified). Next, 0.5-mL portions of a MTT solution in supplemen ted medium were added to each well on the test chemical and QC plates. MTT-treat ed plates were in cubated in a 5% CO 2 

### atmosphere at 37oC for 4 hours, followed by lysis of the cells after overnight incuba tion with 0.5 mL of a 10% SDS lysis solution. Absorbance was dete rmined with a colorimeter (details not provided). A reduction of ≥ 20% in cell viability was consider ed evidence of cytotoxicity.

6. Hormone Measurement System: Concentrations of testos terone and estradiol in the supplemented medium were determined by ELI SA. Details of the ELISA methodology and percent recovery data were not provided.

The following performance criteria were met (indicated by an “x”):

NR Method detection limit (100 pg/mL testosterone; 10 pg/mL estradiol) NR Spiked sample recovery acceptable for two concentrations of testosterone and estrad iol (mean measured amount from triplicate samples ≤ 30% of nominal concentration) NR Hormone cross-reactivity (antibody-based assays only; ≤ 30% of basal production of the respective hormone) NR Solvent control within 75% range be low maximum response on standard curve NR Test compound tested for interf erence with meas urement system

1 Mosman T. (1983). Rapid colorimetric assay for gr owth and survival: application to proliferation and cytotoxicity. J. Immunol. Methods . 100:45-50.Steroidogenesis Assay (2012) / Page 7 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### C. DATA ANALYSIS: Mean values (pg/mL) and standard deviations (SD) for testosterone
and estradiol concentrations were calculated for each concentration of the reference chemicals and the SC, as well as the blank and background wells, on the QC plates and for
each concentration of TCVP and SC on the test chemical plate. Relative changes in hormone production were calculated with the following equation:

Relative change = (hormone concentrati on in each well) ÷ (mean SC hormone concentration)

Concentrations that exhibited ≥ 20% cytotoxicity, or where pr ecipitation was observed, were omitted from further analysis.

Statistical procedures were not provided, a lthough a response (inducti on or inhibition) was considered positive at p ≤ 0.05.

II. RESULTS

A. TEST COMPOUND: The hormone concentrations after exposure to TCVP, and the folddifference changes relative to the SC wells a nd mean ± SD for the two assay runs (Runs 1 and 2) are presented in Table 1. The fold-c hanges in hormone concentration for TCVP in the two runs are also shown graphically in Fi gures 1 and 2 for testos terone and estradiol, respectively. The highest TCVP concentra tion suitable of evaluation was 10 μM in both runs due to cytotoxicity obser ved in both runs at the 100 μM concentration (Table 3).

Only a single hormone concentration value for te stosterone and estradiol, respectively, was reported for the SC replicates for each assay run; no distinction betw een SC values for the test or QC plates was provided. The % CVs for absolute testosterone concentrations for the SC replicates within the test plates were 50% and 26%, with only the second run meeting
the ≤ 30% performance criteria recommended in the Test Guideline. The % CVs for
absolute estradiol concentrations for the SC re plicates within the test plates were 17% and 9%, and both values met the recommended perf ormance criteria. The between-plate % CVs
for the absolute hormone concentrations in the SC were 58% for testosterone and 38% for estradiol, which are greater than th e recommended performance criteria of ≤ 30%. All % CV
determinations were calc ulated by the reviewers.

Although seven concentrations of the test mate rial are recommended for examination in the Guideline (100 to 0.0001 μM), the assay runs wi th TCVP included three additional, lower concentrations (0.01, 0.001, and 0.0001 nM). In addition, the Guideline recommends that three independent assay runs should be conducte d, but only two independent assay runs with TCVP were reported. Due to cy totoxicity at the 100 μM con centration of TCVP, only nine
viable concentrations remained. In the first assay run, only values at six, non-sequential test (TCVP) concentrations were reported for te stosterone (Table 1) , but all nine TCVP concentrations were reported fo r the second run. Both runs repor ted estradiol values at eight TCVP concentrations, with values at 0.0001 nM not being reported. No explanations for these missing data were included in the study re port, and no raw data were included in the study report to allow investig ation by the reviewers.Steroidogenesis Assay (2012) / Page 8 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### In the first run, there was a 22.4-fold inducti on in testosterone pr oduction at 10 μM TCVP, but no induction ( ≤ 0.70-fold) was observed at the other reported TCVP concentrations, and
there was a marked inhibition in testosterone production (0.26-fold) at the lowest TCVP concentration (0.000001 μ M). In the second run, no induction or inhibition of testosterone production (0.87- to 1.24-fold) was observed at 0.000001 to 10 μ M TCVP, but there was a marked reduction in testosterone (0.32-fold) at the lowest concentration tested (0.000001

μ M). There was no consistent i nduction or inhibition of estradio l production in either run at
0.000001 to 10 μ M TCVP, with fold-change values ra nging from 0.80- to 1.70-fold in Run 1
and 0.83- to 1.14-fold in Run 2.

TABLE 1. Mean (±SD) Hormone Con centrations Following Treatment with TCVP for 48 Hours. a

Nominal Concentration (μM) Run 1 Run 2 Run 1 Run 2 Mean b ± SD b Statistical Significance Testosterone (pg/mL) Fold Difference DMSO (SC) 58.45 140.32 — — — — —

0.0000001 NR 45.58 NR 0.3249 0.32 NC NR

0.000001 15.32 163.78 0.2621 1.1672 0.71 0.64

0.00001 32.44 170.95 0.555 1.2183 0.89 0.47

0.0001 NR 174.64 NR 1.2446 1.24 NC

0.001 26.39 125.10 0.4514 0.8915 0.67 0.31

0.01 40.78 133.00 0.6977 0.9478 0.82 0.18

0.1 23.78 121.78 0.4068 0.8697 0.64 0.33

1 NR 147.86 NR 1.0537 1.05 NC

10 1309.94 130.45 22.4105 0.9296 11.67 15.19 NR

100 NA NA NA NA NA NA Estradiol (pg/mL) Fold Difference DMSO (SC) 52.89 92.23 — — — — —

0.0000001 NR NR NR NR NC NC

0.000001 74.09 76.89 1.4007 0.8337 1.12 0.40

0.00001 89.83 84.16 1.6983 0.9125 1.31 0.56

0.0001 65.72 84.66 1.2425 0.9179 1.08 0.23

0.001 61.16 94.49 1.1563 1.0246 1.09 0.09

0.01 48.83 85.71 0.9232 0.9293 0.93 0.004

0.1 69.24 90.58 1.3092 0.9822 1.15 0.23

1 44.37 105.24 0.839 1.1411 0.99 0.21

10 42.13 99.78 0.7964 1.0819 0.94 0.20

100 NA NA NA NA NA NA a Data were obtained from page 27-28 and 31-32 of the study report. b Calculated by the reviewers; SD (n=2)
SC Solvent control NR Not reported
NC Not calculated NA Not applicable; fold change not determined at 100 μ M TCVP due to cytotoxicity.Steroidogenesis Assay (2012) / Page 9 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### FIGURE 1. Changes in Testosterone Production Relative to TCVP Concentration in Test
Runs 1 and 2.Steroidogenesis Assay (2012) / Page 10 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### FIGURE 2. Changes in Estradiol Production Relative to TCVP Concentration in Test
Runs 1 and 2.

B. CYTOTOXICITY: Based on the results from the MTT cell viability assay conducted on the QC and TCVP test plates (Table 2 and Figure 3), TCVP was cyto toxic at the highest tested concentration (100 μM) in both runs. Cell viability was <10% at 100 μ M TCVP, but

was ≥ 89% at concentrations ≤ 10 μ M TCVP. Methanol exposure reduced cell viability to
0.62 to 2.29%.Steroidogenesis Assay (2012) / Page 11 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456

TABLE 2. Mean (±SD) MTT Cell Viabilit y Results after Treatment with Forskolin, Prochloraz, or TCVP
for 48 Hours. a

Compound Concen. (μM) Cell Viability – Run 1 Cell Viability – Run 2 Overall

Mean OD SD Mean %
Viable Mean OD SD Mean %
Viable Mean %
Viable b SD b

Blank NA 0.15 0.06 99.74 0.18 0.11 101.07 100.4 0.94

SC1 NA 0.15 0.02 102.16 0. 21 0.01 119.60 110.9 12.33

SC2 NA 0.14 0.04 88.97 0. 16 0.10 88.83 88.9 0.10

SC3 NA 0.16 0.02 108.87 0. 16 0.08 91.57 100.2 12.23

Blank + MeOH NA 0.02 0.004 0. 62 0.02 0.01 2.29 1.5 1.18

SC + MeOH NA 0.02 0.002 0 0.02 0.001 0 0.0 --

Forskolin b 1 0.19 0.02 129.71 0.23 0.03 132.92 131.3 2.27

Forskolin 10 0.18 0.04 124.42 0.18 0.02 105.00 114.7 13.73

Prochloraz 0.1 0.17 0.03 115.32 0.21 0.03 124.08 119.7 6.19

Prochloraz 1 0.19 0.01 131.75 0.22 0.02 129.24 130.5 1.77

TCVP 100 0.01 0.002 -6.68 c 0.02 0.01 -1.10 c NA c NA c

TCVP 10 0.19 0.04 129.81 0. 18 0.06 101.71 115.8 19.87

TCVP 1 0.17 0.03 110.99 0. 20 0.01 117.17 114.1 4.37

TCVP 0.1 0.14 0.06 90.87 0.15 0.01 87.34 89.1 2.50

TCVP 0.01 0.18 0.03 122.23 0.20 0.03 118.62 120.4 2.55

TCVP 0.001 0.18 0.02 118.07 0.17 0.03 96.76 107.4 15.07

TCVP 0.0001 0.13 0.03 81.22 0.20 0.02 119.49 100.4 27.06

TCVP 0.00001 0.17 0.02 111.91 0.21 0.02 119.87 115.9 5.63

TCVP 0.000001 0.21 0.02 146.01 0.18 0.07 104.21 125.1 29.56

TCVP 0.0000001 0.18 0.03 124.90 0.21 0.03 120.19 122.5 3.33 a Data were obtained from page 25-26 of the study report. b Calculated by the reviewers; SD (n=2) c Omitted from further analysis due to cytotoxicity ≥ 20% NA Not applicable
SC Solvent controlSteroidogenesis Assay (2012) / Page 12 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### FIGURE 3. MTT cell cytotoxicity results for Test Runs 1 and 2.

C. QC PLATE: The hormone concentrations in the wells for the reference chemicals (prochloraz and forskolin), the SC and the bl ank, as well as, the fold-difference change relative to the SC (individual and mean ± SD) fo r the two assay runs, are presented in Table 3. Minimum basal hormone production for testosterone ( ≥ 500 pg/mL) was not met in any blank and SC wells (mean values were ≤ 180 pg/mL), but the minimu m basal production of estradiol (40 pg/mL) was met. The review ers could not determin e if basal hormone production met the fold-increas e criteria in the SC of ≥ 5-fold for testosterone and ≥ 2.5-fold
for estradiol above the MDL of the ELISA a ssay because the MDLs were not reported.

Exposure to 10 μM forskolin i nduced testoste rone production ≥ 2-fold (actual 2.7- to 3.6- fold) and estradiol production ≥ 7.5-fold (actual 11- to 25-fold) over the SC. Exposure to 1 μM prochloraz inhibited synt hesis of testosterone by 2. 22% and 84.62%, and inhibited estradiol synthesis by 47.96% and 56.69%, rela tive to SC (Guideline recommendation is
≥ 50% inhibition). The mean fold-change da ta did not meet the performance criteria recommended by the Guideline.Steroidogenesis Assay (2012) / Page 13 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### As described above (II.A.), only a single horm one concentration value for testosterone and estradiol, respectively, was reported for the SC replicates for each assay run; no distinction between SC values for the test or QC pl ates was provided. The % CVs for absolute
testosterone concentrations for the SC replicates within the test plates from the second run
met the ≤ 30% performance criteria (as recommended in the test Guideline), as did the
% CVs for absolute estradiol concentrations for th e SC replicates from both test plates. The between-plate % CVs for the absolute concentr ations of the SC were greater than the recommended performance criteria of ≤ 30%.

TABLE 3. Mean (±SD) Hormone Concentrations Followi ng Treatment with Forskolin or Prochloraz for
48 Hours. a

Concentration (μM) Run 1 Run 2 Run 1 Run 2 Mean b ± SD b
Testosterone (pg/mL) Fold Difference (Relative to DMSO)

Blank 57.65 179.82 — — — —

DMSO 58.45 140.32 — — — — 1 μM Forskolin 1276.69 400.77 21.84 2.86 12.35 13.42 10 μM Forskolin 156.60 510.24 2.68 3.64 3.16 0.68 0.1 μM Prochloraz 424.76 60.04 7.27 0.43 3.85 4.84 1 μM Prochloraz 57.16 21.58 0.98 0.15 0.58 0.60 Estradiol (pg/mL) Fold Difference (Relative to DMSO)

Blank 50.42 107.38 — — — —

DMSO 52.89 92.23 — — — — 1 μM Forskolin 555.41 640.23 10.50 6.94 8.72 2.52 10 μM Forskolin 1326.02 1016.87 25.07 11.03 18.0 9.93 0.1 μM Prochloraz 45.29 66.84 0.86 0.72 0.79 0.09 1 μM Prochloraz 32.81 39.94 0.62 0.43 0.53 0.13 a Data were obtained from page 27-28 and 31-32 of the study report. b Calculated by the reviewers; SD (n=2)



### III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: The induction/inhibition potential of TCVP was
evaluated at least 6 concentrati ons of the test item in two independent runs. Within both
runs the test item TCVP did not induce or inhibit the production of testosterone and estradiol
at the evaluated concentrations.

B. AGENCY COMMENTS: Critical analytical and laboratory proficiency details were not reported and may not have been determined. Th ese data (detailed in the study deficiencies section) are essential to support the appropriateness and sensitivity of the selected analytical method, the robustness and adequacy of the cell line, and the technica l proficiency of the laboratory personnel.

Minimum basal hormone production for testosterone ( ≥ 500 pg/mL) was not met in any blank and SC wells (mean values were ≤ 180 pg/mL), but basal produc tion of estradiol (40 pg/mL) was met. The reviewers could not de termine if basal horm one production met the
criteria for minimum fold-increase in the SC of ≥ 5-fold for testosterone and ≥ 2.5-fold for estradiol above the MDL of the ELISA assay because the MDLs were not reported. Exposure to 10 μM forskolin i nduced testoste rone production ≥ 2-fold (actual 2.7- to 3.6- fold) and estradiol production ≥ 7.5-fold (actual 11- to 25-fold ) over the SC. Exposure toSteroidogenesis Assay (2012) / Page 14 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



### 1 μM prochloraz inhibited synthesis of te stosterone by 2.22% and 84.62%, and inhibited estradiol synthesis by 47.96% and 56.69%, relati ve to the SC (Guideline recommendation is
≥ 50% inhibition). The mean fold-change relative to the SC did not meet the performance criteria recommended by the Guideline. There was high variability in testosterone induction (forskolin) and inhibitio n (prochloraz) responses between th e two assay runs. In Run 1, the
induction of testosterone in th e presence of 1 μM forskolin was approximately 7-fold greater than the induction achieved at 10 μM forskolin . In addition, testos terone induction at 1 μ M forskolin in Run 1 was also approximately 7- fold greater than the response to 1 μM
forskolin in Run 2. Inhibition of testosterone synthesis in the presen ce of 0.1 μM prochloraz varied approximately 18-fold between the two assay runs (fold differences of 7.27 versus 0.43). This variability may be associated with poor analytical performance (ELISA) or poor cell response; however, the reviewer’s assessment was hampered by the lack of methodological details and pr oficiency testing data.

Only a single hormone concentration value for te stosterone and estradiol, respectively, was reported for the SC replicates for each assay run; no distinction betw een SC values for the test or QC plates was provided. The % CVs for absolute testosterone concentrations for the SC replicates within the test plates were 50% and 26%; therefore, only the second run met
the ≤ 30% performance criteria recommended in the test Guideline. The % CVs for absolute estradiol concentrations for the SC replicates within the test plates were 17% and 9%, with both values meeting the recommended performa nce criteria. The be tween-plate % CVs for
absolute hormone concentrations in the SC were 58% for testosterone and 38% for the estradiol, which were greater than th e recommended performance criteria of ≤ 30%. All % CV determinations were calculated by the reviewers.

Cytotoxicity was observed at the highest test ed concentration of TCVP (100 μM) in Run 1, but no half log or other intermediate TCVP concentrations between 100 and 10 μM TCVP were not selected to replace the 100 μM TC VP concentration in Run 2. Although the
number of TCVP concentration levels tested was adequate, the additi on of concentrations
<0.0001 μ M provided little useful information.

With regards to the effects of TCVP, the re sults from the two runs were variable for
testosterone. In the first r un, there was a 22.4-fold induction in testosterone production at 10 μM TCVP, but no induction ( ≤ 0.70-fold) was observed at the other reported TCVP concentrations. In fact, at the lowest concentration of TCVP (0.000001 μ M), there was a
marked inhibition in testoster one production (0.26-fold). In the second run, no induction or
inhibition of testosterone production (0.87- to 1.24-fold) was observed at 0.000001 to 10 μ M TCVP, but there was again a marked reduction in testosterone (0.32-fold) at the lowest concentration tested (0.000001 μ M). For estradiol production, there was no consistent
induction or inhibition in either run at 0.000001 to 10 μ M TCVP, with fold-change values ranging from 0.80- to 1.70-fold in Run 1 and 0.83- to 1.14-f old in Run 2. Although these results suggest that TCVP is not an inhibitor or inducer of testosterone or estradiol production, the numerous deficiencies noted in the study preclude making a definitive conclusion with regards to the effects of TCVP on hormone production in this assay.

C. STUDY DEFICIENCIES: The following deficiencies were noted:

 Laboratory proficiency testing and/ or results were not reported.Steroidogenesis Assay (2012) / Page 15 of 15 TETRACHLORVINPHOS (TCVP) / 083702 OCSPP 890.1550/ OECD 456



###  Hormone cross-reactivity, spike sample recove ry, and interference data with the ELISA methods were not reported.

 Details of the ELISA method were not provided, including supplier and MDLs.

 Statistical procedures were not elucidat ed, although a statistic al difference at p ≤ 0.05 was
indicated.

 Only two, instead of three, assay runs were conducted.

 Basal hormone production in the SC was well below the 500 pg/mL minimum concentration (approximately 60 to 140 pg/ mL), and the testosterone MDL was not provided to determine a ≥ 5-fold concentration increase above the MDL on the QC plates.

 Between-plate % CVs were not provided, but were greater than the 30% maximum Guideline recommendation as calculated by the reviewers.

 Initial cell culturing and freezing at Passage 5 were not indicated.

 Cells were passaged only three times prior to use, instead of 4

 Sufficient details regarding the cell cultu re medium were not provided, and the background hormone concentrations present in the Nu-Serum for testosterone and estradiol were not reported.

 Although ten concentrations of TCVP were incl uded (instead of th e typical seven), the
three additional tested concentrations we re each <0.1 nM (<0.0001 μM) and therefore are
not considered to be useful.

 The report stated that 24-well plates were used, but 10 concentrations of TCVP were investigated; no plate dosing schematic(s) were provided for review.

# DATA EVALUATION RECORD

TETRACHLORVINPHOS (TCVP)

Study Type: OCSPP 890.1600, In vivo Uterotrophic Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-22-2012 (MRID 48880601)

Prepared for
Health Effects Division Office of Pesticide Programs U.S. Environmental Protection Agency 2777 South Crystal Drive

Arlington, VA 22202

Prepared by CSS-Dynamac Corporation 1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer: Signature: Rebecca L. Bryan, B.S. Date: 9/12/2012

Secondary Reviewer: Signature: Jack D. Early, M.S. Date: 9/19/2012

Program Manager: Signature: Jack D. Early, M.S. Date: 9/20/2012

Quality Assurance: Signature: Steven Brecher, Ph.D., D.A.B.T. Date: 9/20/2012

This Data Evaluation Record may have been alte red by the Health Effects Division subsequent to signing by CSS-Dynamac Corporation personnel.

### The US EPA Endocrine Disruptor Screenin g Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays in tended to identify a chemical’s likely endocrine bioactivity, i.e., its potential to interact with the estrogen, androgen, or thyroid (E, A, or T) pathways. The robustness of the Tier 1 battery is based on the strengths of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and re dundancy across the battery. Thus, the results of each individual assay should not be considered in isolation but rather should be considered in the context of other assays in the battery as well as Other Scientifically Relevant Information (OSRI). In order to determine if a chemical has the potent ial to interact with the E, A or T pathways, a Weight of Evidence ( WoE) evaluation of Tier 1 assay results, in combination with the findings in the OSRI, should be undertaken (refer to the WoE Document).TETRACHLORVINPHOS (TCVP} I 083701 

### In vivo Uterotrophic Assay (2012) I Page I of 8
OCSPP 890.1600/ OECD 440



## Primary Reviewer: Minerva Mercado, Ph.D.

# Signatu**~=:----** Health Effects Division

## Da**~** Secondary Reviewer:**__,J~e=ss:;..;R=o""-w~lan=d** 

### _________ 

### Signature:**~ ~~**  

### Health Effects Division Date: 6/41 · 

## 1-.;;- 

# I DATAEVALUATIONRECORD

STUDY TYPE: Uterotrophic Assay (Rat); OCSPP 890.1600; OECD 440 Template version 09/2011



### PC CODE: 083702 

### DP BARCODE: D404438



### TXR#: 0056284 

### CAS#: 22248- 79-9



### TEST MATERIAL (fURITY): Tetrachlorvinphos (100.05% a.i.)



### SYNONYMS: 2-chloro-1-(2,4,5-trichlorophenyl)vinyl dimethyl phosphate (Z-isomer); TCVP



### CITATION: Boulet, J. (2012). The Uterotrophic Bioassay in Rats: A Short-Tenn Screening

Test for Estrogenic Properties ofTetrachlorvinphos. Product Safety Labs, Dayton, NJ. Laboratory Report No.: 33548, June 26, 2012. MRID 48880601. Unpublished.



### SPONSOR: The Tetrachlorvinphos (TCVP) Task Force, c/o SRA International Inc., 5235 Ragged Point Road, Cambridge, MD



### TEST ORDER#: CON-083702-14



### EXECUTIVE SUMMARY: In a Uterotrophic Assay (MRID 48880601) conducted to screen for potential estrogenic activity, tetrachlorvinphos (100.05% a.i., Lot #TX 100113) in 0.1 %

aqueous methylcellulose was administered daily via oral gavage to groups of 6 ovariectomized
female Sprague Dawley rats at dose levels ofO (vehicle), 50, 150, or 350 mg/kg/day on postnatal days (PND) 56-58. A positive control group of 6 ovariectomized rats was treated with a daily dose of 17a-ethynyl estradiol (EE) in 0.1 % aqueous methylcellulose at 0.3 μg/kg/day by
subcutaneous (sc.) injection. Body weights and food consumption were determined daily. All
animals were terminated and necropsied on PND 59, approximately 24 hours after the final dose
administration to determine wet and blotted uterine weights.

No treatment-related effects were observed on mortality, clinical signs, body weights, or body weight gains. Food consumption on Days 1-4 was increased (p<0.001) by 5-6% in all tetrachlorvinphos treatment groups, but there was no adverse effect on food efficiency. Uterine weights in the tetrachlorvinphos treated groups were comparable to the vehicle control. Absolute

wet and blotted uterus weights for the positive control (EE) group were increased (p<0.001) by
75% and 71 %, respectively, as expected.

Although no evidence of systemic toxicity was observed in this study, the high dose (350 mg/kg/day) was considered adequate based on increases in liver and kidney weights seen at 350 mg/kg/day in the female pubertal assay (MRID 49186901).In vivo Uterotrophic Assay (2012) / Page 2 of 8 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1600/ OECD 440



### No statistically sign ificant changes were seen in uterine weight in this assay. Tetrachlorvinphos is negative in the ut erotrophic assay.

The assay satisfies the EDSP Tier 1 Test Order require ments for a uterotrophic assay (OCSPP 890.1600).

COMPLIANCE: Signed and dated Data Confiden tiality, GLP Compliance, and Quality Assurance statements were provided.In vivo Uterotrophic Assay (2012) / Page 3 of 8 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1600/ OECD 440



### I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Product Safety Labs

Location: Dayton, New Jersey Study Director: J. Boulet
Other Personnel: J. John (Primary Scientist), D. Knox (Primary Investigator-Analysis) Study Period: January 27, 2012 – June 26, 2012



### 2. Test Substance: Tetrachlorvinphos
Description: Off-white to tan powder
Source: The Hartz Mountain Corporation (Secaucus, NJ)
Lot #: TX 10113 (expiration date 6/16/12) Purity: 100.05% Stability: Stable for 4 days in 0.1% aqueous methylcellulose at ambient temperature
CAS #: 22248-79-9
Structure:

P O O Cl

Cl Cl Cl O CH

3

O CH

3



### 3. Reference Estrogen: 17 α -ethynyl estradiol (EE)
Supplier: Sigma-Aldrich (St. Louis, MO)
Lot #: 028K1411 (expiration date 7/7/12) Purity: ≥ 98%
CAS #: 57-63-6



### 4. Solvent/Vehicle Control: Methylcellulose
Supplier: Sigma-Aldrich (St. Louis, MO)
Lot #: 021M0067 Rationale (if other than water): Not reported
Final concentration: 0.1% in distilled or RODI water



### 5. Test Animals:
Species: Rat (female only)
Strain: Sprague Dawley [CRL SD CD IGS] Age/weight at dose initiation: PND 56/ 201-237 g
Source: Charles River Laboratories, Inc. (Raleigh, NC) Housing: Three per polysulfone shoebox cage with Sani-Chips ® hardwood contact bedding
Diet: 2016C Harlan Teklad Global Rodent Diet ®

, ad libitum ; minimal phytoestrogen content (not specified)
Water: Reverse osmosis deionized tap water, ad libitum from polysulfone bottles attached to the cages Environmental conditions: Temperature: Humidity: Air changes: Photoperiod: 19-22 oC
42-55% Not reported 12 hrs light/12 hrs dark Acclimation period: 10 days



### B. STUDY DESIGN

1. In-Life Dates: Start: February 3, 2012 End: February 6, 2012In vivo Uterotrophic Assay (2012) / Page 4 of 8 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1600/ OECD 440



### 2. Study Design: Following a 10-day acclimation period, ovariectomized female rats (surgery performed by Supplier at PND 42) were administ ered the test substanc es from PND 56 to 58. Prior to dosing, rats were tested by vaginal lavage for 5 consecutive days for evidence of estrus. Rats were euthanized approxima tely 24 hours after the last dose (PND 59) and necropsied for uterine weight measurements.

3. Animal Assignment: Animals were assigned to the test groups noted in Table 1 using a stratified randomization procedur e. The body weight of each an imal was within 20% of the overall mean on the day of randomization.

TABLE 1. Study Design a Test Group Dose (mg/kg/day) # of Females Estrogen Agonist Assay

Vehicle Control 0 6 Low (Tetrachlorvinphos) 50 6 Mid (Tetrachlorvinphos) 150 6 High (Tetrachlorvinphos) 350 6

17 α -ethynyl estradiol (EE), Reference Estrogen 0.0003 6 a Data were obtained from page 16 of the study report.



### 4. Dose Selection Rationale: The dose levels were reportedl y selected based on a preliminary range-finding study 1 

### ; however, no results of the range -finding study we re provided.

5. Dose Preparation and Analysis: Dose formulations were prep ared daily prior to treatment by mixing the test substance in 0.1% aqueous methylcellulose, and were used within 2 hours. Dosing formulations for EE were prepar ed once prior to initial dosing by mixing in 0.1% aqueous methylcellulose. As the dose form ulation for the test substance was prepared daily, its stability over the 3-da y dosing period was not determine d. However, its purity was verified on Study Days 1 and 3. Homogeneity was determined by collecting samples from the top, middle, and bottom of each test concentration prior to test initiation.

Results of Dose Analysis

Homogeneity (%RSD): 3.3-4.2%

Stability (% purity): 99.8-100.3%

Concentration (% of nominal): 89.6-111.0% for Day 1, 92.0-113.0% for Day 3

The analytical data indicated that the mixing procedure was ad equate and that the variation between nominal and actual dosage to the animals was acceptable.

6. Dosage Administration: Animals were administered th e test formulations or vehicle control daily via gavage for three consecutive days in a dose volume of 5 mL/kg body

1 Barnett, J. Oral (Gavage) Repeated Dose Range-Findi ng Study of Tetrachlorvinphos in Rats. Testing Facility Study No. 20012366. Charles River Laboratories, Horsham, PA.In vivo Uterotrophic Assay (2012) / Page 5 of 8 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1600/ OECD 440



### weight. The oral route of ad ministration was selected as it is a potential route of human exposure. The positive control, EE, was admi nistered daily via sc. injection for three consecutive days in a dose volume of 0.5 mL/ kg body weight. Dose volumes were adjusted daily based on the concurrent body weight meas urement. Dosing was at approximately the same time each day ±2 hours.

7. Statistics: Statistical analyses were conducted using ProvantisTM version 8.4.2.0 and GraphPad software. Body weight, body wei ght gains, food consumption and wet and blotted uterus weight data were subjected to statistical analys es. Data were analyzed for homogeneity of variance and normality using Ba rtlett’s test. When the Bartlett’s test indicated homogeneous varian ces, means were compared using One-Way Analysis of Variance (ANOVA). When the ANOVA was significant, group means were compared using the Dunnett’s test for multiple comparisons. When variances were significantly different using Bartlett’s test, means were co mpared using the non-parametric analysis of
variance of Kruskal-Wallis test. When the Kr uskal-Wallis test was significant, group means were compared using the Dunn’s test. Significance was denoted at p<0.05.

The statistical analyses were considered adequate.

C. METHODS

1. Clinical Examinations: Cage-side checks for viability were conducted twice daily.

2. Body Weight: Animals were weighed at rando mization, daily thr oughout the dosing period, and prior to necropsy. Mean body weight gain was determined daily and for Days 1-
4.

3. Food Consumption: Food consumption was measured on Days 1 and 4 for each cage and reported as group mean daily food consumption (g/animal/day). Mean food efficiency was determined for Days 1 to 4.

4. Necropsy and Measurement of Uterine Weight: On PND 59 (approximately 24 hours
after final administration of th e test substance), all surviving animals were anesthetized by
isoflurane then euthanized by exsanguination and subjected to a gross necropsy. Ovarian stubs were examined for the presence of any ovarian tissue. Dissecti on of the uterus was performed according to the U.S. EPA Guidelin e. Briefly, the vagina was removed just
below the cervix in order to retain the lumina l fluid in the uterus. The “wet” uterus (i.e., containing the luminal fluid) was weighed. S ubsequently, the uterine horns were slit open
to allow luminal fluid to leak out, the uterus was gently blot ted, and the blotted uterus was weighed.

5. Microscopic Examination (Optional): Microscopic examinations were not conducted.In vivo Uterotrophic Assay (2012) / Page 6 of 8 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1600/ OECD 440



### II. RESULTS

A. OBSERVATIONS

1. Mortality: All animals survived until scheduled termination.

2. Clinical Signs of Toxicity: No clinical signs of toxici ty were observed during the study.

B. BODY WEIGHT AND WEIGHT GAIN: Body weight and overall body weight gain data are presented in Table 2. Body wei ghts and overall body weight gains in the tetrachlorvinphos treated groups and EE group were comparable to the controls.

TABLE 2. Group Body Weights and Cumulative Bo dy Weight Gains (g) In the Estrogen Agonist Assay a

Study Day # Dose (mg/kg/day)

Vehicle Control TCVP (50) TCVP (150) TCVP (350) Reference Estrogen EE (0.0003)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 6 222.7 12.1 6 223.7 9.9 6 223.5 10.3 6 223.5 11.8 6 222.7 10.8

2 6 226.0 11.5 6 227.5 10.5 6 224.5 11.8 6 223.2 12.2 6 226.8 12.8

3 6 234.2 13.9 6 234.8 11.4 6 232.5 12.2 6 229.0 13.8 6 232.5 12.9

4 6 235.5 12.3 6 239.2 12.2 6 236.3 12.5 6 234.2 15.3 6 233.0 12.1 Body Weight Gain (1 - 4) 6 4.28 1.22 6 5.17 1.63 6 4.28 1.04 6 3.56 1.96 6 3.44 0.54

a Data were obtained from Tables 3 and 4 on pages 30 and 31 of the study report. No statistically significant
differences were observed. N Number of animals in the group
SD Standard Deviation



### C. FOOD CONSUMPTION: Food consumption data are presented in Table 3. Food consumption on Days 1-4 was increased (p<0.001) by 5-6% in all tetrachlorvinphos treatment groups. No adverse effect on food efficiency was observed.In vivo Uterotrophic Assay (2012) / Page 7 of 8 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1600/ OECD 440

TABLE 3. Food Consumption (g/animal/d ay) In the Estrogen Agonist Assay a

Study Day

Interval Dose (mg/kg/day)

Vehicle Control Positive Control EE (0.0003) TCVP (50) TCVP (150) TCVP (350)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1-4 6 21.11 0.12 6 21.17 0.67 6 22.39
*** ( ↑ 6) 0.30 6 22.17
*** ( ↑ 5) 0.18 6 22.06
*** ( ↑ 5) 0.06

a Data were obtained from Table 5 on page 32 of the study report. Percent differences from controls, calculated by the reviewers, are included in parentheses. N Number of animals in the group
SD Standard Deviation *** Significantly different from controls at p<0.001



### D. PATHOLOGY

1. Uterine Weights: Uterine weight data are presented in Table 4. Uterine weights in the tetrachlorvinphos treatment groups were comparable to the vehicle controls. Absolute wet and blotted uterus weights for the positive control (EE) group were increased (p<0.001) by 75% and 71%, respectively. The increased uterin e weights were within the expected range.

The mean blotted uterine weight for the ve hicle control group was 0.035% of terminal body weight, which is within the performance criteria (<0.09%) of th e test guideline.

TABLE 4. Uterine Weights from Es trogen Agonist Assay in SD Rats a

Parameter Dose (mg/kg/day)

Vehicle Control TCVP (50) TCVP (150) TCVP (350) Positive Control EE (0.0003)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

Terminal BW (g) 6 235.5 12.3 6 239.2 12.2 6 236.3 12.5 6 234.2 15.3 6 233.0 12.1

Wet, absolute (mg) 6 86.83 16.87 6 92.52 16.79 6 84.32 19.48 6 81.42 16.03 6 152.10
*** ( ↑ 75) 23.59

Wet, relative (%) b 6 0.037 0.007 6 0.039 0.006 6 0.035 0.007 6 0.035 0.008 6 0.066 0.013

Blotted,
absolute (mg) 6 82.58 16.10 6 87.70 14.12 6 80.97 18.93 6 78.03 15.26 6 141.48
*** ( ↑ 71) 13.25

Blotted, relative (%) b 6 0.035 0.007 6 0.037 0.006 6 0.034 0.007 6 0.034 0.007 6 0.061 0.008

a Data were obtained from Table 8 on page 35 of the study re port. Percent differences from vehicle controls, calculated by the reviewers, are included in parentheses. b Calculated by the reviewers using data provided in Appendix M on pages 119-121 of the study report. BW Body weight N Number of animals in the group
SD Standard Deviation *** Significantly different from controls at p<0.001In vivo Uterotrophic Assay (2012) / Page 8 of 8 TETRACHLORVINPHOS (TCVP) / 083701 OCSPP 890.1600/ OECD 440



### 2. Microscopic Examination (Optional): Microscopic examinations were not conducted. However, an incidental macroscopic observa tion included one posit ive control (EE) group
animal with a fluid-filled uterus/cervix.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Given that there were no significant differences in average uterine weights for animals treated with TCVP compared with control, and the lack of treatment-related effects or macroscopi c findings at necropsy, th e result of this assay
indicate that Tetrach lorvinphos is not considered to be estrogenic in nature.

B. AGENCY COMMENTS: All animals survived until scheduled termination, and no clinical signs of t oxicity were observed.

Body weights and overall (Days 1-4) body weight gains in th e tetrachlorvin phos treatment groups were comparable to the control group throughout the study. Food consumption on Days 1-4 was increased (p<0.001) by 5-6% in all tetrachlorvinphos treatment groups, but there was no adverse effect on food efficiency. Both wet and blotted uterine weights in the tetrachlorvinphos treatment groups were comparable to the vehicle controls.

Body weights and overall body weight gain in the positive cont rol (EE) group were comparable to the controls, and absolute we t and blotted uterus we ights for the EE group were increased as expected.

Although no evidence of systemic toxicity was observed in this study, the high dose (350 mg/kg/day) was considered adequate ba sed on increases in liv er and kidney weights seen at 350 mg/kg/day in the female pube rtal assay (MRID 49186901). No statistically significant changes were seen in uterine wei ght in this assay. TCVP is negative in the uterotrophic assay.

C. STUDY DEFICIENCIES: None