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

. 20460



## MEMORANDUM

Date: 6/29/2015 OFFICE OF CHEMICAL SAFETY AND
POLLUTION PREVENTION



## SUBJECT: Pentachloronitrobenzene (PCNB): Data Eva luation Records (DERs) for EDSP

Tier 

## 1 Assays

PC Code: 056502



## Decision No

. : 469792, 472270, 475227


## Petition No.: NA DP Barcode: D405372

, D407069

, D409239 

## Registration No

. : NA

Risk Assessment Type: NA

TXR No.: 0056 474

MRID 

## No.: See Table 

## Regulatory Action: NA

Case No.: NA

CAS No.:

40 CFR: NA

FROM: Greg Akerman, Ph.D.

# ~ Immediate Office

Health Effects Di vision (7509P)



## THROUGH: Jess Rowland

# ~ ..,...n_ Deputy Director

Health Effects Division



## TO: Jolene Truji ll o Biologist/Chemical Review Manager

Risk Management and Implementation Branch V

Pesticide Re

- eva lu ation Division (7505P)



## I. ACTION REQUESTED Ver.Ap r

. 2010



## The Pesticide Re-evaluation Division (PRD) of OPP has requested that the Health Effects

Division (HED) review the Endoc rin e Disruptor Screening Program (EDSP) Tier 1 assays submitted 

## in r esponse to the agency's Test Order for PCNB: Test Order# EDSP -056 502 -10 5.

Pa ge I of2

### Page 2 of 2 

## II. RESPONSE

Attached are the EDSP Tier 1 assay DERs for PCNB

.

III

. MRID Table

Chemical: Pentachloronitrobenzene (PCNB) PC Code: 056502

Guideline Assay MRID

890.1100 Amphibian Metamorphosis Assay (Frog) 49042101

890.1150 Androgen Receptor Binding (Rat Prostate) 48946801

890.1200 Aromatase Assay (Human Recombinant) 48916701

890.1250 Estrogen Receptor Binding NA

890.1300 Estrogen Receptor Transcriptional Activation (Human Cell Line HeLa

- 9903) NA

890.1350 Fish Short

- Term Reproduction 49042102

890.1400 Hershberger (Rat) 48916702

890.1450 Female Pubertal (Rat) 49042103

890.1500 Male Pubertal (Rat) 49042103

890.1550 Steroidogenesis (Human Cell Line

– H295R) 48916704

890.1600 Uterotrophic (Rat) NA
NA= Not Applicable (requirement satisfied by other scientifically relevant information (OSRI))

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐ Ձ

ԡԹՌԹԯԽՉՍՁՊԽՅԽՆՌ    Ԣԭ Ԟ

Ԭ Ԣ

Ԣԭ Ԟ

Ԣԭ Ԟ

ԱԽՋՌԪԹՌԽՊՁԹՄ  ԭԠԫԟԱԽԻՀՆՁԻԹ

ԠՇՅՅՇՆԫԹՅԽ ԭԽՆՌԹԻՀՄՇՊՇՆՁՌՊ Շ

ԠՀԽՅՁԻԹՄԫԹՅԽ  ԦԲԭԞԠ  

 ԠԞ԰ԫԹՅԽ 

ԠԞ԰ԫՇ 

԰ՑՆՇՆՑՅՋ 

ԢԭԞԭԠԠՇԼԽ

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԢՄՁՒԹԺԽՌՀԨՊՍՈՃ Թ

ԢՆՎՁՊՇՆՅԽՆՌԹՄ԰ԻՁԽՆՌՁՋՌԠԡԪ԰ՅՁՌՀ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊ
Ջ ԱԽՊՁ԰ԪՑԽՊՋ ԭ

ԢՆՎՁՊՇՆՅԽՆՌԹՄ԰ԻՁԽՆՌՁՋՌԠԡԪ԰ՅՁՌՀ



### ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԢԼՏԹՊԼ԰ԻՇՄՄՇՆ


ԱՇՐՁԻՇՄՇԿՁՋՌԲ԰ԢԭԞԬԭԭԢԣԢԡԢ ԯ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊ ԠԹՌՀԽՊՁՆԽԞՍԺԽԽ



### ԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԲ԰ԢԭԞԬԭԭԢԣԢ ԡ

ԡԹՌԽԢՎԹՄՍԹՌՁՇՆԠՇՅՈՄԽՌԽԼ#ԼԼՅՅ



ԠԦԱԞԱԦԬԫ ԰ԻՀՆԽՁԼԽՊ԰ԷԱԷԨԽ Ն

ԞՋՋԹՑԾՇՊՌՀԽԡԽՌԽԻՌՁՇՆՇԾԱՀՑՊՇՁ Լ

ԩՌԼԢԹՋՌՇՆԪԹՊՑՄԹՆԼ ԩ

ԠՇՊՈՇՊԹՌՁՇՆ԰ՌՍԼՑԻՇՅՈՄԽՌԽԼԧԹ Ձ ԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡ

ԭԹԿԽ  ՇԾ  Ԟ

ԡԭԟԹՊԻՇԼԽ  

Ԣ ԠԡԡԹՌԹԭՇՁՆՌ  

Ԟ

ԪԯԦԡ   

Ԟ

ԤՍՁԼԽՄՁՆԽ    Ԟ ՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋ Թ 

Մ     ԭՍՊՁՌՑ
     

Շ ԺԽՆՒԽՆԽ

ԫՇՌՊԽՈՇՊՌԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ



ԮՍՁՆՌՇՒԽՆԽ



Թ ԡԹՌԽ 

ԭ Հԡ   ԡԹՌԽ  



###  ԭՀԡ   ԡԹՌԽ   
ՆՇՄՇՆԿԽՊՏՁՌ Հ

ԯԟ ԡԹՌԽ   



### ԡ Ԣԯԟ

 ՑՑՑՑ%

Ն ԼԹՄՄԹՆԼԥԬԨՊՍԽԿԽՊԭԠԫԟԱԽԻՀՆՁԻԹՄԞՅՈՀՁ Ժ

Լ ԞԻՌՁՎԽ԰ՍԺՋՌԹՆԻԽՋԲՆՈՍԺՄՁՋՀԽԼՋՌՍԼՑՈԽՊԾՇՊՅԽԼԺՑ Դ

ԩ ԹԺՇՊԹՌՇՊՑ ՈՊՇՂԽԻՌ ՆՍՅԺԽՊԞ԰ՌՍԼՑՋՈՇՆՋՇՊ Խ

ՆՍԹՊՑ ԫՍՅԺԽՊ

Թ Ց
ԣՊՇԿ

Հ ԢԭԞ

Ժ ՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋ

Դ ՁՄԼՄՁԾԽԦՆՌԽՊՆԹՌՁՇՆԹՄ

Խ ԼԞՅՎԹԻԠՀԽՅՁԻԹՄ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

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

ԱՀԽԼԹՑԹՋՋԹՑՇԾԭԠԫԟՌԽԻՀՆՁԻԹՄ
ՈՍՊՁՌՑՇՆԹՅՈՀՁԺՁԹՆ ՅԽՌԹՅՇՊՈՀՇՋՁՋՇԾԞԾՊՁԻԹՆԻՄԹՏԽԼԾՊՇԿ ԵԽՆՇՈՍՋ

ՄԹԽՎՁՋ ՏԹՋԻՇՆԼՍԻՌԽԼՍՆԼԽՊԾՄՇՏՌՀՊՇՍԿՀԻՇՆԼՁՌՁՇՆՋԞՅՈՀՁԺՁԹՆՄԹՊՎԹԽԹՌԫՁԽՍՏՃՇՇՈԣԹԺԽՊ
ԫԣՋՌԹԿԽ


ՌԹԼՈՇՄԽՋԿՊՇՍՈ  ՌԹԼՈՇՄԽՋՊԽՈՄՁԻԹՌԽՏԽՊԽ ԽՐՈՇՋԽԼ ՌՇ Թ ՆԽԿԹՌՁ ՎԽ ԻՇՆՌՊՇՄ ԹՆԼ ՆՇՅՁՆԹՄ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՇԾ

ԹՆԼՅԿԹՁԩՌՀԽԠԳՇԾՅԽԹՋՍՊԽԼԻՇՆԻԽ ՆՌՊԹՌՁՇՆՋԽՐԻԽԽԼԽԼՇՎԽՊՌՀԽԻՇՍՊՋԽ

ՇԾՌՀԽՋՌՍԼՑ
ՁԽՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼԱՀԽՌՁՅԽՏԽՁԿ ՀՌԽԼԹՎԽՊԹԿԽ
ԱԴԞԻՇՆԻԽՆՌՊԹՌՁՇՆՋ
ԻԹՄԻՍՄԹՌԽԼ

ԺՑՌՀԽՊԽՎՁԽՏԽՊՏԽՊԽ
ԩԬԮԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋ

ՅԹՁՆՌԹՁՆԽԼԹՌՌՇ Շ 

### ԠԹՆԼԹՈԥՇԾՌՇ

ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԹՄՄԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻ ՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ

ԟՑՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՅԽԹՆՋՍՊՎՁՎԹՄՏԹՋՁՆԺՇՌՀՌՀԽՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄԹՆԼՌՀԽՅՁԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՆ

ՌՀԽՄՇՏՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈ ԠՄՁՆՁԻԹՄՋՁԿՆՋ ՁԽ ԺԽՀԹՎՁՇՊԹՄԹՆԼՇՌՀԽՊՋՍԺՄԽՌՀԹՄ

ԽԾԾԽԻՌՋՁՆԻՄՍԼՁՆԿՌԹՁՄԻՍՊՎԹՌՍՊԽԹՆԼՋՅԹՄՄՋՁՒԽՏԽՊԽՇԺՋԽՊՎԽԼ ՁՆԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՏՁՌՀՆՇԹՈՈԹՊԽՆՌՈԹՌՌԽՊՆ

ԱԹՁՄԻՍՊՎԹՌՍՊԽՏԹՋՋԽԽՆՁՆ
ՇԾՌԹԼՈՇՄԽՋՁՆՌՀԽՆԽԿԹՌ ՁՎԽԻՇՆՌՊՇՄԹՆԼՁՆ



ԹՆԼ
ՌԹԼՈՇՄԽՋՌՀԽՄՇՏՅՁԼԹՆԼՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄ ՋՊԽՋՈԽԻՌՁՎԽՄՑ԰ՅԹՄՄՋՁՒԽՏԹՋՋԽԽՆՁՆՇՆԽ

ՌԹԼՈՇՄԽԽԹԻՀՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՅՁԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ

ԡԹՑՅԽԼՁԹՆԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋՊԽԼՍԻԽԼԹՌԹՄՄՌՊԽԹՌԽԼՄԽ ՎԽՄՋ
ԫԣՈԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ

ՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԫԣԣՍՊՌՀԽՊՅՇՊԽԭԠԫԟՋՁԿՆՁԾՁԻԹՆՌՄՑԼԽԻՊԽԹՋԽԼԡԹՑՋՆՇՍՌՌՇՎԽՆՌ
԰Գԩ

Ļ ԹՆԼՏԽՌՏԽՁԿՀՌ Ļ ԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌ ՊՇՄ
ՈԡՍՆՆԽՌՌ0Ջ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋՇԺՋԽՊՎԽԼԱՀԽՊԽՏԽՊԽՆՇՋՁԿՆՁԾՁ ԻԹՆՌԽԾԾԽԻՌՋՇՆՆՇՊՅԹՄՁՒԽԼ
ԾՇՊ԰ԳԩՀՁՆԼՄՁՅԺ

ՄԽՆԿՌՀ
ԥԩԩՇՆԡԹՑՇՊԹՌԹՆՑՌՊԽԹՌՅԽՆՌՄԽՎԽՄԱՀԽՇՆԽՄԹՌԽՋՌԹԿԽ
ԫԣ ՌԹԼՈՇՄԽՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ՏԹՋԽՐԻՄՍԼԽԼԾՊՇՅԹՆԹՄՑՋՁՋԾՇՊԻՇՆՌՁՆՍՇՍՋԽՆԼՈՇՁՆՌՋ
԰ԳԩՏԽՁԿՀ ՌԹՆԼՆՇՊՅԹՄՁՒԽԼԥԩԩ

ԱՀԽՁՆԻՁԼԽՆԻԽԹՆԼՋԽՎԽՊՁՌՑՇԾՌՀՑՊՇՁԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇ ՈԹՌՀՇՄՇԿՑ
ԾՇՄՄՁԻՄԽՋՁՒԽԾՁՆԼՁՆԿՋՏԹՋՎՁՋՍԹՄՄՑ

ՇԺՋԽՊՎԽԼՌՇԺԽԿՊԽԹՌԽՊՏՁՌՀՁՆԻՊԽԹՋՁՆԿՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԱՀԽՋՌՍԼՑԹՍՌՀՇՊԹՆԹՄՑՒԽԼՌՀԽՁՆԻՁԼԽՆԻԽԹՆԼՋԽՎԽՊՁՌՑ

ԻՇՍՆՌՋՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌԽՋՌԹՆԼԼԽՌԽՊՅՁ ՆԽԼՌՀԹՌՌՀԽԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑ

ՋՁԿՆՁԾՁԻԹՆՌ
Ո 

ԱՀԽՌԽՋՌՈԽՊԾՇՊՅԹՆԻԽԹՆԼՎԹՄՁԼՁՌՑԻՊՁՌԽՊՁԹՏԽՊԽԿԽՆԽՊԹՄՄՑՅԽՌ ԽՐԻԽՈՌՌՀԽԠԳՇԾՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԽՐԻԽԽԼԽԼԾՇՊԹՄՄՌԽՋՌՅԹՌԽՊՁԹՄՄԽՎԽՄՋՇՎԽՊՌՀԽՋՌՍԼՑԼՍՊԹՌՁ ՇՆ
ՊԹՆԿԽՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼՏՀՁԻՀ

ՏԹՋԹՌՌՊՁԺՍՌԽԼՌՇՌՀԽԹԾԾՁՆՁՌՑՇԾՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄՌՇԺՁՆԼՌՇ ԿՄԹՋՋՌԹՆՃՋԾՇՇԼՌԹԼՈՇՄԽՋԹՆԼԽՐԻՊԽՌԽԼՇՊԿԹՆՁԻՅԹՌՌԽՊ

ԱՀՁՋՁՆՌՊՇԼՍԻԽՋՍՆԻԽՊՌԹՁՆՌՑՁՆՌՇՌՀԽՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾԽՐՈՇՋՍՊԽ ԹՋՋՇԻՁԹՌԽԼՏՁՌՀԽԾԾԽԻՌՋՁՆՌՀՁՋԹՋՋԹՑԫՇՆԽՌՀԽՄԽՋՋ

ՌՀԽՋՌՍԼՑՁՋՇՌՀԽՊՏՁՋԽԿԽՆԽՊԹՄՄՑՋՇՍՆԼ

ԱՀՁՋԹՋՋԹՑՋԹՌՁՋԾՁԽՋՌՀԽԢԡ԰ԭԱՁԽՊԱԽՋՌԬՊԼԽՊՊԽՉՍՁՊԽՅԽՆՌԾՇՊԹՆԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԬԠ԰ԭԭ

ԤՍՁԼԽՄՁՆԽ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌՇՊԿԹՆՁՋՅԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

ԱԽՋՌՇՊԿԹՆՁՋՅՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՇՈՌՁՇՆԹՄԫՇՌՊ ԽՈՇՊՌԽԼ

ԱԽՋՌՌՑՈԽԣՄՇՏՌՀՊՇՍԿՀ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽ  ԰ՍՅՅԹՊՑ ՇԾ ԡԽՎԽՄՇՈՅԽՆՌԹՄ ԹՆԼ ԱՀՑՊՇՁԼ ԭԹՌՀՇՄՇԿՑԥՁՋՌՇՈԹ ՌՀՇՄՇԿՑ ԢԾԾԽԻՌՋ  

###  ՁՆ ՌՀԽ ԞՅՈՀՁԺՁԹՆ

ԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԞԪԞՏՁՌՀԭԠԫԟ

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ

԰ՌԹԿԽ ԥՁՆԼԩՁՅԺ

ԩԽՆԿՌՀ  

### ԞՋՑՆԻՀՊՇՆՇՍՋ

ԡԽՎԽՄՇՈՅԽՆՌ ԱՀՑՊՇՁԼԤՊՇՋՋԹՆԼ

ԥՁՋՌՇՈԹՌՀՇՄՇԿՑ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

 ԡԹՑ ԡԹՑ ԡԹՑ

 ԫՇ ԶԽՋ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ

 ԫՇ ԶԽՋ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ

 ԫՇ ԶԽՋ ԫՇ ԫՇ ԫՇ ԫՇ ԶԽՋ 

 

###  Ԟ՟ՑԽՋՠՁՆԼՁԻԹՌԽՋԹՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋ ՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄՍՆՄԽՋՋ

ՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼ

 

###  ԱՀԽԻՊՁՌԽՊՁԹԾՇՊՋՁԿՆՁԾՁԻԹՆԻԽԹՊԽԼԽՋԻՊՁԺԽԼՁՆՌՀԽԯԽՎՁԽՏԽՊ0 ՋԞՆԹՄՑՋՁՋԹՆԼ԰ՌԹՌՁՋՌՁԻԹՄԳԽՊՁԾՁԻԹՌՁՇՆՋԽԻՌՁՇՆՋՇԾ

ՌՀԽ ԡԢԯ  ԠՇՆԻՄՍՋՁՇՆՋ ՊԽԿԹՊԼՁՆԿ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ ՅԹՑ ԺԽ ՀԽԹՎՁՄՑ Տ ԽՁԿՀՌԽԼ ԺՑ ՌՀԽ ԽՐՈԽՊՌ ՇՈՁՆՁՇՆ ՇԾ Թ

ԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

 

###  ԥՁՆԼՄՁՅԺՄԽՆԿՌՀՁՋՆՇՊՅԹՄՁՒԽԼՌՇՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰Գԩ

 

###  ԟԹՋԽԼՇՆՎՁՋՍԹՄԹՋՋԽՋՋՅԽՆՌՇԾՁՆԻՁԼԽՆԻԽԹՆԼՋԽՎԽՊՁՌՑԼԹՌԹՀ ՇՏԽՎԽՊՌՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌՌՀԽ

ԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌ 

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  

## Ԧ ԪԞԱԢԯԦԞԩ԰ԞԫԡԪԢԱԥԬԡ԰ 

 ԤՍՁԼԽՄՁՆԽԣՇՄՄՇՏԽԼ ԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼԾՇՄՄՇՏՁՆԿԿՍՁԼԽՄՁՆԽՋՇՍՌՄՁՆԽԼՁՆԲ԰ ԢԭԞԢՆԼՇԻՊՁՆԽ

ԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅԱԽՋՌԤՍՁԼԽՄՁՆԽՋԬԠ԰ԭԭԞՅ ՈՀՁԺՁԹՆ

ԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԣՊՇԿ
ԬԻՌՇԺԽՊԱՀԽԾՇՄՄՇՏՁՆԿԼԽՎՁԹՌ ՁՇՆ
ՋՏԽՊԽ

ՆՇՌԽԼ

 ԱՀԽՈՀՇՌՇՈԽՊՁՇԼ
ՀՊՋՄՁԿՀՌՀՊՋԼԹՊՃՏԹՋՆՇՌԻՇՆՋՁՋՌԽՆՌՏ ՁՌՀՌՀԽՊԽԻՇՅՅԽՆԼԽԼՈՀՇՌՇՈԽՊՁՇԼ


ՀՊՋՄՁԿՀՌՀՇՍՊՋԼԹՊՃ

 ԱՀԽՏԹՌԽՊՀԹՊԼՆԽՋՋԼՍՊՁՆԿՌՀԽԼԽԾՁՆՁՌՁՎԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼ
 ՅԿԩԹՋԠԹԠԬ  

### ԽՐԻԽԽԼԽԼՌՀԽ

ՊԽԻՇՅՅԽՆԼԽԼՊԹՆԿԽ
ՅԿԩԹՋԠԹԠԬ  

### 

 ԱՀԽԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽ ԻԹ ՅԩՅՁՆԽՐԻԽԽԼԽԼՌՀԽՊԽԻՇՅՅԽՆԼԽԼՊԹՌԽ
ՅԩՅՁՆ

 ԱՀԽԾԽԽԼՁՆԿՊԹՌԽՋԾՇՊՌԹԼՈՇՄԽՋԼՍՊՁՆԿՌՀԽԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑՁՆԻՊ ԽԹՋԽԼԾՊՇՅՅԿՄԹՊՎԹԽԼԹՑԹՌՌԽՋՌ

ՁՆՁՌՁԹՌՁՇՆՌՇՅԿՄԹՊՎԹԽԼԹՑԺՑՌՀԽՄԹՋՌՏԽԽՃՇԾՌՀԽՌԽՋՌՏՀ ՁԻՀՏԹՋՆՇՌԻՇՆՋՁՋՌԽՆՌՏՁՌՀՌՀԽ

ՊԽԻՇՅՅԽՆԼԽԼԾԽԽԼՁՆԿՊԹՌԽՇԾՅԿՄԹՊՎԹԼԹՑԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ՌՇՅԿՄԹՊՎԹԼԹՑՁՆՌՀԽՄԹՋՌՏԽԽՃ

ՇԾՌՀԽՌԽՋՌ

 ԱՀԽԹՅՅՇՆՁԹԾՄՍՇՊՁԼԽԻՀՄՇՊԹՌԽԹՆԼՈԽՊԻՀՄՇՊԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՁՆՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ

 ԱՀԽԠԳՇԾՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋԽՐԻԽԽԼԽԼԾՇՊԹՄՄՌԽՋՌՅԹ ՌԽՊՁԹՄՄԽՎԽՄՋՇՎԽՊՌՀԽՋՌՍԼՑԼՍՊԹՌՁՇՆ

 ԱԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԼԽԻՊԽԹՋԽԼԹԾՌԽՊՌՀԽԹԼԼՁՌՁՇՆՇԾՇՊԿԹՆՁՋՅՋՇ ՆԡԹՑՏՀՁԻՀՏԹՋԹՌՌՊՁԺՍՌԽԼՌՇՌՀԽԹԾԾՁՆՁՌՑ

ՇԾՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄՌՇԺՁՆԼՌՇԿՄԹՋՋՌԹՆՃՋԾՇՇԼՌԹԼՈՇՄԽՋԹՆԼ ԽՐԻՊԽՌԽԼՇՊԿԹՆՁԻՅԹՌՌԽՊ

ԱՀԽՎԹՊՁԹԺՁՄՁՌՑՁՆՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՊԽԾՄԽԻՌԽԼՁՆՀՁԿՀԽՊՌՀԹ ՆՊԽԻՇՅՅԽՆԼԽԼԠԳՋՁՆՌՊՇԼՍԻԽՋՍՆԻԽՊՌԹՁՆՌՑ

ՁՆՌՇՌՀԽՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾԽՐՈՇՋՍՊԽԹՋՋՇԻՁԹՌԽԼՏՁՌՀԽԾԾԽԻՌՋՁՆ ՌՀՁՋՋՌՍԼՑԥՇՏԽՎԽՊՌՀԽՋՌՍԼՑՁՋՇՌՀԽՊՏՁՋԽ

ԿԽՆԽՊԹՄՄՑՋՇՍՆԼ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ   ԠՇՅՈՄՁԹՆԻԽ    ԰Ձ ԿՆԽԼԹՆԼԼԹՌԽԼԫՇԡԹՌԹԠՇՆԾՁԼԽՆՌՁԹՄՁՌՑԤՇՇԼԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻ Խ
Ԥԩԭ

ԹՆԼԮՍԹՄՁՌՑԞՋՋՍՊԹՆԻԽՋՌԹՌԽՅԽՆՌՋՏԽՊԽՈՊՇՎՁԼԽԼԱՀՁՋՋՌՍԼՑՏԹՋ ԻՇՆԼՍԻՌԽԼ

ՁՆԻՇՅՈՄՁԹՆԻԽՏՁՌՀԹՄՄՈԽՊՌՁՆԽՆՌԬԢԠԡ
ԬԢԠԡԹՆԼԲ԰ԢԭԞ 
Ԡԣԯ

ԭԹՊՌԤԩԭՊԽԿՍՄԹՌՁՇՆՋՏՁՌՀՌՀԽԾՇՄՄՇՏՁՆԿԽՐԻԽՈՌՁՇՆՋՈԽՊՁՇԼ ՁԻԹՆԹՄՑՋԽՋՇԾ

ՏԹՌԽՊԾՇՊՈՇՌԽՆՌՁԹՄԻՇՆՌԹՅՁՆԹՆՌՋՏԽՊԽՈԽՊԾՇՊՅԽԼՍՋՁՆԿԹԻԽՊՌՁԾՁ ԽԼՄԹԺՇՊԹՌՇՊՑԹՆԼ

ՋՌԹՆԼԹՊԼԲ԰ԢԭԞԹՆԹՄՑՌՁԻԹՄՅԽՌՀՇԼՋՈՊԽՄՁՅՁՆԹՊՑԹՆԹՄՑՋԽՋՇԾՏԹՌԽՊՁՇԼՁԼԽ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՆՇՌՈԽՊԾՇՊՅԽԼԹԻԻՇՊԼՁՆԿՌՇԤԩԭՋՌԹՆԼԹՊԼՋԹ ՆԼՌՀԽ

ԻՀԹՊԹԻՌԽՊՁՒԹՌՁՇՆԹՆԼՋՌԹԺՁՄՁՌՑՇԾՌՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽՍՆԼԽՊՌՀԽՋՌՇՊԹԿԽԻՇՆԼՁՌՁՇՆՋ

ՇԾՌՀԽՌԽՋՌՋՁՌԽՏԹՋՆՇՌԼԽՌԽՊՅՁՆԽԼՁՆԹԻԻՇՊԼԹՆԻԽՏՁՌՀԤՇՇԼԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽ

԰ՌԹՆԼԹՊԼՋ

ԞԱԽՋՌԪԹՌԽՊՁԹՄ     ԭԠԫԟԱԽԻՀՆՁԻԹՄ

ԡԽՋԻՊՁՈՌՁՇՆ    ԭՇՏԼԽՊ

ԩՇՌԫՇԟԹՌԻՀԫՇ  ԩ 

###   ԭՍՊՁՌՑ      

ԦՅՈՍՊՁՌՁԽՋ     ԫ ՇՆԽՄՁՋՌԽԼ

԰ՌԹԺՁՄՁՌՑՇԾԠՇՅՈՇՍՆԼ ԪԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՑՁԽՄԼԽԼՊԽԻՇՎԽՊՁԽՋՇԾՌՇՇԾՆ ՇՅՁՆԹՄՏՁՌՀ

ԻՇԽԾԾՁԻՁԽՆՌՋՇԾՎԹՊՁԹՌՁՇՆՇԾՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼԱԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՋՍԺՋՌԹՆՌՁԹՄՄՑՄՇՏԽՊԹՌԡԹՑՌՀԹՆԡԹՑՏՀՁ ԻՀ

ԹԻԻՇՍՆՌԽԼԾՇՊՌՀԽՄԹՊԿԽՊՊԹՆԿԽՁՆՊԽԻՇՎԽՊՁԽՋԯԹՆԿԽՁՆՅԽԹՆՅԽ ԹՋՍՊԽԼ

ՊԽԻՇՎԽՊՁԽՋԾՊՇՅԡԹՑՌՇՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՏԹՋ

ՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼԱՀԽՊԹՆԿԽՁՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊ Խ

ԹՌՌՊՁԺՍՌԽԼՌՇՌՀԽԹԾԾՁՆՁՌՑՇԾՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄՌՇԺՁՆԼՌՇԿՄԹՋ ՋՌԹՆՃՋԾՇՇԼ

ՌԹԼՈՇՄԽՋԹՆԼԽՐԻՊԽՌԽԼՇՊԿԹՆՁԻՅԹՌՌԽՊ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾ  ԰ՌՇՊԽԼՍՆԼԽՊԹՅԺՁԽՆՌԻՇՆԼՁՌՁՇՆՋ

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

ՁԼԽՆՌՁԾՁԽԼ԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԵԽՆՇՈՍՋՄԹԽՎՁՋ԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼ Բ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅԱՁԽՊԞՋՋԹՑՋ
ԬԠ԰ԭԭԱԽՋՌԤՍՁԼԽՄՁՆԽ԰ԽՊՁԽՋԪԹՊԻՀԬԾԾՁԻԽՇԾԠՀԽՅՁԻԹՄ԰ԹԾԽՌՑԹՆԼԭՇՄՄՍՌՁՇՆԭՊԽՎԽՆՌՁՇՆ
ԬԠ԰ԭԭԴԹՋՀՁՆԿՌՇՆԡԠՀՌՌՈՏՏՏԽՈԹԿՇՎԽՆԼՇՈՍԺՋԹՋՋԹՑՎԹՄՁԼԹՌՁՇՆԻՄԹՊՁԾՁԻԹՌՁՇՆԼՇԻՈԼԾԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԽՊԽՈԹՊԽՆՌՋՅԹՁՆՌԹՁՆԽԼԹՋՁՆՀՇՍՋԽՋՌՇԻՃ!ԶԽՋ ԠՍՄՌՍՊԽՋՏԽՊԽՅԹՁՆՌԹՁՆԽԼԾՇՊՇՆԽՅՇՆՌՀՈՊՁՇՊՌՇՌԽՋՌՁՆՁՌՁԹՌՁՇՆԺՑԴՁՄԼՄՁԾԽԦՆՌԽՊՆԹՌՁՇՆԹՄԩՌԼԹԾՌԽՊԺԽՁՆԿՇԺՌԹՁՆԽԼԾՊՇՅԵԽՆՇՈՍՋԦՇԾԡԽՐՌԽՊԪՁԻՀՁԿԹՆ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՄԹՊՎԹԽ ՍՋԽԼ ՁՆ ՌՀԽ ԹՋՋԹՑԺԽԼԽՊՁՎԽԼԾՊՇՅՁՆՀՇՍՋԽԹԼՍՄՌՋԴԽՊԽՈԹՊԽՆՌԹՄԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!ԶԽՋԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԾՇՊՈԹՊԽՆՌԹՄԾՊՇԿՋ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԻԹԼԹՑՋԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄԾԽԽԼՁՆԿ ԞԼՍՄՌԾՊՇԿՋՏԽՊԽԾԽԼԹՌԹՊԹՌԽՋՍԾԾՁԻՁԽՆՌՌՇՅԹՁՆՌԹՁՆՌՀԽՀԽԹՄՌՀՇԾՌՀԽԻՍՄՌՍՊԽԣՇՇԼՋՇՍՊԻԽՁՋԷԽՁԿՄԽՊԟՊՇՋԦՆԻՇԾԤԹՊԼՆԽՊՋԭԽՆՆՋՑՄՎԹՆՁԹԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄՀԽԹՄՌՀ ԭԹՊԽՆՌԹՄԾՊՇԿՋՏԽՊԽՁՆԿՇՇԼՀԽԹՄՌՀՋՀՇՏՁՆԿՆՇՋՁԿՆՋՇԾԼՁՋԽԹՋԽՇՊՋՌՊԽՋՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԩԹՊՎԹՄ԰ԽՄԽԻՌՁՇՆԹՆԼԠԹՊԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԟԽՋՌՋՁՆԿՄԽՋՈԹՏՆ!ԶԽՋ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌՀԽԺԽՋՌ- ՁՆԼՁՎՁԼՍԹՄՋՈԹՏՆՋՏՁՌՀԹՅՁՆՁՅՍՅՇԾ ՄԹՊՎԹԽՋՈԹՏՆԺԽԽՎԹՄՍԹՌԽԼՌՇՁԼԽՆՌՁԾՑՌՀԽ ԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆԹՆԼՌՀԹՌՌՀԽՄԹՊՎԹԽՋԽՄԽԻՌԽԼ ԾՇՊՌԽՋՌՁՆԿՇՊՁԿՁՆԹՌԽԾՊՇՅՌՀԽԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆ

ՁԽ ՌՀԽՋՈԹՏՆՋԹՊԽՆՇՌԻՇՅՁՐԽԼԫՍՅԺԽՊՇԾՋՈԹՏՆՋԽՎԹՄՍԹՌԽԼ
ՁԾԹՈՈՄՁԻԹԺՄԽԱՀՊԽԽԫՍՅԺԽՊՇԾԽԿԿՋՋԹՅՈՄԽԼՈԽՊՋՈԹՏՆԽԿԿՋԾՊՇՅԹՋՁՆԿՄԽՋՈԹՏՆՏԽՊԽԽՎԹՄՍԹՌԽԼԾՇՊՎՁԹԺՁՄՁՌՑԢՅԺՊՑՇՆՁԻՎՁԹԺՁՄՁՌՑՏԹՋԻՀԽԻՃԽԼԼԹՁՄՑԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԺԽ ՁՆՁՌՁԹՌԽԼՏՁՌՀՄԹՊՎԹԽԹՌԫՁԽՍՏՃՇՇՈ-ԣԹԺԽՊ ԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ ԼԹՑՋ ՈՇՋՌԾԽՊՌՁՄՁՒԹՌՁՇՆԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԼԹՑՋՈՇՋՌԾԽՊՌՁՄՁՒԹՌՁՇՆԼՈԾԪԽԹՆՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՁԾՊԽՈՇՊՌԽԼԫՇՌԹՈՈՄՁԻԹԺՄԽԯԹՆԿԽՇԾՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՊԽՈՇՊՌԽԼԫՇՌԹՈՈՄՁԻԹԺՄԽԴԹՋՌՀԽՇՈՌՁՇՆԹՄՋՁՒԽՋԽՄԽԻՌՁՇՆՅԽՌՀՇԼՍՋԽԼ!ԫՇ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՄԹՊՎԹՄՋԽՄԽԻՌՁՇՆ ԞՋՄԹՊՎԹԽՊԽԹԻՀԽԼԫԣՋՌԹԿԽՌԹԼՈՇՄԽՋՌՀԹՌՅԽՌՌՀԽԻՊՁՌԽՊՁԹԾՇՊՀՁՆԼՄՁՅԺՅՇՊՈՀՇՄՇԿՑՏԽՊԽՈՄԹԻԽԼՇՆԽՇՊՌՏՇԹՌԹՌՁՅԽՁՆՌՇՌՊԹՆՋԾԽՊՎԽՋՋԽՄՋՍՆՌՁՄԽԹԻՀՎԽՋՋԽՄԻՇՆՌԹՁՆԽԼՌԹԼՈՇՄԽՋԩՇԹԼՁՆԿՊԹՌԽ
ՊԽԹՊՁՆԿԼԽՆՋՁՌՑ ՄԹՊՎԹԽԩ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՊԽԹՊՁՆԿ ԼԽՆՋՁՌՑ ՄՇԹԼՁՆԿ ՊԹՌԽ ՆՇՌ ԽՐԻԽԽԼ ԹՈՈՊՇՐՁՅԹՌԽՄՑ  ՄԹՊՎԹԽԩ ԻՍՄՌՍՊՁՆԿ ՋՑՋՌԽՅ ԾՇՊ ԾՄՇՏՌՀՊՇՍԿՀ ՋՑՋՌԽՅՋ ՇՊ  ՌԹԼՈՇՄԽՋԩ ՁՆ ՋՌԹՌՁԻՊԽՆԽՏԹՄ ԽՐՈՇՋՍՊԽՋՑՋՌԽՅՋԱՑՈԽՇԾԾՇՇԼ԰ԽՊԹԪՁԻՊՇՆ ԢԭԞՊԽԻՇՅՅԽՆԼՋ԰ԽՊԹԪՁԻՊՇՆ ն ՌՀՊՇՍԿՀՇՍՌ ՈՊԽԽՐՈՇՋՍՊԽ
ԹԾՌԽՊԫԣՋՌԹԿԽԹՆԼ ԼՍՊՁՆԿՌՀԽԽՆՌՁՊԽԼԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԦԾ԰ՇՍՊԻԽՇԾԾՇՇԼ԰ԽՊԹԪՁԻՊՇՆնԲ԰ԞԪՇՆՌԿՇՅԽՊՑՎՁՄՄԽԭԞԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԦՇԼՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆԼՁԽՌ
ՁԾՃՆՇՏՆԫՇՌՊԽՈՇՊՌԽԼ  ԹՆՇՌՀԽՊԼՁԽՌՁՋՍՋԽԼՌՀԽՋՌՍԼՑՊԽՈՇՊՌՋՀՇՍՄԼ ՈՊՇՎՁԼԽԹՆԹՄՑՋՁՋՇԾՁՇԼՁԼԽԻՇՆՌԽՆՌԹՆԼՈՇՌԽՆՌՁԹՄ ԻՇՆՌԹՅՁՆԹՆՌՋԹՆԼՌՀԽԼՁԽՌՋՀՇՍՄԼ ԼԽՅՇՆՋՌՊԹՌԽԽՉՍԹՄՈԽՊԾՇՊՅԹՆԻԽՌՇ԰ԽՊԹ

ԪՁԻՊՇՆ ն ԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿԱՀՊԽԽՌՁՅԽՋՈԽՊԼԹՑ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾԽԽԼՁՆԿՇԻԻՍՊԹՌՄԽԹՋՌ

ՌՏՁԻԽՈԽՊԼԹՑԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿՊԽԿՁՅԽ ԱՀԽԾԽԽԼՁՆԿՊԽԿՁՅԽՏԹՋՅԿՄԹՊՎԹԼԹՑԹՆԼՁՆԻՊԽԹՋԽԼՌՇՅԿՄԹՊՎԹԼԹՑԺՑՌՀԽԽՆԼՇԾՌՀԽՌԽՋՌ ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋԼՍՊՁՆԿՌՀԽ ՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԺԽՁՆԻՊԽԹՋԽԼԹՄՇՆԿՏՁՌՀ ՄԹՊՎԹՄԿՊՇՏՌՀՌՇԹՈՈՊՇՐՁՅԹՌԽՄՑ ՅԿՄԹՊՎԹԼԹՑԺՑՌԽՋՌՁՆՁՌՁԹՌՁՇՆԢԭԞԹՆԼ ԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋՁՆԻՊԽԹՋԽ ԾՊՇՅՅԿՄԹՊՎԹԼԹՑԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
԰ՌՍԼՑ ԡԹՑՌՇՅԿՄԹՊՎԹԼԹՑՁՆՌՀԽՄԹՋՌՏԽԽՃ ՇԾՌՀԽՌԽՋՌ
԰ՌՍԼՑԡԹՑԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԠԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱՑՈԽՇԾԽՐՈՇՋՍՊԽԣՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏՌՀՊՇՍԿՀ

ՋՑՋՌԽՅԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅ
ՁԾԹՈՈՄՁԻԹԺՄԽԠՇՆՌՁՆՍՇՍՋԾՄՇՏԼՁՄՍՌԽՊ ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ ՊԽԻՇՅՅԽՆԼԽԼ ԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԻԹՅԩՅՁՆԺԹՋԽԼՇՆԹԩԾՁՄՄՎՇՄՍՅԽԹՆԼՎՇՄՍՅԽԹԼԼՁՌՁՇՆՋՈԽՊԼԹՑԱՀԽԽՋՌՁՅԹՌԽԼԾՄՇՏՊԹՌԽՈՊՇՎՁԼԽԼԻՇՅՈՄԽՌԽՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԹՈՈՊՇՐՁՅԹՌԽՄՑԽՎԽՊՑՀՇՍՊՋ ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋ ՅԩՅՁՆ
ԻՇՅՈՄԽՌԽՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԻԹ

ԽՎԽՊՑՀՊՋԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋ
ՁԾԹՈՈՄՁԻԹԺՄԽ԰ՁՆԿՄԽՌԽՋՌՋՌՇԻՃՋՇՄՍՌՁՇՆՏԹՋԼԽՄՁՎԽՊԽԼՌՇՅՁՐՁՆԿԻՀԹՅԺԽՊՋԹՋՋՁԿՆԽԼՌՇԽԹԻՀՌՊԽԹՌՅԽՆՌ԰ՌՇԻՃՋՇՄՍՌՁՇՆՏԹՋԼՁՄՍՌԽԼՏՁՌՀՏԽՄՄՏԹՌԽՊՁՆՌՀԽՅՁՐՁՆԿԻՀԹՅԺԽՊՋՌՇՇԺՌԹՁՆԽԹԻՀՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԱՀԽՈՊՇՈՇՊՌՁՇՆՇԾՌԽՋՌՋՇՄՍՌՁՇՆԼԽՄՁՎԽՊԽԼՌՇԽԹԻՀՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊՏԹՋԻՀԽԻՃԽԼՈՊՁՇՊՌՇՌՀԽՌԽՋՌԹՆԼԹՈՈՊՇՐՁՅԹՌԽՄՑՏԽԽՃՄՑՌՇԽՆՋՍՊԽԾՄՇՏՊԹՌԽՋՎԹՊՁԽԼԺՑՆՇՅՇՊԽՌՀԹՆչՇԾՌՀԽՅԽԹՆԾՄՇՏՊԹՌԽԾՇՊՌՀԽՊԽՈՄՁԻԹՌԽՋԡԽՄՁՎԽՊՑՇԾՌԽՋՌՋՇՄՍՌՁՇՆՋՌՇՌՀԽՌԽՋՌԻՀԹՅԺԽՊՋՏԹՋՁՆՁՌՁԹՌԽԼԽՁԿՀՌԼԹՑՋՈՊՁՇՊՌՇՌՀԽՁՆՌՊՇԼՍԻՌՁՇՆՇԾՌՀԽՌԽՋՌՇՊԿԹՆՁՋՅՋ ԯԽԻՇՅՅԽՆԼԽԼՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊ ԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋԪՁՐՁՆԿԻՀԹՅԺԽՊՁՋ ՊԽԻՇՅՅԽՆԼԽԼԺՍՌՆՇՌՊԽՉՍՁՊԽԼԞԽՊԹՌՁՇՆ ՁՋՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՅՁՐՁՆԿԞ ԼԽՅՇՆՋՌՊԹՌՁՇՆՌՀԹՌՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՁՋ ԻՇՅՈՄԽՌԽՄՑՅՁՐԽԼԺԽԾՇՊԽՁՆՌՊՇԼՍԻԽԼՁՆՌՇՌՀԽ ՌԽՋՌՋՑՋՌԽՅՁՋՊԽԻՇՅՅԽՆԼԽԼԱՀԽ ՊԽԻՇՅՅԽՆԼԽԼԾՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑՁՋ

ՏՁՌՀՁՆԯԽՆԽՏԹՄՈԽՊՁՇԼԾՇՊՋՌԹՌՁԻՊԽՆԽՏԹՄ
ՁԾԹՈՈՄՁԻԹԺՄԽԫՇՌԹՈՈՄՁԻԹԺՄԽ ԦԾՋՌԹՌՁԻՊԽՆԽՏԹՄՁՋՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋ ՀՊՊԽՆԽՏԹՄՊԽՆԽՏԹՄՈԽՊՁՇԼՁՋ ՊԽԻՇՅՅԽՆԼԽԼՆՇՌՌՇԽՐԻԽԽԼՀՇՍՊՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԽՊԹՌՁՇՆ!ԫՇ ԢԭԞՊԽԻՇՅՅԽՆԼՋՅԹՁՆՌԹՁՆՁՆԿԼՁՋՋՇՄՎԽԼ ՇՐՑԿԽՆԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԹՁՊՋԹՌՍՊԹՌՁՇՆ

ՅԿԩ ԞԽՊԹՌՁՇՆՅԹՑԺԽՅԹՁՆՌԹՁՆԽԼ ՌՀՊՇՍԿՀԺՍԺԺՄԽՊՋԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՇՋԽՌ ԺՍԺԺՄԽՊՋԹՌՄԽՎԽՄՋՌՀԹՌԼՇՆՇՌԻԹՍՋԽՋՌՊԽՋՋ

ՇՆՌՀԽՌԹԼՈՇՄԽՋ԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ ԣՊԽՋՀՏԹՌԽՊԾՊՇՅԹՅԽՌԽՊԼԽԽՈՏԽՄՄՄՇԻԹՌԽԼՇՆՌՀԽԴՁՄԼՄՁԾԽԦՆՌԽՊՆԹՌՁՇՆԹՄԩՌԼ԰ՁՌԽԡՁՄՍՌՁՇՆՏԹՌԽՊՏԹՋՈՊԽՈԹՊԽԼԺՑՈԹՋՋՁՆԿՌՀԽՏԽՄՄՏԹՌԽՊՌՀՊՇՍԿՀԹՋԹՆԼԾՁՄՌԽՊՌՇՊԽՅՇՎԽՈԹՊՌՁԻՄԽՋԿՊԽԹՌԽՊՌՀԹՆսՅԹՆԼՌՀԽՆՈՍՅՈՁՆԿՁՌՁՆՌՇԹՋՌՇՊԹԿԽՌԹՆՃՏՀԽՊԽՁՌՏԹՋԹԽՊԹՌԽԼԱՀԽՏԹՌԽՊՏԹՋԾՁՄՌԽՊԽԼՌՇսՅՌՇՊԽՅՇՎԽԾՁՆԽՈԹՊՌՁԻՄԽՋԹՆԼՏԹՋՈԹՋՋԽԼՌՀՊՇՍԿՀԹՆՍՄՌՊԹՎՁՇՄԽՌՋՌԽՊՁՄՁՒԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼ ՏԹՌԽՊՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄՏԹՌԽՊ ԺԽՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊ ՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊ ՈՇՋՋՁԺՄԽԻՇՆՌԹՅՁՆԹՆՌՋՁՆԻՄՍԼՁՆԿՃՆՇՏՆ ՋՍԺՋՌՊԹՌԽՋՇԾՌՀԽՁՇԼՁՆԽՌՊԹՆՋՈՇՊՌԽՊՇԾՌՀԽ ՌՀՑՊՇՁԼԿՄԹՆԼ
ԽԿ ԾՄՍՇՊՁԼԽԻՀՄՇՊԹՌԽ ՈԽՊԻՀՄՇՊԹՌԽԬԢԠԡԹԻԻԽՈՌՋԹՆՑՏԹՌԽՊՁՆ ՏՀՁԻՀՌՀԽՌԽՋՌՋՈԽԻՁԽՋՋՀՇՏԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄ ԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌ

ԿՍՁԼԽՄՁՆԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!ԶԽՋ ԡՁՄՍՌՁՇՆՏԹՌԽՊՏԹՋԹՆԹՄՑՒԽԼԾՇՊՋՈԽԻՁԾՁԻԻՇՆԼՍԻՌԹՆԻԽՀԹՊԼՆԽՋՋԹՄՃԹՄՁՆՁՌՑՈԥՌՇՌԹՄՇՊԿԹՆՁԻԻԹՊԺՇՆՈԽՋՌՁԻՁԼԽՋՇՊԿԹՆՁԻՋԹՆԼՅԽՌԹՄՋԦՇԼՁԼԽՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՆՏԹՌԽՊ!ԫՇՈՊԽՄՁՅՁՆԹՊՑԹՆԹՄՑՋՁՋՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊՁՆԼՁԻԹՌԽԼԹՆՁՇԼՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾ ԻԹՌՇսԿԩ ԦԾՊԽԻՇՆՋՌՁՌՍՌԽԼՏԹՌԽՊՁՋՍՋԽԼՇՊՁԾ ԺԹԻՃԿՊՇՍՆԼՄԽՎԽՄՋՇԾՁՇԼՁԼԽՁՆՆԹՌՍՊԹՄՏԹՌԽՊ ԹՊԽՄԽՋՋՌՀԹՆսԿԩՁՇԼՁԼԽ ՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՋՊԽԻՇՅՅԽՆԼԽԼԱՀՁՋ ՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՋՁՆԹԼԼՁՌՁՇՆՌՇՌՀԽ ՊԽԻՇՅՅԽՆԼԽԼԼՁԽՌԹՊՑՋՇՍՊԻԽՇԾՁՇԼՁԼԽ ԽԿՁՆ԰ԽՊԹԪՁԻՊՇՆԱԽՋՌՎԽՋՋԽՄՌՑՈԽՅԹՌԽՊՁԹՄՋ ԱԽՋՌԻՀԹՅԺԽՊՋՏԽՊԽԿՄԹՋՋԹՉՍԹՊՁԹ ԢԭԞ ԹՆԼ ԬԢԠԡ ՊԽԻՇՅՅԽՆԼ ՌՀԹՌ ՏԹՌԽՊԻՇՆՌԹԻՌ ՈՇՊՌՁՇՆՋ ՇԾ ՌՀԽ ՋՑՋՌԽՅ ՆՇՌ ԻՇՅՈՊՇՅՁՋԽ ՌՀԽ ՋՌՍԼՑ 
ԽԿ ԹՄՄ ԿՄԹՋՋ ՎԽՋՋԽՄՋՇՊԿՄԹՋՋՎԽՋՋԽՄՋՏՁՌՀՋՌԹՁՆՄԽՋՋՋՌԽԽՄ ԾՊԹՅԽՋԹՊԽԹԻԻԽՈՌԹԺՄԽԽՐԹՅՈՄԽՋԱԽՋՌՎԽՋՋԽՄՋՁՒԽ԰ՈԽԻՁԾՁԻԼՁՅԽՆՋՁՇՆՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼԱՀԽՌՇՌԹՄՎՇՄՍՅԽՏԹՋԩԣՁՄՄՎՇՄՍՅԽ ԻԹԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽՋՑՋՌԽՅԢՐՈՇՋՍՊԽՏԹՋԻՇՆԼՍԻՌԽԼՁՆԹՌԽՅՈԽՊԹՌՍՊԽԻՇՆՌՊՇՄՄԽԼԽՆՎՁՊՇՆՅԽՆՌԹՄԻՀԹՅԺԽՊՌՇՅԹՁՆՌԹՁՆՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՌԽՅՈԽՊԹՌՍՊԽՋԹՌ±ոԠ ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԥԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬ ԴԽԽՃՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՀԹՊԼՆԽՋՋՌՇ ՅԿԩԹՋԠԹԠԬ ՈԥԴԽԽՃՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥչ ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ՅԿԩԴԽԽՃՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ԡԬ ՅԿԩ
 ԹՁՊՋԹՌՍՊԹՌՁՇՆԬԢԠԡ ՊԽԻՇՅՅԽՆԼՋԡԬԻՇՆԻԽՆՌՊԹՌՁՇՆ ՅԿԩ ԹՁՊՋԹՌՍՊԹՌՁՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՅՈԽՊԹՌՍՊԽ ԱԽՅՈԽՊԹՌՍՊԽՏԹՋԻՇՆՌՁՆՍՇՍՋՄՑԹՆԼՊԽԻՇՊԼԽԼՏԽԽՃՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչ Շ Ԡ ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼ Շ ԠԦՇԼՁԼԽԳԹՄՍԽՆՇՌՊԽՈՇՊՌԽԼԤԩԭԻՇՅՈՄՁԹՆԻԽՋՌԹՌԽՅԽՆՌՁՆԼՁԻԹՌԽՋՌՀԹՌՈՊԽՄՁՅՁՆԹՊՑԹՆԹՄՑՋՁՋՇԾՏԹՌԽՊՁՇԼՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՆՇՌՈԽՊԾՇՊՅԽԼԹԻԻՇՊԼՁՆԿՌՇԤԩԭ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՉՍԹՌՁԻՁՇԼՁԼԽՊԹՆԿԽ -սԿԩ
ՋՍՈՈՄԽՅԽՆՌԹՄՁՇԼՁԼԽՋՀՇՍՄԼՆՇՌ
ԽՐԻԽԽԼսԿԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞՅՅՇՆՁԹԫՇՌՊԽՈՇՊՌԽԼ ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑՇԾ ՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋԺԽՅԽԹՋՍՊԽԼՁՆԹ ԻՇՆՌՊՇՄԹՆԼԹՌՇՆԽՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ ԹՌՄԽԹՋՌՏԽԽՃՄՑԦՆՋՌԹՌՁԻՊԽՆԽՏԹՄՋՑՋՌԽՅՋ ՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋՁՆԻՄՍԼՁՆԿ ԹՅՅՇՆՁԹՋՀՇՍՄԼԺԽՅԽԹՋՍՊԽԼՂՍՋՌՈՊՁՇՊՌՇ ՊԽՆԽՏԹՄԦՆԹԼԼՁՌՁՇՆԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԡԬԺԽՅԽԹՋՍՊԽԼԹՌԽԹԻՀԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌ ՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌՌԽՅՈԽՊԹՌՍՊԽԹՊԽ ՅԽԹՋՍՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑԬԢԠԡ ՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԡԬԹՆԼՌԽՅՈԽՊԹՌՍՊԽԺԽ ՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌՈԥԹՆԼ ՀԹՊԼՆԽՋՋԺԽՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌԹՌՌՀԽ ԺԽԿՁՆՆՁՆԿԹՆԼԽՆԼՇԾՌՀԽՌԽՋՌԣՄՍՇՊՁԼԽԫՇՌՊԽՈՇՊՌԽԼԭԽՊԻՀՄՇՊԹՌԽԫՇՌՊԽՈՇՊՌԽԼԠՀՄՇՊԹՌԽԫՇՌՊԽՈՇՊՌԽԼ԰ՈԽԻՁԾՁԻԠՇՆԼՍԻՌԹՆԻԽ
ս԰ԻՅ  ԴԽԽՃՄՑԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾ ԡ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ!ԶԽՋԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!ԱՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊՏԹՋԺԹՋԽԼՇՆՌՀԽՏԹՌԽՊՋՇՄՍԺՁՄՁՌՑՇԾԭԠԫԟ
ՅԿԩԹՌոԠ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ  ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ԰ՈԽԻՁԽՋ ԵԽՆՇՈՍՋՄԹԽՎՁՋԩՁԾԽՋՌԹԿԽԫԣՋՌԹԿԽԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԞՊԹՆԿԽԾՁՆԼՁՆԿՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼՏՁՌՀՌԹԼՈՇՄԽՋՁՆՋՁՆԿՄԽՊԽՈՄՁԻԹՌԽՋՇԾՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩԪՇՊՌԹՄՁՌՑՏԹՋՁՆԺՇՌՀՌՀԽԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋԱՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆԾՇՊՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌՏԹՋԺԹՋԽԼՇՆՇԾՌՀԽԽՋՌՁՅԹՌԽԼԼԹՑԩԠՅԿԹՁԩԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ԼՍՊԹՌՁՇՆ ՇԾ ՌՀԽ ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԼԹՑՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԯԹՆԿԽԾՁՆԼԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ  ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽԫՇՌԹՈՈՄՁԻԹԺՄԽ԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ՅԹՐՁՅՍՅ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՋԽՈԹՊԹՌՁՇՆ ԺԽ  ԹՆԼ ՌՀԽ ՅՁՆՁՅՍՅԺԽԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԱՀՊԽԽՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՈՄՍՋԹՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄՁԾԹՈՈՊՇՈՊՁԹՌԽԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!ԫՇ ԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋԱՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽ ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿԹՁԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡ ԫՇՌՊԽՈՇՊՌԽԼԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԞՈՈՊՇՐՁՅԹՌԽՄՑԼԹՑՋ  ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ ԺԽՅԽԹՋՍՊԽԼՁՆՇՆԽՌԹՆՃԹՌԽԹԻՀՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԹՆԼԽՎԽՊՑՏԽԽՃ

ՌՀԽՊԽԹԾՌԽՊԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽԫՇՌԹՈՈՄՁԻԹԺՄԽ  ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԽՍՋԽՇԾԹ ԻՇՆԻՍՊՊԽՆՌՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿ ԹԿԽՆՌՁՋՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՄԹՊՎԹԽՈԽՊՌՊԽԹՌՅԽՆՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ!ԫՇ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԰ԹՌՍՊԹՌՇՊԻՇՄՍՅՆՋՍՋԽԼԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁԾԹՈՈՄՁԻԹԺՄԽԫՇՌԹՈՈՄՁԻԹԺՄԽ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌԽՐԻԽԽԼ

ՅՄԩ ԬԢԠԡՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՇՄՎԽՆՌ ՀԹՎԽՆՇԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊՈՊՇԼՍԻԽԹՆՑ ՇՌՀԽՊԹԼՎԽՊՋԽԽԾԾԽԻՌՋԹՆԼՌՀԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆ ՆՇՌԺԽԿՊԽԹՌԽՊՌՀԹՆՅՄԩ ԴԹՋԹՈՇՋՁՌՁՎԽԻՇՆՌՊՇՄՍՋԽԼ! ԫՇԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՋՁԾԹՈՈՄՁԻԹԺՄԽԫՇՌԹՈՈՄՁԻԹԺՄԽ ԭՀՇՌՇՈԽՊՁՇԼՀՊՋՄՁԿՀՌՀՊՋԼԹՊՃ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ

ՄՁԿՀՌԼԹՊՃԩՁԿՀՌՁՆՌԽՆՋՁՌՑԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ -ԨՄՍՐՅԽԹՆՇԾԨՄՍՐ ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑ-ԨՄՍՐ ԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ ԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏԞՉՍԹՌՁԻԱՇՐՁԻՇՄՇԿՑՈՈ- ԬԢԠԡ
ԤՍՁԼԹՆԻԽԡՇԻՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋՇՆԱԽՋՌՁՆԿԹՆԼԞՋՋԽՋՋՅԽՆՌԫՇԭԹՊՁՋԣՊԹՆԻԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԫՇՌԹՈՈՄՁԻԹԺՄԽ ԱՀԽՌԽՋՌՋՇՄՍՌՁՇՆՋՏԽՊԽԻՄԽԹՊԹՆԼԻՇՄՇՊՄԽՋՋՏՁՌՀՆՇԽՎՁԼԽՆԻԽՇԾՈՊԽԻՁՈՁՌԹՌՁՇՆՋՍՊԾԹԻԽԾՁՄՅՋՇՊՍՆԼՁՋՋՇՄՎԽԼՅԹՌԽՊՁԹՄԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱՊԽԹՌՅԽՆՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑՏՁՌՀԭԠԫԟՌԽԻՀՆՁԻԹՄԱՊԽԹՌՅԽՆՌԦԡԫՇՅՁՆԹՄԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԱԴԞԪԽԹՋՍՊԽԼԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԪԽԹՆԠԳ
ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ   ԫԞԫԞ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌԽՋՌՁՌԽՅ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՅԹՁՆՌԹՁՆԽԼԹՌԹԻՇԽԾԾՁԻՁԽՆՌՇԾ

ՎԹՊՁԹՌՁՇՆ
ԠԳ ԱՊԽԹՌՅԽՆՌ  ԫԞԱՊԽԹՌՅԽՆՌ ԫԞԱՊԽԹՌՅԽՆՌԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ ԠԹՄԻՍՄԹՌԽԼԺՑԯԽՎՁԽՏԽՊ      ԢԬԺՋԽՊՎԹՌՁՇՆՋԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋԡԹՑԫԣՋՌԹԿԽՏԽՌՏԽՁԿՀՌ԰ԳԩԥԩԩՆՇՊՅԹՄՁՒԽԼԥԩԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾ        ԡԹՑԫԣՋՌԹԿԽՏԽՌՏԽՁԿՀՌ԰ԳԩԥԩԩՆՇՊՅԹՄՁՒԽԼԥԩԩՌՀՑՊՇՁԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑ        ԡԹՁՄՑՅՇՊՌԹՄՁՌՑԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ!ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՅՇՊՌԹՄՁՌՑԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋՇԻԻՍՊԼԹՁՄՑԹՌԹՅՁՆՁՅՍՅՇՌՀԽՊՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽՊԽԻՇՅՅԽՆԼԽԼ ԹՋԾՇՄՄՇՏՋԫԣ ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ
ԡԹՑՋԹՆԼԹՆՑԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽ ՆՌՁՆԼՁԻԹՌԽԼԺՑՌԹԼՈՇՄԽՋՌՀԹՌԻԹՆՆՇՌԺԽԹՋՋՁԿՆԽԼԹՆԫԣՋՌԹԿԽ
ԡԹՑՋԹՆԼ ՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԡԹՑՋԹՆԼՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
ԡԹՑՋԹՆԼ ԺՇԼՑՏԽՁԿՀՌ
ՌԽՋՌՁՆՁՌՁԹՌՁՇՆԾՇՊՇՈՌՁՇՆԹՄՋՁՒԽԺԹՋԽԼՄԹ ՊՎԹՄՋԽՄԽԻՌՁՇՆԹՆԼՌՀՑՊՇՁԼ
ԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑ
ԡԹՑԫՇՌԽՌՀԽՀՁ ՋՌՇՈԹՌՀՇՄՇԿՑՋԽԻՌՁՇՆՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԹՄՋՇՁՆԻՄՍԼԽՋՌՀՑՊՇՁԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑՇԺՋԽՊՎԹՌՁՇՆՋ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  

## ԦԦ ԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫ

Ԟ ԯԽՋՍՄՌՋ

ԞԾՌԽՊԼԹՑՋՇԾԽՐՈՇՋՍՊԽՅԽԹՆՋՍՊՎՁՎԹՄՏԹՋՊԽՈՇՊՌԽԼՄՑՁՆԺՇՌՀՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՌՀԽ

ԱԴԞՅԽԹՋՍՊԽԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՁՆՌՀԽԱ ԴԞՅԽԹՋՍՊԽԼԹՆԼ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԟՑՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՅԽԹՆՋՍՊՎՁՎԹՄ ՏԹՋՊԽՈՇՊՌԽԼՄՑՁՆԺՇՌՀՌՀԽՆԽԿԹՌՁՎԽ

ԻՇՆՌՊՇՄԹՆԼՌՀԽԱԴԞՅԽԹՋՍՊԽԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ ՁՆՌՀԽԱԴԞՅԽԹՋՍՊԽԼ

ՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՁՆՌՀԽԱԴԞՅԽԹՋՍՊԽԼՅԿ ԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԦՆՌՀԽ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈՇՆԽՌԹԼՈՇՄԽՏԹՋՁՆԻՁԼԽՆՌԹՄՄՑՃՁՄՄԽԼԼՍՊՁՆԿՋՁՈՀՇՆՁՆԿԹՆԼՌՀԽՋՌՍԼՑԹՍՌՀՇՊՋԼՁԼՆՇՌ

ԻՇՆՋՁԼԽՊՌՀՁՋԼԽԹՌՀՁՆՋՍՊՎՁՎԹՄԻԹՄԻՍՄԹՌՁՇՆՋԹԻՌՍԹՄՋՍՊՎՁՎԹՄԼ ԹՌԹ
ՁՆԻՄՍԼՁՆԿՁՆԻՁԼԽՆՌԹՄԼԽԹՌՀՋԹՊԽՈՊԽՋԽՆՌԽԼ

ԺԽՄՇՏՁՆԱԹԺՄԽ

ԱԹԺՄԽԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑՁՆ ԵԽՆՇՈՍՋՄԹԽՎՁՋ



ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑ

ԡԹՑ  

### ԡԹՑ

ԫ  

### ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ ԫ  

### ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ      

      

      

      

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ 

### ԫՇՌԹՈՈՄՁԻԹԺՄԽ

 

###  ԰ԹՅՈՄԽՋՁՒԽԹՆԼԻՍՅՍՄԹՌՁՎԽՅՇՊՌԹՄՁՌՑՎԹՄՍԽՋԹՌԡԹՑՈՊՁՇՊՌ ՇՁՆՌԽՊՁՅՋԹԻՊՁԾՁԻԽ

 

###  ԫՍՅԺԽՊՇԾՁՆԼՁՎՁԼՍԹՄՌԹԼՈՇՄԽՋՈԽՊՌՊԽԹՌՅԽՆՌ

ԟՑԡԹՑՌՀԽՅԽԼՁԹՆԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋԾՇՊՌՀԽՆԽԿԹՌՁՎ ԽԻՇՆՌՊՇՄԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ

ԱԹԺՄԽԞՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՌՀԽՅԽԼՁԹՆԼԽՎԽՄՇՈՅԽՆՌՋՌԹԿԽՏ ԹՋԾՇՊՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼ

ԾՇՊԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆ ԵԽՆՇՈՍՋՄԹԽՎՁՋ -ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽԹՆԼԞՋՑՆԻՀՊՇՆՇՍՋԡԽՎԽՄՇՈՅԽՆՌ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽ

ԡԹՑ ԡԹՑ

Ն ԪԽԼՁԹՆ

԰ՌԹԿԽ ԞՋՑՆԻՀՊՇՆՇՍՋ Ն ԪԽԼՁԹՆ

԰ՌԹԿԽ ԞՋՑՆԻՀՊՇՆՇՍՋ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ      

      

      

      

ԱՀԽԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩԹՎԽՊԹԿԽԼՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ ԹՆԼՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ԱԹԺՄԽԫՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈԱՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌՌՀԽՅԽԹՆՆՇՊՅԹՄՁՒԽԼԥԩԩՇ ՆԡԹՑՏԹՋՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ՁՆՌՀԽԱԴԞՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԹՆԼՁՆՌՀԽԱԴԞՅԽԹՋՍՊԽԼ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆ ԵԽՆՇՈՍՋՄԹԽՎՁՋ -ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ
ԥԩԩ

ԡԹՑ ԡԹՑ

Ն ԪԽԹՆ

ՅՅ չ԰ԡ ԥԩԩ

԰Գԩ  Ն ԪԽԹՆ

ՅՅ չ԰ԡ ԥԩԩ

԰Գԩ 



### ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ        

        

        

        

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԰ԡ 

### ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

 

###  ԰ՍՅՅԹՊՑՊԽՋՍՄՌՋԾՇՊՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩԹՊԽՈՊԽՋԽՆՌԽԼՁՆ ՌՀԽՆԽՐՌՌԹԺՄԽ ԱԹԺՄԽ 

ԡԹՑ԰ԳԩԹՎԽՊԹԿԽԼՅՅՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼ ՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՅՅ

ԹՆԼՅՅՁՆՌՀԽԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ ՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽԟՑԡԹՑ԰Գԩ

ԹՎԽՊԹԿԽԼՅՅՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼԹՆԼ ՅՅՁՆՌՀԽԹՆԼ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ

ԡԹՑՏԽՌՏԽՁԿՀՌԹՎԽՊԹԿԽԼԿՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼ ԹՆԼԿՁՆՌՀԽ

ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽԡԹՑՏԽՌՏԽՁԿՀՌԹՎԽՊԹԿԽԼԿ

ՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼԹՆԼԿՁՆՌՀԽ ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽԩԹՊՎԹՄԤՊՇՏՌՀՁՆ ԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ԱԴԞ

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



### ԫԽԿԹՌՁՎԽ

ԠՇՆՌՊՇՄ            

            

             

            

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԰ԡ 

### ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

 

###  ԞՄՋՇՊԽԾԽՊՊԽԼՌՇԹՋ՟ՏԽՌՏԽՁԿՀՌՠՁՆՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽ

ԞԻԻՇՊԼՁՆԿՌՇՌՀԽՈԹՌՀՇՄՇԿՁՋՌ0ՋՊԽՈՇՊՌՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿ ԹՌՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ԻՇՆՌԹՁՆԽԼՅՇՊԽԹՆՁՅԹՄՋՌՀԹՌՋՀՇՏԽԼՅՁՄԼԿՄԹՆԼԹՌՊՇՈՀՑ
ԹՆԼՋ ԽՎԽՊԽԿՄԹՆԼՀՑՈԽՊՌՊՇՈՀՑ
ՌՀԹՆՌՀԽՆԽԿԹՌՁՎԽ

ԻՇՆՌՊՇՄԿՊՇՍՈԠՇՆԻՇՅՁՌԹՆՌՄՑՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԹՄՋՇՋՀՇՏԽԼՅՇ ՊԽԹՆՁՅԹՄՋՏՁՌՀՅՁՄԼԾՇՄՄՁԻՄԽՋՁՒԽԼԽԻՊԽԹՋԽ


ԹՆԼՅՇԼԽՊԹՌԽՋԽՎԽՊԽԾՇՄՄՁԻՄԽՋՁՒԽՁՆԻՊԽԹՋԽ
ՌՀԹՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈԥՇՏԽՎԽՊԹԻԻՇՊԼՁՆԿՌՇԽՐԹԻՌ

ՇՆԽՋՁԼԽԼԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌՋԻՇՆԼՍԻՌԽԼԺՑՌՀԽՋՌՍԼ ՑԹՍՌՀՇՊՌՀԽՋԽՎԽՊՁՌՑՋԻՇՊԽՋՁՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ

ԽՐՈՇՋԽԼՌՇՌՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽՏԽՊԽՆՇՌՋՁԿՆՁԾՁԻԹՆՌՄՑԼՁԾԾԽՊԽՆՌ ԾՊՇՅՋԽՎԽՊՁՌՑՋԻՇՊԽՋՊԽԻՇՊԼԽԼԾՇՊՌՀԽԻՇՆՌՊՇՄԿՊՇՍՈ

ԣՁՆԼՁՆԿՋԾՇՊԾՇՄՄՁԻՍՄԹՊՀՑՈԽՊՌՊՇՈՀՑԹՆԼՀՑՈԽՊՈՄԹՋՁԹԹՆԼՇՌՀԽՊԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼԽԼՉՍԹՄՁՌԹՌՁՎԽՇԺՋԽՊՎԹՌՁՇՆՋՏԽՊԽ

ՆՇՌՊԽՈՇՊՌԽԼԺՍՌՌՀԽՈԹՌՀՇՄՇԿՁՋՌԼԽՋԻՊՁԺԽԼՇՌՀԽՊԾՁՆԼՁՆԿՋՏՀՁԻ ՀԹՊԽՋՀՇՏՆՁՆԱԹԺՄԽ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽԤՊՇՋՋԭԹՌՀՇՄՇԿՑԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑՇԾՌՀԽԱՀՑՊՇՁԼԤՄԹ ՆԼՁՆ ԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ԱԴԞ

ՅԽԹՋՍՊԽԼ% ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ 

԰ԽՎԽՊՁՌՑ 

### ԱՀՑՊՇՁԼԤՄԹՆԼ

ԥՑՈԽՊՌՊՇՈՀՑ ԱՀՑՊՇՁԼԤՄԹՆԼ

ԞՌՊՇՈՀՑ ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՌՊՇՈՀՑ ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ



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  ԱՀՑՊՇՁԼԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑԹՊԽԿՊԹԼԽԼ -ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՄԼ

ԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԬԢԠԡԫՇԾՇՊՊԽԾԽՊԽՆԻԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԱՀՑՊՇՁԼԤՄԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆ ԵԽՆՇՈՍՋՄԹԽՎՁՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԮՍԹՄՁՌԹՌՁՎԽԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆԞՊԽԹ
ԦՆԻՊԽԹՋԽԣՇՄՄՁԻՄԽԹՋՑՅՅԽՌՊՑՁՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊ԰ՁՒԽԦՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊ԰ՁՒԽԡԽԻՊԽԹՋԽԤՄԹՆԼԞՋՑՅՅԽՌՊՑԦՆԻՊԽԹՋԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ                                                                                                                         ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԮՍԹՄՁՌԹՌՁՎԽԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆԞՊԽԹ
ԦՆԻՊԽԹՋԽԣՇՄՄՁԻՄԽԹՋՑՅՅԽՌՊՑՁՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊ԰ՁՒԽԦՆԻՊԽԹՋԽԣՇՄՄՁԻՍՄԹՊ԰ՁՒԽԡԽԻՊԽԹՋԽԤՄԹՆԼԞՋՑՅՅԽՌՊՑԦՆԻՊԽԹՋԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽ                                         ԱՀՑՊՇՁԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՁՋԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԬԢԠԡԫՇԾՇՊՊԽԾԽՊԽՆԻԽ԰ՅԹՄՄՋՁՒԽՏԹՋՆՇՌԽԼՁՆՇՆԽՌԹԼՈՇՄԽՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՁՆՇՆԽՌԹԼՈՇՄԽՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԱԹՁՄԻՍՊՎԹՌՍՊԽՏԹՋՈՊԽՋԽՆՌՁՆԹՆԼՇԾՌՀԽՌԹԼՈՇՄԽՋՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՌՀԽԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԠՄՁՆՁԻԹՄ԰ՁԿՆՋՁՆ ԵԽՆՇՈՍՋՄԹԽՎՁՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԠՄՁՆՁԻԹՄ԰ՁԿՆՋԱՑՈԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ԰ՅԹՄՄՋՁՒԽ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑ԰ՅԹՄՄՋՁՒԽ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑ԰ՅԹՄՄՋՁՒԽ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑ԰ՅԹՄՄՋՁՒԽ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑ ԰ԽՎԽՊՁՌՑԫՇՌԽՌՀԹՌԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌ
ՍՆԹԺՄԽՌՇՋՌԹԿԽՁՋՊԽՈՇՊՌԽԼՈՊԽՎՁՇՍՋՄՑՁՆԱԹԺՄԽ  ԰ԽՎԽՊՁՌՑՋԻՇՊԽՋԾՇՊՋՈՁՆԹՄԻՍՊՎԹՌՍՊԽԹՊԽՊԽՈՇՊՌԽԼՀԽՊԽԹՋԹՋՋՁԿՆԽԼԺՑՌՀԽՋՌՍԼՑԹՍՌՀՇՊ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԟ ԰ՌՍԼՑԞՍՌՀՇՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

ԣՇՊԹՄՄՉՍԹՆՌՁՌԹՌՁՎԽԽՆԼՈՇՁՆՌՋ
ԥԩԩ԰ԳԩՏԽՌՏԽՁԿՀՌՌՀԹՌԾՇՄՄ ՇՏԽԼԹՅՇՆՇՌՇՆՁԻԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ

ՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌՏԹՋԹՈՈՄՁԽԼՁՆԹՋՌԽՈԼՇՏՆՅԹՆՆԽՊ ՌՇԽՋՌԹԺՄՁՋՀՋՁԿՆՁԾՁԻԹՆՌՌՊԽԹՌՅԽՆՌԽԾԾԽԻՌՋ

ԣՇՊԻՇՆՌՁՆՍՇՍՋԽՆԼՈՇՁՆՌՋՌՀԹՌՏԽՊԽՆՇՌԻՇՆՋՁՋՌԽՆՌՏՁՌՀԹՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽՌՀԽԼԹՌԹՏԽՊԽԽՎԹՄՍԹՌԽԼ

ԾՇՊՆՇՊՅԹՄՁՌՑ
԰ՀԹՈՁՊՇԴՁՄՃ0ՋՌԽՋՌԹՆԼՀՇՅՇԿԽՆԽՁՌՑ
ԩԽՎԽՆԽ0ՋՌ ԽՋՌԦԾԹԼԹՌԹՋԽՌՏԹՋԾՇՍՆԼՌՇՀԹՎԽԹ

ՆՇՆՆՇՊՅԹՄԼՁՋՌՊՁԺՍՌՁՇՆՇՊԹՀԽՌԽՊՇԿԽՆԽՇՍՋԼՁՋՌՊՁԺՍՌՁՇՆՇԾՎԹՊՁԹՆԻԽԹՆՇՊՅԹՄՁՒՁՆԿՎԹՊՁԹՆԻԽՋՌԹԺՁՄՁՒՁՆԿ

ՌՊԹՆՋԾՇՊՅԹՌՁՇՆՏԹՋՍՋԽԼԦԾՌՀԽՌՊԹՆՋԾՇՊՅԹՌՁՇՆԹԻՀՁԽՎԽԼՆՇՊՅԹՄՁ ՌՑԹՆԼԽՉՍԹՄՎԹՊՁԹՆԻԽԼԹՌԹՏԽՊԽՌԽՋՌԽԼ

ՍՋՁՆԿԡՍՆՆԽՌՌ0ՋՌԽՋՌԦԾՌՀԽԼԹՌԹՏԽՊԽՆՇՊՅԹՄՄՑԼՁՋՌՊՁԺՍՌԽԼՏՁՌ ՀՍՆԽՉՍԹՄՎԹՊՁԹՆԻԽԹԾՌԽՊՌՀԽՌՊԹՆՋԾՇՊՅԹՌՁՇՆ

ՌՀԽԱԹՅՀԹՆԽԡՍՆՆԽՌՌ
ԱՌԽՋՌՇՊՌՀԽԪԹՆՆԴՀՁՌՆԽՑԴՁՄԻՇՐՇՆԲՌԽ ՋՌՏԽՊԽՍՋԽԼՌՇԽՎԹՄՍԹՌԽՌՀԽԼԹՌԹ

ԴՀԽՊԽ ՆՇ ՆՇՊՅԹՄՁՒՁՆԿ ՌՊԹՆՋԾՇՊՅԹՌՁՇՆ ԻՇՍՄԼ ԺԽ ԾՇՍՆԼ ՌՀԽ ԪԹՆՆԴՀ ՁՌՆԽՑԴՁՄԻՇՐՇՆ Բ ՌԽՋՌ ՍՋՁՆԿ Թ

ԟՇՆԾԽՊՊՇՆՁԥՇՄՅԹԼՂՍՋՌՅԽՆՌՌՇՌՀԽՈՎԹՄՍԽՋՏԹՋՍՋԽԼՌՇԽՎԹՄՍԹՌԽ ՌՀԽԼԹՌԹՋԽՌՋ

Ԟ ԠՇԻՀՊԹՆԞՊՅՁՌԹԿԽ ՌԽՋՌ ՏԹՋ ԹՈՈՄՁԽԼ ՁԾ ՌՀԽ ԼԹՌԹ ՋԽՌ ՀԹԼ Թ ԻՇՆՋՁՋՌԽՆՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ

ԞՄՌԽՊՆԹՌՁՎԽՄՑ ՆՇՆՅՇՆՇՌՇՆՁԻ ՅՇՊՌԹՄՁՌՑ ԼԹՌԹ ՋԽՌՋ ՏԽՊԽ ԽՎԹՄՍԹՌԽԼ  ՍՋՁՆԿ ԣՁՋՀԽՊ0Ջ ԢՐԹԻՌ ՌԽՋՌ ՏՁՌՀ Թ

ԟՇՆԾԽՊՊՇՆՁԥՇՄՅԹԼՂՍՋՌՅԽՆՌԦՆՌՀԽԽՎԽՆՌՅԽԼՁԹՆՎԹՄՍԽՋԻՇՍՄԼՆՇՌԺԽԼԽՌԽՊՅՁՆԽԼՊԽՈՄՁԻԹՌԽՅԽԹՆՋՌԹԿԽ

ՎԹՄՍԽՋ ՏԽՊԽ ՍՋԽԼ ԹՆԼ ԽՎԹՄՍԹՌԽԼ ՍՋՁՆԿ ԡՍՆՆԽՌՌ0Ջ ՌԽՋՌ ԠՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ ՅՇՆՇՌՇՆՁԻՁՌՑ ՏԹՋ

ԹՋՋԽՋՋԽԼՎՁՋՍԹՄՄՑԾՊՇՅՌՀԽՊԽՈՄՁԻԹՌԽԹՆԼՌՊԽԹՌՅԽՆՌՅԽԼՁԹՆՋՇՊՅ ԽԹՆՋԦԾՋՇՅԽՇԾՌՀԽՋԽՈՊՇԻԽԼՍՊԽՋՏԽՊԽ

ՆՇՌԹՈՈՊՇՈՊՁԹՌԽԾՇՊՌՀԽՊԽՋՈԽԻՌՁՎԽԼԹՌԹՋԽՌՌՀԽՆՌՀԽԬԢԠԡԠՍՊՊԽՆՌԞՈՈՊՇԹԻՀԽՋՁՆՌՀԽ԰ՌԹՌՁՋՌՁԻԹՄԞՆԹՄՑՋՁՋ

ՇԾԢԻՇՌՇՐՁԻՁՌՑԡԹՌԹԞԤՍՁԼԹՆԻԽՌՇԞՈՈՄՁԻԹՌՁՇՆՏԹՋԻՇՆՋՍՄՌԽԼ
Ԭ ԢԠԡԠԢԱԦ԰ԠՇՅՈՊԽՀԽՆՋՁՎԽ

ԢՆՎՁՊՇՆՅԽՆՌԹՄԱՇՐՁԻՁՌՑԦՆԾՇՊՅԹՌՁՇՆ԰ՑՋՌԽՅ ԱԪ 

### 
ԦՎԽՋԳԽՊՋՁՇՆՋՇԾՌՏԹՊԽՏԹՋՍՋԽԼՌՇՈԽՊԾՇՊՅ

ԹՄՄՋՌԹՌՁՋՌՁԻԹՄԻՇՅՈՍՌԹՌՁՇՆՋ

ԞՄՄՋՌԹՌՁՋՌՁԻԹՄԻՇՆԻՄՍՋՁՇՆՋՏԽՊԽՅԹԼԽԹՌՌՀԽՄԽՎԽՄՇԾԻԽՊՌԹՁՆՌՑԽՐԻԽՈՌ ՁՆՌՀԽԻԹՋԽՇԾՌՀԽԺԹՋՁԻ

ԹՋՋՍՅՈՌՁՇՆՌԽՋՌՋՋՍԻՀԹՋ԰ՀԹՈՁՊՇԴՁՄՃՋ0ԱԽՋՌԹՆԼԟԹՊՌՄԽՌՌ0ՋԱԽՋ ՌՁՆՏՀՁԻՀՌՀԽՄԽՎԽՄՇԾԻԽՊՌԹՁՆՌՑՏԹՋ

ԹՈՈՄՁԽԼ

ԡՍՆՆԽՌՌ0ՋՌԽՋՌՁՆԼՁԻԹՌԽԼԹՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼԽԻՊԽԹՋԽՁ ՆԡԹՑՏԽՌՏԽՁԿՀՌՁՆՌՀԽՀՁԿՀԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽԻՇՆՌՊՇՄԿՊՇՍ Ո Ո ՏՀՁԻՀՏԹՋԻՇՆՋՁԼԽՊԽԼՌՇԺԽ

ՁՆՌՀԽՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԞՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԼԽԻՊԽԹՋԽՁՆ԰ԳԩՇՆԡԹՑՏԹՋ

ՁԼԽՆՌՁԾՁԽԼՁՆՌՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ Ո 

ԹԻԻՇՊԼՁՆԿՌՇԺՇՌՀՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԱՊԽՆԼՌԽՋՌԹՆԼԡՍՆՆԽՌ Ռ	ՋՌԽՋՌԞՋՄՁԿՀՌՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԼԽԻՊԽԹՋԽՁՆԥԩԩՏԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽՅՁԼԼՄԽԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅ ԽՆՌԿՊՇՍՈԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ

ԻՇՆՌՊՇՄԹԻԻՇՊԼՁՆԿՌՇԡՍՆՆԽՌՌ0ՋՌԽՋՌ Ո ԱՀՁՋԼԽԻՊԽԹՋԽՏԹՋՆՇՌԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋՁՎԽԹՆԼՌՀՍՋ

ՆՇՌԻՇՆՋՁԼԽՊԽԼՌՇԺԽՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԞՋՄՁԿՀՌՌՀՇՍԿՀՋՁԿՆՁԾՁ ԻԹՆՌՌՊԽՆԼ Ո ՁՆՅԽԼՁԹՆԡԹՑ

ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՋՁՆՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊ ԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՄԹՌՁՎԽՌՇՌՀԽԻՇՆՌՊՇՄՏԹՋ

ՁԼԽՆՌՁԾՁԽԼԹԻԻՇՊԼՁՆԿՌՇՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌ ԴՀՁՄԽՌՀԽՅԽԼՁԹՆՋՌԹԿԽՏԹՋՁՆԹՄՄՌՀՊԽԽ

ՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՇՆԡԹՑՌՀԽՊԽՏԽՊԽԼՁԾԾԽՊԽՆԻԽՋՁՆՌՀԽԼՁՋՌՊ ՁԺՍՌՁՇՆՇԾԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՋԹՅՇՆԿ

ՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ
ԞՈՈԽՆԼՁՐԣՇՊՁՆՋՌԹՆԻԽՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌ ՊՇՄԹՆԼՄՇՏԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՀԹԼ

ԹՆԼՌԹԼՈՇՄԽՋՊԽՋՈԽԻՌՁՎԽՄՑԹՌՋՌԹԿԽՏՀՁՄԽՌՀԽՅՁԼԹՆԼՀՁ ԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՀԹԼԹՆԼՌԹԼՈՇՄԽՋ

ԹՌՋՌԹԿԽՊԽՋՈԽԻՌՁՎԽՄՑ

ԱԹՁՄԻՍՊՎԹՌՍՊԽ
ՁՆԻՄՍԼՁՆԿԹՄՄՋԽՎԽՊՁՌՑԿՊԹԼԽՋԹՋՋՁԿՆԽԼԺՑՌՀԽՋ ՌՍԼՑԹՍՌՀՇՊՏԹՋՈՊԽՋԽՆՌՁՆ

ԹՆԼ ՇԾՌԹԼՈՇՄԽՋՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ

 ԠԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋ ԞՄՄԼԹՌԹՏԽՊԽՌԽՋՌԽԼԾՇՊՆՇՊՅԹՄՁՌՑՍՋՁՆԿ԰ՀԹՈՁՊՇԴՁՄՃՋՌԽՋՌ Į ԹՆԼԾՇՊ

ՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՋՍՋՁՆԿԽՁՌՀԽՊԩԽՎԽՆԽ0ՋՇՊԟԹՊՌՄԽՌՌ0ՋՌԽ ՋՌ Į ԞՄՄԽՆԼՈՇՁՆՌՋՅԽՌՌՀԽ

ԹՋՋՍՅՈՌՁՇՆՋՇԾՈԹՊԹՅԽՌՊՁԻՋՌԹՌՁՋՌՁԻՋԹՆԼՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿԡՍ ՆՆԽՌՌ0ՋԪՍՄՌՁՈՄԽԠՇՅՈԹՊՁՋՇՆՌԽՋՌՏՁՌՀ

ՌՀԽԽՐԻԽՈՌՁՇՆՇԾԡԹՑԫՇՊՅԹՄՁՒԽԼԥԩԩԹՆԼԡԹՑԡԽՎԽՄՇՈՅԽՆՌԹՄ ԰ՌԹԿԽԱՀԽՋԽՆՇՆՈԹՊԹՅԽՌՊՁԻՋՌԹՌՁՋՌՁԻՋ

ՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԪԹՆՆԴՀՁՌՆԽՑԲԱՏՇՋԹՅՈՄԽԱԽՋՌԞՋՍԿԿԽ ՋՌՁՎԽՁՆԻՊԽԹՋՁՆԿ

ԻՇՆԻԽՆՌՊԹՌՁՇՆԼԽՈԽՆԼԽՆՌՌՊԽՆԼՏԹՋՆՇՌԽԼԾՇՊԡԹՑԫՇՊՅԹՄՁՒԽԼԥԩ ԩԼԹՌԹԞԼԽԻՊԽԹՋՁՆԿ

ԻՇՆԻԽՆՌՊԹՌՁՇՆԼԽՈԽՆԼԽՆՌՌՊԽՆԼՏԹՋՆՇՌԽԼԡԹՑ԰ԳԩԹՆԼԹՋՍԿԿԽՋՌ ՁՎԽԼԽԻՊԽԹՋՁՆԿՌՊԽՆԼՏԹՋՇԺՋԽՊՎԽԼ

ԾՇՊԡԹՑԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽԱՀԽԫԬԞԢԠԩԬԞԢԠԾՇՊՌՀԽՋԽԽՆԼՈՇ ՁՆՌՋՏԽՊԽԻՇՆԾՁՊՅԽԼՍՋՁՆԿԺՇՌՀ

ՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԹՆԼԴՁՄՄՁԹՅ0ՋՌԽՋՌՋԱՀԽՋԽԹՆԹՄՑՋԽՋՏԽՊ ԽԻՇՆԼՍԻՌԽԼՍՋՁՆԿԠԢԱԦ԰ԹՆԼ

ԺԹԻՃԽՆԼՋԽՌՌՁՆԿՋՁՅՈՄԽՅԽՆՌԽԼԺՑԢԣԢԡՇՆ

 ԠՇՆԻՄՍՋՁՇՆՋ

ԬՆԡԹՑՌՀԽՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋՁՋԼԽՌԽԻՌԽԼԹՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻ ՌՁՇՆՁՆ԰ԳԩԹՆԼՏԽՌՏԽՁԿՀՌԹՌՌՀԽՀՁԿՀԽՋՌ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՈՊԽՄԹՌՁՎԽՌՇՌՀԽ ԻՇՆՌՊՇՄԺՍՌՆՇԽԾԾԽԻՌՋՏԽՊԽԼԽՌԽԻՌԽԼՇՆ

ԹՆՑԽՆԼՈՇՁՆՌՋԹՌԡԹՑ԰ՄՁԿՀՌՑԽՌՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋՇՆՅԽԼՁ ԹՆԡԹՑԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԽՊԽԾՇՍՆԼ

ԾՇՊԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ
ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՈԱՀՇՍԿՀ ՌՀԽՅԽԼՁԹՆԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԾՇՊԹՄՄՌՀՊԽԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՇՆԡԹՑՌՀԽԼԹՌԹՋՍԿԿԽՋՌՌ ՀԹՌԼՁԾԾԽՊԽՆԻԽՋԽՐՁՋՌՁՆՌՀԽԼՁՋՌՊՁԺՍՌՁՇՆ

ՇԾԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՋԹՅՇՆԿՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՏՀՁԻՀԹՊԽՁՆԼՁԻԹ ՌՁՎԽՇԾԼԽՄԹՑԽԼԼԽՎԽՄՇՈՅԽՆՌԱՀԽ

ՁՆԻՁԼԽՆԻԽԹՆԼՋԽՎԽՊՁՌՑՇԾՌՀՑՊՇՁԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀ ՇՄՇԿՑ
ԾՇՄՄՁԻՍՄԹՊՋՁՒԽԾՁՆԼՁՆԿՋՏԹՋՎՁՋՍԹՄՄՑ

ԼԽՌԽՊՅՁՆԽԼՌՇԺԽԿՊԽԹՌԽՊԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄԹՄՌՀՇՍԿՀ ՌՀԽՋՌՍԼՑԹՍՌՀՇՊՁՆԼՁԻԹՌԽԼՌՀԹՌՌՀԽԼՁԾԾԽՊԽՆԻԽ

ՁՆՋԻՇՊԽՋՏԹՋՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽՇԾԱԹԺՄԽԡԽՎԽՄՇՈՅԽՆՌԹՄԹՆԼԱՀՑՊՇՁԼԤՊՇՋՋԭԹՌՀՇՄՇԿՑԥՁՋՌՇՈԹՌՀՇՄՇԿՑԢՆԼՈՇՁՆՌՋՁՆՌՀԽԞԪԞՏՁՌՀԭԠԫԟԱԽԻՀՆՁԻԹՄԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽԥՁՆԼԩՁՅԺԩԽՆԿՌՀԞՋՑՆԻՀՊՇՆՇՍՋԡԽՎԽՄՇՈՅԽՆՌԱՀՑՊՇՁԼԤՊՇՋՋԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑԡԹՑԡԹՑԡԹՑԡԹՑԡԹՑԡԹՑԡԹՑԪԽԼՁԹՆՈԪԽԼՁԹՆՈԡՁԾԾՈԡՁԾԾՈԡՁԾԾՈԡՁԾԾՈԱՊԽԹՌՅԽՆՌԯԽՄԹՌԽԼԢԾԾԽԻՌՋ!
ԶԽՋԫՇԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ  ԫԞ  ԫԞ  ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞԫԞ      ԫԞ ԫԞ ԫԞ ԫԞԫՇ      ԫԞ ԫԞ ԫԞ ԫԞԫՇ      ԫԞ ԫԞ ԫԞ ԫԞԶԽՋ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌԡՍՆՆԽՌՌԧՇՆԻՃՀԽԽՊԽԱԽՊՋՈՌՊԹԧՇՆԻՃՀԽԽՊԽԱԽՊՋՈՌՊԹ ԡՍՆՆԽՌՌ ԫԞ ԫԞ ԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԥՁՆԼՄՁՅԺՄԽՆԿՌՀՁՋՆՇՊՅԹՄՁՒԽԼՌՇՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰Գԩ ԟԹՋԽԼ ՇՆ ՎՁՋՍԹՄ ԹՋՋԽՋՋՅԽՆՌ ՇԾ ՁՆԻՁԼԽՆԻԽ ԹՆԼ ՋԽՎԽՊՁՌՑ ԼԹՌԹ ՀՇՏԽՎԽՊ ՌՀԽ ՋՌՍԼՑ ԹՍՌՀՇՊ ՊԽՈՇՊՌԽԼ ՌՀԹՌՌՀԽ ԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽ ՆՇՌ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՈ  ԞՄՌՀՇՍԿՀԹՆՇՆՈԹՊԹՅԽՌՊՁԻՌԽՋՌՏՇՍՄԼԺԽԹՈՈՊՇՈՊՁԹՌԽՌՇԹՋՋԽՋՋՅԽԼՁԹՆՎԹՄՍԽՋԾՇՊԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՁՆՌՀՁՋԻԹՋԽՁՌՏՇՍՄԼՆՇՌԺԽԽՐՈԽԻՌԽԼՌՇՑՁԽՄԼԼՁԾԾԽՊԽՆՌՇՎԽՊԹՄՄԻՇՆԻՄՍՋՁՇՆՋԹՋԻՇՅՈԹՊԽԼՌՇԡՍՆՆԽՌՌ0ՋՌԽՋՌԺԽԻԹՍՋԽՌՀԽՊԽՏԹՋՆՇԼՁԾԾԽՊԽՆՌՁՆՌՊԽԹՌՅԽՆՌՅԽԼՁԹՆՎԹՄՍԽՋ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋ  

### ՁՆՌՀԽԞԪԞՏՁՌՀԭԠԫԟԱԽԻՀՆՁԻԹՄ

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԰ՆՇՍՌԳԽՆՌԩԽՆԿՌՀ ԟՇԼՑԴԽՁԿՀՌ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ  ԫԞ  ԫԞ  ԫԞ  ԫԞ

        

        

        

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՋՈՌՊԹ ԡՍՆՆԽՌՌ ԡՍՆՆԽՌՌ ԡՍՆՆԽՌՌ

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԡՁԾԾ 

### ԡՁԾԾԽՊԽՆԻԽ ԫԞ 

### ԫՇՌԹՈՈՄՁԻԹԺՄԽ

 

###  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈ ԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ

 

###  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄ ՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ

Ԣ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

 ԱՀԽԠԳՇԾՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋԽՐԻԽԽԼԽԼՇՎԽՊՌՀԽԼԹՑ ՋՌՍԼՑ
ԠԳՊԹՆԿԽԼԾՊՇՅ

-ԞՋԹՊԽՋՍՄՌՌՀԽՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼԹՆԼԽՐՈՊԽՋՋԽԼՌՇՐՁԻՁՌՑՎԹՄՍԽՋՍՋՁՆԿԱԴԞ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

 ԱԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԼԽԻՊԽԹՋԽԼԹԾՌԽՊՌՀԽԹԼԼՁՌՁՇՆՇԾՇՊԿԹՆՁՋՅՋՇ ՆԡԹՑՏՀՁԻՀՏԹՋԹՌՌՊՁԺՍՌԽԼ

ՌՇՌՀԽԹԾԾՁՆՁՌՑՇԾՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄՌՇԺՁՆԼՌՇԿՄԹՋՋՌԹՆՃՋԾՇ ՇԼՌԹԼՈՇՄԽՋԹՆԼԽՐԻՊԽՌԽԼՇՊԿԹՆՁԻ

ՅԹՌՌԽՊ

ԱՀԽՊԽՅԹՁՆՁՆԿՈԽՊԾՇՊՅԹՆԻԽԹՆԼՎԹՄՁԼՁՌՑԻՊՁՌԽՊՁԹՏԽՊԽՋԹՌՁՋԾՁԽԼ

ԣԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋ

ԱՀԽՊԽՎՁԽՏԽՊ0ՋՊԽՋՍՄՌՋԹՊԽՊԽՈՇՊՌԽԼՁՆՌՀԽԢՐԽԻՍՌՁՎԽ԰ՍՅՅԹՊՑԹՆ ԼԠՇՆԻՄՍՋՁՇՆՋՋԽԻՌՁՇՆՋՇԾՌՀՁՋԡԢԯԦՆ

ԿԽՆԽՊԹՄՌՀԽՊԽՎՁԽՏԽՊ0ՋՊԽՋՍՄՌՋԹԿՊԽԽԼՏՁՌՀՌՀԽՋՌՍԼՑԹՍՌՀՇՊՋ0 ՀՇՏԽՎԽՊՌՀԽՋՌՍԼՑԹՍՌՀՇՊՋ0ԹՆԹՄՑՋՁՋՇՆՄՑ

### ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇ ՐՁԻՁՌՑՇԾԭԠԫԟՌՇԞՅՈՀՁԺՁԹՆՋԪ ԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ՇԾ  ԼԽՌԽԻՌԽԼԽԾԾԽԻՌՋՇՆԼԹՑԼԽՎԽՄՇՈՅԽՆՌՋՌԹԿԽԹՌՌՀԽՅՁԼԼՄԽԹՆԼ ՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՄԽՎԽՄՋՏՀՁՄԽՌՀԽ

ՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋՁՋԼԽՌԽԻՌԽԼԼԽՄԹՑԽԼԽԾԾԽԻՌՋԹՌԹՄՄՌՊԽԹՌԽԼՄԽՎ ԽՄՋ

ԱՀԽՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼՌՀԽՌՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽ
ԱԴԞԻՇՆԻԽՆՌ ՊԹՌՁՇՆՋՍՋՁՆԿՌՀԽԾՇՄՄՇՏՁՆԿԽՉՍԹՌՁՇՆ

ՏՀԽՊԽ

ԠԱԴԞՁՋՌՀԽՌՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԠՂՁՋՌՀԽԻՇՆԻԽՆՌՊԹՌՁՇՆՅԽԹՋՍՊԽԼԹՌՌՁՅԽՁՆՌԽՊՎԹՄՂ
Ղ Ն

ՌՂՁՋՌՀԽՆՍՅԺԽՊՇԾՀՇՍՊՋ
ՇՊԼԹՑՋՇՊՏԽԽՃՋՍՆՁՌՋՍՋԽԼՂՍՋՌ ՆԽԽԼՌՇԺԽԻՇՆՋՁՋՌԽՆՌՁՆՌՀԽԽՉՍԹՌՁՇՆՇԾ

ՌՀԽՌԽՋՌԹՌՌՁՅԽՁՆՌԽՊՎԹՄՂ

ԽԿՌՀՇՍՊՋ
ՌԽՋՌՁՆՁՌՁԹՌՁՇՆՌՀՇՍՊՋՌ ՀՇՍՊՋ



## ԦԦԦ ԯԢԣԢԯԢԫԠԢ԰

ԤՊՁՅԨԠԽՌԹՄԱՀՑՊՇՁԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑԞՋՋԽՋՋՅԽՆՌՋԾՇՊՌՀԽԞՅ ՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑՌՇԡԽՌԽԻՌ

ԱՀՑՊՇՁԼԞԻՌՁՎԽ԰ՍԺՋՌԹՆԻԽՋԱՇՐՁԻՇՄԭԹՌՀՇՄ

ԫՁԽՍՏՃՇՇՈԭԡԹՆԼԣԹԺԽՊԧԫՇՊՅԹՄԱԹԺՄԽՋՇԾԵԽՆՇՈՍՋՄԹԽՎՁ
ԡԹՍԼՁՆԤԹՊՄԹՆԼԭՍԺՄՁՋՀՁՆԿԩՇՆԼՇՆ

 

# ( ) ( ) ( ) ( )

n nn nn

n n

TWA 

## t tt CC tt CC tt CC tt CC

C 1 1

21 21

12 12

01 01 

## 2 2 2 2 − −

− −



## −  ̧ 1 ·  ̈ © § + +−  ̧ 1 ·  ̈ © § + +−  ̧ 1 ·  ̈ © § + +−  ̧ 1 ·  ̈ © § +

=

# DATA EVALUATION RECORD

P ENTACHLORONITROBENZENE (PCNB )

Study Type: O CSPP 890.1150, Androgen Receptor Binding Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-36-2012 (MRID 48946801)

Prepared for

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

Arlington, VA 22202

Prepared by Dynamac Corporations

1910 Sedwick Road, Building 100, Suite B

Durham, NC 27713

Primary Reviewer Signature: Scott D. Studenberg, Ph.D., D.A.B.T. Date: 12/3/2012

Secondary Reviewer Signature: Michelle J. Sharpe

- Kass, M.S. Date: 12/4 /2012

Program Manager: Signature: Jack D. Early, M.S. Date: 12/13/ /2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 12/13 /2012

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to signing by Dynamac Corporation personnel

.

## The US EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 screening battery is comprised of eleven screening assays intended 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 Tie r 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 redundancy 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 potential 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).

### PCN B I 

### 056502 Androgen Receptor Binding Assay (Rat Prostate Cytosol) (2011) I 

### Page I of 17

OCSPP 890.1150/ OECD None



## Primary Reviewer: Deborah Smegal



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



## Health Effects Division

# Sigoi~Lr Date;

# ~---_...~?fi!LZ-~~..L.--­ Signature:

...

## 4~~,4~· 

# ======-- Date: G; 

## /j.. 

# 'TI 1crTemplate version 0812011



## DATA EVALUATION RECORD

STUDY TYPE: Androgen Receptor Binding Assay Using Rat Prostate Cytosol (AR); OCSPP

890.1150



## PC CODE: 056502 

## DP BARCODE: D407069

TXR#: 0056474 

## CAS No.: 82-68-8



## TEST MATERIAL (PURITY): PCNB (95.6% a.i.)



## SYNONYMS: 1

, 2 ,3,4,5 -pentachloro-6-nitrobenzene, quintozene



## CITATION: Matthews, A. 

## (2012). PCNB Technical: Androgen Receptor Binding (Rat

Prostate Cytosol). Huntingdon Life Sciences, Huntingdon, Cambridgeshire, UK. Laboratory Study No.: BDG0128, July 26

, 2012. MRID 48946801. Unpublished.



## SPONSOR: AMV AC Chemical Corp.

, 4695 MacArthur Court, Suite 1200

, Newport Beach,

CA 92660-1706



## TEST ORDER #: 

## EDSP-056502-105



## EXECUTIVE SUMMARY: In an androgen receptor 

## (AR) binding assay (MRID 48946801),

prostate cytosol from Sprague-Dawley rats was used as the source of AR to conduct binding experiments. Prior to conducting the competitive binding experiments, 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 radiolabeled reference androgen ([3H]-R1881). The competitive binding experiment was conducted to measure the binding of a single concentration of [3H]-Rl 881 (I nM) 

## in the presence of increasing

concentrations (logarithmic increase from 10

- 10 

## to 10- 3 

### .s 

## M) of PCNB (95.6% a.i.). Ethanol was used as the solvent vehicle at a final assay concentration of 3%. The highest soluble

concentration for PNCB was 10

- 3

. 5 

## M. Three valid independent runs were performed, and each

run included dexamethasone as a weak positive control

, and R 1881 as the ligand reference

standard.

For the saturation binding assay
, the appropriate protein concentration was determined to be 4.67 mg/mL as it bound 24% of the [3H]-R1881. The mean Kd for [ 3 

## H]-R1881was1.6246±0.3283



## nM

, and the mean estimated Bmax was 0.1805±0.0199 

## nM for the prepared rat prostate cytosol.

The Kd was within the guideline recommended range of 0.03 to 1.5 

## nM for two of the three runs
, but the Kd for Run 2 (2.2810±0.2936 nM) was above the recommended range.And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 2 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## The protein concentration for the c ompetitive binding assay was determined to be 2.0 mg/mL as it bound 13% of the [ 3 

## H] -R1881 at 1 nM. Across all three valid runs, the estimated mean IC 50 

## was 1.95 × 10 −9 

## M for R1881 and 1.01 × 10 −4 

## M for the weak positive control, dexamethasone. The corresponding log IC 50 

## values for R1881 and dexamethasone were −8.72 and −4.00 M, respectively. Th e mean relative binding affinity (RBA) for dexamethasone compared to R1881 was 0.0019%, for a log RBA of −4.72 %. Three valid assay runs were completed out of a total of eight runs; five of the runs were appropriately rejected as they failed to meet variou s performance or acceptance criteria.

For PCNB, the minimum mean specific binding of [ 3 

## H] -R1881 to the AR was 64, 83 and 80% in the three valid runs, which corresponded to an equivocal classification (50 -75% [ 3 

## H] -R1881 binding) for the first valid run and non-binder (>75% [ 3 

## H] -R1881 binding ) i n the other two valid

runs.

Based on the results from the three runs, PCNB is classified as a N on-Binder in the Androgen Receptor Binding Assay.

Th e assay satisfies the EDSP Tier 1 Test Order requirement s for an Androgen R eceptor Binding Assay (OCSPP 890.1150).

COMPLIANCE : Signed and dated Data Confidentiality, GLP Compliance , Flagging, and Quality Assurance statements were provided.And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 3 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility : Huntingdon Life Sciences

Location: Huntingdon, Cambridgeshire, UK Study Director: A. Matthews

Other Personnel: B. Mann, Assistant Study Scientist; S. Bate, Senior Statistician Study Period: February 1 0

, 2012

– July 26

, 201 2



## 2

. Test substance : PCNB

Description: Off

- white to dark tan crystalline solid or powder

Source: AMVAC Chemical Corp.

Lot #: 107030L052 Purity: 9 5 .6 % a.i. (Expiry July 2016) Solubility : Soluble in ethanol up to 50 mM Volatility : Not reported Stability: Not reported Storage conditions: Away from direct sunlight in a closed container at room temperature

CAS #: 82

- 68

- 8 Molecular weight: 295 .3

Structure:



### Cl

Cl

Cl Cl Cl NO 2



## 3

. Non

- labeled ligand : R1881

Supplier : S teraloids Catalog # E 3164

- 000

Batch #: B1023 (expiry June 2014) Purity: 98.8 %

CAS #: 965

- 93

- 5



## 4

. Radioactive ligand : [ 3 

## H]

- R1881

Supplier : Perkin

- Elmer Catalog #: NET

- 5 90

Batch #: 6 79512, 1582134 Radiochemical p urity: Not reported Specific activity : 85.1 μCi/nmol

Concentration of stock : 1 m Ci/m L



## 5

. Weak Positive control : Dexamethasone

Supplier: Sigma

- Aldrich Catalog # D

- 1756

Batch #: 1419230 (expiry Nov 2013) Purity: 9 8. 9%

CAS # : 50

- 02

- 2



## 6

. Solvent/vehicle control : Ethanol

Justification for choice of solvent : Not reported ; ethanol is the recommended solvent for the AR Binding assay.

Final Concentration : 3 %And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 4 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## B. METHODS

1. Preparation of R at Prostate Cytosol : Trimmed prostate tis sue was collected from 60 male Sprague

- Dawley [CD(Crl:CD(SD))] rats that were purchased from Charles River

Laboratories. Animals were 80 -90 days old at the time of euthanasia, and rats had been castrated approximately 24 hour s prior to tissue harvest. The tissues were placed into ice

cold low salt b uffer, on ice, immediately after collection . The study authors did not report prostate weights , but tissues were homogenized in ice -cold (4 ° C) low salt TEDG (Tris, sodium molybdate, EDTA, DTT, glycerol) + PMSF (phenylmethylsulfonyl fluoride) buffer, pH 7.4. Homogenates were centrifuged for 30 minutes at 30,000 × g , discarding the resulting pellets. Protein concentration of the cytosol was determined to be 7.126 mg/mL using the Bradford method . Cytosol was divided into aliquots (volume not reported ) and

stored at -75 ° C for up to 90 days until use.

The appropriate protein concentration that would give binding of 25-35% of the total
[ 3 

## H] -R1881 in the s aturation binding assay was determined by combining the following components in silanized glass tubes: triamcinolone ac eto nide (60 μM, 50 μL) ; [ 3 

## H] -R1881 (10 nM, 7.5 μL ); and non- radiolabelled R1881 (1 nM, 7.5 μL). After evaporation of the solvent, varying cyt osolic protein concentrations (1.8 to 2.14 mg/300 μ L) were diluted with

TEDG+PMSF buffer in the initial incubation . A second incubation range of 1.4 to 2.0 mg/300 μL followed the initial incubation. All samples were run in triplicate. The tubes were maintained at 4°C, vortex mixed, and incubated in a rotary mixer at 15 rpm for 20

hou rs.

2. Satura tion (Radioligand) B inding E xperiment : A saturation binding e xperiment measuring total and non-specific binding of [ 3 

## H] -R1881 was performed to demonstra te that

the AR was present in reasonable concentrations and had the appropriate affinity for the native ligand. The conditions for the saturation binding are summarized in Table 1.

TABLE 1. Summary of Conditions for Saturation Binding Experiment a



### Source of receptor Rat prostate cytosol

Concentration of radioligand (as serial dilutions) 0.25

- 1 0 nM

Concentration of non

- labeled ligand (100X [radioligand]) 25

- 10 00 nM
Concentration of receptor Sufficient to bind 2 5 to 35 % of radioligand at 0.1 mg/mL b



### Temperature 4 oC

Incubation time 20 hours

Composition of assay buffer Tris 1 M (pH 7.4 )

EDTA 200 mM

Sodium molybdate 1 M

Glycerol 10%

Phenylmethylsulfonyl fluoride 100 mM

DTT 0.154 mg/mL

a Data were obtained from page s 14

- 16 of the study report. b 1.4 mg/assay tubeAnd rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 5 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## The study report did not state whether or not the specific activity of the stock solution of
[ 3 

## H] -R1881 was adjusted for decay over time. Additionally, although two different batches

of [ 3 

## H] -R1881 (with the s ame specific activity) were used over the course of the assay, the use dates for each batch were not reported. S erial dilutions of [ 3 

## H] -R1881 were prepared in TEDG + PMSF buffer to achieve final concentrations of 0.25, 0.5, 0.7, 1, 1.5, 2.5, 5, and

10 nM. Solutions of non-labeled R1881 were prepared in a similar manner to achieve

concentrations that were 100- fold greater than each respective radiolabeled concentration to result in final concentrations of 25, 50, 70, 100, 150, 250, 500, and 1000 nM. For e ach batch of cytosol, the optimal protein concentration was determined by testing serial amounts of protein per tube, using 10 nM [ 3 

## H] -R1881 (7.5 μ L) , until a concentration was reached

that bound approximately 25-35% of the total radioactivity added. E ach assay consisted of

three non- concurrent runs, and each run contained three concurrent replicates at each

concentration ( Table 2 ).

TABLE 2. Saturation Binding Experiment Run a



### Total binding b 

### Non

- specific binding c 

### Radioligand alone d 

### Assay Components

NR NR

--- TEDG + PMSF buffer

1 0 μL 1 0 μL 1 0 μL [ 3 

### H]

- R1881 (8 serial dilutions) e



### --- 1 0 μL

--- Non

- labeled R1881 (8 serial dilutions, 100× each respective labeled concentration) f



### 3 00 μL 3 00 μL

--- Prostate cytosol (diluted to appropriate conc.)

30 0 μL 30 0 μL 1 0 μL Total volume in each assay tube

a Data were obtained from page 15 of the study report. Tube numbers corresponding to assay conditions were not provided.

b Total binding = [ 3 

### H]

- R1881 bound to A R

c Non

- specific binding = [ 3 

### H]

- R1881 and 100

- fol d greater non

- labeled bound to A R

d Total [ 3 

### H]

- R1881 alone for dpm determination at each concentration

e Final concentrations of [ 3 

### H]

- R1881 = 0.25, 0.5, 0.7, 1, 1.5, 2.5, 5, and 10 nM

. f Final concentrations of non

- labeled R1881 = 25, 50, 70, 100, 150, 250, 500, and 1000 nM

.



## Tubes were incubated with gentle vortexing for 20 hours at 4 ° C. To separate bound from

free [ 3 

## H] -R1881, a 60% hydroxyapatite (HAP) sl urry was added to 100-μL portions of each

reaction mixture and vortexed at 5- minute intervals over 20 minutes, followed by centrifugation at 600 × g for 3 minutes at 4°C. Subsequently, the contents of each tube were

washed four times as follows: 50 mM Tris buffer was added, vortexed, centrifuged for

3 min utes at 600 x g , and the supernatant decan te d and discarded. E thanol was then added to the HAP pellet remaining in each tube to extract the [ 3 

## H] -R1881, followed by vortexing

over a 10- minute period , and centrifugation for 10 min at 600 × g . An aliquot of supernatant from each tube (1 mL) was rad ioassayed by liquid scintillation counting. The temperature

was maintained at 4oC throughout the assay prior to extraction with ethanol.

3. Competitive B inding E xperiment : A summary of the experiment conditions for the

c ompetitive bind ing e xperiment is presented in Table 3.And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 6 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



### TABLE 3 . Summary of Conditions for Competitive Binding Experiment a



### Source of receptor Rat Prostate C ytosol

Concentration of radioligand 1 nM

Concentration of receptor Sufficient to bind 10 to 15 % of radioligand at 2.0 mg/m L b



### Concentration of PCNB (as serial dilutions) 10

− 10 

### to 10

− 3 .5 

### M

Temperature 4 ° C

Incubation time 20 hours
Composition of assay buffer Tris 1 M (pH 7.4)

EDTA 200 mM

Glycerol 1 0%

Phenylmethylsulfonyl fluoride 100 mM

DTT 0.154 mg/mL

a Data were obtained from page s 1 5, 16, and 19 of the study report. b 0.6 mg/assay tube



## PCNB was initially determined to be soluble in ethanol at up to 30 mM, but precipitation was noted after spiking 10 μL of this PCNB stock solution into 300 μL of prostate cytosol. The highest achievable concentration of PCNB in cytosol was determined to be 1 × 10

− 3.5


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

## H]-R1881 was not reported, and it was not reported to have been adjusted for decay over time. [ 3 

## H] -R1881

was diluted in TEDG + PMSF buffer to achieve a final concentration of 1 nM

. Serial

dilutions of PCNB

, weak positive control ( dexamethasone ), and reference material ( nonlabeled R1881 ) were prepared to achieve the concentrations shown in Table 4. E ach assay

co nsisted of three runs, and each run contained three replicates at each co ncentration (except for six replicates of the solvent control and non-specific binding) , resulting in a total of 75

tubes/run.And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 7 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



### TABLE 4. Molar (M) concentrations in Competitive Binding Assay Run a,b



### PCNB Weak Positive control Reference Chemical

Solvent Control

Ethanol c 

### Dexamethasone Non

- labeled

R1881

Tubes 1

- 3, 73

- 75 Tubes 2 5

- 48 d 

### Tubes 49

- 7 2 d 

### Tubes 4

- 2 4 d



### 10

− 10 

### 10

− 10 

### 10

− 11



### 10

− 9 

### 10

− 9 

### 10

− 10



### 10

− 8 

### 10

− 8 

### 10

− 9



### 10

− 7 

### 10

− 7 

### 10

− 8



### 10

− 6 

### 10

− 6 

### 10

− 7



### 10

− 5 

### 10

− 5 

### 10

− 6 

### (NSB) e



### 10

− 4 

### 10

− 4



### - 10

− 3.5 

### 10

− 3



### -

a Data were obtained from page s 19 and 70

- 81 of the study report.

b Each tube contains: 10μL of the PCNB , positive control, negative control, solvent contr ol, or non

- labeled

R1881 ; 390 μL of TEDG + PMSF buffer with [ 3 

### H]

- R1881; and 100 μL of prostate cytosol (with A R), for a total of 500 μL.

c Solvent was ethanol (3%).

d Each concentration of each chemical was run in triplicate

, except for the solvent control and non

- specific binding , for a total of 75 tubes per run. Tube numbers were not provided, but were assigned by reviewer based on data spreadsheets on pages 51

- 59.

e Tubes 19

- 24



## Tubes were incubated and processed as described previously for the saturation binding experiment. An aliquot of supernatant from each tube (1 mL) was radioassayed by liquid scintillation counting. The temperature was maintained at 4oC throughout the assay prior to

extractio n with ethanol.

4. D ata Analysis : For the saturation binding experiment, total binding and non- specific binding data were modeled via non-linear regression with PROC NLIN SAS 9.1.3 (SAS Institute 2002). For the competitive binding assay, similar methods of nonlinear regression

were used to fit a curve (for R1881, dexamethasone, and PCNB ) to the Hill equat ion formula which incorporated log IC 50 

## as a parameter to be estimated. For parameters reported fro m the saturation binding e xperiment ( K d 

## and B
max 

## ) and c ompetitive binding

e xperiment ( log IC 50 

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

and mean and standard error were calculated fo r the composite three runs with Microsoft Excel (Microsoft Corporation, Redmond, WA).

5. Definitions :

a. Classification of test material

If the data fit a 4

- parameter nonlinear regression model, the test chemical is classified as:

Binder: The average curve for the test chemical across runs crosses 50% of radioligand

bound.

Equivocal: The average lowest portion of curves across runs is between 50% and 75%And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 8 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## radioligand binding ( i.e. radioligand displacement is at least 25% but less than 50%), or the curve falls outside the range for the weak positive control (-0.6 to -1.4).

Non

- Binder: The average lowest portion of curves across runs is greater than 75% activity ( i.e. less than 25% displacement of radioligand), 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 : The appropriate protein concentration for

the saturation binding a ssay was determine d to be 1.4 mg/300 μL (4.67 mg/mL) as it bound

24 % of the [ 3 

## H] -R1881, just below the Guideline specified range of 25-35% binding. The

results from the three s aturation binding a ssay s are summarized in Table 5 and shown graphically in Figures 1 -6. The mean K d 

## for [ 3 

## H] -R1881 was 1.6246±0.3283 nM, and the

mean estimated B
max 

## was 0.1805±0.0199 nM for the prepared rat prostate cytosol. The K d 

## was within the expected range of 0.03 to 1.5 nM for two of the three runs, but outside the range for Run 2 ( 2.2810±0.2936 nM ), a nd the mean K d 

## (1.6246 nM ) was also slightly above the recommended Guideline range . T he data were fit to a linear Scatchard plot in all three runs; visual observation indicates a moderate degree of scatter

. Co nfidence in these numbers is high due to the minimal variation among runs

.

TABLE 5. Saturation Binding Experiment of R1881 with Androgen Receptor from Rat Prostate Cy tosol a



### Parameter Run 1 Run 2 Run 3 Mean ± SEM

r 2 

### (unweighted) NR NR NR NA

B
max 

### (nM) 0.1426 ±0.0 107 0.2102 ±0.0 111 0.1887 ±0.0 110 0.1805 ±0.0 199

B
max 

### (fmol/100 μg protein) 1 0.1864 15.0108 13.4772 12.8915 ± 1.4231

K d 

### (nM) 1.3131 ±0. 2647 2.2810 ±0. 2936 1.2798 ±0. 2117 1.6246 ±0. 3283

a Data were obtained from page 30 of the study report.

r 2 

### Goodness of fit (calculated by reviewers)

. SEM Standard E rror. NR Not reported.

NA Not Applicable.And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 9 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## FIGURE 1. Specific, non

- specific, and total b inding of [ 3 

## H] -R1881 to the and rogen

r eceptor during the Saturation Binding Experiment (Run 1)

.

F IGURE 2. Specific, non

- specific, and total binding of [3H] -R1881 to the androgen receptor during the Saturation Binding Experiment (Run 1).And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 10 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## F IGURE 3. Specific, non- specific, and total binding of [3H] -R1881 to the androgen receptor during the Saturation Binding Experiment (Run 1).

F IGURE 4. Scatchard plot for the Saturation Binding Experiment (R un 1 ).And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 11 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## F IGURE 5. Scatchard plot for the Saturation Binding Experiment (Run 2)

.

F IGURE 6. Scatchard plot for the Saturation Binding Experiment (Run 3)

.And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 12 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## B. COMPETITIVE BINDING EXPERIMENT : The appropriate protein concentration for

the c ompetitive binding assay was determined to be 0.6 mg/300 μL (2.0 mg/mL) as it bound 13% of the [ 3 

## H] -R1881, which was within the Guideline range of 10 -15% binding.

The results from the three c ompetitive binding a ssay s are shown in Table 6, summarized in

Table 7, and shown graphically in Figures 7-9. The goodness- of fit (r 2 

## ) values for each run

were not reported

. The mean log IC 50 

## was

− 8.72 M for R1881 and

− 4.00 M for the weak positive control.

The s tudy author reported estimated log IC 50 

## values for PCNB, however it was noted that

the calculated log IC 50 

## estimates for PCNB were not reliable because the confidence limits (not reported) were large. PCNB did not reduce [ 3 

## H] -R1881 binding by ≥50% at any concentration up to 10

- 3.5 

## M, therefore an IC 50 

## value for PCNB was not calculated. The

mean RBA was 0.0019 % for the weak positive control, and could not be calculated for

PCNB . V ariability of the data within each run for R1881 and dexamethasone w ere low;

therefore

, the c onfidence in these numbers is high

. Three valid assay runs were completed out of eight runs in total

. The five remaining runs were rejected as they failed to meet various performance or acceptance criteria. PCNB is demonstrated equivocal binding (25

- 50% reduction in [ 3 

## H] -R1881 binding), in Run 1 but was classified as a non -binder (<25% reduction in [ 3 

## H] -R1881 binding) in Runs 2 and 3. Overall, based on the results of the three valid runs, PCNB is classified as a non-binder in this assay.

TABLE 6

. Mean Specific Binding (%) of [ 3 

### H]

- R1881 in the Presence of R1181, Dexamethasone and PCNB for

the Three Valid C ompetitive Binding Experiments a

Chemical Concen. (M) Mean Specific Binding by Run

Mean S E Run 1 Run 2 Run 3

R1881 (positive control) − 11 103 100 108 104 2.3

− 10 110 102 97 103 3.8

− 9 72 68 58 66 4.2

− 8 21 14 20 18 2.2

− 7 2 3 2 2 0.3

Dexamethasone (weak positive control) − 10 93 111 90 98 6.6

− 9 103 95 114 104 5.5

− 8 115 88 100 101 7.8

− 7 100 106 108 105 2.4

− 6 101 100 114 105 4.5

− 5 100 103 94 99 2.6

− 4 54 49 49 51 1.7

− 3 12 13 19 15 2.2

PCNB

− 10 92 98 84 91 4.1

− 9 82 97 77 85 6.0

− 8 82 96 91 90 4.1

− 7 92 96 101 96 2.6

− 6 89 103 92 95 4.3

− 5 100 100 105 102 1.7

− 4 64 83 80 76 5.9

− 3.5 66 92 90 83 8.4

a Data were obtained from pages 51

- 59 of the study report.

b The mean and Standard Error (SE ) of specific binding across all three runs were calculated by the reviewer.And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 13 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



### TABLE 7 . Competitive Binding Assay of PCNB with Androgen Receptor from Rat Prostate Cytosol a



### Parameter Run 1 Run 2 Run 3 Mean ± SEM c



### r 2 

### (unweighted) R1881 NR NR NR NA

Dexamethasone NR NR NR N A

PCNB N R N R N R NA Log IC 50 

### (M) R1881

− 8.60

− 8.73 −8.83

− 8.72 ± 0.0 67

Dexamethasone

− 3.96 −4.01 −4.03

− 4.00 ± 0.0 22

PCNB NA b 

### NA b 

### NA b 

### NA b



### IC 50 

### (M) c 

### R1881 2.5 3 × 10 −9 

### 1.85 × 10 −9 

### 1.48 × 10 −9 

### 1.95 × 10 −9 

### ( ±0.31 )

Dexamethasone 1.10 × 10 −4 

### 9 .8 9 × 10 −5 

### 9 .29 × 10 −5 

### 1

. 0 1 × 10 −4 

### ( ± 0.0 51 )

PCNB NA NA NA NA Log RBA c 

### Dexamethasone

- 4.64

- 4.7 3

- 4. 80

- 4.72 ± 0.05

PCNB NA NA NA NA RBA (%) c 

### Dexamethasone 0.0023 0.0019 0.0016 0.0019 ± 0.0002

PCNB NA NA NA NA

a Data were obtained from pages 31

- 33 of the study report , and were converted to M equivalents by the reviewer

. b Although l og IC 50 

### values were estimated for PCNB by the study author, they are not included because radiolabeled ligand binding was not reduced by PCNB by ≥ 50%.

c All values are reviewer

- calculated from the log IC 50 

### values reported in the study report. For means expressed in scientific notation, the SE values in parentheses are presented in the same order of magnitude as t he mean

value.

r 2 

### Goodness of fit

SEM Standard Error RBA (%) R elative binding affinity

NR Not reported

NA Not applicableAnd rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 14 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## F IGURE 7. Plo t of 4

- parameter fitted curve during the Competitive B inding Experiment (R un 1 ).

FIGURE 8. Plot of 4- parameter fitte d curve during the Competitive Binding Experiment (Run 2).And rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 15 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## F IGURE 9. Plot of 4- parameter fitte d curve during the Competitive Binding Experiment (Run 3).

C. PERFORMANCE CRITERIA : To ensure that the competitive binding assay function ed properly, each run was evaluated with the following criteria (Table 8) :

TABLE 8. Criterion a 

### Tolerance Limit(s) Value Yes No

R1881 fitted curve parameters Log
e 

### residual SD Top (% binding) 82 to 114 99.1 to 105.9 X Bottom (% binding)

− 2 to 2 1.104 to 1.794 X Hill Slope (log 10 

### (M)

- 1 

### )

− 1.2 to

− 0.8

- 1.174 to

- 0.890 X Weak Positive control ( Dexamethasone ) fitted curve parameters Log
e 

### residual SD Top (% binding) 87 to 106 97.3 to 101.9 X Bottom (% binding)

− 12 to12 7.369 to 15.65 X b,c



### Hill Slope (log 10 

### (M)

- 1 

### )

− 1.4 to

− 0.6

- 8.947 to

- 1.179 X b



### Solvent concentration

Ethanol ≤3% 3% X Ligand Depletion <10

- 15% 1

- 2% X

a Data were obtained from page s 30, 31, and 70

- 81 of the study report.

b Run 2

c Run 3

NA Not applicableAnd rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 16 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## The data for R1881 met the acceptance criteria described in the Guideline. The study author

stated that the data for weak positive control, dexamethasone

, met the acceptance criteria described in the g uideline, with th e following exceptions: in Run 2, bottom p lateau level upper limit was 12.672 (target was -12 to 12); in Run 2, Hill slope was -8.947 (target

was -1.4 to -0.6); and in Run 3, bottom plateau level upper limit was 15.654 (target was

target was -12 to 12 ).

Additionally, the curve for the reference material showed that increasing concentra tions of unlabeled R1881 displaced [ 3 

## H] -R1881 in a manner consistent with one-site binding, as indicated by a descent from 97-110 % to 1 4-21% binding over approximately a 100-fold

increase in concentration of the test chemica l (i.e., 1.65 to 2 log units).

PCNB was tested over a concentration range that fully defined the top of the curve. In the

second and third valid assay runs, th e percent binding at th e top plateau w as generally within 25 percentage points of the value for the lowes t concentration of the R1881 standard

, although inter

- assay variation was high. The results of the first assay run were equivocal

and did not meet this criterion.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR ’ S CONCLUSIONS : With unlabeled R1881, the average curve across

the three valid tests crossed 50% and an IC 50 

## was obtained for every run. Therefore, R1881 is classified as being a 'binder' with the androgen receptor. With dexamethasone, the

average curve ac ross the three valid tests crossed 50% and an IC 50 

## was obtained for every run. Therefore, dexamethasone is classified as being a 'binder' with the androgen receptor.

The mean RBA for dexamethasone was 0.0019% and with a log RBA of − 2.72%.

The curve for the test compound, PCNB, did not cross 75% binding in two of the three valid tests, but did cross 75% in the first test. Although an IC 50 

## was calculated for PCNB in every run, these values were not considered to be reliable estimates as the confidence limits were very large. As PCNB is classified as equivocal in the first valid test and a non -binder for the second and third valid tests, overall PCNB is classified as being a non-binder with the AR

. The data obtained from R1881 and the weak p ositive control were generally in line with the ranges provided in the Guideline. Although not all the performance criteria for the weak positive control were met for every valid test, the results with dexamethasone showed that

the assay was sensitive to weakly active chemicals.

B. AGENCY COMMENTS : The protein concentration for the saturation binding a ssay was determined to be 4.67 mg/mL as it bound 24 % of the [ 3 

## H] -R1881, which is just below the Guideline range of 25 -35%. The mean K d 

## for [ 3 

## H] -R1881 was 1.6246 nM, and the mean

estimated B
max 

## was 0.1805 nM for the prepared rat prostate cytosol. The K d 

## was within the expected range of 0.03 to 1.5 nM for two of the three runs, but was above the recommended

K d 

## in Run 2 (2.2810 nM). The mean K d 

## for all three runs (1.6246 nM ) was also slightly

above the Guideline recommended range.

The protein concentration for the c ompetitive b indin g assay was determined to be 2.0 mg/mL as it bound 13% of 1 nM of [ 3 

## H] -R1881. An estimated mean IC 50 

## for PCNB couldAnd rogen Receptor Binding Assay (Rat Prostate Cytosol ) ( 2011 ) / Page 17 of 17

PCNB / 056502 O CSPP 89 0.11 50/ OECD None



## not be determined as it did not result in 50% displacement of [ 3 

## H] -R1881 from the AR

. The

mean log IC 50 

## was

− 8.72 M for R1881 and

− 4.00 M for the weak positive control. The

mean RBA was 0.0019% for the weak positive control, but an RBA could not be calculated

for PCNB. Variability within each run with R1881 and dexamethasone was low; therefore, the confidence in these numbers is high.

T hree valid assay runs were completed out of a total of eight runs. F ive of the runs were appropriately rejected as they failed to meet various performance or acceptance criteria ( e.g.,

non- specific binding too high, drift in the final solvent control values relative to the initial values, performance criteria not met for the weak positive control). Continued issue s with the performance criteria for dexamethasone were observed in valid Runs 2 and 3. For PCNB, the minimum mean specific binding of [ 3 

## H] -R1881 to the AR was 64, 83 and 80% in the three valid runs, which corresponded to an equivocal classification (50 -75% bind ing) for the first valid run and non-binder (>75% binding ) i n the other two valid runs.

C. STUDY DEFICIENCIES : The following deficiencies were noted that did not have an adverse effect on the results, interpretation or conclusions of this study:

• The calculated K d 

## for Run 2, and the mean K d 

## , were above the recommended g uideline range in the saturation binding e xperiment.

• Several performance criteria were not met for dexamethasone

.

• The radiochemical purity of [ 3 

## H] -R1881 , and the calculated specifi c activity values (adjusted for decay) on each day of use, were not reported

.

# DATA EVALUATION RECORD

PCNB

Study Type: OCSPP 890.1200, Aromatase Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-26-2012 (MRID 48916701)

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: 10/11 /2012

Secondary Reviewer : Signature: Scott D. Studenberg, Ph.D., D.A.B.T. Date: 10/13 /2012

Program Manager: Signature: Jack D. Early, M.S. Date: 10 / 17 /2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 10/17 /2012

This Data Evaluation Record may have been altered 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 intended 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 redundancy 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 potential 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).PCNB I 056502



## Primary Reviewer"'--: -= D"-'e"""'b"""o"""'ra=h"""S=m=e=g=a"""l

__ _ ___ _ 

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



## Health Effects Division Signature:

Date :

DATA EVALUATION RECORD

STUDY TYPE: Aromatase (Human Recombinant); OCSPP 890.1200

# -~z!; Template version 10/2011



## PC CODE: 056502 DP 

## BARCO DE: D4053 72



## TXR#: 0056474 

## CAS No.: 82-68-8



## TEST MATERIAL (PURITY) : PCNB (95.6% a.i.)



## SYNONYMS: 1, 2

, 3, 4, 5-pentachloro-6-nitrobenzene

, Quintozene



## CITATION: Foster, J.R. (2012) PCNB Technical: Aromatase (Human Recombinant) Assay. Huntingdon Life Sciences Ltd.

, Huntingdon, Cambridgeshire, England

. Laboratory Report No.: BDG0124

, June 15

, 2012

. MRID 48916701. Unpublished.



## SPONSOR: AMVAC Chemical Corporation

, 4695 MacArthur Court, Suite 1200, Newport

Beach

, CA



## TEST ORDER#: EDSP-056502-105



## EXECUTIVE SUMMARY: In an 

## in vitro aromatase (CYP19) assay (MRID 48916701),

PCNB (95.6% a.i. Lot # 107030L052) was incubated with human recombinant aromatase and

tritiated androstenedione ([I 

# P- 3 

## H(N)]-androst-4-ene-3

, 17-dione; [3H]-ASDN) in SI% ethanol at log concentrations from 10- 1 0 

## to 10- 4 

## M for 15 minutes to assess the potential of PCNB 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)

u s ing a known inhibitor (4-hydroxyandrostenedione; 4-0H ASDN; formestane)

, and the test
chemical series (10- 1 0 

## to 10- 4 

## M) with three repetitions per concentration.

Aromatase activity in the full activity controls ranged from 0.251 to 0.340 nmol·mgprotein- 1 ·rnin- 1 for the three test runs
, with a mean and standard deviation of0.297 ± 

## 0

. 044 nmol·mg-protein

- 1 

## ·min

- 1

• 

## Activity in the background controls ranged from 0.38 to 1.78% and averaged 0.78% of the full control activity. The response of the full activity controls and

b a ckground controls was generally acceptable for each run.Aromatase (Human Recombinant) Assay ( 2012 ) / Page 2 of 13

PCNB / 056502 O CSPP 89 0. 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 concentration within runs. The estimated mean log IC 50 

## for 4

- OH ASDN was −7.39 M and the mean Hill slope was −0.955.

For PCNB, aromatase activity averaged 0.286 ± 0.051 nmol

∙ mg -protein −1



## ∙ min −1 

## at the lowest

tested concentration of 10 −10 

## M and 0.275 ± 0.038 nmol

∙ mg -protein −1



## ∙ min −1 

## at the highest tested

concentration of 10 −4 

## M. Aromatase activity ranged from 92.5 to 98.9% of the full activity

control at PCNB concentrations from 10

− 10 

## to 10

− 4 

## M. Although the study author used the 4- parameter nonlinear regression model to extrapolate possible log IC 50 

## and Hill slope values for PCNB (−1.23 M and −0.465, respectively ), these values are not supported by the experimental

data and are well outside the bounds of the tested concentrations.

Based on the data from the average response curve

, PCNB is classified as a Non-inhibitor of aromatase activity in this assay.

The assay satisfies the EDSP Tier 1 Test Order requirement s for an Aromatase a ssay (OCSPP 890.1200).

COMPLIANCE : Signed and dated Data Confidentiality, GLP Compliance, Flagging, and Quality Assurance statements were provided.Aromatase (Human Recombinant) Assay ( 2012 ) / Page 3 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility : Huntingdon Life Sciences Ltd.

Location: Cambridgeshire, England Study Director: J. R. Foster

Other Personnel: M. C. Jordan, Technical Specialist J. D. Holding, Consultant Pharmacokineticist S. J. Bartlett, Lead Scientist Study Period: February 3, 2012 through June 15, 2012



## 2

. Test S ubstance : PCNB

Description: Technical, light brown powder

Source: AMVAC Chemical Corporation, CA

Lot/Batch #: 107030L052, Exp iration date July 2016 Purity: 95.6% Volatility: NR Storage conditions: In a closed container, away from direct sunlight, at room temperature Stability: Approximately 4 years

Solvent : Ethanol Solubility (in test solvent): 10

– 2 M in Ethanol Highest Concentration Tested: 10

– 4 M Molecular weight: 295.3

CAS #: 82

- 68

- 8

Structure:



### Cl

Cl

Cl Cl Cl NO 2



## 3

. Non

- L abeled S ubstrate : Androstenedione (ASDN)

CAS # : 63

- 05

- 8

Source ( c atalog #) : Sigma (46033)

Lot/Batch # (expiration date) : S Z B931XV (Nov 13, 2014) Purity: 99.1



## 4

. Radiolabeled S ubstrate : 1

- β [ 3 

## H(N)]

- Androst

- 4

- ene

- 3,17

- dione ; ( [ 3 

## H] ASDN)

Source ( c atalog #): American Radiolabeled Chemicals, Inc. (ART 1673) Lot/Batch # (expiration date): 110512 (not reported) Radiochemical Purity (Supplier): 99% Specific activity: 26.3 Ci/ μ mol (on date of use) Radiochemical Purity (In

- lab determination): 99.6

- 99.0%



## 5

. Positive C ontrol : 4

- hydroxyandrostenedione (4

- OH ASDN ; Formestane)

CAS # 566

- 48

- 3
Source ( c atalog #): Sigma (F552) Lot/Batch # (expiration date): 081K2133 (Nov 24, 2014 ) Purity: 99.6 %Aromatase (Human Recombinant) Assay ( 2012 ) / Page 4 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## 6

. Solvent (V ehicle C ontrol ) : Ethanol

Lot/Batch # (expiration date): BDH/VWR , Catalog # 20821.321 (not reported)

Justification for choice of solvent Solubility

Final concentration ≤1% of final assay volume



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

Source (catalog #): Gentest/BD Biosciences (456260) Lot/Batch # (expiration date): 03897 (February 2014)

Protein concentration: 7.4 mg protein per mL Cytochrome C reductase activity: 290 nmole cytochrome c reduced/mg protein/minute Aromatase activity: 6 pmol/(min × pmol P450); 0.81 nmol∙mg

- protein −1 ∙min −1



## B. METHODS

1. Assay C omponent s and Preparations : A mixture of non- labeled and radiolabeled
[ 3 

## H]ASDN was prepared such that the final concentration of ASDN in the assay was approximately 100 nM, and the amount of tritium added to each incubation tube was approximately 0.1 μCi in a volume of 100 μL

.

PCNB stock solutions were prepared such that the total volume of each test chemical formulation used per assay was ≤ 1% of the total assay volume to minimize the potential for

the solvent to inhibit the enzyme. Selection of the solvent, ethanol, was based upon the solubility of PCNB in the solution following addition of the buffer.

A stock solution of the positive control substance, 4- OH ASDN, was formulat ed in ethanol.

Fresh dilutions of the stock solution w ere prepared in the same solvent as the stock solution on the day of use. Dilutions were prepared such that the target concen trations of the positive control substance (0.1–10,000 nM; Table 4 ) wer e achieved by the addition of 10 μ L of the dilution for a final assay volume of 1 mL.

Human recombinant microsomes were purchased from Gentest through BD Biosciences,

and stored at ≤− 75oC . Microsomes were thawed and sub-aliquoted before being refrozen at

–75 ° C.

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

T ABLE 1. Assay Components and Conditions a
Assay Factor Values

0.1M sodium phosphate buffer (pH 7.4)

Microsomal Protein 0.00 37 mg/mL

NADPH 6 mM

[ 3 H]ASDN 2μ M Propylene Glycol 5%
Temperature 37°C

Incubation Time 15 min

a Data were obtained from page 15

- 16 of the study reportAromatase (Human Recombinant) Assay ( 2012 ) / Page 5 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## 2. Suitability Ass es s ments : The protein concentration of the microsomes was supplied by the vendor (BD Gentest; 7.4 mg/mL). Aromatase activity in each lot of human recombinant microsomes was demonstrated to be sufficient for analysis of PCNB . The aromatase activity was calculated t o be 0.81 nmol

∙ mg -protein −1



## ∙ min −1 

## , which was greater than the minimum acceptable aromatase activity of 0.1 nmol

∙ mg -protein −1



## ∙ min −1



## .

3. Aromatase A ssay : Each assay run contained 4 tubes for the full enzyme activity and background activity controls, respectively, and a full concentration curve in triplicate for the positive control and PCNB

. The aromatase assay was conducted according to the procedures described in O CSP P 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 LS C, and

aromatase a ctivity was reported in units of nmol

∙ mg

- protein

− 1



## ∙ min

− 1



## .

4. Demonstration of P roficiency : Proficiency testing of the CYP19 aromatase assay was conducted as part of study CWM39 (Report title: Validation of the Aromatase (Human Recombinant) Assay Performed Using a Hamilton STAR Robot). Each of the proficiency chemicals (atrazine, econazole, fena rimol and nitrofen) were incubated alongside the positive control inhibitor (formestane) on 3 separate occasions.

a. Positive Control

(1) Initial Demonstration of Laboratory P roficiency : The positive control data met the following criteria:

• Mean aromatase activity in the absence 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.

• C oefficient of variation (CV) for replicates within each sample type and concentration

of 4

- OH ASDN was <15%, with one exception (see B.4.b. ), and the log IC 50 

## values were within historical laboratory ranges (although below the lower limit of the performance criteria ).

• Performanc e criteria (Table 2 ) were generally met , and serve d as guidance in identifying runs that provided parameters in the preferred ranges.

(2) Demonstration o f P roficiency of N ew T echnician for C onducting Assay (when applicable) : The positive control data met the criteria as listed in section (i ) of OCSPP

890.1200 , except for log IC 50 

## of -7.74 M which was slightly less than the guideline range (- 7.3 to 7.0 M).

TABLE 2. Performance Criteria for the Positive Control (Formestane; 4

- OH ASDN) a

Parameter Lower Limit Criteria Upper Limit Criteria Actual Lower Limit Actual Upper Limit
Slope

− 1.2

− 0.8

– 1.010

– 0.812
Top (%) 90 110 90.1 107.2
Bottom (%)

− 5 +6 0.1 1.1
Log IC 50 (M)

− 7.3

− 7.0

– 7.74

– 7.30

a Data were obtained from page 54 of the study report.Aromatase (Human Recombinant) Assay ( 2012 ) / Page 6 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## b. Proficiency C hemicals : The full activity control was greater than 100 pmol/min/mg protein for all 12 runs conducted, ranging from 193.6 to 496.8 pmol/min/mg protein. The background activity control was <15% of the mean full activity control for all twelve runs conducted, rangin g from -0.5% to 0.6% of full activity control. Of the twelve runs with proficiency chemicals and positive control, the positive control was run in triplicate on three occasions and in duplicate for the remaining nine occasions. The % CV between replicates was <15% for all the runs with formestane run in triplicate. Of the remaining nine runs with formestane run in duplicate, six of the runs had a %CV of <15%. The three runs that had replicates with a percent CV >15% were at no more than two concentration s of positive control and for these runs log IC 50 

## values were calculated to be –7.61, –7.65 and –7.32 M, which were within the range achieved by this laboratory (Table 3). These runs were therefore deemed acceptable.

Proficiency chemicals were run in triplicate on all occasions. However, on one occasion during a run with the proficiency chemical fenarimol, a hardware error was noted on the Hamilton STAR robot. The error occurred during the addition of [ 3 

## H ] androstenedione to a single replicate only. This led to the results being based on duplicate fenarimol incubations for this run only. The % CV between replicates was <15% for all data points with proficiency chemicals.

During proficiency testing, the positive cont rol (formestane) met the criteria in the EPA Guideline with the exception of the log IC 50 

## range (Table 2 ).

T ABLE 3. Proficiency Chemicals

Compound CAS# Class Concentrations

Econazole 24169

- 02

- 6 Inhibitor 10

– 11 to 10

– 6

Fenarimol 60168

- 88

- 9 Inhibitor 10

– 9 to 10

– 4

Nitrofen 1836

- 75

- 5 Inhibitor 10

– 10 to 10

– 4.5

Atrazine 1912

- 24

- 9 Non

- inhibitor 10

– 9 to 10

– 3.5



## 5. Determination of Aromatase A ctivity with T est C hemical(s) : T he response of aromatase activity to the presence of eight concentrations of PCNB per run, in triplicate, was tested during three independent runs (Table 4)

. After complet ion of the first run, the data we re reviewed and no adjustments to the test chemical concentrations were deemed necessary.Aromatase (Human Recombinant) Assay ( 2012 ) / Page 7 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



### T ABLE 4. Test Chemical Study De sign for each Test Run a

Sample Type Repe titions (Tubes) Description Reference or

Test 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

− 6.5

4

- OH ASDN Conc 4 2 All test components plus 4

- OH ASDN 1×10

− 7

4

- OH ASDN Conc 5 2 All test components plus 4

- OH ASDN 1×10

− 7.5

4

- OH ASDN Conc 6 2 All test components plus 4

- OH ASDN 1×10

− 8

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

PCNB Conc 1 3 All test components plus PCNB 1×10 −4

PCNB Conc 2 3 All test components plus PCNB 1×10 −4.5

PCNB Conc 3 3 All test components plus PCNB 1×10 −5

PCNB Conc 4 3 All test components plus PCNB 1×10 −6

PCNB Conc 5 3 All test components plus PCNB 1×10 −7

PCNB Conc 6 3 All test components plus PCNB 1×10 −8

PCNB Conc 7 3 All test components plus PCNB 1×10 −9

PCNB Conc 8 3 All test components plus PCNB 1×10 −10

a Data were obtained from page 15 of the study report.

b The complete assay contained buffer, propylene glycol, microsomal protein, [ 3 H]ASDN, and NADPH

.



## C. D ATA ANALYSIS

1. Raw D ata : Raw data were converted to aromatase activity ( nmol

∙ mg

- protein −1



## ∙ min −1 

## ) and percent control for the positive control, proficiency chemicals and test chemical(s) . The following raw data and calculated endpoints for each run were included in the report (Table 5).

T ABLE 5. Raw and Calculated Data a

Raw/Calculated Data Included (X)
DPM/mL for each portion of extracted 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 X The percentage of substrate converted to product X

Total DPM after extraction corrected for background X Aromatase activity expressed in nmol∙ mg protein −1

∙ min −1 X Average aromatase activity in the full activity control tubes X Percentage of control activity remaining in the presence of various inhibitor concentrations X

a Data were obtained from pages 26

- 43 of the study report.

DPM Disintegrations per minute



## 2. S tatistical M ethods : Mean% control activities were calculated. The response curve was fitted by weighted least squares nonlinear regression analysis with WinNonlin Pro v 5.0. A

4- parameter logistic dose response curve was fitted by weight e d least -squares non- linear regression analysis, with weights equal to 1/(% control activity).Aromatase (Human Recombinant) Assay ( 2012 ) / Page 8 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## 3. Interpretation of Results : Interpretation of the assay results was b ased on the average of three runs, using the categories presented in Table 6.

TABLE 6 . Interpretation 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 equi vocal.

b If the test compound was not soluble above 10

− 6 M and the inhibition curve does not cross 50%, the chemical is typically

determined to be untestable in the aromatase assay

.



## II

. RESULTS

A. CONTROL ACTIVITY : Aromatase activity in the full activity controls ranged from

0.251 to 0.340 nmol

∙ mg -protein

− 1



## ∙ min

− 1 

## for the three test runs, with a mean and standard

deviation of 0.297 ± 0.044 nmol

∙ mg -protein

− 1



## ∙ min

− 1 

## . Activity in the background controls ranged from 0.38 to 1.78% and averaged 0.78 % of the full activ ity control. The individual values generally fell in the range of

− 0.5% to 1.0 % of the full control activity , and t he response of the full activity controls and background controls was considered acceptable for

each run.

B. POSITIVE CONTROL : For the positive control substance (4

- OH ASD N) , a romatase activity averaged 0.278 ± 0.031 nmol

∙ mg -protein

− 1



## ∙ min

− 1 

## at the lowest tested concentration

10

− 10 

## M and 0.0018 ± 0.0003 nmol

∙ mg -protein

− 1



## ∙ min

− 1 

## at the highest tested concentration

10

− 5 

## M. The mean aromatase activity of the positive control (expressed as % full control activity) for each concentration tested across all three runs is presented in Table 7, along

with the overall standard deviation (SD), standard error of the mean (SEM) and %

c oefficient of variance ( CV ). Inhibition response curves for the positive control from each

run are shown in Figure 1, and the average inhibition response curve across all runs is shown in Figure 2. These results were generally within the recommended ranges for the %CV, top of the curve, bottom curve, Hill slope and log IC 50



## .Aromatase (Human Recombinant) Assay ( 2012 ) / Page 9 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



### TABLE 7 . Effect of PCNB on Aromatase Activity (as percent of control) from Three Independent Runs a

Chemical Concen. ( Log M ) # Runs Overall Mean Overall SD Overall SEM Overall %CV



### 4

- OH ASDN (positive control) −5 3 0.62 0.16 0.09 26.1

−6 3 6.20 0.61 0.35 9.8

−6.5 3 13.45 0.53 0.31 3.9

−7 3 34.38 0.67 0.38 1.9

−7.5 3 56.9 2.58 1.49 4.5

−8 3 81.3 1.45 0.84 1.8

−9 3 95.0 5.64 3.25 5.9

−10 3 93.3 4.38 2.53 4.7

PCNB −4 3 92.5 0.70 0.41 0.8

−4.5 3 95.7 1.93 1.12 2.0

−5 3 94.0 1.61 0.93 1.7

−6 3 98.8 1.58 0.91 1.6

−7 3 98.9 0.57 0.33 0.6

−8 3 97.3 4.33 2.50 4.4

−9 3 99.3 2.42 1.40 2.4

−10 3 95.2 4.49 2.59 4.7

a Data were obtained from page 50 of the study report, and calculated by reviewers from pages 23

- 25 of the study report.

SD Standard Deviation

SEM Standard Error of the Mean

CV Coefficient of Variance



## C. TEST SUBSTANCE : For PCNB , aromatase activity averaged 0.286 ± 0.051 nmol

∙ mg

protein

− 1



## ∙ min

− 1 

## , or 95.2% of the full activity control at the lowest tested concentration

10

− 10 

## M, and 0.275 ± 0.038 nmol

∙ mg -protein

− 1



## ∙ min

− 1 

## , or 92.5% of the full activity control at the highest tested concentration 10

− 4 

## M . The mean aromatase activity of PCNB (expressed as %full control activity) for each concentration tested across all three runs is presented in

Table 7 , along with the overall SD, SEM and % CV. Inhibition response curves for PCNB

fro m each run are shown in Figure 1, and the average inhibition response curve across all runs is shown in Figure 2.Aromatase (Human Recombinant) Assay ( 2012 ) / Page 10 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## F IGURE 1. Inhibition R esponse C urves for PCNB and 4

- OH ASDN F rom E ach T est

R un.Aromatase (Human Recombinant) Assay ( 2012 ) / Page 11 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## F IGURE 2. Mean I nhibition R esponse C urve for PCNB and 4

- OH ASDN

.

Although inhibition of aromatase activity was <10% at concentrations up to 10

− 4 

## M, the study author utilized the 4- parameter regression model to extrapolate log IC 50 

## and Hill slope values for PCNB (Table 8). For PCNB, the extrapolated log IC 50 

## values ranged from

− 0.044 to

− 2.07 M and averaged –1.23 M ; these values are well outside the performance boundaries of the assay and are not supported by the experimental data . For t he positiveAromatase (Human Recombinant) Assay ( 2012 ) / Page 12 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## control 4- OH ASD N, the log IC 50 

## averaged –7.39 M. The average slope of the concentration response curve was –0.465 for PCNB and

− 0.955 for 4

- OH ASD N.

TABLE 8 . Effect of PCNB on Aromatase Activity (as P ercent of C ontrol) F rom Independent Runs a

Chemical Run 1 Run 2 Run 3 Mean S EM %CV

Log IC 50 (M)

PCNB b

– 2.07

– 1.57

– 0. 0 44

– 1.23 0.61 86

4

- OH ASD N

– 7.53

– 7.30

– 7.34

– 7.39 0.07 1.6

Hill Slope

PCNB b

– 0.691

– 0.465

– 0.23 9

– 0.465 0.13 48

4

- OH ASD N

– 0.955

– 0.958

– 0.951

– 0.955 0.002 0.42

a Data were obtained from page 51 of the study report, SEM and %CV for all runs were calculated by the reviewer.

b Although the study author calculated values for PCNB using the 4

- parameter curve model, th is is of limited use as they are well outside the boundaries of the experimental data.

S EM Standard error of the mean

NA Not applicable; log IC 50 and Hill slope could not be calculated.



## Based on the data from the average response curve and the criteria listed above in Table 8,

PCNB is classified as a non -inhibitor of aromatase activity under the conditions of this

assay.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS CONCLUSIONS : PCNB Technical was calculated to have a mean log IC 50 

## (mol/L) of –1.23 ± 1.06 M with a range from –2.07 to –0.044 M. The positive

control 4- OH ASDN was calculated to have a mean log IC 50 

## (mol/L) of –7.39 ±0.12 with a range from –7.53 to –7.30. Two of these log IC 50 

## values ( –7.53 and –7.34) were marginally

outside the Guideline suggested range ( –7.3 to –7.0), but were consistent with previous laboratory findings. The mean slope of the 4-OH ASDN dose response curve from the 3

runs averaged –0.955 ± 0.004 and ranged from –0.958 to –0.951, which were within the

Guideline range ( –1.2 to –0.8). The top of the 4-OH ASDN dose response curve ranged between 89% and 98% of the mean full activity control and the bottom of the dose response curve ranged between 0.5% and 0.8%. Except for one instance where the top of the dose

response curve was 89%, these results meet the criteria stated in the EPA Guideline

. Except for one data point, which had a CV of 17.3% (Run 1; 10 –6.5 

## M ), the percent CV between replicates was <15% for all 4 -OH ASDN data points within each run. The addition of 4- OH ASDN to the assay resulted in almost total inhibition of the enzyme activity at the highest concentration (10

− 4 

## M ) used.

The lowest measured data point of the average dose response curve for PCNB was 90.4% of the full activity control. Based on these finding, PCNB is classified as a non -inhibitor of CYP19 aromatase activity

.

B. AGENCY COMMENTS : Aromatase activity in the full activity controls ranged from

0.251-0.3397 nmol

∙ mg

- protein −1



## ∙ min −1 

## for the three test runs, with a mean and standard

deviation of 0.297 ± 0.039 nmol

∙ mg -protein −1



## ∙ min −1 

## . Activity in the background controls averaged 0.0023 ± 0.0018 nmol

∙ mg -protein −1



## ∙ min −1 

## , or 0.78±0.41% of the full activityAromatase (Human Recombinant) Assay ( 2012 ) / Page 13 of 13

PCNB / 056502 O CSPP 89 0. 1200 / OECD None



## control. The response of the full activity controls and background controls were generally acceptable for each run.

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 concentration within runs. The estimated mean log IC 50 

## for

4- OH ASDN averaged −7.39 M and the mean Hill slope was −0.955.

For PCNB, aromatase activity averaged 0.286 ± 0.051 nmol

∙ mg -protein −1



## ∙ min −1 

## at the

lowest tested co ncentration 10 −10 

## M and 0.275 ± 0.038 nmol

∙ mg -protein −1



## ∙ min −1 

## at the highest tested concentration 10 −4 

## M.

The lowest portion of the response curve across all runs was greater than 75% activity at all concentrations, therefore PCNB is classified as a non

- inhibitor of aromatase activity.

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

• Information on data analysis was not provided

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀ Խ

ԡԹՌԹԯԽՉՍՁՊԽՅԽՆՌ    Ԣԭ Ԟ

Ԣԭ Ԟ

Ԣԭ Ԟ

ԱԽՋՌԪԹՌԽՊՁԹՄ  ԭԠԫԟԱԽԻՀՆՁԻԹ

ԠՇՅՅՇՆԫԹՅԽ ԭԠԫԟԱԽԻՀՆՁԻԹ

ԠՀԽՅՁԻԹՄԫԹՅԽ  ԦԲԭԞԠ  

 ԠԞ԰ԫԹՅԽ 

ԠԞ԰ԫՇ 

԰ՑՆՇՆՑՅՋ 

ԢԭԞԭԠԠՇԼԽ

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԧՇՀՆԪԹՊՌՇՆ ԭ

ԢՆՎՁՊՇՆՅԽՆՌԹՄ԰ԻՁԽՆՌՁՋՌԠԡԪ԰ՅՁՌ Հ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊ
Ջ ԱԽՊՁ԰ԪՑ Խ

ԢՆՎՁՊՇՆՅԽՆՌԹՄ԰ԻՁԽՆՌՁՋՌԠԡԪ԰ՅՁՌ Հ

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԢԼՏԹՊԼ԰ԻՇՄՄՇ Ն

ԱՇՐՁԻՇՄՇԿՁՋՌԲ԰ԢԭԞԬԭԭԢԣԢԡԢ ԯ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊ ԢՄՁՒԹԺԽՌՀ
ԯՁՄ Խ

ԟՁՇՄՇԿՁՋՌԲ԰ԢԭԞԬԭԭԢԣԢԡԢԯԟ Գ

ԞԼԼՁՌՁՇՆԹՄԯԽՎՁԽՏԽՊ ԠԹՌՀԽՊՁՆԽԞՍԺ Խ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԲ԰ԢԭԞԬԭԭԢԣԢ ԡ

ԡԹՌԽԢՎԹՄՍԹՌՁՇՆԠՇՅՈՄԽՌԽԼ #ԼԼՅ Յ 

## ԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌ Հ

ԢԭԞԪԯԦԡ

ԭԹԿԽ  ο Ծ  

### Ԟ

ԡԭԟԹՊԻՇԼԽ 

Ԟ

ԪԯԦԡ   

Ԟ

ԤՍՁԼԽՄՁՆԽ  

    ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊ ՇԼՍԻՌՁՇՆԞՋՋ Թ

Մ    ԭՍՊՁՌՑ
  

Մ

ԫՇՌՊԽՈՇՊՌԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ



ԭԽՆՌԹԻՀՄՇՊՇՆՁՌՊՇԺԽՆՒԽՆԽ



ԭ Հԡ    ԡԹՌԽ 

Հ

Խ ՊՋԭՀԡ   ԡԹՌԽ 

Հ

Ն ԭՀԡ    ԡԹՌԽ  
ՆՇՄՇՆԿԽ Պ

ԯԟԦԳ

Խ ՑԡՇՆՇՎԹՆ    ԡԹՌԽ 

Գ Ԧ

Խ Խ      ԡԹՌԽ 

ԡ ԢԯԟԦԳ

Յ ՅՑՑՑՑ% 

## ԭԠԫԟ

ԫՍՅԺԽՊ

Թ Ց

Պ ՏՁՌՀԢԭԞ

Digitally signed by Elizabeth

Donovan DN: cn=Elizabeth Donovan,
o=EPA, ou=EFED, email=donovan.elizabeth@epa. gov, c=US

Date: 2015.06.10 09:03:15 -04'00'

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԠԦԱԞԱԦԬԫ ԰ԻՀՆԽՁԼԽՊ԰ԷԨԥԪԹՊՌՁՆԱԷԨԽՆԼԹՄՄԹՆԼԥԬԨՊՍԽԿԽՊ ԭԠԫԟԱԽԻՀՆՁԻԹՄԣՁՋՀ԰ՀՇՊՌԱԽՊՅ

ԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀՌՀԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ ԲՆՈՍԺՄՁՋՀԽԼՋՌՍԼՑՈԽՊԾՇՊՅԽԼԺՑ

ԴՁՄԼՄՁԾԽԦՆՌԽՊՆԹՌՁՇՆԹՄԩՌԼԢԹՋՌՇՆԪԹՊՑՄԹՆԼԩԹԺՇՊԹՌՇՊՑՊԽՈՇ ՊՌՆՍՅԺԽՊԞԞ԰ՌՍԼՑՋՈՇՆՋՇՊԽԼԺՑ

ԞՅՎԹԻԠՀԽՅՁԻԹՄԠՇՊՈՇՊԹՌՁՇՆԫԽՏՈՇՊՌԟԽԹԻՀԠԹՄՁԾՇՊՆՁԹ԰ՌՍԼՑԻՇ ՅՈՄԽՌԽԼԧԹՆՍԹՊՑ

ԡՁՋԻՄԹՁՅԽՊ ԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՁՆՌՀՁՋԡԢԯՌԽՅՈՄԹՌԽԹՊԽՇԾԾԽՊԽԼ ԹՋԹԿԽՆԽՊԹՄՊԽԾԽՊԽՆԻԽՌՇԹՁԼՁՆՈՊԽՈԹՊԹՌՁՇՆ

ՇԾՌՀԽԡԢԯԱՀԽՈՍՊՈՇՋԽՇԾՌՀԽՋԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՁՋՆՇՌՌՇՋԽՊ ՎԽԹՋՋՍԺՋՌՁՌՍՌԽԾՇՊՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋՆՇՊՌՇՈՊՇՎՁԼԽ

ԹՆՑԿՍՁԼԹՆԻԽՇՆՀՇՏՌՀԽՋՌՍԼՑՋՀՇՍՄԼԺԽԻՇՆԼՍԻՌԽԼ



### ԫՇՌԽ ԱՀԽԲ԰ԢԭԞԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅ
Ԣԡ԰ԭԱՁԽՊՋԻՊԽԽՆՁՆԿԺԹՌՌԽՊՑՁՋԻՇՅՈՊՁՋԽԼՇԾԽՄԽՎԽՆ

ՋԻՊԽԽՆՁՆԿԹՋՋԹՑՋՁՆՌԽՆԼԽԼՌՇՁԼԽՆՌՁԾՑԹԻՀԽՅՁԻԹՄ0ՋՄՁՃԽՄՑԽՆԼՇԻ ՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՁԽՁՌՋՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀ

ՌՀԽԽՋՌՊՇԿԽՆԹՆԼՊՇԿԽՆՇՊՌՀՑՊՇՁԼ
ԢԞՇՊԱՈԹՌՀՏԹՑՋԱՀԽՊ ՇԺՍՋՌՆԽՋՋՇԾՌՀԽԱՁԽՊԺԹՌՌԽՊՑՁՋԺԹՋԽԼՇՆ

ՌՀԽՋՌՊԽՆԿՌՀՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՌՇՁԼԽՆՌՁԾՑՈՇՌԽՆՌՁԹՄԽՆ ԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՏՁՌՀԻՇՅՈՄԽՅԽՆՌԹՊՑԽՆԼՈՇՁՆՌՋ

ՏՁՌՀՁՆՌՀԽԹՋՋԹՑՏՀԽՊԽԹՎԹՁՄԹԺՄԽԹՆԼՊԽԼՍՆԼԹՆԻՑԹԻՊՇՋՋՌՀԽԺԹ ՌՌԽՊՑԱՀՍՋՌՀԽՊԽՋՍՄՌՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄ

ԹՋՋԹՑՋՀՇՍՄԼՆՇՌԺԽԻՇՆՋՁԼԽՊԽԼՁՆՁՋՇՄԹՌՁՇՆԺՍՌՊԹՌՀԽՊՋՀՇՍՄԼԺ ԽԻՇՆՋՁԼԽՊԽԼՁՆՌՀԽԻՇՆՌԽՐՌՇԾՇՌՀԽՊԹՋՋԹՑՋ

ՁՆՌՀԽԺԹՌՌԽՊՑԹՋՏԽՄՄԹՋԬՌՀԽՊ԰ԻՁԽՆՌՁԾՁԻԹՄՄՑԯԽՄԽՎԹՆՌԦՆԾՇՊՅԹ ՌՁՇՆ
Ԭ԰ԯԦԦՆՇՊԼԽՊՌՇԼԽՌԽՊՅՁՆԽՁԾԹԻՀԽՅՁԻԹՄ

ՀԹՋՌՀԽՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀՌՀԽԢԞՇՊԱՈԹՌՀՏԹՑՋԹԴԽ ՁԿՀՌՇԾԢՎՁԼԽՆԻԽ
ԴՇԢԽՎԹՄՍԹՌՁՇՆՇԾԱՁԽՊ

ԹՋՋԹՑՊԽՋՍՄՌՋՁՆԻՇՅԺՁՆԹՌՁՇՆՏՁՌՀՌՀԽԾՁՆԼՁՆԿՋՁՆՌՀԽԬ԰ԯԦՋՀ ՇՍՄԼԺԽՍՆԼԽՊՌԹՃԽՆ
ՊԽԾԽՊՌՇՌՀԽԴՇԢ

ԡՇԻՍՅԽՆՌ

ԢԵԢԠԲԱԦԳԢ԰ԲԪԪԞԯԶ

ԱՀԽԼԹՑՋՀՇՊՌՌԽՊՅՊԽՈՊՇԼՍԻՌՁՇՆԹՋՋԹՑՇԾԭԠԫԟՏՁՌՀԾԹՌՀԽԹԼՅ ՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ ՏԹՋԻՇՆԼՍԻՌԽԼ

ՍՆԼԽՊԾՄՇՏՌՀՊՇՍԿՀԻՇՆԼՁՌՁՇՆՋԞԼՍՄՌԾՁՋՀ
ՅԹՄԽՋԹՆԼԾԽՅԹՄԽ ՋԿՊՇՍՈԿՊՇՍՈՋՌՊԽԹՌՅԽՆՌ+ՅՇՆՌՀՋՇՄԼ

ՏԽՊԽԽՐՈՇՋԽԼՌՇՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԭԠԫԟ
ՈՍՊՁՌՑՇ Ծ
ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼ

ՅԿԹՁԩՅԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽ ԩԬԮԻՇՆՌՊՇՄԹՆԼ

ՅԿԹՁԩԯԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼՌՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽ
ԱԴԞ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽ

ԹՆԼՅԿԹՁԩԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋՅԹՁՆՌԹՁՆԽԼԹՌՌՇ ոԠԹՆԼԹՈԥՇԾՌՇ

ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԹՄՄԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻ ՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ

԰ՍՊՎՁՎԹՄՏԹՋՁՆԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԹՆԼԹՄՄԾՁՋՀԹՈՈԽԹՊԽԼՆՇՊՅԹՄԹՆԼՀԽԹՄՌՀՑՌՀՊՇՍԿՀՇՍՌՌՀԽԽՐՈՇՋՍՊԽ

ՈԽՊՁՇԼՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՇԾՌՏՇԾԽՅԹՄԽՋՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈՏՀՇԹՈՈԽԹՊԽԼՌՇԺԽԽԿԿԺՇՍՆԼԬՆԽԾԽՅԹՄԽ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ՏԹՋՇԺՋԽՊՎԽԼՌՇԺԽԽԿԿԺՇՍՆԼԾՊՇՅԡԹՑՋՌՇՏՀՁՄԽՌՀԽՇՌՀԽՊ ԾԽՅԹՄԽՏԹՋՇԺՋԽՊՎԽԼՌՇԺԽԽԿԿԺՇՍՆԼՇՆԡԹՑՋ

ԹՆԼԭԠԫԟԽՐՈՇՋՍՊԽՏԹՋԹՋՋՇԻՁԹՌԽԼՏՁՌՀԹԻՇՆԻԽՆՌՊԹՌՁՇՆԼԽՈԽՆԼԽՆՌՁՆԻՊԽԹՋԽՁՆԺՇԼՑՏԽՁԿՀՌՁՆԾԽՅԹՄԽ

ԾՁՋՀՏՁՌՀՋՁԿՆՁԾՁԻԹՆՌՈՊՇՅՇՌՁՇՆՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՊ ԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԣԽԻՍՆԼՁՌՑ ԽՐԻԽԽԼԽԼ  ԽԿԿՋԾԽՅԹՄԽԼԹՑ ՁՆ ԽԹԻՀ ՇԾ ՌՀԽ ԻՇՆՌՊՇՄ ՊԽ ՈՄՁԻԹՌԽՋ 
ՅԽԹՆ 

ԽԿԿՋԾԽՅԹՄԽԼԹՑՊԽՈՄՁԻԹՌԽՊԹՆԿԽԹՄՌՀՇՍԿՀԽԹԻՀՊԽՈՄ ՁԻԹՌԽՁՆԻՄՍԼԽԼՇՊԼԹՑՈԽՊՁՇԼՋՏՁՌՀՇՍՌ

ՋՈԹՏՆՁՆԿԣԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋՁՆԻՇՆՌՊՇՄՋՏԹՋԭԠԫԟՋՁԿ ՆՁԾՁԻԹՆՌՄՑԼԽԻՊԽԹՋԽԼԾԽԻՍՆԼՁՌՑԺՑ
Ո

ԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋՏԹՋ ԻՇՅՈԹՊԹԺՄԽԺԽՌՏԽԽՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈՋԭՄԹՋՅԹՎՁՌԽՄՄՇԿԽՆՁՆ
ԳԱԤՄԽՎԽՄՋՁՆՅԹՄԽԹՆԼԾԽՅԹՄԽԾՁՋ ՀՏԽՊԽՍՆԹԾԾԽԻՌԽԼԹՌԹՄՄՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՄԹՌՁՎԽ

ՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԫՇՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՇՆԿՇՆԹԼԹ ՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑՏԽՊԽՇԺՋԽՊՎԽԼՁՆՅԹՄԽԾՁՋՀԹՌԹՆՑ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄՀՇՏԽՎԽՊՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՏԽՊԽՆՇՌԽԼՁՆԾԽՅԹՄԽՋԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄԱՀԽՊԽՏԹՋ

ԹՆՁՆԻՊԽԹՋԽՁՆՅԽԼՁԹՆԿՇՆԹԼԹՄՋՌԹԿՁՆԿ
ՎՋՁՆԻՇՆՌՊՇՄ ԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԽԾԾԽԻՌՋՁՆԻՄՍԼԽԼԼԽԻՊԽԹՋԽԼ

ՈՇՋՌՇՎՍՄԹՌՇՊՑ ԾՇՄՄՁԻՄԽՋ ԹՆԼ ՁՆԻՊԽԹՋԽԼ ՇՇԻՑՌԽ ԹՌՊԽՋՁԹ Ԟ ՋՁԿՆՁԾ ՁԻԹՆՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆԼԽՈԽՆԼԽՆՌ ՁՆԻՊԽԹՋԽ ՁՆ

ԿՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
Ԥ԰ԦՏԹՋՇԺՋԽՊՎԽԼՁՆՅԹՄԽԾՁՋՀՁՆՌՀԽՅՁԼԹՆԼՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ Ĺ ԹՆԼ

ՈԹՆԼԹՆԼՁՆԾԽՅԹՄԽԾՁՋՀՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈ Ĺ ՈԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԫՍՈՌՁԹՄ

ՌՍԺԽՊԻՄԽՋԻՇՊԽՏԹՋՍՆԹԾԾԽԻՌԽԼԺՑԭԠԫԟԽՐՈՇՋՍՊԽՁՆՅԹՄԽՋՆՇՌՍԺ ԽՊԻՄԽՋՏԽՊԽՇԺՋԽՊՎԽԼՇՆԾԽՅԹՄԽՋ

ԱՀԽԿՍՁԼԽՄՁՆԽՎԹՄՁԼՁՌՑԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹՏԽՊԽԿԽՆԽՊԹՄՄՑ ՅԽՌ ԱՀՁՋԹՋՋԹՑ ՋԹՌՁՋԾՁԽՋ ՌՀԽԢԡ԰ԭԱՁԽՊԱԽՋՌ

ԬՊԼԽՊՊԽՉՍՁՊԽՅԽՆՌԾՇՊԹԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԬԠ԰ ԭԭԤՍՁԼԽՄՁՆԽ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌՇՊԿԹՆՁՋՅԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՅՇՆՌՀՋ

ԪԽԹՆԺՇԼՑՏԽՁԿՀՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԿԾՇՊՅԹՄԽՋԿԾՇ ՊԾԽՅԹՄԽՋ

ԪԽԹՆՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԫՇՌՊԽՈՇՊՌԽԼ

ԱԽՋՌՌՑՈԽԣՄՇՏՌՀՊՇՍԿՀԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢԾԾԽԻՌՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԣ԰ԱԯԞՏՁՌՀԭԠԫԟԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԣԽԻՍՆԼՁՌՑԣԽՊՌ԰ՍԻԻԽՋՋԱՍԺԽՊԻՄԽ԰ԻՇՊԽԤ԰ԦԤՇՆԹԼԹՄԥՁՋՌՇԭՄԹՋՅԹԳԱԤԭՄԹՋՅԹԱԭՄԹՋՅԹԢԪԣԪԣԪԣԪԣԪԣԪԣԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫԞ ԫԞ ԫԞ ԫԞԫՇ ԫՇ ԫՇ ԫՇ ԶԽՋ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫԞ ԫԞ ԫԞ ԫԞԶԽՋԫՇ ԫՇ ԫՇԶԽՋ ԶԽՋԫՇԶԽՋԫՇ ԫՇ ԫԞ ԫԞ ԫԞ ԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԢȕԽՋՌՊԹԼՁՇՄԣԣԽՅԹՄԽԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԪԪԹՄԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ Ԟ՟ՑԽՋՠՁՆԼՁԻԹՌԽՋԹՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄՍՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼ ԱՀԽԻՊՁՌԽՊՁԹԾՇՊՋՁԿՆՁԾՁԻԹՆԻԽԹՊԽԼԽՋԻՊՁԺԽԼՁՆՌՀԽԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼ԰ՌԹՌՁՋՌՁԻԹՄԳԽՊՁԾՁԻԹՌՁՇՆՋԽԻՌՁՇՆՋՇԾՌՀԽԡԢԯԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### Ԧ ԪԞԱԢԯԦԞԩ԰ԞԫԡԪԢԱԥԬԡ԰ 

ԤՍՁԼԽՄՁՆԽԣՇՄՄՇՏԽԼ ԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼԾՇՄՄՇՏՁՆԿԿՍՁԼԽՄՁՆԽՋՇՍՌՄՁՆԽԼՁՆՌՀԽ Բ԰ԢԭԞ԰ԽՊՁԽՋ-

ԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊ ԹՅԱԽՋՌԤՍՁԼԽՄՁՆԽՋԬԠ԰ԭԭԫՍ ՅԺԽՊ

ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ ԹՆԼՌՀԽԬԢԠԡԤՍՁԼԽՄՁՆԽՋԾՇՊԱԽՋՌՁՆԿՇԾ

ԠՀԽՅՁԻԹՄՋԤՍՁԼԽՄՁՆԽ ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ ԱՀԽԾՇՄՄՇՏՁՆԿ

ԼԽՎՁԹՌՁՇՆՋՏԽՊԽՆՇՌԽԼ

 ԯԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽԹՆԼՍՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹԻՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ

 ԬՆԡԹՑԹԼՁՄՍՌԽՊՅԹՄԾՍՆԻՌՁՇՆՇԻԻՍՊՊԽԼՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽ ՆՌԿՊՇՍՈԞԼԼՁՌՁՇՆԹՄՋԹՅՈՄԽՋՏԽՊԽ

ՌԹՃԽՆՇՆԡԹՑԹՋՋՇՇՆԹՋՌՀԽՈՊՇԺՄԽՅՏԹՋԼՁՋԻՇՎԽՊԽԼԹՆԼՌՀԽՈ ՊՇԺՄԽՅՏԹՋՊԽՈԹՁՊԽԼ԰ԹՅՈՄԽՋ

ՏԽՊԽԹՄՋՇՌԹՃԽՆՇՆԡԹՑՌՇԻՇՆԾՁՊՅԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԾՌԽՊՌՀԽԼՁՄՍՌԽՊՅԹՄԾՍՆԻՌՁՇՆԱՀԽՁՆՌԽՊՊՍՈՌՁՇՆ

ՁՆԼԽՄՁՎԽՊՑՏԹՋՋՀՇՊՌՁՆԼՍՊԹՌՁՇՆ
ՀՇՍՊՋԞՆԹՄՑՌՁԻԹՄՊԽԻՇՎ ԽՊՁԽՋՏԽՊԽՇԾՆՇՅՁՆԹՄՇՆ

ԡԹՑԹՆԼՇԾՆՇՅՁՆԹՄՇՆԡԹՑԱՀԽՋԽԹՆԹՄՑՌՁԻԹՄՊԽՋՍՄՌՋՏԽՊԽՆՇՌՁՆԻՄՍԼԽԼՁՆՅԽԹՆ

ՅԽԹՋՍՊԽԼԻԹՄԻՍՄԹՌՁՇՆՋ

ԱՀԽԼՁՄՍՌԽՊՅԹՄԾՍՆԻՌՁՇՆԹՆԼԹՋՋՇԻՁԹՌԽԼՁՅՈԹԻՌՋՇՆՌԽՋՌՋՍԺՋՌԹՆԻԽԻՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՊՇԼՍԻԽՋՍՆԻԽՊՌԹՁՆՌՑՁՆՌՇ

ՌՀԽՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾԽՐՈՇՋՍՊԽԹՋՋՇԻՁԹՌԽԼՏՁՌՀԽԾԾԽԻՌՋՁՆՌՀԽՀ ՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈԥՇՏԽՎԽՊՌՀԽՋՌՍԼՑՁՋ

ՇՌՀԽՊՏՁՋԽԿԽՆԽՊԹՄՄՑՋՇՍՆԼ

ԠՇՅՈՄՁԹՆԻԽ ԰ՁԿՆԽԼԹՆԼԼԹՌԽԼԫՇԡԹՌԹԠՇՆԾՁԼԽՆՌՁԹՄՁՌՑԤԩԭԹՆԼԮՍԹՄՁՌՑԞՋ ՋՍՊԹՆԻԽՋՌԹՌԽՅԽՆՌՋՏԽՊԽ

ՈՊՇՎՁԼԽԼԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼՁՆԻՇՅՈՄՁԹՆԻԽՏՁՌՀԤՇՇԼԩԹԺՇ ՊԹՌՇՊՑԭՊԹԻՌՁԻԽ԰ՌԹՆԼԹՊԼՋԹՋՈՍԺՄՁՋՀԽԼԺՑ

ՌՀԽԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԠԣԯԭԹՊՌՋԹՆԼ ԹՆԼԬԢԠԡԭՊՁՆԻՁՈՄԽՋՇԾԤՇՇԼ

ԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽ
ԢԫԳԪԠԠԥԢԪ
ՏՁՌՀՌՀԽԾՇՄՄՇՏՁՆԿԽՐԻԽՈՌՁՇՆՋՈԽՊՁՇԼՁԻԹՆԹՄՑՋԽՋՇԾՏԹՌԽՊԾՇՊ

ՈՇՌԽՆՌՁԹՄԻՇՆՌԹՅՁՆԹՆՌՋՏԽՊԽՆՇՌՈԽՊԾՇՊՅԽԼԹԻԻՇՊԼՁՆԿՌՇԤՇՇԼԩԹԺ ՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽ԰ՌԹՆԼԹՊԼՋԺՍՌՏԽՊԽ

ՈԽՊԾՇՊՅԽԼՍՋՁՆԿԹԻԽՊՌՁԾՁԽԼՄԹԺՇՊԹՌՇՊՑԹՆԼՋՌԹՆԼԹՊԼԲ԰ԢԭԞԹՆԹՄՑՌՁԻԹՄՅԽՌՀՇԼՋԹՆԼՌՀԽԻՀԹՊԹԻՌԽՊՁՒԹՌՁՇՆՇԾ

ՌՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽԹՆԼՌՀԽՋՌԹԺՁՄՁՌՑՇԾՌՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽՍՆԼ ԽՊՌՀԽԻՇՆԼՁՌՁՇՆՋՇԾՋՌՇՊԹԿԽԹՌՌՀԽՌԽՋՌՋՁՌԽԹՊԽ

ՌՀԽՊԽՋՈՇՆՋՁԺՁՄՁՌՑՇԾՌՀԽ԰ՈՇՆՋՇՊ

Ԟ ԱԽՋՌԪԹՌԽՊՁԹՄ   ԭԠԫԟԱԽԻՀՆՁԻԹՄ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԡԽՋԻՊՁՈՌՁՇՆ    ԩՁԿՀՌԺՊՇՏՆՈՇՏԼԽՊ

ԩՇՌԫՇԟԹՌԻՀԫՇ  ԩ

ԢՐՈՁՊԹՌՁՇՆԡԹՌԽ  

ԭՍՊՁՌՑ     

ԦՅՈՍՊՁՌՁԽՋ    ԫ ՇՆԽՊԽՈՇՊՌԽԼ

԰ՌԹԺՁՄՁՌՑՇԾԠՇՅՈՇՍՆԼ  ԫՇՌՊԽՈՇՊՌԽԼԥՇՏԽՎԽՊՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼԱԴԞԻՇՆԻԽՆՌՊԹՌՁՇՆՋՑ ՁԽՄԼԽԼ

ՊԽԻՇՎԽՊՁԽՋՇԾՇԾՆՇՅՁՆԹՄ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾ 

ԱԽՋՌԠՀԽՅՁԻԹՄՋ   ԰ՌՇՊԽԼՍՆԼԽՊԹՅԺՁԽՆՌԻՇՆԼՁՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԟԱԽՋՌԬՊԿԹՆՁՋՅԱԹԺՄԽԤԽՆԽՊԹՄԦՆԾՇՊՅԹՌՁՇՆԞԺՇՍՌՌՀԽԱԽՋՌ԰ՈԽԻՁԽՋԹՆԼԞԻԻՄՁՅԹՌՁՇՆԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՈԽԻՁԽՋԻՇՅՅՇՆՆԹՅԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԹՌՀԽԹԼՅՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋ

ՈՊՇՅԽՄԹՋ԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼԫՇՌՊԽՈՇՊՌԽԼԴԽՊԽԾՁՋՀՇԺՌԹՁՆԽԼԾՊՇՅԹՋՁՆԿՄԽՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃ!ԶԽՋ ԰ՌՇԻՃԻՍՄՌՍՊԽՏԹՋՇՊՁԿՁՆԹՄՄՑՇԺՌԹՁՆԽԼԾՊՇՅԬՋԹԿԽԠԹՌԾՁՋՀԽՊՁԽՋԦՆԻ
ԬՋԹԿԽԟԽԹԻՀԪՁՋՋՇՍՊՁ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ԾՁՋՀ ԺԽ ԾՊՇՅ Թ ՋՁՆԿՄԽ

ՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃԴԽՊԽԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԹԻԻՄՁՅԹՌԽԼՍՆԼԽՊ ՏԹՌԽՊՉՍԹՄՁՌՑԹՆԼՁՄՄՍՅՁՆԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՌՀԹՌԹՊԽ ՋՁՅՁՄԹՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼՅՇՆՌՀՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՌՏՇՏԽԽՃ ԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԫՇՌԽՌՀԹՌՌՀԽԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼ ՁՋԼՁԾԾԽՊԽՆՌԾՊՇՅՌՀԽՋՍԺՋԽՉՍԽՆՌՁՆՋՁՌՍ ՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՀԽԹՄՌՀԡՍՊՁՆԿՌՀԽՏԽԽՃՋՈՊՁՇՊՌՇՌՀԽՋՌԹՊՌՇԾՌՀԽՌԽՋՌԾՁՋՀՋՀՇՏԽԼՆՇՋՁԿՆՋՇԾԼՁՋԽԹՋԽՇՊՋՌՊԽՋՋԹՆԼՆՇՅՇՊՌԹՄՁՌՁԽՋՏԽՊԽՇԺՋԽՊՎԽԼԣՁՋՀԼՁԼՆՇՌՊԽԻԽՁՎԽԹՆՑՌՊԽԹՌՅԽՆՌԾՇՊԼՁՋԽԹՋԽԼՍՊՁՆԿՌՀԽԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼՌՀԽՌՏՇՏԽԽՃՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼՇՊՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽԼԹՑՋ ՈՊՁՇՊՌՇՌՀԽՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽԺԽՄԽՋՋՌՀԹՆՇԾ ՌՀԽԻՍՄՌՍՊԽՈՇՈՍՄԹՌՁՇՆԦԾՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽՋԽ ԼԹՑՋՁՋԿՊԽԹՌԽՊՌՀԹՆԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ՌՀԽԾՁՋՀԺԽՊԽՂԽԻՌԽԼԦԾՅՇՊՌԹՄՁՌՑՁՋԺԽՌՏԽԽՆ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽՀԽՄԼԹՆՇՌՀԽՊԼԹՑՋ  ԦԾՅՇՊՌԹՄՁՌՁԽՋԿՊԽԹՌԽՊՌՀԹՆՇԻԻՍՊԼՍՊՁՆԿՌՀՁՋ ԽՐՌԽՆԼԽԼԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԢԭԞՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌՌՀԽԾՁՋՀՆՇՌԺԽՍՋԽԼԱՑՈԽՇԾԾՇՇԼԠՇՅՅԽՊԻՁԹՄԾՄԹՃԽԾՇՇԼՋՍՈՈՄԽՅԽՆՌԽԼՏՁՌՀԺՊՁՆԽՋՀՊՁՅՈՆԹՍՈՄՁՁ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԾԽԼԾՊՇՒԽՆԺՊՁՆԽ ՋՀՊՁՅՈՌՏՁԻԽՈԽՊԼԹՑՌՇՈՊՇՅՇՌԽԹԻՌՁՎԽՊԽՈՊՇԼՍԻՌՁՇՆ ԹՆԼՅԹՁՆՌԹՁՆԺՇԼՑԻՇՆԼՁՌՁՇՆ԰ՇՍՊԻԽՇԾԾՇՇԼԣՄԹՃԽԾՇՇԼ԰ԽՊԹԫՇՊՌՀԞՅԽՊՁԻԹ
ԪՇՆՌԿՇՅԽՊՑՎՁՄՄԽԭԞԟՊՁՆԽՋՀՊՁՅՈԟՊՁՆԽ԰ՀՊՁՅՈԡՁՊԽԻՌ
ԬԿԼԽՆԲԱԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿՌՁՅԽՋԼԹՑԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿԣՁՋՀՏԽՊԽԾԽԼԹՌԹՋՍԾԾՁԻՁԽՆՌՊԹՌԽՌՇՈՊՇՅՇՌԽԹԻՌՁՎԽՊԽՈՊՇԼՍԻՌՁՇՆԹՆԼՅԹՁՆՌԹՁՆԺՇԼՑԻՇՆԼՁՌՁՇՆԣՁՋՀՏԽՊԽՆՇՌԾԽԼԾՇՊԹՌՄԽԹՋՌՀՇՍՊՋՈՊՁՇՊՌՇՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՌՇԹՄՄՇՏԾՇՊԻՄԽԹՊԹՆԻԽՇԾՌՀԽԼՁԿԽՋՌՁՎԽՌՊԹԻՌՋԺԽԾՇՊԽՌԽՊՅՁՆԹՄՏԽՁԿՀՌՅԽԹՋՍՊԽՅԽՆՌՋՏԽՊԽՅԹԼԽԲՆԽԹՌԽՆԾՇՇԼԹՆԼԾԽԻԹՄՅԹՌԽՊՁԹՄՏԽՊԽՊԽՅՇՎԽԼԾՊՇՅՌՀԽՌԽՋՌԻՀԹՅԺԽՊՋԺՑՋՁՈՀՇՆՁՆԿԼԹՁՄՑԱԹԺՄԽԣՁՋՀ԰ԽՄԽԻՌՁՇՆԹՆԼԭՊԽԢՐՈՇՋՍՊԽԭԽՊԾՇՊՅԹՆԻԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՅՇՆՌՀՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՊՇԼՍԻՌՁՎԽՄՑՅԹՌՍՊԽ
ՋԽՐՍԹՄՄՑ ԼՁՅՇՊՈՀՁԻԾՁՋՀՅՇՆՌՀՋՇՄԼԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԪԽԹՆՏԽՁԿՀՌՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՁԾԼԽՌԽՊՅՁՆԽԼԿ ԟԹՋԽԼՇՆՋՍԺՋԹՅՈՄԽ
Ն ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԹՋՍԺՋԹՅՈՄԽՇԾԾՁՋՀԺԽ ՏԽՁԿՀԽԼԺԽԾՇՊԽՌՀԽՌԽՋՌՌՇԽՋՌՁՅԹՌԽՌՀԽՅԽԹՆՏԽՁԿՀՌ ԾՇՊԽԹԻՀՋԽՐԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌՀԽՁՆԼՁՎՁԼՍԹՄ ՏԽՁԿՀՌՇԾԽԹԻՀԾՁՋՀՋԽՄԽԻՌԽԼԾՇՊՌՀԽՌԽՋՌԺԽՏՁՌՀՁՆ չՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԾՇՊԽԹԻՀՋԽՐԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋ
ՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼ ԦՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋՏԽՊԽՊԽՈՇՊՌԽԼՄՑՏՁՌՀՁՆչՇԾՌՀԽՅԽԹՆԪԽԹՆՏԽՁԿՀՌՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԿ ԟԹՋԽԼՇՆՋՍԺՋԹՅՈՄԽ
ՆԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼԦՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋՏԽՊԽՊԽՈՇՊՌԽԼՄՑՏՁՌՀՁՆչՇԾՌՀԽՅԽԹՆԪԽԹՆՄԽՆԿՌՀՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼԪԽԹՆՄԽՆԿՌՀՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼԫՇՌՊԽՈՇՊՌԽԼԡՍՊԹՌՁՇՆՇԾՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾԼԹՑՋԴԽՊԽՈՊԽԽՐՈՇՋՍՊԽԻՇՆԼՁՌՁՇՆՋՁԼԽՆՌՁԻԹՄՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽԻՇՆԼՁՌՁՇՆՋ ՁՆԻՄՍԼՁՆԿՌԽՅՈԽՊԹՌՍՊԽՈՀՇՌՇՈԽՊՁՇԼԾԽԽԼՁՆԿԽՌԻ ԺԽՁԼԽՆՌՁԻԹՄՌՇԼԽԾՁՆՁՌՁՎԽՌԽՋՌԻՇՆԼՁՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԫՍՅԺԽՊՇԾՈՊԽԽՐՈՇՋՍՊԽՌԹՆՃՋ ԞԼԼՁՌՁՇՆԹՄՊԽՈՄՁԻԹՌԽՋՏԽՊԽԽՋՌԹԺՄՁՋՀԽԼՋՇՌՀԹՌԺՊԽԽԼՁՆԿԿՊՇՍՈՋՏՁՌՀԹՈՊՇՎԽՆՀՁՋՌՇՊՑՇԾՋՈԹՏՆՁՆԿՏՇՍՄԼԺԽԹՎԹՁՄԹԺՄԽԾՇՊՌՀԽԽՐՈՇՋՍՊԽՈՀԹՋԽՇԾՌՀԽՌԽՋՌ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹԼԼՁՌՁՇՆԹՄՌԹՆՃՋՋԽՌՍՈԹՌՌՀԽ ԺԽԿՁՆՆՁՆԿՇԾՈՊԽԽՐՈՇՋՍՊԽՏՁՄՄԽՆՋՍՊԽՌՀԹՌՋՍԾԾՁԻՁԽՆՌ ՊԽՈՄՁԻԹՌԽՋՏՁՌՀՌՀԽԻՇՊՊԽԻՌՋԽՐՊԹՌՁՇԹՊԽԹՎԹՁՄԹԺՄԽԾՇՊ

ՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԫՍՅԺԽՊՇԾՅԹՄԽՋՈԽՊՌԹՆՃ ԫՍՅԺԽՊՇԾԾԽՅԹՄԽՋՈԽՊՌԹՆՃ ԭՊԽԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՊԽՈՄՁԻԹՌԽ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑՁՆ ԽԹԻՀՊԽՈՄՁԻԹՌԽ
ՌԹՆՃՋԽՄԽԻՌԽԼԾՇՊՍՋԽՁՆՌՀԽ ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԹՌՄԽԹՋՌ ԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՊԽՈՄՁԻԹՌԽԼՍՊՁՆԿ ՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԫՍՅԺԽՊՇԾՋՈԹՏՆՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽՌՁՅԽՋՁՆԼԹՑՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՈԹՏՆՁՆԿՇԻԻՍՊԹՌՄԽԹՋՌ ՌՏՁԻԽՁՆՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՈՊԽԽՐՈՇՋՍՊԽԱՀԽԿՊՇՍՈՋՏԽՊԽՊԹՆՃԽԼԾՊՇՅՄՇՏՌՇՀՁԿՀԾԽԻՍՆԼՁՌՑԹՆԼՌՀԽՌՇՈՈԽՊԾՇՊՅՁՆԿՋՈԹՏՆՁՆԿԿՊՇՍՈՋՏԽՊԽՋԽՄԽԻՌԽԼԱՀԽՌՇՈԾՇՍՊՈԽՊԾՇՊՅԽՊՋՏԽՊԽՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇՇՆԽՊԽՈՄՁԻԹՌԽԾՇՊԽԹԻՀՌՊԽԹՌՅԽՆՌԱՀԽՆԽՐՌԾՇՍՊՈԽՊԾՇՊՅԽՊՋՏԽՊԽՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇԹՋԽԻՇՆԼՊԽՈՄՁԻԹՌԽԾՇՊԽԹԻՀՌՊԽԹՌՅԽՆՌԹՆԼԻՇՆՌՊՇՄԹՆԼՋՇՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԠԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱՑՈԽՇԾԽՐՈՇՋՍՊԽԣՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏՌՀՊՇՍԿՀ ՋՑՋՌԽՅԞՋՆՇՌԽԼՁՆՌՀԽԠՇՊՊԽԻՌՁՇՆՋԹՆԼ ԠՄԹՊՁԾՁԻԹՌՁՇՆՋԼՇԻՍՅԽՆՌ  ՌՀԽՍՋԽՇԾԹՋՌԹՌՁԻ ՊԽՆԽՏԹՄՋՑՋՌԽՅՁՋՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՌՀՁՋ

ԹՋՋԹՑԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅԠՇՆՌՁՆՍՇՍՋԾՄՇՏ ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ ՊԽԻՇՅՅԽՆԼԽԼ ԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽՅԩՅՁՆԠԹՄԻՍՄԹՌԽԼԺԹՋԽԼՇՆԾՁՄՄՎՇՄՍՅԽԩԹՆԼՎՇՄՍՅԽԹԼԼՁՌՁՇՆՋՈԽՊԼԹՑ ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋՅԩՅՁՆ ԩՀՊՇՊԹՌՄԽԹՋՌՌՇՌԹՄՎՇՄՍՅԽԽՐԻՀԹՆԿԽՋ

ՈԽՊԼԹՑԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅԱՁԽՊԞՋՋԹՑՋ
ԬԠ԰ԭԭԱԽՋՌԤՍՁԼԽՄՁՆԽ԰ԽՊՁԽՋԪԹՊԻՀԬԾԾՁԻԽՇԾԠՀԽՅՁԻԹՄ԰ԹԾԽՌՑԹՆԼԭՇՄՄՍՌՁՇՆԭՊԽՎԽՆՌՁՇՆ
ԬԠ԰ԭԭԴԹՋՀՁՆԿՌՇՆԡԠՀՌՌՈՏՏՏԽՈԹԿՇՎԽՆԼՇՈՍԺՋԹՋՋԹՑՎԹՄՁԼԹՌՁՇՆԻՄԹՊՁԾՁԻԹՌՁՇՆԼՇԻՈԼԾԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋԣՄՍՁԼՅԽՌԽՊՁՆԿՈՍՅՈՋՏԽՊԽՍՋԽԼՌՇԼԽՄՁՎԽՊՎՇՄՍՅԽՋՇԾԹՋՁՆԿՄԽՌԽՋՌՋՍԺՋՌԹՆԻԽՋՌՇԻՃՋՇՄՍՌՁՇՆՌՇՅՁՐՁՆԿԻՀԹՅԺԽՊՋԹՋՋՁԿՆԽԼՌՇԽԹԻՀՌՊԽԹՌՅԽՆՌ԰ՌՇԻՃՋՇՄՍՌՁՇՆՋՏԽՊԽԼՁՄՍՌԽԼՏՁՌՀՏԽՄՄՏԹՌԽՊՁՆՅՁՐՁՆԿԻՀԹՅԺԽՊՋՁՆՇՊԼԽՊՌՇՇԺՌԹՁՆՌՀԽԼԽՋՁՊԽԼՆՇՅՁՆԹՄՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՈՊՁՇՊՌՇԼԽՄՁՎԽՊՑՌՇՌՀԽՌԽՋՌԻՀԹՅԺԽՊՋԣՄՇՏՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊՏԹՋԻՇՆՌՊՇՄՄԽԼՍՋՁՆԿՊՇՌԹՅԽՌԽՊՋԤԽՆԽՊԹՄՇՈԽՊԹՌՁՇՆՇԾՌՀԽԽՐՈՇՋՍՊԽՋՑՋՌԽՅՏԹՋԻՀԽԻՃԽԼՎՁՋՍԹՄՄՑԹՌՄԽԹՋՌՌՏՇՌՁՅԽՋՈԽՊԼԹՑԼՍՊՁՆԿՌՀԽՌԽՋՌԹՆԼԹՌՄԽԹՋՌՇՆԻԽՇՆՌՀԽԾՁՊՋՌԹՆԼՄԹՋՌԼԹՑՇԾՌՀԽՌԽՋՌ ԯԽԻՇՅՅԽՆԼԽԼՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀ ՋՑՋՌԽՅՋԪՁՐՁՆԿԻՀԹՅԺԽՊՁՋՊԽԻՇՅՅԽՆԼԽԼ ԺՍՌՆՇՌՊԽՉՍՁՊԽԼԞԽՊԹՌՁՇՆՁՋՆՇՌ ՊԽԻՇՅՅԽՆԼԽԼԾՇՊՅՁՐՁՆԿԞԼԽՅՇՆՋՌՊԹՌՁՇՆ ՌՀԹՌՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՁՋԻՇՅՈՄԽՌԽՄՑՅՁՐԽԼԺԽԾՇՊԽ ՁՆՌՊՇԼՍԻԽԼՁՆՌՇՌՀԽՌԽՋՌՋՑՋՌԽՅՁՋՊԽԻՇՅՅԽՆԼԽԼ ԱՀԽՊԽԻՇՅՅԽՆԼԽԼԾՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑՁՋ

ՏՁՌՀՁՆԞԽՊԹՌՁՇՆ!ԫՇ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹԽՊԹՌՁՇՆՁԾԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ

ՊԽԹԻՀԽՋ ՅԿԩ
 ՋԹՌՍՊԹՌՁՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊԬԺՌԹՁՆԽԼԾՊՇՅԹՏԽՄՄԹՈՈՊՇՐՁՅԹՌԽՄՑՅԽՌԽՊՋԼԽԽՈՄՇԻԹՌԽԼՇՆՋՁՌԽԴԽՄՄՏԹՌԽՊՏԹՋՈԹՋՋԽԼՌՀՊՇՍԿՀԹՋԹՆԼԾՁՄՌԽՊՌՇՊԽՅՇՎԽՈԹՊՌՁԻՄԽՋԿՊԽԹՌԽՊՌՀԹՆ+սՅԹՆԼՈՍՅՈԽԼՁՆՌՇԹՋՌՇՊԹԿԽՌԹՆՃՏՀԽՊԽՁՌՏԹՋԹԽՊԹՌԽԼԭՊՁՇՊՌՇՍՋԽՏԹՌԽՊՏԹՋԾՁՄՌԽՊԽԼՌՇսՅՌՇՊԽՅՇՎԽԾՁՆԽՈԹՊՌՁԻՄԽՋԹՆԼՏԹՋՈԹՋՋԽԼՌՀՊՇՍԿՀԹԲԳՋՌԽՊՁՄՁՒԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼՏԹՌԽՊ ՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄՏԹՌԽՊԺԽ ՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋ ՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊՈՇՋՋՁԺՄԽԻՇՆՌԹՅՁՆԹՆՌՋ ԬԢԠԡԹԻԻԽՈՌՋԹՆՑՏԹՌԽՊՁՆՏՀՁԻՀՌՀԽՌԽՋՌ ՋՈԽԻՁԽՋՋՀՇՏԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋ ՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!ԶԽՋ԰ԽԽԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋԱԽՋՌՎԽՋՋԽՄՌՑՈԽՅԹՌԽՊՁԹՄՋ ԤՄԹՋՋ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՏԹՌԽՊԻՇՆՌԹԻՌ ՈՇՊՌՁՇՆՋՇԾՌՀԽՋՑՋՌԽՅՆՇՌԻՇՅՈՊՇՅՁՋԽՌՀԽՋՌՍԼՑ

ԽԿ ԹՄՄԿՄԹՋՋՎԽՋՋԽՄՋՇՊԿՄԹՋՋՎԽՋՋԽՄՋՏՁՌՀ ՋՌԹՁՆՄԽՋՋՋՌԽԽՄԾՊԹՅԽՋԹՊԽԹԻԻԽՈՌԹԺՄԽ

ԽՐԹՅՈՄԽՋԱԽՋՌՎԽՋՋԽՄՋՁՒԽԩ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԩՌԽՋՌԻՀԹՅԺԽՊՋ ԽԿՐՐԻՅԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԣՁՄՄՎՇՄՍՅԽԩ ԢԭԞՊԽԻՇՅՅԽՆԼՋԩՋՇՄՍՌՁՇՆՈԽՊՌԹՆՃ԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՅԹՌԽՊՁԹՄ ԰ԽՅՁԻՁՊԻՍՄԹՊՋԽԻՌՁՇՆՋՇԾԭԳԠԱՀՊԽԽՋՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋՏԽՊԽԽՋՌԹԺՄՁՋՀԽԼՁՆԽԹԻՀԻՀԹՅԺԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԽԹԻՀՌԹՆՃԻՇՆՌԹՁՆՌՀՊԽԽ ՋԽՅՁԻՁՊԻՍՄԹՊՋՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋԽԿԹԿԽԼ ԭԳԠՈՁՈԽԻՅՁՆՄԽՆԿՌՀՋՈՄՁՌՄԽՆԿՌՀՏՁՋԽ԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋՁՒԽ ԻՅԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽՋՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՅՈԽՊԹՌՍՊԽ
ոԠԪԽԹՋՍՊԽԼՏԽԽՃՄՑՁՆԽԹԻՀԻՀԹՅԺԽՊԱԽՅՈԽՊԹՌՍՊԽԹՄՋՇՏԹՋՅՇՆՁՌՇՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑՁՆՇՆԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՊԽՈՄՁԻԹՌԽԼՍՊՁՆԿՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչ Շ Ԡ ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌԼՁԾԾԽՊԽՆՌՁԹՄՋ ՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼ Շ ԠՈԥԪԽԹՋՍՊԽԼՏԽԽՃՄՑՁՆԽԹԻՀԻՀԹՅԺԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥՌՇԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ՅԿԩԪԽԹՋՍՊԽԼՏԽԽՃՄՑՁՆԽԹԻՀԻՀԹՅԺԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ԡԬ  ՅԿԩ
 ԹՁՊՋԹՌՍՊԹՌՁՇՆԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱՇՌԹՄԹՄՃԹՄՁՆՁՌՑ
ՅԿԩԹՋԠԹԠԬ ԪԽԹՋՍՊԽԼՁՆՇՆԽՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊՇԾՌՀԽԻՇՆՌՊՇՄԹՆԼՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՏԽԽՃՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՇՌԹՄԹՄՃԹՄՁՆՁՌՑ ՅԿԩԹՋ

ԠԹԠԬ ԥԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬԪԽԹՋՍՊԽԼՁՆՇՆԽՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊՇԾՌՀԽԻՇՆՌՊՇՄԹՆԼՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՏԽԽՃՄՑԱՇՌԹՄՇՊԿԹՆՁԻԻԹՊԺՇՆ
ՅԿԩԣՇՍՊՏԽԽՃՈԽՊՁՇԼՁՅՅԽԼՁԹՌԽՄՑՈՊՁՇՊՌՇՌՀԽՌԽՋՌ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՇՌԹՄՇՊԿԹՆՁԻԻԹՊԺՇՆՁՆ ԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ ՅԿԩԲՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹμԿԩ ԫՇՌԯԽՈՇՊՌԽԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՍՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹՁՆ ՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ  μ ԿԩԯԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽμԿԩ ԫՇՌԯԽՈՇՊՌԽԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽՁՆ ԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ μ ԿԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԪՁՆՁՅՍՅԪԹՐՁՅՍՅԪԽԹՆԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՈԽԻՁԾՁԻԠՇՆԼՍԻՌԹՆԻԽ
ս԰ԻՅ ԪԽԹՋՍՊԽԼՁՆՇՆԽՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊՇԾՌՀԽԻՇՆՌՊՇՄԹՆԼՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՏԽԽՃՄՑ ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑՇԾ ՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ՌԽՅՈԽՊԹՌՍՊԽՈԥԹՆԼԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆԺԽ ՅԽԹՋՍՊԽԼՁՆԹՄՄՌԽՋՌՌԹՆՃՋԹՌՄԽԹՋՌՏԽԽՃՄՑԹՆԼ ՌՀԹՌՀԹՊԼՆԽՋՋԹՆԼԹՄՃԹՄՁՆՁՌՑԺԽՅԽԹՋՍՊԽԼՁՆ ԻՇՆՌՊՇՄՋԹՆԼՁՆՇՆԽՌԹՆՃԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՄԽԹՋՌՏԽԽՃՄՑԦՆԹԼԼՁՌՁՇՆ ԻՇՆՌՁՆՍՇՍՋՌԽՅՈԽՊԹՌՍՊԽՅՇՆՁՌՇՊՁՆԿՇԾԹՌՄԽԹՋՌ ՇՆԽՌԹՆՃՁՋԽՆԻՇՍՊԹԿԽԼԡ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ!ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊՁԾ

ՀՇՍՊԩԠ  ԼԹՌԹԾՇՊՌՀԽԾԹՌՀԽԹԼՅՁՆՆՇՏԹՊԽ

ՍՆԹՎԹՁՄԹԺՄԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!ԟԹՋԽԼՇՆՌՀԽՊԽՈՇՊՌԽԼՏԹՌԽՊՋՇՄՍԺՁՄՁՌՑՇԾՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄ
ՅԿԩ"ոԠԹՆԼՌՀԽՊԽՈՇՊՌԽԼԩԠԾՇՊՊԹՁՆԺՇՏՌՊՇՍՌԹՆԼԺՄՍԽԿՁՄՄՏՀՁԻՀՊԹՆԿԽԼԾՊՇՅՅԿԩ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽՋԽՄԽԻՌԽԼԺԹՋԽԼՇՆՌՇՐՁԻՁՌՑԼԹՌԹԾՇՊ ՇՌՀԽՊԾՁՋՀՋՌՍԼՁԽՋՇՊՋՈԽԻՁԽՋՁԾԹՎԹՁՄԹԺՄԽ ԬՌՀԽՊՏՁՋԽԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽՌԽՋՌ ԻՇՅՈՇՍՆԼՇՊՅԿԩ
ՏՀՁԻՀԽՎԽՊՁՋՄՇՏԽՊՁՋ

ԹՈՈՊՇՈՊՁԹՌԽ԰ՈԽԻՁԽՋ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԩՁԾԽՋՌԹԿԽԞԼՍՄՌՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԹՆԿԽԾՁՆԼՁՆԿՌԽՋՌՋԺԽ ՈԽՊԾՇՊՅԽԼՏՁՌՀԾՁՋՀՇԾՋՁՅՁՄԹՊԹԿԽԹՆԼՋՁՒԽՌՇՌՀՇՋԽ ՌՀԹՌՏՇՍՄԼԺԽՍՌՁՄՁՒԽԼՁՆՌՀԽՌԽՋՌԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՀՇՍՊԽՐՈՇՋՍՊԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԱՀԽՌԽՋՌՏԹՋԻՇՆԼՍԻՌԽԼՏՁՌՀՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԹՆԼՅԿԹՁԩԫՇՅՇՊՌԹՄՁՌՁԽՋՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՀԽԻՇՆՌՊՇՄՋՇՊԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՅՇՊՌԹՄՁՌՑՁՆՌՀԽՅԿԹՁԩԿՊՇՍՈՏԹՋԩԽՌՀԹՊԿՑՋՍՊԾԹԻՁՆԿՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅԹՆԼՄՑՁՆԿՇՆՌՀԽԺՇՌՌՇՅՇԾՌՀԽԻՀԹՅԺԽՊՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՀՁՋԿՊՇՍՈԢԿԿՈՊՇԼՍԻՌՁՇՆՏԹՋՇԺՋԽՊՎԽԼԼՍՊՁՆԿՌՀԽԼԹՑՌԽՋՌՁՆՌՀԽԻՇՆՌՊՇՄՋԹՆԼԹՆԼՅԿԹՁԩԿՊՇՍՈՋԫՇԽԿԿՈՊՇԼՍԻՌՁՇՆՏԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽՅԿԹՁԩԿՊՇՍՈԹՆԼՇՆՄՑՇՆԽՋՈԹՏՆՏԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽՀՁԿՀԽՋՌԿՊՇՍՈԞԼԹՑԩԠՎԹՄՍԽՇԾՅԿԹՁԩՏԹՋԻԹՄԻՍՄԹՌԽԼԹՆԼԹՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՅԿԹՁԩՏԹՋՋԽՄԽԻՌԽԼԾՇՊՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊՏՁՌՀ ԾՁՎԽՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՈՄՍՋԹԻՇՆՌՊՇՄ
ՋՁՐՌՇՌԹՄ ՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՏՁՌՀԾՇՍՊԾԽՅԹՄԽՋԹՆԼՌՏՇՅԹՄԽՋ ՈԽՊԽՐՈՇՋՍՊԽՌԹՆՃ
ԾՁՋՀՌՇՌԹՄԱՀԽՆՍՅԺԽՊՇԾ ՅՇՊՌԹՄՁՌՁԽՋՌՀԹՌՇԻԻՍՊՅԹՑԺԽՍՋԽԼՌՇԼԽՎԽՄՇՈԹ ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԻՍՊՎԽ ԟԹՋԽԼՍՈՇՆՌՀԽՊԽՋՍՄՌՋՌՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ ՌՀԹՌԼՇԽՋՆՇՌՊԽՋՍՄՌՁՆՁՆԻՊԽԹՋԽԼՅՇՊՌԹՄՁՌՑՇՊՋՁԿՆՋ ՇԾՇՎԽՊՌՅՇՊԺՁԼՁՌՑԻՇՅՈԹՊԽԼՌՇԻՇՆՌՊՇՄՋՇՊՌՀԽ

ԼԽՊՁՎԽԼՀՊԩԠ  ՅԹՑԺԽՋԽՄԽԻՌԽԼԹՋՌՀԽՀՁԿՀԽՋՌ ԽՐՈՇՋՍՊԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԹՑՌԽՋՌԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՋՌԼՍՊԹՌՁՇՆԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԼՍՊԹՌՁՇՆՇԾՌՀԽԼԽԾՁՆՁՌՁՎԽ

ՌԽՋՌԺԽԼԹՑՋԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԯԹՆԿԽԾՁՆԼԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽՌԽՋՌ ԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋԹԼԽՉՍԹՌԽ ԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿՌՀԽՀՇՍՊԩԠ   ՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽԫԞ԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԢԭԞՋՍԿԿԽՋՌՋՌՀԹՌԹԻՇՆԻԽՆՌՊԹՌՁՇՆՋԽՈԹՊԹՌՁՇՆՇԾ ԺԽՌՏԽԽՆ
ՇՊՌՀՊԽԽԾՇՄԼԹՆԼ
ՇՊՌԽՆԾՇՄԼ ՁՋՋԻՁԽՆՌՁԾՁԻԹՄՄՑԹԻԻԽՈՌԹԺՄԽ  ԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌԻՇՆՌՊՇՄՁԾԹՈՈՊՇՈՊՁԹՌԽԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!ԶԽՋ ԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋԪԽԹՆՅԽԹՋՍՊԽԼ ԱՀԽՊԽՎՁԽՏԽՊԹՄՋՇԻԹՄԻՍՄԹՌԽԼՌՀԽՌՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽ
ԱԴԞԻՇՆԻԽՆՌՊԹՌՁՇՆՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿԹՁԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡԫՇՌՊԽՈՇՊՌԽԼԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԰ԹՅՈՄԽՋՏԽՊԽԻՇՄՄԽԻՌԽԼԾՇՊԹՆԹՄՑՋՁՋՇՆԡԹՑՋԹՆԼ ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽ ՅԽԹՋՍՊԽԼՈՊՁՇՊՌՇՌՀԽԹԼԼՁՌՁՇՆՇԾԾՁՋՀՁՆԹՄՄՌԹՆՃՋԹՆԼ ԹՌՄԽԹՋՌՏԽԽՃՄՑՌՀԽՊԽԹԾՌԽՊՁՆՌՏՇՊԽՈՄՁԻԹՌԽՋՈԽՊ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄԴԹՋՌՀԽՊԹՆԼՇՅՁՒԽԼԻՇՅՈՄԽՌԽԺՄՇԻՃԼԽՋՁԿՆՍՋԽԼ!ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹՄՄԾՁՋՀԺԽՊԹՆԼՇՅՄՑ ԹՋՋՁԿՆԽԼՌՇՌԹՆՃՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽԱԹՆՃՋԹՊԽ ՌՀԽՆՊԹՆՃԽԼԹԻԻՇՊԼՁՆԿՌՇՈՊԽԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑ ԹՆԼՌՀԽՌԹՆՃՋՏՁՌՀՌՀԽՀՁԿՀԽՋՌԾԽԻՍՆԼՁՌՑԹՊԽ ՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇԹԼԽԾՁՆՁՌՁՎԽՌԽՋՌՌՊԽԹՌՅԽՆՌԹՆԼ ԺՄՇԻՃԾՁՊՋՌԢԹԻՀԺՄՇԻՃԻՇՆՌԹՁՆՋՇՆԽՊԽՈՄՁԻԹՌԽՇԾ ԽԹԻՀՌՊԽԹՌՅԽՆՌՁՆԻՄՍԼՁՆԿԻՇՆՌՊՇՄՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽԫԞ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԻՇՆԻՍՊՊԽՆՌՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿԹԿԽՆՌՁՋՍՋԽԼԢԭԞ ՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽ ԫՍՅԺԽՊՇԾԾԽՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԽՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ!ԫՇ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽԫԞ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌԽՐԻԽԽԼ

ՅՄԩ ԬԢԠԡՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՇՄՎԽՆՌՀԹՎԽՆՇ ԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊՈՊՇԼՍԻԽԹՆՑՇՌՀԽՊԹԼՎԽՊՋԽ ԽԾԾԽԻՌՋԹՆԼՌՀԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆՆՇՌԺԽԿՊԽԹՌԽՊՌՀԹՆ

ՅՄԩ ԴԹՋԹՈՇՋՁՌՁՎԽԻՇՆՌՊՇՄՍՋԽԼ! ԫՇԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏԞՉՍԹՌՁԻԱՇՐՁԻՇՄՇԿՑՈՈ-ԬԢԠԡ
ԤՍՁԼԹՆԻԽԡՇԻՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋՇՆԱԽՋՌՁՆԿԹՆԼԞՋՋԽՋՋՅԽՆՌԫՇԭԹՊՁՋԣՊԹՆԻԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԭԹՊԹՅԽՌԽՊԳԹՄՍԽ
ՋԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄԻՇՆԻԽՆՌՊԹՌՁՇՆ
Ջ
ՁԾԹՈՈՄՁԻԹԺՄԽԫԞ ԭՀՇՌՇՈԽՊՁՇԼՀՊՋՄՁԿՀՌՀՊՋԼԹՊՃ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ
ՄՁԿՀՌԼԹՊՃԩՁԿՀՌՁՆՌԽՆՋՁՌՑԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ ՄՍՐ ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑ-ՄՍՐ
ԹՌ

ՏԹՌԽՊ0ՋՋՍՊԾԹԻԽԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋԫԞԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱՊԽԹՌՅԽՆՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԱՊԽԹՌՅԽՆՌԦԡԫՇՅՁՆԹՄԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԪԽԹՋՍՊԽԼԠՇՆԻԽՆՌՊԹՌՁՇՆՅԿԹՁԩԪԽԹՆԠԳ
ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄԩԬԮԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽ ՅԹՁՆՌԹՁՆԽԼԹՌԹԻՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ
ԠԳ ԱՊԽԹՌՅԽՆՌԱԴԞԱՊԽԹՌՅԽՆՌԱԴԞԱՊԽԹՌՅԽՆՌԱԴԞԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԢԬԺՋԽՊՎԹՌՁՇՆՋԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋ ԣԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՌՑՆՍՈՌՁԹՄՌՍԺԽՊԻՄԽՋԻՇՊԽՋԺՇԼՑՏԽՁԿՀՌՄԽՆԿՌՀԳԱԤԻՇՆԻԽՆՌՊԹՌՁՇՆՋԤ԰ԦԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ!ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՋՍՊՎՁՎԹՄԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄ ՁՒԹՌՁՇՆՋՍԻԻԽՋՋՋԽԻՇՆԼԹՊՑՋԽՐԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼՇՌՀԽՊԻՄՁՆՁ ԻԹՄՋՁԿՆՋՇԻԻՍՊԹՌՄԽԹՋՌԼԹՁՄՑԞՌՌԽՋՌ ՌԽՊՅՁՆԹՌՁՇՆ
ԡԹՑԹԼԼՁՌՁՇՆԹՄՇԺՋԽՊՎԹՌՁՇՆՋՁՆԻՄՍԼԽԺՇԼՑՏԽՁԿՀՌԹՆԼՄԽՆԿՌՀՆՍՈՌՁԹՄՌՍԺԽՊԻՄԽՋԻՇՊԽԿՇՆԹԼԹՄՋՌԹԿՁՆԿԹՆԼՀՁՋՌ ՇՈԹՌՀՇՄՇԿՑՈՄԹՋՅԹՎՁՌԽՄՄՇԿԽՆՁՆԹՆԼ

ՈՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋ
ՌԽՋՌՇՋՌԽՊՇՆԽԹՆԼȕ ԽՋՌՊԹԼՁՇՄՁԾՅԽԹՋՍՊԽԼԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
Ԥ԰ԦՁՋԻԹՄԻՍՄԹ ՌԽԼՍՋՁՆԿԹՊԹՌՁՇՇԾԿՇՆԹԼՏԽՁԿՀՌՌՇԺՇԼՑՏԽՁԿՀՌ
ԿՇՆԹԼ ՏԽՁԿՀՌՌՇՌՀԽՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌՁՆՅԿՐԹՌՌԽՋՌ ՌԽՊՅՁՆԹՌՁՇՆ ԠՄՁՆՁԻԹՄՋՁԿՆՋՇԾՇՎԽՊՌՌՇՐՁԻՁՌՑՅԹՑՁՆԻՄՍԼԽ
ԺՍՌԹՊԽՆՇՌՄՁՅՁՌ ԽԼՌՇՀԽՅՇՊՊՀԹԿԽԻԽՋՋԹՌՁՇՆՇԾԾԽԽԼՁՆԿԹՆԼՇՌՀԽՊԹԺՆՇՊՅԹՄԺԽՀԹՎՁՇՊԦԦԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫԞԯԽՋՍՄՌՋԪԽԹՆՅԹՄԽԹՆԼԾԽՅԹՄԽՋՍՊՎՁՎԹՄՏԽՊԽՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼԱԴԞԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ
ԱԹԺՄԽԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱԹԺՄԽԞԼՍՄՌԣՁՋՀ԰ՍՊՎՁՎԹՄՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ #ԱԴԞՅԽԹՋՍՊԽԼ%ԪԹՄԽՋԣԽՅԹՄԽՋՆ԰ՍՊՎՁՎՁՆԿ԰ՍՊՎՁՎԹՄՆ԰ՍՊՎՁՎՁՆԿ԰ՍՊՎՁՎԹՄԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮԩԬԮՅԿԹՁԩԟՑՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՌՀԽԿՊՇՍՈՅԽԹՆՋՇԾՅԹՄԽՄԽՆԿՌՀՊԹՆԿԽԼԾՊՇՅՌՇՅՅԹՆԼՌՀԽԿՊՇՍՈՅԽԹՆՋՇԾԾԽՅԹՄԽՄԽՆԿՌՀՊԹՆԿԽԼԾՊՇՅՌՇՅՅ
ԱԹԺՄԽԤՊՇՍՈՅԽԹՆՋԾՇՊՏԽՌՏԽՁԿՀՌՁՆՅԹՄԽՋՊԹՆԿԽԼԾՊՇՅԿՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌՇԿՁՆՌՀԽԱԴԞՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՏՀՁՄԽԾԽՅԹՄԽՏԽՁԿՀՌՊԹՆԿԽԼԾՊՇՅՌՇԿԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱԹԺՄԽ԰ՁՒԽԹՌԱԽՋՌԱԽՊՅՁՆԹՌՁՇՆՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԟՇԼՑԴԽՁԿՀՌԩԽՆԿՌՀԪԹՄԽՋԣԽՅԹՄԽՋԪԹՄԽՋԣԽՅԹՄԽՋՆԪԽԹՆԿչ԰ԡՆԪԽԹՆԿչ԰ԡՆԪԽԹՆՅՅչ԰ԡՆԪԽԹՆՅՅչ԰ԡԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄԩԬԮ                                          ԩԬԮՅԿԹՁԩ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԪԽԹՆԾԽԻՍՆԼՁՌՑՎԹՄՍԽՋՏԽՊԽԹՆԼԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎ ԽԼԹՑՁՆՌՀԽԱԴԞԹՆԼՅԿ

ԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑԥՇՏԽՎԽՊԾԽՊՌՁՄՁՒԹՌՁՇՆՋ ՍԻԻԽՋՋՏԹՋ  ՁՆԹՄՄԿՊՇՍՈՋԞՄՌՀՇՍԿՀ

ԾԽԻՍՆԼՁՌՑՁՆՌՀԽԻՇՆՌՊՇՄԿՊՇՍՈԽՐԻԽԽԼԽԼԽԿԿՋԾԽՅԹՄԽԼԹՑՁՆԽ ԹԻՀՇԾՌՀԽՊԽՈՄՁԻԹՌԽՋԽԹԻՀՊԽՈՄՁԻԹՌԽՁՆԻՄՍԼԽԼ

ՇՊԼԹՑՈԽՊՁՇԼՋՏՁՌՀՇՍՌՋՈԹՏՆՁՆԿ

ԱԹԺՄԽԣԽԻՍՆԼՁՌՑԹՆԼԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ  ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԣԽԻՍՆԼՁՌՑ  ԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋ
 

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ չ չ

 չ չ

 չ չ

 չ չ

 ԣԽԻՍՆԼՁՌՑՁՋԻԹՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋՈԽՊՋՍՊՎՁՎՁՆԿԾԽՅ ԹՄԽՈԽՊՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՈԽՊՊԽՈՄՁԻԹՌԽ

 ԣԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋ
ՁՋԻԹ ՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽՅԺՊ ՑՇՋԼՁՎՁԼԽԼԺՑՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋՅՍՄՌՁՈՄՁԽԼԺՑ

ԩԬԮՅԿԹՁԩ



### ԪԽԼՁԹՆՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՋՊԹՆԿԽԼԾՊՇՅԹՈՈՊՇՐՁՅԹՌԽՄՑՌՇ ԱԹԺՄԽԫՇՌՍԺԽՊԻՄԽՋՏԽՊԽՆՇՌԽԼՇՆ

ԾԽՅԹՄԽՋ

ԱԹԺՄԽԫՍՈՌՁԹՄԱՍԺԽՊԻՄԽ԰ԻՇՊԽՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆԱՍԺԽՊԻՄԽ

԰ԻՇՊԽ Ն ԪԽԼՁԹՆԱՍԺԽՊԻՄԽ

԰ԻՇՊԽ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ    

    

    

    

ԩԬԮՅԿԹՁԩ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԪԽԹՆՅԹՄԽԤ԰ԦՁՆԻՊԽԹՋԽԼԾՊՇՅՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌՇՁՆՌՀԽԱԴԞՅԿԹՁԩՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈ
ԱԹԺՄԽ԰ՁՅՁՄԹՊՄՑՅԽԹՆԾԽՅԹՄԽԤ԰ԦՁՆԻՊԽԹՋԽԼԾՊՇՅ ՁՆՌՀԽԻՇՆՌՊՇՄՌՇԹՌՌՀԽՀՁԿՀԽՋՌ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԱԹԺՄԽԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐ
Ԥ԰ԦՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԹՆԤ԰Ԧ 

 չ԰ԡ Ն ԪԽԹՆԤ԰Ԧ 

 չ԰ԡ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ      

      

      

      

 ԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
ՁՋԻԹՄԻՍՄԹՌԽԼԹՋԿՇՆԹԼՏԽՁԿՀՌ
ՌՇՌՀԽ ՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌ
ՅԿՐ

ԩԬԮՅԿԹՁԩ



### ԪԽԼՁԹՆՅԹՄԽԿՇՆԹԼԹՄՋՌԹԿԽՊԹՆԿԽԼԾՊՇՅՌՇԹՆԼՏԹՋԻՇՅՈԹՊ ԹԺՄԽԺԽՌՏԽԽՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈՋ
ԱԹԺՄԽԠՇՆՎԽՊՋԽՄՑՅԽԼՁԹՆԾԽՅԹՄԽԿՇՆԹԼՋՌԹԿԽՁՆԻՊԽԹՋԽԼԾՊՇՅՁՆՌՀԽԻՇՆՌՊՇՄՌՇՁՆՌՀԽ

ՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԱԹԺՄԽԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆ԰ՌԹԿԽ  Ն ԪԽԼՁԹՆ԰ՌԹԿԽ 

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ    

    

    

    

 ԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼՋՌՀԽԾՇՄՄՇՏՁՆԿԿՇՆԹԼԹՄՋՌԹԿՁՆԿՋԻԹՄԽ ԾՇՊՅԹՄԽԾԹՌՀԽԹԼՅՁՆՆՇՏՍՆԼԽՎԽՄՇՈԽԼԽԹՊՄՑ

ՋՈԽՊՅԹՌՇԿԽՆՁԻՅՁԼՋՈԽՊՅԹՌՇԿԽՆՁԻՄԹՌԽՋՈԽՊՅԹՌՇԿԽՆՁԻՋՈԽ ՆՌ

 ԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼՋՌՀԽԾՇՄՄՇՏՁՆԿԿՇՆԹԼԹՄՋՌԹԿՁՆԿՋԻԹՄԽ ԾՇՊԾԽՅԹՄԽԾԹՌՀԽԹԼՅՁՆՆՇՏՍՆԼԽՎԽՄՇՈԽԼԽԹՊՄՑ

ԼԽՎԽՄՇՈՅԽՆՌՅՁԼԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՀՑԼՊԹՌԽԼՈՇՋՌՇՎՍՄԹՌՇՊՑ

ԩԬԮՅԿԹՁԩ



### ԱԽՋՌԽՋՋՀՇՏԽԼՆՇՀՁՋՌՇՄՇԿՁԻԹՄՄՑԽՎՁԼԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՄԹՌԽԼԻՀԹՆԿԽՋՁՆՌՀԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՄԹՌՁՎԽՌՇՌՀԽ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌՀՇՍԿՀՅՁՆՁՅԹՄԿՊԹՆՍՄՇՅԹՌՇՍՋՁՆԾՄԹՅՅԹՌՁՇՆՏԹՋ ՇԺՋԽՊՎԽԼՁՆԾՁՋՀՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ԱԹԺՄԽՋԹՆԼԱՀԽՊԽՏԽՊԽՆՇՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՁՆ ՇՎԹՊՁԽՋՁՆՌՀԽՄՇՏԹՆԼՅՁԼԻՇՆԻԽՆՌՊԹՌՁՇՆ

ՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՇԾԹՋՄՁԿՀՌՍՈՏԹՊԼՋՀՁԾՌՁՆՌՀԽՅԽԼՁԹՆ

ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՇԾՌՀԽՇՎԹՊՁԽՋՁՆՌՀԽՅՁԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈ ԱԹԺՄԽՋԹՆԼԥՁԿՀՋԽՎԽՊՁՌՑՋԻՇՊԽՋԾՇՊ

ԼԽԻՊԽԹՋԽԼՈՇՋՌՇՎՍՄԹՌՇՊՑԾՇՄՄՁԻՄԽՋՏԽՊԽԹՄՋՇՇԺՋԽՊՎԽԼՁՆՌՀՁՋՌ ՊԽԹՌՅԽՆՌԿՊՇՍՈՏՀՁԻՀԹՊԽԹՆՇՊՅԹՄՇԻԻՍՊՊԽՆԻԽ

ՁՆՋՌԹԿԽԹՆԼՇՎԹՊՁԽՋԱՀԽՊԽԾՇՊԽԼՁԾԾԽՊԽՆԻԽՋԾՊՇՅՌՀԽԻՇՆՌՊ ՇՄՏԽՊԽԹՌՌՊՁԺՍՌԽԼՌՇԹԿՊԽԹՌԽՊՆՍՅԺԽՊՇԾՇՎԹՊՁԽՋ

ՁՆՌՀՁՋԿՊՇՍՈԹՌՋՌԹԿԽԹՆԼԱՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՏԽՊԽՆՇՌԽԼՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՏՁՌՀԹ

ՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՁՆԻՊԽԹՋԽՁՆԾԽՅԹՄԽԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽԱՀԽՊԽԹՄՋՇՏԹՋԹՆՁՆԻՊԽԹՋԽՁՆՋԽՎԽՊԽՇՇԻՑՌԽ

ԹՌՊԽՋՁԹՁՆՇԾՌՀԽԾՁՋՀԹՌՌՀՁՋՄԽՎԽՄԻՇՅՈԹՊԽԼՌՇՇՆՄՑՇԾՁՆՌՀԽԻՇՆՌՊՇՄԣՍՊՌՀԽՊՌՀԽՊԽՏԹՋԹՋՁԿՆՁԾՁԻԹՆՌ

ՁՆԻՊԽԹՋԽՁՆՌՀԽՆՍՅԺԽՊՇԾՋԽՎԽՊԽՈՇՋՌԹՌՊԽՌՁԻԾՇՄՄՁԻՄԽՋԱՀԽՋԽ ՁՆԻՊԽԹՋԽՋՁՆԼՁԻԹՌԽՌՀԹՌՌՀԽՆՍՅԺԽՊՇԾՎՁԹԺՄԽ

ՋՈԹՏՆԽԼՇՇԻՑՌԽՋՈՊՇԼՍԻԽԼԺՑՌՀԽՋԽՇՎԹՊՁԽՋՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑԼՁՅ ՁՆՁՋՀԽԼՏՀՁԻՀՏԹՋԻՇՆԾՁՊՅԽԼԺՑՄՇՏ

ԾԽԻՍՆԼՁՌՑԱՀԽՊԽՏԹՋԹՄՋՇԹՋՁԿՆՁԾՁԻԹՆՌՁՆԻՊԽԹՋԽՁՆՁՆՌՊԹՎԹՋԻՍՄ ԹՊՁՆՌԽՊՋՌՁՌՁԹՄՈՊՇՌԽՁՆԹԻԽՇՍՋԾՄՍՁԼՋԽԽՆՁՆՇԾՌՀԽ

ԾԽՅԹՄԽՋԹՌՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ 

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ 

԰ԽՎԽՊՁՌՑ ԦՆԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ ԭՊԽՋԽՆԻԽՇԾ

ԱԽՋՌՁՋԬՎԹ ԦՆԻՊԽԹՋԽԼ

ԱԽՋՌՁԻՍՄԹՊ

ԡԽԿԽՆԽՊԹՌՁՇՆ ԦՆՌԽՊՋՌՁՌՁԹՄԠԽՄՄ

ԥՑՈԽՊՌՊՇՈՀՑ

ԥՑՈԽՊՈՄԹՋՁԹ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԩԬԮ         

        

        

        

        

         

        

        

        

        

         

        

        

        

        

         

        

        

        

        

  ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ- ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼ

ԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊ ՊԽԾԽՊԽՆԻԽ

ԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌ ՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԡԽԻՊԽԹՋԽԼԭՊՇՈՇՊՌՁՇՆՇԾ԰ՈԽՊՅԹՌՇԿՇՆՁԹԦՆԻՊԽԹՋԽԼԳԹՋԻՍՄԹՊՇՊԦՆՌԽՊՋՌՁՌՁԹՄԭՊՇՌԽՁՆԹԻԽՇՍՋԣՄՍՁԼԞՋՑՆԻՀՊՇՆՇՍՋԤՇՆԹԼԡԽՎԽՄՇՈՅԽՆՌԞՄՌԽՊԽԼԭՊՇՈՇՊՌՁՇՆՋՇԾ԰ՈԽՊՅԹՌՇԻՑՌԽՋՇՊ԰ՈԽՊՅԹՌՁԼՋԤՊԹՆՍՄՇՅԹՌՇՍՋԦՆԾՄԹՅՅԹՌՁՇՆՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ                                                                                                                                                       ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱՊԽԹՌՅԽՆՌ ՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ԰ԽՎԽՊՁՌՑԡԽԻՊԽԹՋԽԼԭՊՇՈՇՊՌՁՇՆՇԾ԰ՈԽՊՅԹՌՇԿՇՆՁԹԦՆԻՊԽԹՋԽԼԳԹՋԻՍՄԹՊՇՊԦՆՌԽՊՋՌՁՌՁԹՄԭՊՇՌԽՁՆԹԻԽՇՍՋԣՄՍՁԼԞՋՑՆԻՀՊՇՆՇՍՋԤՇՆԹԼԡԽՎԽՄՇՈՅԽՆՌԞՄՌԽՊԽԼԭՊՇՈՇՊՌՁՇՆՋՇԾ԰ՈԽՊՅԹՌՇԻՑՌԽՋՇՊ԰ՈԽՊՅԹՌՁԼՋԤՊԹՆՍՄՇՅԹՌՇՍՋԦՆԾՄԹՅՅԹՌՁՇՆՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽՆԦՆԻՁԼԽՆԻԽ                                                   ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽԩԬԮՅԿԹՁԩ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ 

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ 

԰ԽՎԽՊՁՌՑ ԦՆԻՊԽԹՋԽԼԬՇԻՑՌԽ

ԞՌՊԽՋՁԹ ԭԽՊՁԾՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

ԥՑՈԽՊՌՊՇՈՀՑ ԡԽԻՊԽԹՋԽԼԶՇՄՃ

ԣՇՊՅԹՌՁՇՆ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ       

      

      

      

      

       

      

      

      

      

       

      

      

      

      

       

      

      

      

      

  ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ- ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼ

ԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊ ՊԽԾԽՊԽՆԻԽ

ԩԬԮՅԿԹՁԩ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԣԽՅ ԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋ

ՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ 

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋ ՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ 

԰ԽՎԽՊՁՌՑ ԦՆՌԽՊՋՌՁՌՁԹՄ

ԣՁԺՊՇՋՁՋ ԢԿԿԡԽԺՊՁՋՁՆ

ԬՎՁԼՍԻՌ ԤՊԹՆՍՄՇՅԹՌՇՍՋ

ԦՆԾՄԹՅՅԹՌՁՇՆ ԡԽԻՊԽԹՋԽԼ

ԭՇՋՌԬՎՍՄԹՌՇՊՑ

ԣՇՄՄՁԻՄԽՋ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ

ԩԬԮ         

        

        

        

        

         

        

        

        

        

         

        

        

        

        

         

        

        

        

        

  ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ- ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼ

ԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊ ՊԽԾԽՊԽՆԻԽ

ԩԬԮՅԿԹՁԩ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԪԽԹՆՅԹՄԽԹՆԼԾԽՅԹՄԽԳԱԤԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՀՁԿՀՄՑՎԹՊՁԹԺՄԽԹՆ ԼՏԽՊԽԻՇՅՈԹՊԹԺՄԽԺԽՌՏԽԽՆՌՀԽԻՇՆՌՊՇՄ

ԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ
ԱԹԺՄԽ

ԱԹԺՄԽԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ 

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆ
ԳԱԤ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԹՆ

ՆԿՅԩՈՄԹՋՅԹ չ԰ԡ Ն ԪԽԹՆ

ՆԿՅԩՈՄԹՋՅԹ չ԰ԡ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ     Ր   Ր 

     Ր   Ր 

     Ր   Ր 

     Ր   Ր 

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ ԫԡ ԫՇՌԼԽՌԽՊՅՁՆԽԼ ԰ԡ ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

ԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾ ԱԹԺՄԽԭՄԹՋՅԹ԰ԽՐ԰ՌԽՊՇՁԼՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ  ԫՇՌՅԽԹՋՍՊԽԼԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԭՄԹՋՅԹԱԽՋՌՇՋՌԽՊՇՆԽ
ԱԭՄԹՋՅԹȕԽՋՌՊԹԼՁՇՄ
ԢԪԹՄԽՋԣԽՅԹՄԽՋԪԹՄԽՋԣԽՅԹՄԽՋՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡՆԪԽԹՆՆԿՅԩՈՄԹՋՅԹչ԰ԡԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ  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 ԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԞՄՄԾՁՋՀԹՈՈԽԹՊԽԼՆՇՊՅԹՄԹՆԼՀԽԹՄՌՀՑՌՀՊՇՍԿՀՇՍՌՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՇԾՌՏՇԾԽՅԹՄԽՋՏՀՇԹՈՈԽԹՊԽԼՌՇԺԽԽԿԿԺՇՍՆԼՁՆՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈ
ԱԹԺՄԽԬՆԽԾԽՅԹՄԽՏԹՋՇԺՋԽՊՎԽԼՌՇԺԽԽԿԿԺՇՍՆԼԾՊՇՅԡԹՑՋՌՇՏՀՁՄԽՌՀԽՇՌՀԽՊԾԽՅԹՄԽՏԹՋՇԺՋԽՊՎԽԼՌՇԺԽԽԿԿԺՇՍՆԼՇՆԡԹՑՋԹՆԼԱԹԺՄԽ԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋԪԹՄԽՋԣԽՅԹՄԽՋԱՑՈԽՆԦՆԻՁԼԽՆԻԽԱՑՈԽՆԦՆԻՁԼԽՆԻԽԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮԫՇՆԽ ԫՇՆԽ ԫՇՆԽ ԫՇՆԽ ԫՇՆԽ ԫՇՆԽ ԫՇՆԽ ԫՇՆԽԢԿԿԺՇՍՆԼԩԬԮՅԿԹՁԩ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԟ ԰ՌՍԼՑԞՍՌՀՇՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋՏԽՊԽՈԽՊԾՇՊՅԽԼՇՆՋՍՊՎՁՎԹՄՏԽՌՏԽՁԿՀՌՌՇ ՌԹՄՄԽՆԿՌՀԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՌՑԤ԰ԦՈՄԹՋՅԹ

ԳԱԤԻՇՆԻԽՆՌՊԹՌՁՇՆՋՌՍԺԽՊԻՄԽՋԻՇՊԽՋՁՆԻՁԼԽՆԻԽԹՆԼՋԽՎԽՊՁՌՑՇԾ ԿՇՆԹԼԹԺՆՇՊՅԹՄՁՌՁԽՋԹՆԼԿՇՆԹԼ

ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽԪԽԹՋՍՊԽՅԽՆՌՋՇԾԳԱԤԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՊԽՁՆՀ ԽՊԽՆՌՄՑՎԹՊՁԹԺՄԽԹՆԼԺՇՐՈՄՇՌՋՇԾՄՇԿ

ՌՊԹՆՋԾՇՊՅԽԼԳԱԤՎԹՄՍԽՋՏԽՊԽՍՋԽԼՌՇՁԼԽՆՌՁԾՑՈՇՌԽՆՌՁԹՄՇՍՌՄՁԽՊՋ 
ԱՍՃԽՑ0ՋՅԽՌՀՇԼԫՇՇՍՌՄՁԽՊՋՏԽՊԽ

ԽՐԻՄՍԼԽԼԾՊՇՅԹՆԹՄՑՋԽՋՁՆՌՀՁՋՋՌՍԼՑԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՆՇՌԽԼՌ ՀԽՍՆՁՌՇԾՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋՁՋՏԹՋՌՀԽ

ՊԽՈՄՁԻԹՌԽՌԽՋՌԻՀԹՅԺԽՊԪԹՄԽՋԹՆԼԾԽՅԹՄԽՋՏԽՊԽԹՆԹՄՑՒԽԼՋԽՈԹՊԹՌ ԽՄՑԾՇՊԽԹԻՀԽՆԼՈՇՁՆՌՏՀԽՆԹՈՈՊՇՈՊՁԹՌԽ

ԞՄՄԽՆԼՈՇՁՆՌՋՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՏՇԻՇՅՈՄԽՅԽՆՌԹՊՑՋՌԹՌՁՋՌՁԻԹՄ ԹՈՈՊՇԹԻՀԽՋԦԾՊԽՋՈՇՆՋԽՋԹՈՈԽԹՊԽԼՌՇ

ԺԽՅՇՆՇՌՇՆՁԻԹՋՌԽՈԼՇՏՆԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌՏԹՋՍՋԽԼՌՇԽՎԹՄՍԹՌԽՈՇՋՋՁԺՄԽՌՊԽՆԼՋՁՆՌՀԽ

ՊԹՆՃՋՇԾՊԽՈՄՁԻԹՌԽՅԽԹՆՋՌՇԼԽՌԽՊՅՁՆԽԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋՁՎԽ ՌՊԽՆԼՋԹՅՇՆԿՌՀԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԞՄՄ

ԽՆԼՈՇՁՆՌՋԽՐԻԽՈՌԾՇՊՋՍՊՎՁՎԹՄԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՋԽՎԽՊՁՌՑՋԻՇՊԽՋԹՆԼՋՌԹԿԽՋԹՄՋՇՏԽՊԽԹՆԹՄՑՒԽԼԺՑ

ՈԽՊԾՇՊՅՁՆԿՈԹՁՊՏՁՋԽԻՇՅՈԹՊՁՋՇՆՋՍՋՁՆԿԡՍՆՆԽՌՌ0ՋՅՍՄՌՁՈՄԽԻՇՅՈԹ ՊՁՋՇՆՌԽՋՌՌՇԼԽՌԽՊՅՁՆԽՏՀՁԻՀՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈՋԼՁԾԾԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑԾՊՇՅՌՀԽԻՇՆՌՊՇՄԡԹՌԹԾՇՊԽՆԼՈՇՁ ՆՌՋԹՆԹՄՑՒԽԼԺՑԡՍՆՆԽՌՌ0ՋՌԽՋՌՏԽՊԽԾՁՊՋՌ

ԽՎԹՄՍԹՌԽԼԾՇՊՆՇՊՅԹՄՁՌՑՍՋՁՆԿ԰ՀԹՈՁՊՇԴՁՄՃ0ՋՌԽՋՌԹՆԼԾՇՊՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՍՋՁՆԿԩԽՎԽՆԽ0ՋՌԽՋՌ

Į ԞՄՄԼԹՌԹՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՇԾԳԱԤԾՇՊՌՀՁՋՋՌՍԼՑՈԹՋՋԽԼՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՆՇՊՅԹՄՁՌՑԹՆԼ

ՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽԱՀԽԳԱԤԼԹՌԹՏԽՊԽՄՇԿՌՊԹՆՋԾՇՊՅԽԼԹՆԼ ՈԹՋՋԽԼՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՆՇՊՅԹՄՁՌՑ

ԹՆԼՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽ

԰ՍՊՎՁՎԹՄԼԹՌԹԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՋԽՎԽՊՁՌՑՋԻՇՊԽՋԹՆԼՋՌԹԿԽՋՏԽՊ ԽՆՇՌԹՅԽՆԹԺՄԽՌՇՌՀԽՋՌԹՌՁՋՌՁԻԹՄՅԽՌՀՇԼՋ

ՍՋԽԼԾՇՊԹՆԹՄՑՋՁՋՇԾՇՌՀԽՊԽՆԼՈՇՁՆՌՋԦՆՈԹՊՌՁԻՍՄԹՊՌՀԽՅՇՋՌՋՍՁՌԹԺՄԽՍՆՁՌՇԾՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋՁՋԾՇՊՌՀԽՋԽ

ԽՆԼՈՇՁՆՌՋՏԹՋՌՀԽՁՆԼՁՎՁԼՍԹՄԹՆՁՅԹՄԱՀԽՊԽԾՇՊԽՋՍՊՎՁՎԹՄՏԹՋԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՋՌԽՈԼՇՏՆ

ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌԹՆԼԣՁՋՀԽՊՋԢՐԹԻՌԱԽՋՌԥՁՋՌՇՈԹՌ ՀՇՄՇԿՑՋԽՎԽՊՁՌՑՋԻՇՊԽՋԹՆԼՋՌԹԿԽՋՇԾ

ՁՆԼՁՎՁԼՍԹՄՋՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՋՌԽՈԼՇՏՆԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌ ՊԹՌՊԽՆԼՌԽՋՌ

ԞՄՄԹՆԹՄՑՋԽՋՍՆՄԽՋՋՇՌՀԽՊՏՁՋԽՆՇՌԽԼՏԽՊԽԻՇՆԼՍԻՌԽԼԹՌ Į ՏՁՌՀ԰Ԟ԰ՋՇԾՌՏԹՊԽ

ԱՀԽՋՌՍԼՑԹՍՌՀՇՊՋՊԽՈՇՊՌԽԼՆՇՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՇՆԹՆՑ ԽՆԼՈՇՁՆՌՁՆՄՇՏԹՆԼՅՁԼԻՇՆԻԽՆՌՊԹՌՁՇՆ

ՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԦՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՌՀԽՊԽՏԹՋԹԼԽԻՊԽԹՋԽՁՆ

ԾԽԻՍՆԼՁՌՑԹՆՁՆԻՊԽԹՋԽՁՆԾԽՅԹՄԽՏԽՌՏԽՁԿՀՌԹՆԼԹՆՁՆԻՊԽԹՋԽՁՆ ՅԹՄԽԹՆԼԾԽՅԹՄԽԤ԰ԦԥՁՋՌՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋ

ՁՆՌՀԽՇՎԹՊՁԽՋՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՁՆԻՄՍԼԽԼԹՆՁՆԻՊԽԹՋԽ ՁՆՌՀԽՅԽԼՁԹՆԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՀՁԿՀԽՊ

ՋԽՎԽՊՁՌՑՋԻՇՊԽՋԾՇՊԼԽԻՊԽԹՋԽԼՈՇՋՌՇՎՍՄԹՌՇՊՑԾՇՄՄՁԻՄԽՋՁՆԻՊԽԹՋ ԽԼՇՇԻՑՌԽԹՌՊԽՋՁԹՁՆԻՊԽԹՋԽԼՆՍՅԺԽՊՇԾ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ՈՇՋՌԹՌՊԽՌՁԻԾՇՄՄՁԻՄԽՋԹՆԼՁՆԻՊԽԹՋԽՁՆՁՆՌՊԹՎԹՋԻՍՄԹՊՁՆՌԽՊՋՌՁՌՁ ԹՄՈՊՇՌԽՁՆԹԻԽՇՍՋԾՄՍՁԼԱՀԽՋՌՍԼՑԹՍՌՀՇՊՋ

ՋՍԿԿԽՋՌՌՀԹՌՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋԹՆԼՁՆԻՊԽԹՋԽԼԤ԰ԦՁ ՆԾԽՅԹՄԽԾՁՋՀԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԹՊԽԻՇՆՋՁՋՌԽՆՌՏՁՌՀՌՀԽՊԽԼՍԻԽԼԾԽԻՍՆԼՁՌՑՇԺՋԽՊՎԽԼԹՌՌՀՁՋՄԽՎԽՄԹՆԼԹՊԽՄՁՃԽՄՑԼՍԽՌՇԿԽՆԽՊԹՄՌՇՐՁԻՁՌՑՊԹՌՀԽՊ

ՌՀԹՆՌՇԹՆԽՆԼՇԻՊՁՆԽԽԾԾԽԻՌ

Ԡ ԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋ ԣԽՅԹՄԽԹՆԼՅԹՄԽԺՇԼՑՏԽՁԿՀՌԾԽՅԹՄԽԹՆԼՅԹՄԽԤ԰ԦԹՆԼԾԽՅԹՄԽԳ ԱԤԽՐՀՁԺՁՌԽԼ

ՅՇՆՇՌՇՆՁԻՌՊԽՆԼՋԹՆԼՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌ
ՇՆԽՋՁԼԽԼ

ԼՁՊԽԻՌՁՇՆԹՄՄՑԼԽՈԽՆԼԽՆՌՇՆՌՀԽՊԽՋՈՇՆՋԽԣԽՅԹՄԽԹՆԼՅԹՄԽՄԽՆԿՌ ՀԾԽՊՌՁՄՁՌՑԾԽԻՍՆԼՁՌՑՅԹՄԽՌՍԺԽՊԻՄԽ

ՋԻՇՊԽՋԹՆԼՅԹՄԽԳԱԤԼՁԼՆՇՌԽՐՀՁԺՁՌՅՇՆՇՌՇՆՁԻՌՊԽՆԼՋԹՆԼՏԽՊԽԹՆԹՄՑՒԽԼԾՇՊՆՇՊՅԹՄՁՌՑ
԰ՀԹՈՁՊՇԴՁՄՃ0Ջ

Į ԹՆԼՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽ
ԟԹՊՌՄԽՌՌ0Ջ Į ԞՄՄԽՐԻԽՈՌՅԹՄԽԳԱԤՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋ

ՇԾԞԫԬԳԞԹՆԼՏԽՊԽՌՀԽՊԽԾՇՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿԡՍՆՆԽՌՌ0ՋՅՍՄՌՁՈՄԽԻ ՇՅՈԹՊՁՋՇՆՌԽՋՌԪԹՄԽԳԱԤՏԹՋԹՆԹՄՑՒԽԼ

ՍՋՁՆԿՌՀԽԪԹՆՆԴՀՁՌՆԽՑԲԱՏՇ԰ԹՅՈՄԽՌԽՋՌԞՄՄԹՆԹՄՑՋԽՋՏԽՊԽԻՇՆ ԼՍԻՌԽԼՍՋՁՆԿԠԢԱԦ԰ՎՏՁՌՀ

ԺԹԻՃԽՆԼԼԹՌԹԺԹՋԽՋԽՌՌՁՆԿՋՁՅՈՄԽՅԽՆՌԽԼԺՑԢԣԢԡՇՆԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋՏԽՊԽ

ԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌ Ո 

ԠՇՆԻՄՍՋՁՇՆՋ ԱՀԽՊԽՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՁՆԻՊԽԹՋԽՋՁՆԾԽՅԹՄԽԺՇԼՑՏԽՁԿՀՌ
Ձ ՆԻՊԽԹՋԽ

ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ Ո ԹՆԼԾԽՅԹՄԽԤ԰Ԧ
ՁՆԻՊԽԹՋԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ Ո ՁՆՌՀԽ

ՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԪԹՄԽԤ԰Ԧ ՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՁՆԻՊԽԹՋԽԼԾՊՇՅՌՀԽ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՌՌՀԽՅՁԼԹՆԼՀՁԿՀՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ  ՁՆԻՊԽԹՋԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ Ո  

ԣԽԻՍՆԼՁՌՑՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄ ՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ


ՊԽԼՍԻՌՁՇՆԡՍՆՆԽՌՌ0Ջ Ո ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԭԠԫԟԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԱՍԺԽՊԻՄԽ԰ԻՇՊԽԤ԰ԦԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿԹՆԼԥՁՋՌՇԭՄԹՋՅԹԳԱԤԭՄԹՋՅԹԱԭՄԹՋՅԹԢԪԽԼՁԹՆ ՈԡՁԾԾ ՈԢԾԾԽԻՌ!ԶԽՋԫՇԡՁԾԾ ՈԡՁԾԾ ՈԡՁԾԾ ՈԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄԩԬԮ ԫԞ  ԫԞԫՇ ԫԞԫԞ ԫԞ ԫԞ ԫԞ    ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ  ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ  ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌԡՍՆՆԽՌ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԫԞ ԪԹՆՆԴՀՁՌՆԽՑԲԫԞԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՆԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌ Ո ԞՄՌՀՇՍԿՀԹՆՇՆՈԹՊԹՅԽՌՊՁԻՌԽՋՌՏՇՍՄԼԺԽԹՈՈՊՇՈՊՁԹՌԽՌՇԹՋՋԽՋՋՅԽԼՁԹՆՎԹՄՍԽՋԾՇՊՌՍԺԽՊԻՄԽՋԻՇՊԽՁՆՌՀՁՋԻԹՋԽՁՌՏՇՍՄԼՆՇՌԺԽԽՐՈԽԻՌԽԼՌՇՑՁԽՄԼԼՁԾԾԽՊԽՆՌՇՎԽՊԹՄՄԻՇՆԻՄՍՋՁՇՆՋԹՋԻՇՅՈԹՊԽԼՌՇԡՍՆՆԽՌՌ0ՋՌԽՋՌԩԬԮՅԿԹՁԩԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭԠԫԟԢԭԞԪԯԦԡԫՍՅԺԽՊԭԹԿԽοԾԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԭԠԫԟԱՊԽԹՌՅԽՆՌՅԿԹՁԩ#ԱԴԞՅԽԹՋՍՊԽԼ%ԣԽԻՍՆԼՁՌՑԣԽՊՌ԰ՍԻԻԽՋՋԱՍԺԽՊԻՄԽ԰ԻՇՊԽԤ԰ԦԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿԹՆԼԥՁՋՌՇԭՄԹՋՅԹԳԱԤԭՄԹՋՅԹԱԭՄԹՋՅԹԢԡՁԾԾ ՈԡՁԾԾ ՈԪԽԼՁԹՆ ՈԡՁԾԾ ՈԢԾԾԽԻՌ!
ԶԽՋԫՇԡՁԾԾ ՈԡՁԾԾ ՈԡՁԾԾ ՈԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄԩԬԮ ԫԞ  ԫԞ ԫԞԫԞ ԫԞԫՇ ԫԞ ԫԞԫԞԫԞԫԞ     ԫԞԫԞ ԫՇ  ԫԞԫԞԫԞԫԞ    ԫԞԫԞ ԫՇ  ԫԞԫԞԫԞԫԞ  ԫԞԫԞ ԶԽՋ  ԫԞԫԞԫԞԫԞ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԡՍՆՆԽՌՌ ԡՍՆՆԽՌՌԫԞ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԫԞԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԫԞԫԞԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՆԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌ ՈԩԬԮՅԿԹՁԩ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋ  

### ՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԣ԰ԱԯԞՏՁՌՀԭԠԫԟ

ԱՊԽԹՌՅԽՆՌ

ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ% ԟՇԼՑԴԽՁԿՀՌ ԩԽՆԿՌՀ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ ԪԹՄԽՋ ԣԽՅԹՄԽՋ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

        

        

        

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԡՍՆՆԽՌ Ռ ԡՍՆՆԽՌՌ

ԞԺԺՊԽՎՁԹՌՁՇՆՋ ԡՁԾԾ ԡՁԾԾԽՊԽՆԻԽ ԫԞ ԫՇՌԹՈՈՄՁԻԹԺՄԽ

  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽՊԽՈՇՊՌ ԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊ

ԻՇՆՌՊՇՄ

  ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌ Ո 

ԩԬԮՅԿԹՁԩ



### ԡ ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

ԞՄՌՀՇՍԿՀՌՀԽՊԽՏԽՊԽՅՁՆՇՊԼԽՎՁԹՌՁՇՆՋԾՊՇՅՌՀԽԿՍՁԼԽՄՁՆԽԹՋՆՇՌ ԽԼՁՆՌՀԽԪԹՌԽՊՁԹՄՋԹՆԼԪԽՌՀՇԼՋՋԽԻՌՁՇՆՇԾՌՀԽ

ԡԢԯՌՀԽՋՌՍԼՑՅԽՌԹՄՄՎԹՄՁԼՁՌՑԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԱՀԽԼ ԽՎՁԹՌՁՇՆՋՆՇՌԽԼԼՁԼՆՇՌՁՅՈԹԻՌՌՀԽԹԺՁՄՁՌՑՌՇ

ՁՆՌԽՊՈՊԽՌՌՀԽՊԽՋՍՄՌՋՇԾՌՀՁՋՋՌՍԼՑ

Ԣ ԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋ

ԱՀԽՊԽՎՁԽՏԽՊ0ՋՊԽՋՍՄՌՋՏԽՊԽԺԹՋԽԼՇՆՌՀԽՌՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽ ԱԴԞԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏՀԽՊԽԹՋՌՀԽՋՌՍԼՑ

ԹՍՌՀՇՊՋՊԽՈՇՊՌԽԼՊԽՋՍՄՌՋԺԹՋԽԼՇՆՅԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԱՀԽՊԽԾՇՊԽՌՀԽՊԽՎՁԽՏԽՊ0ՋՊԽՋՍՄՌՋԹՊԽ

ՊԽՈՇՊՌԽԼՁՆՌՀԽԢՐԽԻՍՌՁՎԽ԰ՍՅՅԹՊՑՋԽԻՌՁՇՆՇԾՌՀՁՋԡԢԯԱՀԽՊԽՎՁ ԽՏԽՊ0ՋԻՇՆԻՄՍՋՁՇՆՊԽԿԹՊԼՁՆԿՅԹՄԽԤ԰ԦՏԹՋ

ՅՇՊԽՋԽՆՋՁՌՁՎԽՌՀԹՆՌՀԽՋՌՍԼՑԹՍՌՀՇՊ0ՋԺԽԻԹՍՋԽՌՀԽՊԽՎՁԽՏԽՊՊԽՄՁԽԼՇՆՌՀԽՊԽՋՍՄՌՇԾՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ

ՌԽՋՌԿՁՎԽՆՌՀԽՅՇՆՇՌՇՆՁԻՁՆԻՊԽԹՋԽԽՐՀՁԺՁՌԽԼԺՑՌՀԽՅԽԼՁԹՆՎԹՄՍ ԽՋԬՌՀԽՊՌՀԹՆՌՀՁՋԼՁԾԾԽՊԽՆԻԽՌՀԽՋՌԹՌՁՋՌՁԻԹՄ

ՊԽՋՍՄՌՋՇԾԾԽՊԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋՁՋԹԿՊԽԽԼՏՁՌՀՌՀԽՋՌՍԼ ՑԹՍՌՀՇՊ0ՋԱՀԽՋՌՍԼՑԹՍՌՀՇՊՀՇՏԽՎԽՊԹՌՌՊՁԺՍՌԽԼ

## ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹ ՑՏՁՌՀԭԠԫԟ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  ο Ծ  

### ԽԾԾԽԻՌՋՇՆԤ԰ԦԹՆԼՀՁՋՌՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋՌՇՊԽԼՍԻԽԼԾԽԻՍՆԼՁՌՑԹ ՆԼՌԽՋՌՅԹՌԽՊՁԹՄՌՇՐՁԻՁՌՑՊԹՌՀԽՊՌՀԹՆՌՀԽՁՅՈՄՁԻԹՌՁՇՆ

ՇԾՈՇՋՋՁԺՄԽԥԤԱԹՐՁՋՁՆՌԽՊԾԽՊԽՆԻԽ

ԱՀԽՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼՌՀԽԱԴԞԻՇՆԻԽՆՌՊԹՌՁՇՆՋՍՋՁՆԿՌՀԽԾՇՄՄՇՏ ՁՆԿԽՉՍԹՌՁՇՆ

ՏՀԽՊԽ

ԠԱԴԞՁՋՌՀԽՌՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԠՂՁՋՌՀԽԻՇՆԻԽՆՌՊԹՌՁՇՆՅԽԹՋՍՊԽԼԹՌՌՁՅԽՁՆՌԽՊՎԹՄՂ
Ղ Ն

ՌՂՁՋՌՀԽՆՍՅԺԽՊՇԾՀՇՍՊՋ
ՇՊԼԹՑՋՇՊՏԽԽՃՋՍՆՁՌՋՍՋԽԼՂՍՋՌ ՆԽԽԼՌՇԺԽԻՇՆՋՁՋՌԽՆՌՁՆՌՀԽԽՉՍԹՌՁՇՆՇԾՌՀԽ

ՌԽՋՌԹՌՌՁՅԽՁՆՌԽՊՎԹՄՂ
ԽԿՌՀՇՍՊՋ
ՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ՌՀՇՍՊՋՌՀՇՍՊՋ

ԤՄԹՋՋՋԹՌՍՊԹՌՇՊԻՇՄՍՅՆՋՏԽՊԽՈՊԽՈԹՊԽԼԾՇՊՌՀԽԼԽՄՁՎԽՊՑՇԾԭԠԫԟԢԹԻՀԿՄԹՋՋԻՇՄՍՅՆ
ՠԦԡՐՠԩՏԹՋՈԹԻՃԽԼ

ՏՁՌՀԹՈՈՊՇՐՁՅԹՌԽՄՑՠՇԾՅՁԻՊՇՆԿՄԹՋՋՏՇՇՄՌՀԹՌՏԹՋՈՊԽՏԹՋՀ ԽԼՏՁՌՀՊԽԹԿԽՆՌԿՊԹԼԽԹԻԽՌՇՆԽԹՆԼԻՇԹՌԽԼ

ՏՁՌՀԹԻՇՆԻԽՆՌՊԹՌԽԼՋՌՇԻՃՋՍՋՈԽՆՋՁՇՆՇԾԭԠԫԟԞՎԹԻՍՍՅՈՍՅՈՏԹՋ ՍՋԽԼՌՇԽՆՋՍՊԽՌՀԽՋՇՄՍՌՁՇՆԽՎԽՆՄՑԻՇԹՌԽԼ

ՌՀԽԿՄԹՋՋՏՇՇՄԹՆԼՌՀԽԻՇՄՍՅՆՏԹՋՎԹԻՍՍՅԼՊՁԽԼՌՇՊԽՅՇՎԽՌՀԽԹԻ ԽՌՇՆԽԬՆԻԽՌՀԽԹԻԽՌՇՆԽՏԹՋՊԽՅՇՎԽԼ

ՌՀԽԻՇՄՍՅՆՏԹՋՏՊԹՈՈԽԼՁՆԹՄՍՅՁՆՍՅԾՇՁՄԹՆԼՋՌՇՊԽԼՊԽԾՊՁԿԽՊԹՌԽԼՍՆՌՁՄՍՋԽԱԽՆԻՇՄՍՅՆՋՏԽՊԽՍՋԽԼՌՇՈՊԽՈԹՊԽ

ՌՀԽՈՊՁՅԹՊՑՋՌՇԻՃՋՇՄՍՌՁՇՆԾՇՊՌՀԽԼՍՊԹՌՁՇՆՇԾՌՀԽՋՌՍԼՑ԰ՁՆԻԽ ՌՀԽԻՇՄՍՅՆՋՏԽՊԽՋՌԹԺՄԽԾՇՊԹՌՄԽԹՋՌԼԹՑՋ

ԻՇՄՍՅՆՋՏԽՊԽՊԽՈՄԹԻԽԼՇՆԹՏԽԽՃՄՑԺԹՋՁՋ

ԯԽՋՍՄՌՋԾՊՇՅՌՀԽՈԽՊՁՇԼՁԻՋԻՊԽԽՆՁՆԿԹՆԹՄՑՋՁՋՇԾՌՀԽԼՁՄՍՌՁՇՆՏԹ ՌԽՊՁՆԼՁԻԹՌԽԼՌՀԽՈՊԽՋԽՆԻԽՇԾՌՀԽԾՇՄՄՇՏՁՆԿ

ԹՆԹՄՑՌԽՋ ԻԹՄԻՁՍՅ 
ՅԿԩ ԻՀՄՇՊՁԼԽ 
ՅԿԩԾՄՍՇՊՁԼԽ 
 ՅԿԩՅԹԿՆԽՋՁՍՅ 
ՅԿԩ

ՈՇՌԹՋՋՁՍՅ
ՅԿԩՋՇԼՁՍՅ
ՅԿԩԹՆԼՋՍՄԾԹՌԽ
ՅԿԩ 

ԱՀԽՁՆՄՁԾԽՈՇՊՌՁՇՆՇԾՌՀԽԼԽԾՁՆՁՌՁՎԽՌՇՐՁԻՁՌՑՌԽՋՌՏԹՋԻՇՆԼՍԻՌԽԼԾՊՇՅ԰ԽՈՌԽՅԺԽՊՌՇԬԻՌՇԺԽՊ 

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n nn nn

n n

TWA 

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### CETIS Summary Report Report Date: 28 Aug-13 18:05 (p 1 of 5)

Test Code: 056502 49042102 | 03-9257-0391

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Sample ID: 17-8324-7209

Sample Date: 26 Sep-12

Receive Date: 17 Oct-12 Code: 49042102

Sample Age: NA Source: AMVAC Chemical Corporation

Station: Client: CDM Smith

Project: Endocrine Disruptor Screening Progra Material: Pentachloronitrobenzene (PCNB)

flow-through 056502 49042102

056502 49042102 Batch Note:

Sample Note:

Comparison Summary

NOEL LOEL TOEL Endpoint Analysis ID Method PMSD TU

6.9 74.42 22.66 00-3675-8381 Dunnett Multiple Comparison Test 42.9% Fecundity

6.9 74.42 22.66 09-2176-9624 Jonckheere-Terpstra Step-Down Test NA FemaleBodyWt

6.9 74.42 22.66 05-8240-6262 Dunnett Multiple Comparison Test 10.1% FemaleBodyWt

6.9 74.42 22.66 18-0020-9072 Jonckheere-Terpstra Step-Down Test NA FemaleGSI

74.42 >74.42 NA 05-2068-8500 Dunnett Multiple Comparison Test 35.4% FemaleGSI

74.42 >74.42 NA 03-2266-2722 Dunnett Multiple Comparison Test 4.61% FemaleLength

74.42 >74.42 NA 14-3841-1363 Jonckheere-Terpstra Step-Down Test NA FemaleVTG

74.42 >74.42 NA 21-3503-7035 Dunnett Multiple Comparison Test 87.8% FemaleVTG

74.42 >74.42 NA 07-0436-1675 Dunnett Multiple Comparison Test 5.42% Fertility

74.42 >74.42 NA 06-5938-6080 Jonckheere-Terpstra Step-Down Test NA MaleBodyWt

74.42 >74.42 NA 01-8011-0904 Dunnett Multiple Comparison Test 20.7% MaleBodyWt

0.635 6.9 2.093 02-9170-5609 Jonckheere-Terpstra Step-Down Test NA MaleGSI

6.9 74.42 22.66 07-6895-8495 Dunnett Multiple Comparison Test 49.1% MaleGSI

74.42 >74.42 NA 09-4547-8918 Dunnett Multiple Comparison Test 6.46% MaleLength

74.42 >74.42 NA 18-3354-6518 Dunnett Multiple Comparison Test 23.3% MaleMedianTubercleScore

74.42 >74.42 NA 14-6379-8478 Mann-Whitney U Two-Sample Test 342.0% MaleVTG

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 28 Aug-13 18:05 (p 2 of 5)

Test Code: 056502 49042102 | 03-9257-0391

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L Fecundity Summary

95% LCL 95% UCL %Effect

0 Negative Control 18.6 16.4 23.8 3.49 4 18.7% 1.74 13.1 24.2 0.0%

0.635 17.1 10.1 22 5.42 4 31.7% 2.71 8.47 25.7 8.31%

6.9 21.7 18.6 26.7 3.51 4 16.2% 1.75 16.1 27.3 -16.5%

74.42 6.1 1.3 11.1 4.16 4 68.2% 2.08 -0.524 12.7 67.3%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L FemaleBodyWt Summary

95% LCL 95% UCL %Effect

0 Negative Control 1.19 1.11 1.24 0.0614 4 5.18% 0.0307 1.09 1.28 0.0%

0.635 1.23 1.12 1.34 0.0904 4 7.38% 0.0452 1.08 1.37 -3.38%

6.9 1.22 1.17 1.26 0.037 4 3.04% 0.0185 1.16 1.27 -2.53%

74.42 1.31 1.23 1.34 0.0507 4 3.88% 0.0253 1.22 1.39 -10.1%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L FemaleGSI Summary

95% LCL 95% UCL %Effect

0 Negative Control 13.2 12 15.1 1.45 4 11.0% 0.724 10.8 15.5 0.0%

0.635 15.3 13.7 16 1.06 4 6.96% 0.531 13.6 17 -16.2%

6.9 14.8 12.9 18.6 2.56 4 17.2% 1.28 10.8 18.9 -12.9%

74.42 17.8 13 22 3.79 4 21.3% 1.89 11.8 23.8 -35.2%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L FemaleLength Summary

95% LCL 95% UCL %Effect

0 Negative Control 47.3 46.3 48.8 1.08 4 2.28% 0.54 45.6 49 0.0%

0.635 47.7 46.8 50 1.53 4 3.22% 0.767 45.3 50.2 -0.9%

6.9 47.3 46.3 47.8 0.665 4 1.41% 0.333 46.2 48.3 0.05%

74.42 48.4 47.5 49.8 1.14 4 2.36% 0.572 46.6 50.3 -2.43%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L FemaleVTG Summary

95% LCL 95% UCL %Effect

0 Negative Control 1.90E+7 9.65E+6 3.37E+7 1.14E+7 4 60.0% 5.71E+6 8.61E+5 3.72E+7 0.0%

0.635 1.68E+7 8.50E+6 3.03E+7 9.43E+6 4 56.1% 4.71E+6 1.80E+6 3.18E+7 11.8%

6.9 1.39E+7 8.96E+6 2.00E+7 5.23E+6 4 37.6% 2.62E+6 5.59E+6 2.22E+7 26.9%

74.42 1.33E+7 5.84E+6 2.42E+7 8.01E+6 4 60.4% 4.00E+6 5.26E+5 2.60E+7 30.3%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L Fertility Summary

95% LCL 95% UCL %Effect

0 Negative Control 97.4 95 98.7 1.75 4 1.79% 0.873 94.6 100 0.0%

0.635 97.9 95.9 99.2 1.57 4 1.6% 0.784 95.4 100 -0.49%

6.9 97.5 94.2 99.6 2.53 4 2.59% 1.26 93.5 102 -0.13%

74.42 96 89.6 99 4.37 4 4.55% 2.19 89.1 103 1.41%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L MaleBodyWt Summary

95% LCL 95% UCL %Effect

0 Negative Control 2.5 2.3 2.68 0.164 4 6.57% 0.0821 2.24 2.76 0.0%

0.635 2.6 2.4 2.9 0.231 4 8.89% 0.116 2.23 2.97 -4.2%

6.9 2.6 2.27 2.92 0.286 4 11.0% 0.143 2.14 3.05 -4.0%

74.42 2.84 2.44 3.21 0.367 4 12.9% 0.183 2.26 3.43 -13.8%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L MaleGSI Summary

95% LCL 95% UCL %Effect

0 Negative Control 1.25 0.9 1.7 0.334 4 26.8% 0.167 0.716 1.78 0.0%

0.635 1.77 1.44 2.11 0.283 4 16.0% 0.142 1.32 2.22 -41.7%

6.9 1.77 1.47 2.05 0.295 4 16.6% 0.148 1.3 2.24 -42.1%

74.42 1.99 1.48 2.35 0.372 4 18.7% 0.186 1.4 2.58 -59.3%

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 28 Aug-13 18:05 (p 3 of 5)

Test Code: 056502 49042102 | 03-9257-0391

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L MaleLength Summary

95% LCL 95% UCL %Effect

0 Negative Control 58.9 57.5 60 1.03 4 1.75% 0.515 57.2 60.5 0.0%

0.635 58.1 57.5 58.5 0.479 4 0.82% 0.239 57.4 58.9 1.27%

6.9 58.4 55 61 2.87 4 4.91% 1.43 53.8 62.9 0.85%

74.42 59.9 57 62.5 2.56 4 4.28% 1.28 55.8 64 -1.7%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L MaleMedianTubercleScore Summary

95% LCL 95% UCL %Effect

0 Negative Control 25.4 24 28.5 2.14 4 8.42% 1.07 22 28.8 0.0%

0.635 23.8 22 25.5 1.44 4 6.08% 0.722 21.5 26 6.4%

6.9 27 22 34.5 5.49 4 20.3% 2.75 18.3 35.7 -6.4%

74.42 23.6 22 25.5 1.44 4 6.08% 0.718 21.3 25.9 6.9%

Control Type Mean Min Max Std Dev Count CV% Std Err C- μ g ai/L MaleVTG Summary

95% LCL 95% UCL %Effect

0 Negative Control 1780 271 5920 2760 4 155.0% 1380 -2610 6170 0.0%

0.635 1830 378 5120 2220 4 121.0% 1110 -1700 5370 -3.07%

6.9 664 133 1350 528 4 79.5% 264 -176 1510 62.7%

74.42 3790 218 12800 6050 4 160.0% 3020 -5830 13400 -113.0%

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 28 Aug-13 18:05 (p 4 of 5)

Test Code: 056502 49042102 | 03-9257-0391

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type C- μ g ai/L Fecundity Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 16.6 16.4 17.8 23.8

0.635 20.7 10.1 22 15.6

6.9 20.2 21.4 26.7 18.6

74.42 4.6 7.4 11.1 1.3

Control Type C- μ g ai/L FemaleBodyWt Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 1.24 1.23 1.11 1.16

0.635 1.21 1.34 1.12 1.23

6.9 1.21 1.26 1.17 1.22

74.42 1.34 1.32 1.23 1.33

Control Type C- μ g ai/L FemaleGSI Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 12.1 13.4 12 15.1

0.635 16 15.6 13.7 15.8

6.9 14.2 18.6 13.7 12.9

74.42 17 19.1 13 22

Control Type C- μ g ai/L FemaleLength Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 48.8 46.8 47.3 46.3

0.635 47.3 50 46.8 46.8

6.9 47.8 46.3 47.5 47.5

74.42 49.8 49 47.5 47.5

Control Type C- μ g ai/L FemaleVTG Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 9.65E+6 1.03E+7 2.25E+7 3.37E+7

0.635 1.32E+7 1.52E+7 8.50E+6 3.03E+7

6.9 1.65E+7 8.96E+6 1.02E+7 2.00E+7

74.42 5.84E+6 9.12E+6 1.39E+7 2.42E+7

Control Type C- μ g ai/L Fertility Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 97.3 95 98.7 98.7

0.635 99.2 95.9 97.4 99.1

6.9 99.4 97 99.6 94.2

74.42 97.1 99 98.5 89.6

Control Type C- μ g ai/L MaleBodyWt Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 2.57 2.44 2.68 2.3

0.635 2.67 2.4 2.44 2.9

6.9 2.73 2.92 2.27 2.47

74.42 2.44 3.09 3.21 2.63

Control Type C- μ g ai/L MaleGSI Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 1.15 1.7 1.24 0.9

0.635 2.11 1.67 1.85 1.44

6.9 2.05 2 1.47 1.57

74.42 2.15 2.35 1.48 1.97

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________

### CETIS Summary Report Report Date: 28 Aug-13 18:05 (p 5 of 5)

Test Code: 056502 49042102 | 03-9257-0391

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Control Type C- μ g ai/L MaleLength Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 60 59 59 57.5

0.635 58.5 57.5 58 58.5

6.9 60.5 61 55 57

74.42 58.5 62.5 61.5 57

Control Type C- μ g ai/L MaleMedianTubercleScore Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 24 28.5 25 24

0.635 24 22 25.5 23.5

6.9 34.5 27.5 24 22

74.42 23.5 25.5 23.5 22

Control Type C- μ g ai/L MaleVTG Detail

Rep 1 Rep 2 Rep 3 Rep 4

0 Negative Control 5.92E+3 4.32E+2 4.98E+2 2.71E+2

0.635 1.20E+3 6.33E+2 5.12E+3 3.78E+2

6.9 1.35E+3 1.33E+2 7.81E+2 3.95E+2

74.42 7.31E+2 2.18E+2 1.28E+4 1.38E+3

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 1 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:57 Endpoint: Fecundity CETIS Version: CETISv1.8.7 Analysis ID: 00-3675-8381
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.519 2.68 8 0.9156 Non-Significant Effect Negative Control 0.635 6 CDF

1.03 2.68 8 0.6179 Non-Significant Effect 6.9 6 CDF

4.21 2.68 8 0.0033 Significant Effect 74.42* 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

6.9 74.42 42.9% 22.66 C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 555.8919 185.2973 3 10.4 0.0012 Significant Effect

Error 213.6575 17.80479 12

769.5494 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

0.723 11.3 0.8677 Equal Variances Bartlett Equality of Variance Variances

0.915 0.841 0.1386 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL Fecundity Summary

18.6 16.4 23.8 17.2 0 4 Negative Control 1.74 18.7% 0.0% 13.1 24.2

17.1 10.1 22 18.2 0.635 4 2.71 31.7% 8.31% 8.47 25.7

21.7 18.6 26.7 20.8 6.9 4 1.75 16.2% -16.5% 16.1 27.3

6.1 1.3 11.1 6 74.42 4 2.08 68.2% 67.3% -0.524 12.7CenteredUntransformed

Rankits -1

-2

-3

-4

-5

-6

-7 0 1 2 3 4 5 6

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0Fecundity

C- μ g ai/L Reject Null

Reject Null

0 5 10 15 20 25 30

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 2 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:56 Endpoint: FemaleBodyWt CETIS Version: CETISv1.8.7 Analysis ID: 05-8240-6262
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.898 2.68 0.119 0.7040 Non-Significant Effect Negative Control 0.635 6 CDF

0.674 2.68 0.119 0.8405 Non-Significant Effect 6.9 6 CDF

2.69 2.68 0.119 0.0490 Significant Effect 74.42* 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

6.9 74.42 10.1% 22.66 C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 0.03150002 0.01050001 3 2.65 0.0966 Non-Significant Effect

Error 0.04760001 0.003966668 12

0.07910003 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

2.19 11.3 0.5344 Equal Variances Bartlett Equality of Variance Variances

0.976 0.841 0.9287 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL FemaleBodyWt Summary

1.19 1.11 1.24 1.19 0 4 Negative Control 0.0307 5.18% 0.0% 1.09 1.28

1.23 1.12 1.34 1.22 0.635 4 0.0452 7.38% -3.38% 1.08 1.37

1.22 1.17 1.26 1.22 6.9 4 0.0185 3.04% -2.53% 1.16 1.27

1.31 1.23 1.34 1.33 74.42 4 0.0253 3.88% -10.1% 1.22 1.39CenteredUntransformed

Rankits -0.04

-0.08

-0.12 0.00 0.04 0.08 0.12

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0FemaleBodyWt

C- μ g ai/L Reject Null

Reject Null

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 3 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 18:00 Endpoint: FemaleBodyWt CETIS Version: CETISv1.8.7 Analysis ID: 09-2176-9624
Analysis: Nonparametric-Control vs Ord. Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) Ties vs Control C- μ g ai/L Jonckheere-Terpstra Step-Down Test

DF P-Type

0.438 1.64 1 0.3309 Non-Significant Effect Negative Control 0.635 -2 Asymp

0.442 1.64 2 0.3294 Non-Significant Effect 6.9 -2 Asymp

1.92 1.64 2 0.0272 Significant Effect 74.42* -2 Asymp NOEL LOEL TU TOEL Alt Hyp Data Transform Zeta Trials Seed

6.9 74.42 22.66 C < T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 0.03150002 0.01050001 3 2.65 0.0966 Non-Significant Effect

Error 0.04760001 0.003966668 12

0.07910003 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

2.19 11.3 0.5344 Equal Variances Bartlett Equality of Variance Variances

0.976 0.841 0.9287 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL FemaleBodyWt Summary

1.19 1.11 1.24 1.19 0 4 Negative Control 0.0307 5.18% 0.0% 1.09 1.28

1.23 1.12 1.34 1.22 0.635 4 0.0452 7.38% -3.38% 1.08 1.37

1.22 1.17 1.26 1.22 6.9 4 0.0185 3.04% -2.53% 1.16 1.27

1.31 1.23 1.34 1.33 74.42 4 0.0253 3.88% -10.1% 1.22 1.39CenteredUntransformed

Rankits -0.04

-0.08

-0.12 0.00 0.04 0.08 0.12

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0FemaleBodyWt

C- μ g ai/L 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 4 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:55 Endpoint: FemaleGSI CETIS Version: CETISv1.8.7 Analysis ID: 05-2068-8500
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

1.22 2.68 4.66 0.4959 Non-Significant Effect Negative Control 0.635 6 CDF

0.979 2.68 4.66 0.6511 Non-Significant Effect 6.9 6 CDF

2.66 2.68 4.66 0.0516 Non-Significant Effect 74.42 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 35.4% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 43.7825 14.59417 3 2.42 0.1165 Non-Significant Effect

Error 72.29501 6.024584 12

116.0775 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

4.69 11.3 0.1958 Equal Variances Bartlett Equality of Variance Variances

0.955 0.841 0.5664 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL FemaleGSI Summary

13.2 12 15.1 12.8 0 4 Negative Control 0.724 11.0% 0.0% 10.8 15.5

15.3 13.7 16 15.7 0.635 4 0.531 6.96% -16.2% 13.6 17

14.8 12.9 18.6 13.9 6.9 4 1.28 17.2% -12.9% 10.8 18.9

17.8 13 22 18 74.42 4 1.89 21.3% -35.2% 11.8 23.8CenteredUntransformed

Rankits -1

-2

-3

-4

-5 0 1 2 3 4 5

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0FemaleGSI

C- μ g ai/L Reject Null

Reject Null

0 5 10 15 20 25

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 5 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 18:00 Endpoint: FemaleGSI CETIS Version: CETISv1.8.7 Analysis ID: 18-0020-9072
Analysis: Nonparametric-Control vs Ord. Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Jonckheere-Terpstra Step-Down Test

DF P-Type

15 NA 0.1061 Non-Significant Effect Negative Control 0.635 -2 Exact

1.25 1.64 1 0.1061 Non-Significant Effect 6.9 -2 Asymp

2.1 1.64 1 0.0177 Significant Effect 74.42* -2 Asymp NOEL LOEL TU TOEL Alt Hyp Data Transform Zeta Trials Seed

6.9 74.42 22.66 C < T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 43.7825 14.59417 3 2.42 0.1165 Non-Significant Effect

Error 72.29501 6.024584 12

116.0775 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

4.69 11.3 0.1958 Equal Variances Bartlett Equality of Variance Variances

0.955 0.841 0.5664 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL FemaleGSI Summary

13.2 12 15.1 12.8 0 4 Negative Control 0.724 11.0% 0.0% 10.8 15.5

15.3 13.7 16 15.7 0.635 4 0.531 6.96% -16.2% 13.6 17

14.8 12.9 18.6 13.9 6.9 4 1.28 17.2% -12.9% 10.8 18.9

17.8 13 22 18 74.42 4 1.89 21.3% -35.2% 11.8 23.8CenteredUntransformed

Rankits -1

-2

-3

-4

-5 0 1 2 3 4 5

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0FemaleGSI

C- μ g ai/L 0 5 10 15 20 25

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 6 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:54 Endpoint: FemaleLength CETIS Version: CETISv1.8.7 Analysis ID: 03-2266-2722
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.523 2.68 2.18 0.9139 Non-Significant Effect Negative Control 0.635 6 CDF

0.0308 2.68 2.18 1.0000 Non-Significant Effect 6.9 6 CDF

1.42 2.68 2.18 0.3876 Non-Significant Effect 74.42 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 4.61% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 3.612502 1.204167 3 0.913 0.4637 Non-Significant Effect

Error 15.825 1.31875 12

19.4375 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

1.69 11.3 0.6395 Equal Variances Bartlett Equality of Variance Variances

0.873 0.841 0.0306 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL FemaleLength Summary

47.3 46.3 48.8 47 0 4 Negative Control 0.54 2.28% 0.0% 45.6 49

47.7 46.8 50 47 0.635 4 0.767 3.22% -0.9% 45.3 50.2

47.3 46.3 47.8 47.5 6.9 4 0.333 1.41% 0.05% 46.2 48.3

48.4 47.5 49.8 48.3 74.42 4 0.572 2.36% -2.43% 46.6 50.3CenteredUntransformed

Rankits -0.5

-1.0 0.0 0.5 1.0 1.5 2.0 2.5

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0FemaleLength

C- μ g ai/L Reject Null

Reject Null

0 10 20 30 40 50

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 7 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:54 Endpoint: FemaleVTG CETIS Version: CETISv1.8.7 Analysis ID: 21-3503-7035
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.359 2.68 2E+07 0.9686 Non-Significant Effect Negative Control 0.635 6 CDF

0.822 2.68 2E+07 0.7526 Non-Significant Effect 6.9 6 CDF

0.926 2.68 2E+07 0.6859 Non-Significant Effect 74.42 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 87.8% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 8.581012E+13 2.860337E+13 3 0.368 0.7774 Non-Significant Effect

Error 9.324587E+14 7.770489E+13 12

1.018269E+15 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

1.54 11.3 0.6736 Equal Variances Bartlett Equality of Variance Variances

0.91 0.841 0.1181 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL FemaleVTG Summary

1.90E+7 9.65E+6 3.37E+7 16400000 0 4 Negative Control 5.71E+6 60.0% 0.0% 8.61E+5 3.72E+7

1.68E+7 8.50E+6 3.03E+7 14200000 0.635 4 4.71E+6 56.1% 11.8% 1.80E+6 3.18E+7

1.39E+7 8.96E+6 2.00E+7 13400000 6.9 4 2.62E+6 37.6% 26.9% 5.59E+6 2.22E+7

1.33E+7 5.84E+6 2.42E+7 11500000 74.42 4 4.00E+6 60.4% 30.3% 5.26E+5 2.60E+7CenteredUntransformed

Rankits -2.0E+06

-4.0E+06

-6.0E+06

-8.0E+06

-1.0E+07 0.0E+00 2.0E+06 4.0E+06 6.0E+06 8.0E+06 1.0E+07 1.2E+07 1.4E+07 1.6E+07

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0FemaleVTG

C- μ g ai/L Reject Null

Reject Null

0.0E+00 5.0E+06 1.0E+07 1.5E+07 2.0E+07 2.5E+07 3.0E+07 3.5E+07 4.0E+07

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 8 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 18:00 Endpoint: FemaleVTG CETIS Version: CETISv1.8.7 Analysis ID: 14-3841-1363
Analysis: Nonparametric-Control vs Ord. Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Jonckheere-Terpstra Step-Down Test

DF P-Type

9 NA 0.4429 Non-Significant Effect Negative Control 0.635 -2 Exact

28 NA 0.3090 Non-Significant Effect 6.9 -2 Exact

58 NA 0.1910 Non-Significant Effect 74.42 -2 Exact NOEL LOEL TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 NA C > T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 8.581012E+13 2.860337E+13 3 0.368 0.7774 Non-Significant Effect

Error 9.324587E+14 7.770489E+13 12

1.018269E+15 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

1.54 11.3 0.6736 Equal Variances Bartlett Equality of Variance Variances

0.91 0.841 0.1181 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL FemaleVTG Summary

1.90E+7 9.65E+6 3.37E+7 16400000 0 4 Negative Control 5.71E+6 60.0% 0.0% 8.61E+5 3.72E+7

1.68E+7 8.50E+6 3.03E+7 14200000 0.635 4 4.71E+6 56.1% 11.8% 1.80E+6 3.18E+7

1.39E+7 8.96E+6 2.00E+7 13400000 6.9 4 2.62E+6 37.6% 26.9% 5.59E+6 2.22E+7

1.33E+7 5.84E+6 2.42E+7 11500000 74.42 4 4.00E+6 60.4% 30.3% 5.26E+5 2.60E+7CenteredUntransformed

Rankits -2.0E+06

-4.0E+06

-6.0E+06

-8.0E+06

-1.0E+07 0.0E+00 2.0E+06 4.0E+06 6.0E+06 8.0E+06 1.0E+07 1.2E+07 1.4E+07 1.6E+07

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0FemaleVTG

C- μ g ai/L 0.0E+00 5.0E+06 1.0E+07 1.5E+07 2.0E+07 2.5E+07 3.0E+07 3.5E+07

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 9 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:53 Endpoint: Fertility CETIS Version: CETISv1.8.7 Analysis ID: 07-0436-1675
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.241 2.68 5.28 0.9899 Non-Significant Effect Negative Control 0.635 6 CDF

0.0635 2.68 5.28 0.9998 Non-Significant Effect 6.9 6 CDF

0.698 2.68 5.28 0.8268 Non-Significant Effect 74.42 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 5.42% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 7.926877 2.642292 3 0.341 0.7964 Non-Significant Effect

Error 93.0875 7.757292 12

101.0144 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

3.62 11.3 0.3055 Equal Variances Bartlett Equality of Variance Variances

0.883 0.841 0.0437 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL Fertility Summary

97.4 95 98.7 98 0 4 Negative Control 0.873 1.79% 0.0% 94.6 100

97.9 95.9 99.2 98.3 0.635 4 0.784 1.6% -0.49% 95.4 100

97.5 94.2 99.6 98.2 6.9 4 1.26 2.59% -0.13% 93.5 102

96 89.6 99 97.8 74.42 4 2.19 4.55% 1.41% 89.1 103CenteredUntransformed

Rankits -1

-2

-3

-4

-5

-6

-7 0 1 2 3

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0Fertility

C- μ g ai/L Reject Null

Reject Null

0 20 40 60 80 100 120

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 10 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:50 Endpoint: MaleBodyWt CETIS Version: CETISv1.8.7 Analysis ID: 01-8011-0904
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.545 2.68 0.517 0.9045 Non-Significant Effect Negative Control 0.635 6 CDF

0.519 2.68 0.517 0.9156 Non-Significant Effect 6.9 6 CDF

1.79 2.68 0.517 0.2244 Non-Significant Effect 74.42 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 20.7% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 0.2577 0.08590001 3 1.16 0.3658 Non-Significant Effect

Error 0.8899 0.07415833 12

1.1476 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

1.7 11.3 0.6363 Equal Variances Bartlett Equality of Variance Variances

0.947 0.841 0.4437 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL MaleBodyWt Summary

2.5 2.3 2.68 2.51 0 4 Negative Control 0.0821 6.57% 0.0% 2.24 2.76

2.6 2.4 2.9 2.56 0.635 4 0.116 8.89% -4.2% 2.23 2.97

2.6 2.27 2.92 2.6 6.9 4 0.143 11.0% -4.0% 2.14 3.05

2.84 2.44 3.21 2.86 74.42 4 0.183 12.9% -13.8% 2.26 3.43CenteredUntransformed

Rankits -0.1

-0.2

-0.3

-0.4

-0.5 0.0 0.1 0.2 0.3 0.4 0.5

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0MaleBodyWt

C- μ g ai/L Reject Null

Reject Null

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 11 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:58 Endpoint: MaleBodyWt CETIS Version: CETISv1.8.7 Analysis ID: 06-5938-6080
Analysis: Nonparametric-Control vs Ord. Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) Ties vs Control C- μ g ai/L Jonckheere-Terpstra Step-Down Test

DF P-Type

0.438 1.64 1 0.3309 Non-Significant Effect Negative Control 0.635 -2 Asymp

0.66 1.64 1 0.2545 Non-Significant Effect 6.9 -2 Asymp

1.45 1.64 1 0.0731 Non-Significant Effect 74.42 -2 Asymp NOEL LOEL TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 NA C < T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 0.2577 0.08590001 3 1.16 0.3658 Non-Significant Effect

Error 0.8899 0.07415833 12

1.1476 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

1.7 11.3 0.6363 Equal Variances Bartlett Equality of Variance Variances

0.947 0.841 0.4437 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL MaleBodyWt Summary

2.5 2.3 2.68 2.51 0 4 Negative Control 0.0821 6.57% 0.0% 2.24 2.76

2.6 2.4 2.9 2.56 0.635 4 0.116 8.89% -4.2% 2.23 2.97

2.6 2.27 2.92 2.6 6.9 4 0.143 11.0% -4.0% 2.14 3.05

2.84 2.44 3.21 2.86 74.42 4 0.183 12.9% -13.8% 2.26 3.43CenteredUntransformed

Rankits -0.1

-0.2

-0.3

-0.4

-0.5 0.0 0.1 0.2 0.3 0.4 0.5

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0MaleBodyWt

C- μ g ai/L 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 12 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:49 Endpoint: MaleGSI CETIS Version: CETISv1.8.7 Analysis ID: 07-6895-8495
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

2.28 2.68 0.613 0.1017 Non-Significant Effect Negative Control 0.635 6 CDF

2.3 2.68 0.613 0.0980 Non-Significant Effect 6.9 6 CDF

3.24 2.68 0.613 0.0184 Significant Effect 74.42* 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

6.9 74.42 49.1% 22.66 C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 1.188275 0.3960917 3 3.79 0.0401 Significant Effect

Error 1.2529 0.1044083 12

2.441175 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

0.246 11.3 0.9698 Equal Variances Bartlett Equality of Variance Variances

0.965 0.841 0.7516 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL MaleGSI Summary

1.25 0.9 1.7 1.19 0 4 Negative Control 0.167 26.8% 0.0% 0.716 1.78

1.77 1.44 2.11 1.76 0.635 4 0.142 16.0% -41.7% 1.32 2.22

1.77 1.47 2.05 1.79 6.9 4 0.148 16.6% -42.1% 1.3 2.24

1.99 1.48 2.35 2.06 74.42 4 0.186 18.7% -59.3% 1.4 2.58CenteredUntransformed

Rankits -0.1

-0.2

-0.3

-0.4

-0.5

-0.6 0.0 0.1 0.2 0.3 0.4 0.5

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0MaleGSI

C- μ g ai/L Reject Null

Reject Null

0.0 0.5 1.0 1.5 2.0 2.5

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 13 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:58 Endpoint: MaleGSI CETIS Version: CETISv1.8.7 Analysis ID: 02-9170-5609
Analysis: Nonparametric-Control vs Ord. Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Jonckheere-Terpstra Step-Down Test

DF P-Type

14 NA 0.0571 Non-Significant Effect Negative Control 0.635 -2 Exact

36 NA 0.0463 Significant Effect 6.9* -2 Exact

74 NA 0.0075 Significant Effect 74.42* -2 Exact NOEL LOEL TU TOEL Alt Hyp Data Transform Zeta Trials Seed

0.635 6.9 2.093 C < T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 1.188275 0.3960917 3 3.79 0.0401 Significant Effect

Error 1.2529 0.1044083 12

2.441175 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

0.246 11.3 0.9698 Equal Variances Bartlett Equality of Variance Variances

0.965 0.841 0.7516 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL MaleGSI Summary

1.25 0.9 1.7 1.19 0 4 Negative Control 0.167 26.8% 0.0% 0.716 1.78

1.77 1.44 2.11 1.76 0.635 4 0.142 16.0% -41.7% 1.32 2.22

1.77 1.47 2.05 1.79 6.9 4 0.148 16.6% -42.1% 1.3 2.24

1.99 1.48 2.35 2.06 74.42 4 0.186 18.7% -59.3% 1.4 2.58CenteredUntransformed

Rankits -0.1

-0.2

-0.3

-0.4

-0.5

-0.6 0.0 0.1 0.2 0.3 0.4 0.5

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0MaleGSI

C- μ g ai/L 0.0 0.5 1.0 1.5 2.0 2.5

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 14 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:49 Endpoint: MaleLength CETIS Version: CETISv1.8.7 Analysis ID: 09-4547-8918
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.529 2.68 3.8 0.9116 Non-Significant Effect Negative Control 0.635 6 CDF

0.353 2.68 3.8 0.9701 Non-Significant Effect 6.9 6 CDF

0.705 2.68 3.8 0.8227 Non-Significant Effect 74.42 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 6.46% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 7.1875 2.395833 3 0.596 0.6297 Non-Significant Effect

Error 48.25 4.020833 12

55.4375 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

7.87 11.3 0.0487 Equal Variances Bartlett Equality of Variance Variances

0.958 0.841 0.6302 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL MaleLength Summary

58.9 57.5 60 59 0 4 Negative Control 0.515 1.75% 0.0% 57.2 60.5

58.1 57.5 58.5 58.3 0.635 4 0.239 0.82% 1.27% 57.4 58.9

58.4 55 61 58.8 6.9 4 1.43 4.91% 0.85% 53.8 62.9

59.9 57 62.5 60 74.42 4 1.28 4.28% -1.7% 55.8 64CenteredUntransformed

Rankits -0.5

-1.0

-1.5

-2.0

-2.5

-3.0

-3.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0MaleLength

C- μ g ai/L Reject Null

Reject Null

0 10 20 30 40 50 60 70

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 15 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:49 Endpoint: MaleMedianTubercleScore CETIS Version: CETISv1.8.7 Analysis ID: 18-3354-6518
Analysis: Parametric-Control vs Treatments Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) MSD vs Control C- μ g ai/L Dunnett Multiple Comparison Test

DF P-Type

0.737 2.68 5.91 0.8042 Non-Significant Effect Negative Control 0.635 6 CDF

0.737 2.68 5.91 0.8042 Non-Significant Effect 6.9 6 CDF

0.794 2.68 5.91 0.7730 Non-Significant Effect 74.42 6 CDF NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 23.3% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 30.3125 10.10417 3 1.04 0.4102 Non-Significant Effect

Error 116.625 9.71875 12

146.9375 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

7.15 11.3 0.0673 Equal Variances Bartlett Equality of Variance Variances

0.92 0.841 0.1661 Normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL MaleMedianTubercleScore Summary

25.4 24 28.5 24.5 0 4 Negative Control 1.07 8.42% 0.0% 22 28.8

23.8 22 25.5 23.8 0.635 4 0.722 6.08% 6.4% 21.5 26

27 22 34.5 25.8 6.9 4 2.75 20.3% -6.4% 18.3 35.7

23.6 22 25.5 23.5 74.42 4 0.718 6.08% 6.9% 21.3 25.9CenteredUntransformed

Rankits -1

-2

-3

-4

-5 0 1 2 3 4 5 6 7 8

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0MaleMedianTubercleScore

C- μ g ai/L Reject Null

Reject Null

0 5 10 15 20 25 30 35

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________Report Date: 28 Aug-13 18:02 (p 16 of 16)

Test Code: 056502 49042102 | 03-9257-0391 

### CETIS Analytical Report

OPPTS 890.1350 EDSP Fish Short-Term Reproduction Assay (FSTRA) Wildlife International

Analyzed: 28 Aug-13 17:48 Endpoint: MaleVTG CETIS Version: CETISv1.8.7 Analysis ID: 14-6379-8478
Analysis: Nonparametric-Two Sample Official Results: Yes

Batch ID: 00-3404-4484

Start Date: 26 Sep-12

Ending Date: 17 Oct-12 Test Type: EDSP FSTRA Tier 1

Duration: 21d 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: 5.5m

Test Stat Critical P-Value Decision( α :5%) Ties vs Control C- μ g ai/L Mann-Whitney U Two-Sample Test

DF P-Type

10 NA 0 0.6857 Non-Significant Effect Negative Control 0.635 6 Exact

9 NA 0 0.8857 Non-Significant Effect 6.9 6 Exact

10 NA 0 0.6857 Non-Significant Effect 74.42 6 Exact NOEL LOEL PMSD TU TOEL Alt Hyp Data Transform Zeta Trials Seed

74.42 >74.42 342.0% NA C <> T NA Untransformed NA NA

ANOVA Table

Source Sum Squares Mean Square DF F Stat P-Value Decision( α :5%)

Between 20256000 6752002 3 0.547 0.6598 Non-Significant Effect

Error 148244200 12353680 12

168500200 15 Total

Distributional Tests

Attribute Test Test Stat Critical P-Value Decision( α :1%)

10.8 11.3 0.0128 Equal Variances Bartlett Equality of Variance Variances

0.817 0.841 0.0046 Non-normal Distribution Shapiro-Wilk W Normality Distribution

Mean Min Max Median Count Control Type Std Err C- μ g ai/L CV% %Effect 95% LCL 95% UCL MaleVTG Summary

1.78E+3 2.71E+2 5.92E+3 465 0 4 Negative Control 1.38E+3 155.0% 0.0% -2.61E+3 6.17E+3

1.83E+3 3.78E+2 5.12E+3 918 0.635 4 1.11E+3 121.0% -3.07% -1.70E+3 5.37E+3

6.64E+2 1.33E+2 1.35E+3 588 6.9 4 2.64E+2 79.5% 62.7% -1.76E+2 1.51E+3

3.79E+3 2.18E+2 1.28E+4 1050 74.42 4 3.02E+3 160.0% -113.0% -5.83E+3 1.34E+4CenteredUntransformed

Rankits -2000

-4000

0 2000 4000 6000 8000 10000

-0.5 -1.0 -1.5 -2.0 0.0 0.5 1.0 1.5 2.0MaleVTG

C- μ g ai/L 0 2000 4000 6000 8000 10000 12000 14000

0 N 0.635 6.9 74.42 Graphics

CETISTM v1.8.7.10 000-516-187-1 QA:________ Analyst:________

# DATA EVALUATION RECORD

PCNB

Study Type: O CSPP 890.1400, In vivo Hershberger Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-26-2012 (MRID 48916702)

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: 10/9 /2012

Secondary Reviewer Signature: Michelle J. Sharpe

- Kass, M.S. Date: 10/12 /2012

Program Manager: Signature: Jack D. Early, M.S. Date: 10/ 19 /2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 10/ 19 /2012

This Data Evaluation Record may have been altered 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 intended 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 strengt hs of each individual assay to identify potential endocrine bioactivity with complementary endpoints within the assay, where available, and redundancy 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 potential 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).

### PCNB 

### I 056502



## Primary Reviewer :**N~a~ c**  

## .....**v~M'-'"-""c** 

## ..... Carr.-.=

...... 

## oll=-------

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

Health Effects Division In vivo Her shberger Assay (2012)/ Page 

### 1 of 1 3

OCSPP 890.1400/ OECD 441

# Sign•~:::~**J~t;:{:.r.~s-** Signature:**~** 

# ,A:

Date: 

# Git> )1 c Template version 101201 l



## DATA EVALUATION RECORD

STUDY TYPE: In Vivo 

## Hershberger Assay (Rat); OCSPP 890.1400 ; OECD 441

PC CODE: 056502 DP BARCODE: 0405372

TXR#: 0056474 CAS#: 82-68-8

TEST MATERIAL (PURITY): PCNB (95.6% a .i .; Lot# 107030L052)

SYNONYMS: Pentachloronitrobenzene ; Quinto ze ne

CITATION: Donington

, S. (20 1 2). PCNB Technical: Hershberger bioassay in the castrated

rat (oral administration). Huntingdon Life Sciences

, Cambridgeshire, England. Laboratory Project Study ID: BDG0121, June 19

, 2012. MRID 48916702. Unp ubli shed.

SPONSOR: Donoghue

, K (2012) PCNB Technical ; Development and Validation of an Analytical Method and Liquid Formulation Preparation, Homogeneity and

Stabi li ty. Huntingdon Life Sciences

, Cambridgeshire

, England. Laboratory Project Study ID BDG0122. April 27, 2012. MRID 48916703 Unpublished.

AMY AC Chemical Corporation

, 4100 E. Washington Blvd.

, Los Angeles, CA

TEST ORDER #: EDSP -0 56502 -105

EXECUTIVE SUMMARY: In 

## a Hershberger assay (MRID 48916702) screeni n g for androgenic activity, PCNB ( 95.6% a.i., Lot# 1 07030L052) in 

## aqueous sodium carboxymethyl

cellulose (1 % 

## SCMC) was administered dail y v ia oral g avage to groups of 55 -d ay old, castrated

male Sprague Dawley (Crl:CD[SD]) rats ( IO / group) at dose le vels of 0 (vehicle), 300, or 1000 mg/kg/day. The androgenic assay included a positive control group consisting of 10 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

, PCNB in 1 % SCMC was administered daily via

oral gavage to 54-day old, castrated male Sprague Dawley r ats (10 / group) at dose le ve l s of 100

, 300, or 1000 mg/kg/da y in conjunction with a dail y dose ofreference androgen TP at 0.4

m g/kg/ da y by s.c. injection. The control group for the anti-androgenic assay consisted of ten

cas trated male rats do se d dail y with TP (0.4 mg/k g/ day ) in com oil by s.c. inj ec tion

, and the positive control group consisted of ten castrated male rats dosed orally w i th flutamide (FT) in

com oil at 3 mg/kg / day in conjugation with a daily s.c. dose of TP (0.4 mg/kg / day).In vivo Hershberger Assay (2012 ) / Page 2 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## For both components of the assay, the animals were dosed for 10 consecutive days and necropsied approximately 24 hours after the final dose administration to determine weights of the five androgen- dependent tissues.

In the androgen agonist assay, body weights and body weight gains for the 300 and 1000 mg/kg/day treatment groups were comparable to controls throughout the assay. Animals dosed with TP had increased (p≤0.05) body weights on Days 8 -11 ( ↑ 5- 8%) and overall body weight gains ( ↑ 48%) compared to controls. There were no treatment

- related weight increases in any of the accessory sex organs of animals dosed with PCNB. At 1000 mg/kg/day, the adjusted liver weights were increased by 8% (p≤0.05) and the unadjuste d liver weights were increased by 7% (not significant , NS ). Animals in the TP group had increases (p≤0.01) in unadjusted accessory sex organ weights as follows: 750% in seminal vesicles, 1316% in ventral prostate, 179% in

levator ani -bulbocavernosus ( LAB C) , 518% in Cowper’s gland, and 50% in glans penis. The unadjusted liver weights in the TP group were increased by 15% (p≤0.01) and the adjusted liver weights were increased by 8% (p≤0.05). All %CV values were less than or equal to the

maximum recommende d values.

In the anti-androgen assay, body weights and body weight gains for the 100, 300, and 1000 mg/kg/day dose groups were comparable to controls throughout the assay. No treatment

- related decreases in weights of androgen sensitive tissues were observed in any PCNB dose group, although t here was a 15% increase (p≤0.05) in Cowper’s gland weights at 1000 mg/kg/day. No

treatment

- related decreases were observed in any of the accessory sex organs of PCNB -dosed animals. The unadjusted liver weights w ere increased by 8% ( NS ) at 1000 mg/kg/day. Animals dosed with TP + FT (positive control) had decreases (p≤0.01) in unadjusted accessory sex organ weights as follows: 76% in seminal vesicles , 72% in ventral prostate, 53% in LABC , 58% in Cowper’s gland , and 27% in glans penis. The unadjusted liver weights in the TP + FT group were increased by 11% (p≤0.05) and the adjusted liver weights were increased by 10% (p≤0.01). All %CV values were less than or equal to the maximum recommended values.

The dosing l evels selected for the study were acceptable as animals were dosed up to limit dose (1000 mg/kg/day) for the assay.

S tatistically significant changes were not seen in two or more of the five androgen sensitive

tissue weight s. PCNB was negative for androgenicity and anti -androgenicity in the Hershberger

assay.

The assay satisfies the EDSP Tier 1 Test Order requirements for a Hershberger assay (OCSPP 890.1400).

COMPLIANCE : Signed and dated GLP Compliance an d Quality Assurance statements were

pro vided.In vivo Hershberger Assay (2012 ) / Page 3 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility : Huntingdon Life Sciences, Ltd.

Location: Cambridgeshire, England Study Director: S. Donington

Other Personnel: Ballantine, A. (Team Leader), Clarke, R. (Senior Animal Technician), Rodgers, D. (Senior Pharmacology Assistant), and Viles, T. (Senior Technician) Study Period: February 1, 2012 to June 19, 2012



## 2. Test Substance : PCNB

Description: Light brown powder

Source: AMVAC Chemical Corporation ( Los Angeles, CA )

Lot/Batch #: 107030L052 ( expires July 2016 ) Purity: 95.6 % a.i. Stability: Stable in the vehicle for up to 15 days refrigerated and at room temperature (Huntingdon Life Sciences Study No. BDG0122 ).

CAS #: 82

- 68

- 8

Structure:

Cl

Cl

Cl Cl Cl NO 2



## 3

. Reference Androgen : Testosterone propionate (TP)

Supplier : Sigma

- Aldrich

Batch #: 048K1328 ( expires April 30, 2012 ) Purity: Not provided

CAS # : 57

- 85

- 2



## 4

. Reference Anti

- androgen : Flutamide ( FT )

Supplier : Sigma

- Aldrich

Lot #: 009K1112 ( expires June 15, 2012 ) Purity: Not provided

CAS # : 13311

- 84

- 7



## 5. Solvent/Vehicle Control ( PCNB ): Aqueous sodium carboxymethyl cellulose (1% SCMC)

Supplier: BDH

Lot/Batch #: 82122 (expires November 21, 2013) Rationale (if other than water) : Test substance had very low water solubility.

Final concentration: 1% w/v



## 6

. Solvent/Vehicle Control ( Testosterone propionate and Flutamide) : Corn Oil

Supplier : Sigma

- Aldrich

Lot/Batch #: MKBD 2427 ( expires September 27 , 2012 ) Rationale (if other than water) : Background data collected using this vehicle.

Final concentration : Not applicableIn vivo Hershberger Assay (2012 ) / Page 4 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## 7

. Test Animals : Species: Rat

Strain: Sprague Da w ley (Crl:CD[SD]) Age/weight at dose initiation: Phase I: Androgen Agonist Assay : Post

- natal day (PND) 55 ; 228.6

- 312.5 g Phase II: Anti

- Androgen Assay : PND 54 ; 227.8

- 280.5 g Source : Charles River UK Ltd, Kent, UK Housing: Rats were housed up to 3 /cage in suspended plastic cages with solid floors

and wood flake bedding (Lignocel ® Grade 3⁄4 bedding)

. Diet: Special Diet Services, UK standard certified laboratory rodent diet (RM1(E)SQC) , ad libitum (phytoestrogen concentration results not reported).

Water: T ap water , ad libitum

Environmental conditions: Temperature: Humidity: Air changes: Photoperiod: 21±2 oC

55±15 % Not reported 12 hrs light/12 hrs dark Acclimation period: Prior to castration: 7 days

Post

- castration: 9 days prior to initiation of dosing



## B. STUDY DESIGN

1. In

- life dates : Androgen Agonist Assay: Start: 3/5/2012 End: 3/15/2012

Anti -Androgen Assay: Start: 4/2/2012 End: 4/12/2012

2. Study Design : Th is Hershberger Assay was conducted to screen for both potential androgenic and anti

- androgenic a ctivity. In the test for androgenic activity (Phase 1)

, PCNB was administered daily via oral gavage to groups of castrated male rats. Positive androgenic activity is defined as a significant increase in two or more target organ weights compared to the vehicle control group. The positive control group for androgen ic activity consisted of

castrated male rats dosed by subcutaneous ( s.c. ) injection with TP at 0.4 mg/kg/day. In the

test for anti -androgenic activity (Phase 2)

, PCNB was administered daily via oral gavage to groups of castrated male rats in conjunction w ith TP at 0.4 mg/kg/day by s .c. injection.

Anti

- androgenic activity is indicated by a statistically significant 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 consisted 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 10 consecutive days and necropsied approximately 24 hours after the final dose administration for measurement of target organ weights.

3. Study Schedule : Following the initial 7- day acclimation period, sexually mature male rats

were castrated on PND 43 -44 according to standard procedures and allowed 9 days for recovery and regression of accessory sex organ weights prior to initiation of dosing. The dose administration period was from PND 54-55 through PND 64-65 . Rats were euthanized

on PND 65-66 approximately 24 hours after the last dose and necropsied for organ weight

measurements.In vivo Hershberger Assay (2012 ) / Page 5 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## 4. Animal Assignment : Animals were randomly assigned, stratified by body weight, to the test groups noted in Table 1. Statistical analysis indicated that there were no significant differences in group means at study initiation. Furthermore, the body weight of each animal

was within 20% of the overall mean.

TABLE 1. Study design a


### Test group Dose (mg/kg/day) # of Males
Androgen Agonist Assay

Vehicle control (negative control) 0 10

Low ( PCNB ) 300 10
High ( PCNB ) 1000 10
Testosterone propionate (TP) (s.c.), positive control 0.4 10

Anti

- Androgen Assay

1% SCMC + TP (negative control) 0 10

Low ( PCNB +TP ) 100 10

Mid ( PCNB +TP ) 300 10
High ( PCNB +TP) 1000 10
Flutamide (oral gavage) + TP (s.c.), positive control 3 10

a Data were obtained from page s 14 and 1 5 of the study report (MRID 48916702)

.



## 5. Dose Selection Rationale: The limit dose (1000 mg/kg/day) w as selected as the high dose for the androgen agonist and anti-androgen assays based on EPA guidelines. For theandrogen agonist assay, one additional dose of 300 mg/kg/day was tested. For the antiandrogen assay, two additional doses of 100 and 300 mg/kg/day were tested.

6. (a) Dose Preparation : Dose formulations were prepared once prior to initiation of treatment by mixing the appropriate amounts of test substance in 1% SCMC

. Flutamide and

TP prepared were daily prior to dosing by mixing in corn oil. Concentration analyses were performed prior to administration on all dose levels. H omogeneity and stability analyses on

PCNB formulations (10 and 200 mg/mL) were performed prior to administration (Huntingdon Study No. BDG0122 ; MRID 48916703, see Appendix I) . Stability of the dosing suspensions was validated for 15 days under ambient and refrigerated storage
conditions.

( b) Dose Analysis

Results

Homogeneity (%CV) : 0.57-4.69%

Stability (% of nominal) : 97-104%

Concentration (% of nominal): 91-95%

The analytical data indicated that the mixing procedure was adequate and that the variation between nominal and actual dosage to the animals was acceptable.In vivo Hershberger Assay (2012 ) / Page 6 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## 7. Dosage administration: Test formulations of PCNB were administered to the animals daily via o ral gavage (5 mL/kg bw) for 10 days. TP was given via s.c. injection at 0.5 mL/kg bw, and FT was administered via oral 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, liver weight and accessory sex organ weights were first analyzed by Bartlett’s test for homogeneity of variances. Treatment groups were compared to the control using Williams’ test. For the accessory sex organ weights, analysis

of cova riance (ANCOVA) was also performed with terminal body weight as the covariate. For the androgenic agonist test, the TP group was compared to the control using Student’s

t test. For the anti-androgenic test, the flutamide and TP group was compared to the control using Student’s t test

. Significance was denoted at p ≤ 0.05. Statistical analyses were performed using StarTox (version 3.2.1) and Quasar (version 1.1). The stat istical analyses were considered adequate.

C. METHODS

1. Clinical Examinations : Clinical observations were conducted immediately after dosing, 1- 2 hours after dosing, and at the end of the working day.

2. Body Weight: Animals were weighed on the day of castration surgery, for 6 days postsurgery, daily throughout the dosing period, and on the day of necropsy.

3. Food Consumption (Optional) : Food consumption was not determined.

4. Serum Hormone Measurements (Optional) : Serum hormone measurements were not

conducted.

5. Dissection and Measurement of Tissue and Organ Weights : On PND 65-66 (approximately 24 hours after the final administration of the test substance)

, all animals were euthanized by cervical di slocation and subjected to a gross necropsy. The five mandatory androgen-dependent organs (ventral prostate, seminal vesicles, LABC, Cowper’s gland, and glans penis) were excised, trimmed free of adhering tissue, and weighed fresh (unfixed) according to the standard operating procedures detailed in the U.S. EPA Guideline (OCSPP 890.1400). Additionally, the liver was collected and weighed.

II. RESULTS

A. OBSERVATIONS

1. Mortality : All animals survived until scheduled termination.

2. Clinical signs of toxicity : No treatment

- related clinical signs of toxicity were observed in

animals f rom any dose groups.In vivo Hershberger Assay (2012 ) / Page 7 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## B. BODY WEIGHT AND WEIGHT GAIN : Selected body weight and body weight gains for the androgen agonist assay are presented in Table 2. No effects on body weights or body weight gains were observed for any PCNB dose groups. Animals dosed with TP had

increased (p≤0.05) body weights on Days 8 -11 ( ↑ 5-8%) and an overall body weight gain of 48% compared to controls.

TABLE 2

. Selected Group Mean (±SD) Body Weights and Cumulative Body Weight Gains (g) in the Androgen Agonist Assay with PCNB a

Study Day # Dose (mg/kg/day)

Vehicle Control Positive Control

Vehicle + TP (0.4) PCNB (300 ) PCNB (1000 )

N Mean SD N Mean SD N Mean SD N Mean SD

1 10 271.0 18.4 10 270.6 20.7 10 271.9 21.0 10 268.7 15.3

4 10 287.0 19.6 10 297.1 21.3 10 289.3 24.4 10 286.2 15.1

7 10 304.8 21.7 10 324.6 22.5 10 306.4 27.7 10 304.1 17.8

11 (Necropsy) 10 324.9 22.5 10 350.5* (↑8) 21.3 10 324.9 30.2 10 322.7 17.9

BWG (Days 1

- 11) 10 53.9 7.0 10 79.9 * (↑ 48 ) 6.8 10 53.0 11.0 10 54.1 8.8

a D ata were obt ained from Table 3 on page 32 of the study report 

### (MRID 48916702) . Percent differences from controls ( calculated by the reviewers ) a re included in parentheses.

N Number of animals in the group

SD Standard Deviation

* Significantly different from controls at p ≤ 0.05



## Selected b ody weight and body weight gain data for the anti-androgen assay are presented in

Table 3. Body weights and body weight gains in all dose groups we re comparable to controls throughout the duration of the assay.

TABLE 3

. Selected Group Mean (±SD) Body Weights and Cumulative Body Weight Gains (g) in the Anti

Androgen Assay with PCNB a

Study Day # Dose (mg/kg/day)

Vehicle Control

+ TP (0.4) Positive Control

TP + FT (0.4 + 3.0) PCNB+TP (100 + 0.4) PCNB +TP (300 + 0.4) PCNB +TP (1000 + 0.4)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 10 260.8 14.7 10 262.5 10.8 10 262.3 14.3 10 262.1 13.8 10 261.5 13.8

4 10 283.7 16.7 10 287.1 11.9 10 289.3 16.2 10 287.9 14.0 10 285.8 16.2

7 10 307.9 17.8 10 308.2 15.2 10 314.7 16.2 10 312.6 17.0 10 309.6 17.8

11 b 10 332.0 17.4 10 334.6 18.1 10 339.8 19.6 10 337.7 18.9 10 337.5 24.0

BWG (days 1

- 11) 10 71.2 10.3 10 72.1 11.2 10 77.5 11.4 10 75.6 10.4 10 76.0 12.6

a Data were obtained from Table 3 on page 33 of the study report 

### (MRID 48916702)

. b Necropsy

N Number of animals in the group

SD Standard Deviation



## C. FOOD CONSUMPTION (Optional) : Food consumption was not determined.In vivo Hershberger Assay (2012 ) / Page 8 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## D. SERUM HORMONE CONCENTRATIONS (Optional) : Serum hormone concentrations

were not determined.

E. ORGAN WEIGHTS : Accessory sex organ weights for the androgen agonist assay are presented in Table 4. There were no treatment

- related weight increases in any of the accessory sex organs of animals dosed with PCNB. At 100 0 mg/kg/day, the adjusted liver weights were in creased by 8 % (p≤0.05) and the unadjusted liver weights were increased by 7% (not significant). Animals in the TP group had increases (p ≤ 0.01 ) in unadju sted accessory sex organ weight s as follows: 750 % in seminal vesicles, 1316% in ventral prostate, 179 % in LABC , 518% in Cowper’s gland, and 50% in glans penis. The unadjusted liver weight in the TP group w as increased by 15% (p≤0.01 ) and the adjusted liv er weight

w as increased by 8% (p≤0.05). All %CV values were less than or equal to the maximum

recommended va lues.

T ABLE 4. Accessory Sex Organ Weights (mg) from Androgen Agonist Assay with P C N B in Sprague

Dawley Rats a

Organ Dose (mg/kg/day)

Vehicle control PCNB ( 300 ) PCNB ( 100 0) Positive Control

Vehicle + TP (0.4)

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Seminal

vesicles U 10 69.7 12.3 18 10 74.8 12.0 16 10 74.3 14.1 19 10 592.6** (↑ 750 ) 108.7 18

A 10 69.3 NA NA 10 74.5 NA NA 10 73.7 NA NA 10 569.9** (↑ 722 ) NA NA

Ventral

prostate U 10 24.2 8.52 35 10 26.8 7.84 29 10 30.5 12.2 40 10 342.6** (↑ 1316 ) 61.4 18

A 10 23.1 NA NA 10 25.9 NA NA 10 28.9 NA NA 10 337.6** (↑ 1361 ) NA NA

LABC U 10 245.6 39.7 16 10 232.4 32.3 14 10 243.5 12.1 5 10 685.0** (↑ 179 ) 70.1 10

A 10 244.8 NA NA 10 232.4 NA NA 10 246.0 NA NA 10 662.3** (↑ 171 ) NA NA

Cowper’s glands U 10 7.2 1.27 18 10 8.2 2.67 33 10 8.6 2.72 32 10 44.5** (↑ 518 ) 6.54 15

A 10 7.1 NA NA 10 7.8 NA NA 10 8.2 NA NA 10 44.6** (↑ 528 ) NA NA

Glans penis U 10 61.0 8.80 14 10 58.1 8.97 15 10 57.7 8.03 14 10 91.2** (↑ 50 ) 10.8 12

A 10 61.3 NA NA 10 58.4 NA NA 10 58.1 NA NA 10 90.3** (↑ 47 ) NA NA

Liver U 10 11.7 1.15 10 10 12.3 1.62 13 10 12.5 (↑ 7 ) 1.06 8 10 13.5** (↑ 15 ) 0.92 7

A 10 11.9 NA NA 10 12.5 NA NA 10 12.8* (↑ 8 ) NA NA 10 12.8* (↑ 8 ) NA NA

a Data were obtained from Tables 1 and 2 on pages 28 and 30 of the study report (MRID 48916702) . Percent differences from controls were calculated by the reviewers and included in parentheses.

N Number of animals in the group

SD Standard Deviation

CV Coefficient of Variation

NA Not applicable

U Unadjusted for terminal body weight

A Adjusted for terminal body weight

* Significantly different from controls at p ≤ 0.05

** Significantly different from controls at p≤0.01In vivo Hershberger Assay (2012 ) / Page 9 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## Accessory sex organ weights for the anti

- androgen assay are presented in Table 5. There were

no treatment

- related weight decreases in any of the accessory sex organs of animals dosed with PCNB. The Cowper’s gland weights were increased by 15% (p≤0.05) at 1000 mg/kg/day. The unadjusted liver weights were increased by 8% (not significant) at 1000 mg/kg/day. Animals dosed with TP + FT (positive control) had decreases (p≤0.01) in unadjusted accessory sex organ weights as follows: 76% in seminal vesicles , 72% in ventral prostate, 53% in L ABC , 58% in Cowper’s gland , and 27% in glans penis. The unadjusted liver weights in the TP + FT group were increased by 11% (p≤0.05) and the adjusted liver weights were increased by 10% (p≤0.01). All %CV values were less than or equal to the maximum reco mmended values.In vivo Hershberger Assay (2012 ) / Page 10 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



### TABLE 5. Accessory Sex Organ Weights (g) from Anti

- Androgen Agonist Assay with PCNB in Sprague

- Dawley Rats a

Organ Dose (mg/kg/day)

Water Vehicle Control

+ TP (0.4) PCNB+TP (100 + 0.4) PCNB +TP (300 + 0.4) PCNB +TP (1000 + 0.4) TP + FT (0.4+3.0)

Positive Control

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Seminal

ve sicles U 10 558.8 47.4 8 10 541.4 44.6 8 10 597.8 106.3 18 10 580.6 72.6 13 10 133.8 ** (↓ 76 ) 33.5 25

A 10 555.4 NA NA 10 542.5 NA NA 10 594.6 NA NA 10 579.2 NA NA 10 133.5** (↓ 76 ) NA NA

Ventra l

prostate U 10 169.8 32.6 19 10 177.0 30.4 17 10 164.9 45.3 27 10 183.9 41.9 23 10 48.0** (↓ 72 ) 9.64 20

A 10 166.6 NA NA 10 174.6 NA NA 10 159.3 NA NA 10 179.0 NA NA 10 47.2** (↓ 72 ) NA NA

LABC U 10 624.9 76.7 12 10 604.9 55.2 9 10 635.4 65.3 10 10 633.4 60.5 10 10 296.5** (↓ 53 ) 18.48 6

A 10 623. 5 NA NA 10 600.5 NA NA 10 631.4 NA NA 10 630.0 NA NA 10 296.5** (↓ 52 ) NA NA

Cowper’s

g lands U 10 35.7 4.28 12 10 37.7 5.34 14 10 37.9 6.20 16 10 41.0* ( ↑15 ) 7.43 18 10 15.0** (↓ 58 ) 2.76 18

A 10 35.7 NA NA 10 37.8 NA NA 10 37.9 NA NA 10 41.0* ( ↑15 ) NA NA 10 15.0** (↓ 58 ) NA NA

Glans penis U 10 93.6 8.91 10 10 92.6 12.0 13 10 92.2 10.9 12 10 99.3 10.8 11 10 68.2** (↓ 27 ) 9.97 15

A 10 94.4 NA NA 10 92.0 NA NA 10 91.9 NA NA 10 99.1 NA NA 10 68.5** (↓ 27 ) NA NA

Liver U 10 12.5 1.35 11 10 13.4 1.54 11 10 13.3 1.06 8 10 13.5 (↑ 8 ) 1.32 10 10 13.9* ( ↑ 11 ) 1.13 8

A 10 12.7 NA NA 10 13.2 NA NA 10 13.2 NA NA 10 13.4 (↑ 6 ) NA NA 10 14.0** ( ↑ 10 ) NA NA

a Data were obtained from Table s 1 and 2 on page s 29 and 31 of the study report (MRID 48916702) . Percent differences from controls were calculated by the reviewers and included in parentheses.

N N umber of animals in the group

SD Standard Deviation

CV Coefficient of Variation

NA Not applicable ; U Unadjusted for terminal body weight

A Adjusted for terminal body weight

* Significantly different from controls at p≤0.05

** Significantly different from controls at p≤0.01In vivo Hershberger Assay (2012 ) / Page 11 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS : In the androgenic phase of the assay, dosing of



## castrated male rats with PCNB at 

## doses of 300 and 1000 mg/kg/day for 10 consecutive days showed no significant increases in any of the five androgen- dependent tissues compared

with vehicle

- treated control animals. Systemic toxicity was limited to a slight but statistically significant in crease in relative liver weight at the 1000 mg/kg/day dose, which is

the limit dose for this assay. Based on these findings PCNB is considered to have no androgenic effects under the conditions of this assay.

In the anti-androgenic phase of the assay, dosing of castrated male rats with PCNB at 100, 300 and 1000 mg/kg/day for 10 consecutive days, in conjunction with s.c. dosing of TP (0.4 mg/kg/day) showed no significant reductions in any of the five androgen- de pendent tissues compared with the TP- treated control animals. No systemic toxicity was noted at any dose in this study phase, including the 1000 mg/kg/day limit dose. Based on these findings

PCNB is considered to have no anti- androgenic effects under the conditions of this assay.

Overall, PCNB showed no evidence of interaction with the androgen pathway by either an androgenic or anti -androgenic mechanism under the conditions of this assay.

B. AGENCY COMMENTS : All animals survived until scheduled terminati on. There were

no treatment

- related clinical signs of toxicity.

In the androgen agonist assay, body weights and body weight gains for the 300 and 1000 mg/kg/day treatment groups were comparable to controls throughout the assay. Animals dosed with TP had increased (p≤0.05) body weights on Days 8 -11 ( ↑ 5- 8%) and an overall body weight gain of 48% compared to the control. There were no treatment

- related weight increases in any of the accessory sex organs of animals dosed with PCNB. At 1000 mg/kg/day, the adjusted liver weights were increased by 8% (p≤0.05) and the unadjusted liver weights were increased by 7% ( NS ). 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 and body weight gains for the 100, 300, and 1000 mg/kg/day treatment groups were comparable to controls throughout the assay. There were no decreases in weights of accessory sex organs of PCNB

- treated animals, but th e Cowper’s gland weights were increased by 15% (p≤0.05) at 1000 mg/kg/day. The unadjusted liver weights were increased by 8% ( NS ) at 1000 mg/kg/day. Animals dosed with FT + TP (positive control) showed the expected decreases in accessory sex organ weigh ts.

All %CV values were less than or equal to the maximum recommended values in both phases of the assay

. The dosing levels selected for the study were acceptable as animals were dosed up to limit dose (1000 mg/kg/day) for the assay. No statistically significant changes were seen in two or more of the five androgen sensitive tissue weight s. PCNB was negative for androgenicity and anti -androgenicity in the Hershberger assay.

C. STUDY DEFICIENCIES : NoneIn vivo Hershberger Assay (2012 ) / Page 12 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



# Appendix I: PCNB Technical: Development and Validation of an Analytical Method and Liquid Formulation Preparation, Homogeneity and Stability.

The analytical laboratory provided validation data (MRID 48916703) for the HPLC/UV method (FIA/M005/12) used to determine PCNB concentrations in the dosing suspensions. PCNB concentrations in the dosing suspensions w ere determined directly by HPLC analysis without

extraction , using an Inertsil ODS

- 3 column with an isocratic mobile phase of acetonitrile:water (7:3, v/v). PCNB was detected and quantified using a UV detector (254 nm). The analytical laboratory also provided data demonstrating the homogeneity and stability of PCNB Technical in the 1% SCMC dosing suspensions.

I. Method Validation. A standard solution of PCNB Technical (Batch # 107030L052, 95.6% a.i., expires July 2016) was prepared by dissolving in acetonitrile, for a concentration of 100 μg/mL Solutions for calibration were prepared by appropriate dilution to ge nerate nominal

co ncentrations of 1, 4, 6, 8 ad 10 μg/mL. The analytical procedure was validated by determining the following parameters; The specificity of the chromatographic analysis in the control sample chromatograms, the Limit of detection, the linearity of detector response over the calibration standard range, the precision of injection of the lowest and highest concentration calibration standards, and the accuracy and precision of the method. Procedural recoveries were prepared by fortifying samples of control mat rix (1% SCMC)

with known amounts of PCNB Technical.

The analytical procedure was successfully validated for PCNB technical in 1% SCMC. The specificity was demonstrated by the absence of a peak at the characteristic retention time for PCNB Technical, the Limit of detection was 72.3 ng/mL, Linearity was con fi rmed with

a r 2 

## of >0.999, the precision of injection was <1%, and the method accuracy and precision (Table 1) were within acceptable values, the overall mean procedural recovery was 98.6%.

Table A 1: Method Validation for PCNB Technical in 1% SCMC a


### Sample Nominal Fortification (mg/mL)

10 200

1 94.7 98.4

2 98.9 99.4

3 99.0 98.7

4 101.7 97.9

5 98.7 99.0

6 99.7 96.5

Mean (%) 98.8 98.3

%CV 2.31 1.04

n 6 6.

Overall mean (%) 98.6

%CV 1.73

n 12

a 

### Data were obtained from page 22 of the reportIn vivo Hershberger Assay (2012 ) / Page 13 of 13

PCNB / 056502 O CS PP 8 9 0. 1400/ OECD 441



## II . Homogeneity and stability. The homogeneity and stability of P CNB Technical in 1% SCMC Formulation was assessed at concentrations of 10 mg/mL and 200 mg/ml, under

ambient a n d refrigerated (4°C) storage conditions . Samples were stored at ambient temperature, and samples from the top, middle and bottom of each concentration were analyzed after 24 hours and 15 days to assess storage stability. Samples that were refrigerated were sampled on days 1, 8 and 15 to assess refrigerated storage stability.

The h omogeneity and storage stability of PCNB in 1% SCMC were confirmed

. H omogeneity (%CV) ranged from 0.57 -4.69%, and stability of PCNB was 97 -104% of the

time zero concentration.

TABLE A 2

. Homogeneity and stability of PCNB Technical in 1% SCMC a



### Concentration (mg/mL) Storage Conditions Analyzed Concentration (mg/mL)
Temperature Time Top Middle Bottom Mean % Time

Zero CV(%)

10 Ambient (21°C) 0h 8.31 8.68 8.92 8.64 100 3.54

1h 8.74 8.63 8.87 8.75 101.3 1.38

2h 8.91 8.72 8.64 8.75 101.3 1.55

24h 8.77 8.89 9.27 8.98 103.9 2.88 15 days 8.65 8.6 9.24 8.83 102.2 4.01 Refrigerated (4°C) 1 day 8.37 8.41 8.73 8.51 98.5 2.33 8 days 8.6 8.86 9.42 8.96 103.7 4.69 15 days 8.59 9.28 9.09 8.98 103.9 4

200 Ambient (21°C) 0h 194 196 191 194 100 1.16

1h 193 195 194 194 100 0.57

2h 190 194 193 193 99.5 1.02

24h 191 187 193 191 98.5 1.62 15 days 185 184 194 188 96.9 3.02 Refrigerated (4°C) 1 day 193 191 186 190 97.9 1.7 8 days 190 195 200 195 100.5 2.7 15 days 187 194 188 190 97.9 1.95

s 

### Data were obtained from page 23 of the report

.

# DATA EVALUATION RECORD

PCNB

Study Type: O CSPP 890.1450, Female Pubertal Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-45-2013 (MRID 49042103)

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:
Michael E. Viana, Ph.D., D.A.B.T. Date: 0 3 / 2 9 /2013

Secondary Reviewer : Signature: Scott Studenberg, Ph.D. , D.A.B.T. Date: 0 4 / 01 /201 3

Program Manager: Signature: Jack D. Early, M.S. Date: 04/11/ 201 3

Quality Assurance: Signature: Jack D. Early, M.S. Date: 04 / 11 /201 3

This Data Evaluation Record may have been altered 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 intended 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 redundancy 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 potential 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).

### P CNB I 

### 056502



## Primary Reviewer: Nancy McCarroll



## RAB VI, Health Effects Division Secondary Reviewer: E lizabeth Mendez, Ph.D.



## Health Effec ts Di visio n Fema l e P u berta l Assay (2012) I 

### Page 1of15

OCSPP 890.1450/ OECD None



## Signature: 

# /IOA\'1 fltcCw.JJ

Date:

# M~**,** Signature:

# ~**~** Date: Tomp l otom22



## DATA EVALUATION RECORD

STUDY TYPE: Female Pubertal Assay; OCSPP 890.1450; OECD None.



## PC CODE: 056502 

## DP BARCODE: D409239



## TXR# : 0056474 

## CAS No: 82-68-8



## TEST MATERIAL (PURITY): PCNB Technical (95.6% a.i.)



## SYNONYMS: 1

, 2

, 3

, 4

, 5 -p entacbloro

- 6-nitrobenzene ; Quintozene



## CITATION: Baxter

, G.E. (2012) PCNB: Assessment of Pubertal Development and Thyroid F un ct ion in Juvenile Ma l e and Fema l e Rats. Huntingdon Life

Sciences

, East Millstone, NJ. La b o r atory Study No.: 12-4389, December 19

, 2012. MRID 49042 1 03A. Unpub li s h ed

.



## SPONSOR: AMV AC Chemical Corporat i on
, 2110 Davie A venue
, Commerce

, CA



## TEST ORDER #: 

## EDSP

- 056502-105



## EXECUT IVE SUMMARY : In 

## a Female Pubertal Assay (MRID 49042103A)

, 15 Sprague

Daw l ey [ Crl :CD ® (SD) IGS BR] rats / dose group were treated dail y v i a ora l gavage with PCNB (95.6% a.i.; Lot # 1070 30L052) in aqueous 1 % sodi um carboxymethyl ce llul ose at dose s of

0 (ve hicl e), 500, or 1000 ( limit dose) mg/kg/day from post-natal day (PND) 22 to 42. Animals

were exam in ed fo r vagina l opening (VO) daily beginning on PND 22

, and age and weigh t at day

of attainme nt were recorded. Following sacrifice o n PND 42, blood was collected for clinical chemistry and hormone analyses. Total serum thyroxine (T4) was determined b y radioimmunoassay
, but the method used for determination of thyroid st imul ating h ormone (TSH) levels was

not reported. Adre n al

, live r
, pituitary, thyroid

, and urogenital organs were**we ghed** **~** 

## and microscopic examinations were p erformed on the ovaries, uterus

, thyroid, liver

, and kidneys.

There we r e no effects of tre atmen t on mortality, clin i ca l s i g ns of toxicity, final body weights or body weig ht gains, food co n su mption

, or gross pat h o l ogy. Compared to the contro l gro up
, absolute

, adjusted, and relative (to body) liver weights were increased (p < 0.05) by 6-8% at 500 mg/kg/day and by 6% at 1000 mg/kg/day, and abso l ute

, adjuste d and relative kidney weig h ts

we r e increased (p < 0.01) by 6-8% at500 mg/kg/day and by 8% at 1000 mg/kg/day. The

fo ll owing dose-dependent c h anges in clinical chemistry parameters were observed at 500 and

I 000 mg/kg/day

, respectively: alkaline phosphatase (ALP) activity was increased (p<0.05) by

20 and 26%; alanine aminotransferase (ALT) activ i ty was decreased (p < 0.001) by 42 an d 51% ; total bi li rubin was increased (p<0.01) by 44 and 56%; and urea nitro gen was in c reased (p<0

. 05)Female Pubertal Assay ( 2012 ) / Page 2 of 15

PCNB / 056502 O CSPP 89 0. 1 45 0/ OECD None



## by 8 and 15%. Additionally at 1000 mg/kg/day, albumin was decreased (p<0.05) by 3% and total protein was decreased (p<0.01) by 4%.

There were no effects of treatment on age and body weight at attainment of VO. All females

achieved complete VO. There were no effect s of treatment on mean age at first vaginal estrus, mean cycle length, % cycling or regularly cycling, or cycle status at necropsy. Antral and tertiary follicles, corpora lutea, and atretic follicles were present in the ovary of all individuals, and the numbers of primordial and primary follicles showed no biologically relevant differences across groups. The number of 1000 mg/kg/day females classified in metestrus by examination of the uterus (with cervix) was increased (6 treated vs. 1 control; p<0.05); however, the biological significance of this finding i s unclear.

Serum T 4 

## levels were decreased (p<0.001) by 70% at 500 mg/kg/day and by 72% at 1000 mg/kg/day. Concomitantly, serum TSH levels were increased (p<0.001) by 53% at 500 mg/kg/day and by 59% at 1000 mg/kg/day. No significant changes were observed in thyroid histology ; h owever, there was a slight, dose- related trend toward decreased colloid area and increase follicular cell height.

The dose levels tested in assay are adequate since the high dose was the Limit Dose ( 1000 mg/kg/day)

.

The assay satisfies the EDSP Tier 1 Test Order requirement s for a Female Pubertal Assay (OCSPP 890.1450).

COMPLIANCE : Signed and dated Data Confidentiality, GLP Compliance, and Quality Assurance statements were provided.Female Pubertal Assay ( 2012 ) / Page 3 of 15

PCNB / 056502 O CSPP 89 0. 1 45 0/ OECD None



## I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility : Huntingdon Life Sciences

Location: East Millstone, NJ Study Director: G.E. Baxter

Other Personnel: C

. Willard

- Mack (Pathologist), Y

. Wang (Dose Formulation analysis), L

. Ramaih (Clinical Pathologist), S

. Polivy (TSH Hormone analysis), G

. Thomas (Statistics) Study Period: March 30, 2012 to December 19, 2012



## 2

. Test S ubstance : PCNB Technical

Description: O ff

- white to dark tan crystalline solid or powder

Source: AMVAC Chemical Corporation (Los Angeles, CA)

Lot #: 107030L052 (Expiration July 2016) Purity : 95.6% a.i. Stability: 15 days under refrigerated ( 2

- 8 ̊C) or room temperature conditions

CAS #: 82

- 68

- 8

Structure:



## 3

. Vehicle : 1% Aqueous carboxymethyl cellulose (sodium)

4

. Test A nimals : Species: Rat

Strain: Sprague Dawley [Crl:CD ® (SD)IGS BR] Age/ W eight at Allocation : PND 21 / 47.3

- 55.4 g

Source: Charles River Laboratories (Portage, MI) Housing: Dams were individually housed in plastic shoebox cages with aspen bedding through parturition and weaning. Selected pups were housed in the same type cage with up to 3/pups/sex/cage.

Diet: Certified Global 18% Protein Rodent Diet, 2018C, in pellet form (Harlan Teklad, Madison, WI), ad libitum . It was stated that the genistein

- equivalent content of the diet was ≤300 μg/g.

Water: Deionized water without chlorine supplementation (made on

- si te), ad libitum

. Environmental

C onditions: Temperature: Humidity: Air changes: Photoperiod: 22.1

- 25.0 ° C

44

- 52% Not provided 14 h light / 10 h dark



## B. ST UDY DESIGN

1. In -L ife D ates : Start: May 1, 2012 End: May 21, 2012

2. Mating : Time

- mated pregnant dams were received from the supplier on gestation day (GD) 8. The day evidence of mating was observed was designated as GD 0. Litters with

fewer than 9 pups were excluded from the study; litters with 10 pups but less than four of a

se x were retained. Litters with more than 10 pups were standardized by culling on PND 4 to 5 pups/sex/litter where possible; culling to 6 males and 4 females or 4 males and 6 females was also acceptable

. NH 2 Cl Cl

Cl Cl

ClFemale Pubertal Assay ( 2012 ) / Page 4 of 15

PCNB / 056502 O CSPP 89 0. 1 45 0/ OECD None



## 3. Animal A ssignment : Offspring were weaned on PND 21, wei ghed , and ranked by body weight . The 5 heaviest and 5 lightest female pups were then eliminated from use. The remaining females were then assigned to the groups noted in Table 1 starting with the heaviest females by assigning to the groups sequentially (Group s 1, 2 and 3) until each group contained 15 females. It was not stated if placing littermates in the same group was avoided.

TABLE 1. Study Design a
Test group Dose (mg/kg/day) # of Fem ales

Control 0 15

Low 500 15 High 1000 15

a Data were obtained from Text Table 2.3

- 1 on page 17 of the study report (MRID 49042103)

.



## 4. Dose S election Rationale : It was stated that the dose levels used in the present study were

selected based on the results of four previously performed studies. In a developmental toxicity study, pregnant females were dosed with PCNB (10 mL/kg) at 0, 250, 750, or

1500 mg/kg/day during GD 6 -15. No clinical signs were noted up to 1500 mg/kg/day; however decreased body weight gains an d food consumption were noted during GD 6- 9 at 750 and 1500 mg/kg/day. Food consumption rebounded post-dosing (GD 15-20) at 1500 mg/kg/day. In a 2- year rat oncogenicity study, males and females were dosed with 0, 5, 50, 500, or 1000 mg/kg/day. Body weig hts were decreased in the 1000 mg/kg/day males and in the 500 and 1000 mg/kg/day females. I n a 2 -generation reproduction toxicity study, rats were dosed with 0, 10, 100, or 1000 mg/kg/day from 10 weeks prior to mating in the P generation through weaning o f the F2 generation. No clinical effects were observed. Therefore, doses of 0, 500, and 1000 mg/kg/day were chosen for a non-GLP dose

range -finding pubertal study that also assessed the tolerability of a lower dose volume (5 mL/kg) compared to what was p reviously used (10 mL/kg). The dose levels and dose volume were acceptably tolerated.

5. Dose P reparation and Analysis : Dose formulations were prepared every 3 -4 days, and

were stored at room temperature protected from light. An appropriate amount of t he test
substance (not adjusted for purity) was ground with a mortar and pestle into a fine powder and mixed with a small volume of the vehicle to form a paste. Th e paste was brought up to final volume with additional vehicle, homogenized, and stirred to yield a uniform suspension. Stirring was continuous during sampling and aliquoting. Homogeneity (top, middle, and bottom) and stability analyses were performed prior to study initiation on samples of the same concentrations used in the present study. Stability was determined after storage for up to 15 days at both ambient and refrigerated temperatures. Concentration analyses were performed on all dose levels from the first preparation (administered on Days

1- 4).

Results of D ose Analysis

Homogeneity (%CV) : 0.57-4.01%

Stability (% of time 0) : 97.1-97.7%Female Pubertal Assay ( 2012 ) / Page 5 of 15

PCNB / 056502 O CSPP 89 0. 1 45 0/ OECD None



## Concentration (% of nominal): 88.1-99.5%

The analytical data indicated that the mixing procedure was adequate and that the variation between nominal and actual dosage to the animals was acceptable

. Concentration analysis

for t he Week 1 (Days 1 -4) 500 mg/kg/day formulation w as 88.1% of nominal, which is outside the protocol- specified acceptance criteria of ±10% . However, this slight deviation did not affect the study results.

6. Dosage A dministration : All doses were administered once daily by gavage, from PND 22 through PND 42, in a dose volume of 5 mL/kg. Individual doses were based on the most recently recorded body weights. D osing was performed between 0700 and 0900 hours daily.

7. Statistics : The following parameters were subjected to statistical analysis: body weights, body weight gains, food consumption, age and body weight at attainment of VO, clinical chemistry, hormone levels, organ weights, estrus stage, and histopathology. For c ontinuous

p arameters

, Bartlett's test for variance homogeneity was applied. I f Bartlett's test was not significant at the 1% level, parametric methods were applied , using an F1 approximate test for monotonicity. If the F1 test was not significant at the 1% level, Williams' test for a monotonic trend was applied. If the F1 test was significant, suggesting that the doseresponse was not monotonic, Dunnett's test was performed instead. If Bartlett's test was significant at the 1% level, logarithmic and square root transformations were tried. If Bartlett's test was still significant, non

- parametric methods were applied to mean ranks

, with

an H1 approximate test for monotonicity. If the H1 was not significant at the 1% level, Shirley's test for a mon otonic trend was applied. If the H1 test was significant, Steel's test was performed instead. For discrete parameters involving more than two groups, the

Jonckheere- Terpstra test was applied. If the Jonckheere- Terpstra test was significant at the

5% lev el, the direction of the trend was established and one- tailed step

- down testing in this direction was performed. If the Jonckheere- Terpstra test was not significant at the 5% level,

the Kruskal- Wallis test was applied. If the Kruskal- Wallis test was significant at the 5% level, the treated groups were compared to the control using exact Wilcoxon rank sum tests; otherwise, no further comparisons were made. For b inary p arameters involving more than

two groups, the Cochran

- Armitage test was applied. I f the Cochran

- Armitage test was significant at the 5% level, the direction of the trend was established and one- tailed step

down testing in this direction was performed. If the Cochran

- Armitage test was not significant at the 5% level, the χ 2 

## test (Armitage e t al 2002) was applied. If the χ 2 

## test was significant at the 5% level, the test- article treated groups were compared to the control with Fisher's Exact tests, otherwise, no further comparisons were made.

VO (day of VO and bodyweight) and organ weight dat a were also analyzed as follows.

Bartlett's test was applied ; i f this test was not significant at the 1% level, parametric analysis was applied. The bodyweight at PND 21 was used as a covariate in the analyses and comparisons were performed on the adjusted means after the analysis of covariance. The F 1 approximate test was applied ; i f the F 1 test was not significant at the 1% level, Williams' test for a monotonic trend was applied, otherwise Dunnett's test was performed instead. If Bartlett's test was significant at the 1% level, logarithmic and square root transformations

were tried. If Bartlett's test was still significant, non

- parametric tests were applied. The H1Female Pubertal Assay ( 2012 ) / Page 6 of 15

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## approximate test was applied ; i f the H 1 test was not significant at the 1% level, Shirley's test was applied, otherwise Steel's test was performed instead.

For histopathology, t est

- article treated groups were compared to the control with Fis her's

Exact tests

.

Statistical significance was declared at the 5%, 1% and 0. 1% levels. The statistical analyses were considered appropriate.

C. METHODS

1. Mortality and C linical Examinations : All animals were observed twice daily for mortality and moribundity beginning on PND 21 and continuing throughout the study.

Individual c linical examinations were conducted daily prior to dosing through the day of

euthanasia

.

2. Body W eight : Animals were weighed at randomization, daily prior to dosing, and on the day of euthanasia

. Mean body weight gains were calculated for each weighi ng interval, and

for PND 22 -42.

3. Food Consumption : Food consumption (g/rat/day) was measured by placing a weighed feeder in each cage, reweighing it after 2-4 days, and dividing by the number of rats/cage. Food consumption was reported for PND 22-25, 25-29, 29-32, 32-36, 36-39, and 39-42.

4. Vaginal O pening (VO) : Each female was observed daily after dosing for vaginal perforation beginning on PND 22. The age and body weight on the day at which the vaginal lumen was first observed to open was recorde d for each animal.

5. Estr o us C yclicity : Beginning on the day of VO , up to and including the day of necropsy, daily vaginal smears were obtained. The vaginal smears were classified as proestrus, estrus, metestrus, or diestrus , and estrus stage at euthanasia was reported . The age at first vaginal estrus was recorded, and the average cycle length was calculated and reported for complete cycles . Additionally, t he percentage of females cycling and regularly cycling was calculate d

and reported

.

6. Sacrifice and Pathology : All animals were euthanized by exsanguination on PND 42 at

least two hours post-dosing. All terminal procedures were completed by 1300 hours.

Unfasted animals were anesthetized with isoflurane and b lood was collected from the aorta. The blood was allowed to clot for at least 30 minutes and centrifuged to obtain serum

. Samples were stored at <−20°C (as required) for subsequent hormone and clinical chemistry

evaluations.

a. Hormone Analysis : Serum T 4 

## concentrations were determined with a radioimmunoassay. Serum TSH levels were determined by an external laboratory (AniLytics, Inc., Gathersburg, MD); the method used was not reported.

b. Clinical C hemistry : The following CHECKED (X) parameters were examined.Female Pubertal Assay ( 2012 ) / Page 7 of 15

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ELECTROLYTES OTHER

Calcium X Albumin

Chloride X Creatinine*

Magnesium X Urea nitrogen*

Phosphorus Total cholesterol

Potassium X Globulins

Sodium Glucose

ENZYMES X Total bilirubin

X Alkaline phosphatase (AL P ) X Total protein

Cholinesterase (ChE) Triglycerides

Creatine phosphokinase X Albumin/globulin ratio

Lactic acid dehydrogenase (LDH)

X Alanine aminotransferase (ALT/also SGPT)

X Aspartate aminotransferase (AST/also SGOT)

Sorbitol dehydrogenase (SDH)

Gamma glutamyl transferase (GGT)

Glutamate dehydrogenase

* Recommended for the pubertal assay in female rats based on Guideline 890.1 45 0.



## c. Organ W eights and Histopathology : The following CHECKED (X) tissues were collected and weighed. The (XX) organs, in addition, were subjected to histological

examination

.

UROGENITAL OTHER

XX Ovaries ( paired, without oviducts) * + X X Thyroid * +

X X Uterus* + X X Liver *

XX Kidneys (paired)*+ X Adrenals (paired) *

X Pituitary *

* Weights required based on Guideline 890.1 4 50

+ Histopathological examination required based on Guideline 890.1 4 50



## Complete macroscopic examinations were performed on all animals

. All organs collected except the thyroid/trachea were weighed prior to fixation. Paired organs (kidneys, adrenals, and ovaries) were weighed 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).

Kidneys were fixed in 10% neutral buffered formalin for no more than 24 hours; the left kidney was retained in 10% neutral buffered formalin, the right kidney was rinsed and

stored in 70% ethanol. All other tissues were fixed in 10% neutral buffered formalin for no more than 24 hours, then rinsed and stored in 70% ethanol. After fixation , the thyroid w as dissected from the trachea. The thyroid, kidneys, liver, ovaries, and uterus were routinely processed, sectioned, stained with hematoxylin and eosin, and examined microscopically.

Thyroid/parathyroid 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 with the most abundant colloid, and 5 = tallest epithelium with the l east abundant colloid. A minimum of two sections of each of the two lobes of the thyroid/parathyroid

were evaluated. Evaluation of the ovaries included a qualitative evaluation of follicular development. Five sections

, taken at least 100 μm apart from t he middle third of the ovary,Female Pubertal Assay ( 2012 ) / Page 8 of 15

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## were evaluated. The ovarian sections were examined for presence or absence of antral/tertiary follicles, presence or absence of corpora lutea, changes in corpus luteum development and a qualitative evaluation of numbers of at retic follicles. In addition, a count of primordial and primary follicles (follicles with intact oocytes surrounded by a single layer of granulosa cells) was performed. The uterus was evaluated for uterine hyper

- or hypotrophy, as characterized by change s in uterine horn diameter, as well as myometrial, stroma, or endometrial gland development. The stage of the estrous cycle of the female at the time of necropsy was considered in the final pathology assessment due to the dependence of ovarian and uterine cellular changes on endocrine status. The left kidney was evaluated by means of standard histopathology.

II. RESULTS

A. MORTALITY : There was no treatment

- related mortality . One 1000 mg/kg/day rat was

euthanized on PND 25 when it was discovered to be a male rather than a female. All data for this animal were removed from calculations and analyses.

B. CLINICAL S IGNS OF T OXICITY : No treatment

- related clinical signs of toxic ity were observed during the daily examinations. The only finding noted was moderate general

dermal alopecia of the torso in one 500 mg/kg/day female (#2588) on PND 36-39.

C. GENERAL G ROWTH , V AGINAL O PENING , AND FOOD CONSUMPTION : Body weights, body weight gains, and age and body weight at attainment of VO are presented in

Table 2. There were no effects of treatment on body weights, body weight gains, or age and body weight at attainment of VO. All females achieved complete VO.

During PND 22 -25, food consumption was decreased (NS) by 37% at 500 mg/kg/day and by 39% (p<0.05) at 1000 mg/kg/day. However, food consumption rebounded and was

similar to controls for the remainder of the s tudy.

The mean s and %CV for age and body weight at VO and final body weight in the control group were within the recommended range of the performance criteria provided in the Guideline (890.1450).Female Pubertal Assay ( 2012 ) / Page 9 of 15

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### TABLE 2

. General Growth and Vaginal Opening (VO) a

Parameter Evaluated Vehicle Control 500 mg/kg/day 1000 mg/kg/day

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Initial body weight (PND 22; g) U 15 54.6 2.96 5.42 15 54.8 2.04 3.72 14 54.5 1.78 3.27

A NA NA NA
Body weight at vaginal opening (g) U 15 116.4 13.3 11.43 15 119.6 11.6 9.70 14 120.0 9.6 8.00

A 116.6 119.5 119.9
Final body weight (g) U 15 164.0 8.97 5.47 15 167.6 8.82 5.26 14 164.4 7.61 4.63

A 164.2 167.5 164.3
Final body weight (% of control) U NA 102.2 100.2

A NA NA NA
Body weight gain (final

– initial; g) U 15 109.4 7.66 7.00 15 112.8 8.85 7.85 14 110.0 6.73 6.12

A NA NA NA
Age at vaginal opening (PND) U 15 33.6 1.7 5.06 15 33.5 1.4 4.18 14 34.2 1.3 3.80

A 33.6 33.5 34.2
Proportion unopened (#/N) 0/15 0/15 0/1 4

a Data were obtained from Table 2 on page s 68

- 69, Table 3 on page 7 4, Table 5 on page 78 , and Table 9 on page 91 of the study report (MRID 49042103)

. CV(%) values were calculated by the reviewers

. 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

NA Not applicable



## D. ORGAN W EIGHTS : Organ weights at necropsy are presented in Table 3. Absolute, adjusted, and relative (to body) liver weights were increased (p<0.05) at 500 (↑6

- 8%) and 1000 (↑6%) mg/kg/day, and absolute, adjusted and relative kidney weights were increased (p<0.01) at 500 (↑6

- 8%) and 1000 (↑8%) mg/kg/day. All other organ weights were similar

to the controls.

The means and %CV of unadjusted values for all organ weights in the control group were

within the recommended range of the performance criteria provided in the Guideline (890.1450).Female Pubertal Assay ( 2012 ) / Page 10 of 15

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### TABLE 3

. Organ Weights at Necropsy a

Organ Vehicle Control 500 mg/kg/day 1000 mg/kg/day

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Liver (g) U 15 7.12 0.456 6.40 15 7.71* (↑8) 0.759 9.84 14 7.58* (↑6) 0.618 8.15

A 7.13 7.71* (↑8) 7.57* (↑6)

R 15 4.343 0.180 4.14 15 4.595* (↑6) 0.318 6.92 14 4.605** (↑6) 0.258 5.60

Kidneys (g) U 15 1.36 0.092 6.76 15 1.47** (↑8) 0. 122 8.30 14 1.48** (↑8) 0.103 6.96

A 1.36 1.47** (↑8) 1.48** (↑8)

R 15 0.830 0.039 5.53 15 0.876** (↑6) 0.0559 6.35 14 0.898*** (↑8) 0.0427 4.76

Pituitary (mg) U 15 8.3 1.30 15.66 15 8.5 1.27 14.94 14 7.7 1.46 18.96

A 8.4 8.5 7.7

R 15 0.0051 0.0008 15.69 15 0.0051 0.0008 15.69 14 0.0047 0.0008 17.02

Adrenals (mg) U 15 39.6 6.75 17.05 15 44.1 4.93 11.18 14 40.2 5.54 13.78

A 39.6 44.1 40.2

R 15 0.0243 0.0047 19.34 15 0.0263 0.0027 10.27 14 0.0244 0.0030 12.30

Ovaries (mg) U 15 59.6 9.17 15.39 15 63.8 8.76 13.73 14 63.7 7.36 11.55

A 59.7 63.8 63.7

Uterus, wet (mg) U 15 397.2 184.41 46.43 15 392.8 155.64 39.62 14 413.0 192.56 46.62

A 401.6 391.2 410.0

Uterus, blotted (mg) U 15 328.0 93.35 28.46 15 351.9 70.35 19.99 14 338.0 94.76 28.04

A 329.6 351.3 336.8 Thyroid, fixed (mg) U 15 16.3 2.69 16.50 15 15.1 2.10 13.91 14 15.4 1.09 7.08

A 16.2 15.0 15.4

a Data were obtained from Table 9 on page 91

- 93 of the study report (MRID 49042103)

. Percent differences from controls, calculated by the reviewers, are included in parentheses. CV(%) values were calculated by the review ers

. 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

R Organ

- to

- body weight ratio (relative to body weight)



### * Significantly different from control; p<0.05

** Significantly different from control; p<0.01

*** Significantly different from control; p<0.001



## E. ESTROUS CYCLICITY : Estr ous cycle data are provided in Table 4. There were no

effect s of treatment on mean age at first vaginal estrus, mean cycle length, % cycling or regularly cycling, or cycle status at necropsy.Female Pubertal Assay ( 2012 ) / Page 11 of 15

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### TABLE 4

. Estrous Cyclicity a

Treatment Groups N Mean A ge at

F irst V aginal

E strus (PND) Mean C ycle

L ength (days) Cycling (%) Regularly

C ycling

(%) Cycle S tatus at N ecropsy (# F emales)

Diestrus Proestrus Estrus Metestrus

Vehicle Control 15 34.5±1.73 4.0±0.79 100 60.0 6 7 1 1

500 mg/kg/day 15 34.8±1.57 4.3±0.61 100 73.3 4 2 3 6

1000 mg/kg/day 1 4 35.0±1.30 4.5±0.99 100 71.4 4 4 1 4

a Data were obtained from Table 6 on page 79 and Table 10 on page 101 of the study report (MRID 49042103)

. N Number of animals

NP Not provided



## F. CLINICAL C HEMISTRY AND H ORMONE L EVELS : Mean hormone and clinical chemistry levels are presented in Table 5. Serum T 4 

## levels were decreased (p<0.001) by 70% at 500 mg/kg/day and by 72% at 1000 mg/kg/day. Concomitantly, serum TSH levels were increased (p<0.001) by 53% at 500 mg/kg/day and by 59% at 1000 mg/kg/day. The following dose- dependent changes in clinical chemistry parameters were observed at 500 and 1000 mg/kg/day , respectively : ALP activity was increased (p<0.05) by 20 and 26%;

ALT activity was decreased (p<0.001) by 42 and 51%; total bilirubin was increased (p<0.01) by 44 and 56%; and urea nitrogen was increased (p<0.05) by 8 and 15%. Additionally at 1000 mg/kg/day, albumin was decreased (p<0.05) by 3% and total protein was decreased (p<0.01) by 4%.

The mean and %CV for serum T 4 

## in the control group were within the re commended range of the performance criteria provided in the Guideline (890.1450).Female Pubertal Assay ( 2012 ) / Page 12 of 15

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### TABLE 5

. Hormone Levels and Clinical Chemistry a

Parameter

Evaluated Vehicle Control 500 mg/kg/day 1000 mg/kg/day

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Hormones

Serum T 4 , Total (μg/dL) 15 4.16 1.076 25.87 14 b 1.25*** (↓70) 0.282 22.56 13 b 1.15*** (↓72) 0.280 24.35

Serum TSH (ng/mL) 15 1.35 0.386 28.59 15 2.07*** (↑53) 0.355 17.15 1 4 2.15*** (↑59) 0.898 41.77

Clinical Chemistry

A/G Ratio 15 1.9 0.09 4.74 15 1.9 0.09 4.74 14 1.9 0.12 6.32

A lbumin (g/d L ) 15 3.6 0.08 2.22 15 3.6 0.09 2.50 14 3.5* (↓3) 0.10 2.86

ALP ( U / L ) 15 249 74.0 29.72 15 300* (↑20) 56.2 18.73 14 313** (↑26) 31.3 10.00

ALT ( U / L ) 15 53 7.6 14.34 15 31*** (↓42) 5.4 17.42 14 26*** (↓51) 2.0 7.69

AST ( U / L ) 15 130 21.3 16.38 15 133 14.0 10.53 14 129 17.4 13.49

C reatinine (mg/d L ) 15 0.1 0.04 40.00 15 0.1 0.05 50.00 14 0.1 0.05 50.00

G lobulin (g/d L ) 15 1.9 0.06 3.16 15 1.9 0.09 4.74 14 1.8 0.08 4.44

T otal B ili (mg/ dL ) 15 0.09 0.033 36.67 15 0.13** (↑44) 0.033 25.38 14 0.14*** (↑56) 0.020 14.29

T otal P rotein (g/ dL ) 15 5.5 0.10 1.82 15 5.4 0.14 2.59 14 5.3** (↓4) 0.14 2.64

U rea N itrogen (mg/ dL ) 15 13 0.9 6.92 15 14* (↑8) 1.9 13.57 14 15** (↑15) 1.2 8.00

a Data were obtained from Table 7 on page 82 and Table 8 on page 85 of the study report (MRID 49042103) . Percent differences from controls, calculated by the reviewers, are included in parentheses. CV(%) values were calculated by the

review ers

. b One animal each in the 500 and 1000 mg/kg/day groups had serum T 4 levels below the method LOD (0.82 μg/dL);
therefore, the T 4 levels for these animals were not used in calculation of the mean or SD.

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from control ; p<0.05

** Significantly different from control; p<0.01

*** Significantly different from control; p<0.001



## G. MACROSCOPIC EXAMINATIONS : There were no gross findings reported at necropsy.

H. HISTOPATHOLOGY : The incidences of histopathological findings of the thyroid gland are presented in Table 6

. No significant differences were observed in the ratio of follicular cell height or colloid area between the controls and treatment groups. However, there was a slight , dose- related trend toward decreased colloid area and increase follicular cell height.Female Pubertal Assay ( 2012 ) / Page 13 of 15

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### TABLE 6

. Incidence of Histopathological Lesions of the Thyroid Gland a

Treatment Groups Parameter Evaluated
Follicular Cell Height to

Colloidal Area Score

Grade b Incidence

Vehicle Control 1 0

2 6

3 9

4 0

5 0



### 500 mg/kg/day 1 0

2 5

3 10

4 0

5 0



### 1000 mg/kg/day 1 0

2 3

3 11

4 0

5 0

a Data were obtained from Table 11 on page 10 2 of the study report (MRID 49042103)

. b Thyroid histopathology is graded 1-5 , with 1 = shortest epithelium with the most abundant colloid, and 5 = tallest epithelium with the

least abundant colloid

.



## The incidence of histopathological findings of the kidney, liver, and uterus are presented in

Table 7. There were no treatment

- related mi croscopic findings. Minimal basophilic tubules, cyst, and mononuclear inflammatory cell infiltrate were observed in the kidneys, but occurred in a non-dose-dependent fashion. Minimal increased inflammatory foci with or without single cell necrosis was noted in the liver in only 1-2 animals/dose group. Antral and tertiary follicles, corpora lutea, and atretic follicles were present in the ovary of all individuals, and the numbers of primordial and primary follicles showed no biologically

- relevant d ifferences across groups. The number of 1000 mg/kg/day females classified in metestrus by examination of the uterus (with cervix) was increased (6 treated vs. 1 control; p<0.05 ).Female Pubertal Assay ( 2012 ) / Page 14 of 15

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### TABLE 7

. Incidence of Histopathological Lesions of the Ovaries, Uterus and Kidney a

Findings Dose L evel

Vehicle Control 500 mg/kg/day 1000 mg/kg/day

Number examined 15 15 14

Kidney (left) Basophilic tubules Minimal 6 6 4
Cyst Minimal 1 0 0
Mononuclear inflammatory cell infiltrate Minimal 0 1 0

Liver

Increased inflammatory foci with/without Minimal single cell necrosis 1 1 2

Uterus (w/cervix)

Proestrus 6 1 2

Estrus 3 8 2

Metestrus 1 4 6*

Diestrus 5 2 4

a Data were obtained from Table 11 on page s 101

- 10 5 of the study report (MRID 49042103)

. * Signi ficantly different from control; p<0.05



## III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS’ CONCLUSIONS : PCNB was tested in a female pubertal study at doses up to and including the limit dose (1000 mg/kg/day). There were no test article

related effects on clinical signs, body weights, or feed consumption. The most consistent organ weight changes were statistically

- significant, marginal increases in absolute and relative liver weights in both sexes at 500 and 1000 mg/kg/day, with no correlative histopathology. The liver weight increases correlate with significantly decreased ALT activity at >500 mg/kg/day, and represent systemic hepatic effects from PCNB exposure.

The liver weight increases are considered to signify mixed -function oxidase induction as has

been reported previously. Liver weight increases and decreased ALT have been reported in previous PCNB chronic toxicity studies. Additionally, decreased ALT activity has been reported in some cases to be as sociated with increased Cyp(p450) enzyme induction, which is a potential mechanism for the decreases in circulating T 4 

## (through enhancing excretion) observed in the current study. Overall, these findings do appear exposure- related and suggest a possible indirect thyroid pathway interaction mediated by hepatic enzyme induction.

B. AGENCY COMMENTS : There was no treatment

- related mortality , and no treatment

related clinical signs of toxicity were observed during the daily examinations. There were no effects of treatment on body weights or body weight gains . There were no gross findings reported at necropsy. During PND 22 -25, food consumption was decreased (NS) by 37% at 500 mg/kg/day and by 39% (p<0.05) at 1000 mg/kg/day. However, food consumption rebounded and was similar to controls for the remainder of the study.

Compared to the control group, absolute, adjusted, and relative (to body) liver weights were increased (p<0.05) by 6 -8% and 6% at 500 and 1000 mg/kg/day, respectively, and absolute, adjusted and relative kidney weights were increased (p<0.01) by 6 -8% and 8% at 500 and 1000 mg/kg/day. The following dose- dependent changes in clinical chemistry parameters were observed at 500 and 1000 mg/kg/day , respectively : ALP activity was increased (p<0.05) by 20 and 26%; ALT activity was decreased (p<0.001) by 42 and 51%; totalFemale Pubertal Assay ( 2012 ) / Page 15 of 15

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## bilirubin was increased (p<0.01) by 44 and 56%; and urea nitrogen was increased (p<0.05) by 8 and 15%. Additionally at 1000 mg/kg/day, albumin was decreased (p<0.05) by 3% and total protein was decreased (p<0.01) by 4%.

The means and %CV of final body weight and unadjusted values for all organ weights in the control group were within the recommended range of the performance criteria provided in the Guideline (890.1450).

Th ere were no effects of treatment on age and body weight at attainment of VO. All females achieved complete VO. There were no effect s of treatment on mean age at first vaginal estrus, mean cycle length, % cycling or regularly cycling, or cycle status at

n ecropsy. Antral and tertiary follicles, corpora lutea, and atretic follicles were present in the ovary of all individuals, and the numbers of primordial and primary follicles showed no biologically relevant differences across groups. The number of 1000 m g/kg/day females classified in metestrus by examination of the uterus (with cervix) was increased (6 treated vs. 1 control; p<0.05); however, the biological significance of this finding is unclear.

The mean s and %CV for age and body weight at VO in the co ntrol group were within the

recommended range of the performance criteria provided in the Guideline (890.1450).

Serum T 4 

## levels were decreased (p< 0.001) by 70% at 500 mg/kg/day and by 72% at 1000 mg/kg/day. Concomitantly, serum TSH levels were increased (p<0.001) by 53% at 500 mg/kg/day and by 59% at 1000 mg/kg/day. However, no significant differences were

observed in the ratio of follicular cell height to colloid area between the control and

treatment groups. However, there was a slight, dose- related trend toward decreased colloid area and increase follicular cell height. The changes in serum T 4 

## and TSH concentrations, combined with modest increases in liver weight and a trend in thyroid histopathology may be related to hepatic enzyme induction, but the data are not definitive for this effect.

The mean and %CV for serum T 4 

## in the control group were within the recommended range of the performance criteria provided in the Guideline (890.1450).

The high dose tested (1000 mg/kg/day) was the Limit Dose; effects observed included ncreased liver and kidney weights, changes in clinical chemistry parameters, and effects on

serum T 4 

## and TSH levels.

C. STUDY DEFICIENCIES : None

# DATA EVALUATION RECORD

PCNB

Study Type: OCSPP 890.1500, Male Pubertal Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-45-2013 (MRID 49042103)

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:
Michael E. Viana, Ph.D., D.A.B.T. Date: 0 4 / 01 /2013

Secondary Reviewer : Signature: Scott Studenberg, Ph.D. , D.A.B.T. Date: 0 4 / 4 /201 3

Program Manager: Signature: Jack D. Early, M.S. Date: 04/10 /201 3

Quality Assurance: Signature: Jack D. Early, M.S. Date: 04/10 /201 3

This Data Evaluation Record may have been altered 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 intended 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 redundancy 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 potential 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).

### PCNB I 056502 Male Pubertal Assay (2012) I 

### Page 1 o f J S

OCSPP 890.1500 / OE C D None



## Primary Reviewer:

..... N

.....**an ==c,,,_y-=-** **-=-c"""'C"'"' arr~o'"""'ll'--** 


## _ _ _ ___ _ 

## S ignature: -------+ ---..---.--- - 

## RAB VI, Health Effects Divi s ion Date:**__,,~~ ~~r:;:;:;.** **~** 

## Secondary Re vie wer : J o hn Liccione. Ph.D. 

## S ignature :**_) ~~::!::;::;e~=-**  

## HeaJth Effects Division Date :**--=-&ff-G-1-~~-**



## DATA EVALUATION RECORD

STUDY TYPE: Male Pubertal Assay; OCSPP 890.1500; OECD No ne

.



## PC CODE: 056502 

## DP BARCODE: D409 239

TXR#: 0056474 

## CAS No: 82-68-8



## TEST MATERIAL (P URITY): PCNB Technical (95.6% a .i .; Lot# 1070 30L052)



## SYNONYMS: 1 ,2,3,4,5-pen t ac hloro-6-nitro be n ze ne ; Quintozene



## CITATION: Baxter

, G.E. (2 012) PCNB: Asses sment of Puberta l De ve lopment and Thyroid Funct i on in Ju venile Ma l e and Female R ats. Huntin gdo n Life

Sc i ences
, East Millstone

, NJ. Laboratory Study No.: 1 2-4389

, December 19

, 20 1 2. MRID 49042103

. Unpub li shed

.



## SPONSOR: AMV AC C h e mical Corporation

, 2 11 0 Da v i e Avenue

, Commerce

, CA



## TEST ORDER#: EDSP-056502-105



## EXECUTIVE SUMMARY: In a Male Pub ertal Assay (MRlD 4 9042 1 03)

, 1 5 Sp rague D aw le y [ C rl:CD ® (SD) IGS BR] rats/dose group we r e treated dai l y v i a oral gavage with PCNB ( 95 .6% a.i.; Lot # 10 7030L052) in aqueous 1% sodium carboxymethy l ce llulo se at do ses ofO (vehic l e),

50 0

, or 100 0 (li mit do se) m g/kg/ d ay from p ost- n ata l day (PND) 23 to 53. Animals were examined for preputial separat i o n (PPS) daily beginning on P ND 30, and age and we ight at day

of attainment we r e recorded

. Fo llowin g sacrifice on PND 53, blood was collected fo r clinical

c h e mi stry and horm one analy ses. To tal thyroxine ( T4) and testosterone seru m levels were
determined b y r a dioimmuno assay, but th e m et h od u sed for d ete rmination of thyroid stim ulatin g
hormone (TSH) l eve l s was not reported. Adrenal, liver

, pituitary

, th y roid

, and urogenital organ s

were weighed

, a nd microscopic exam inati o n s were performed o n the epididym i s, te s ti s, thyroid

, liver

, and kidne ys.

There were n o treatment-related effects on mortality

, clini cal sig n s of toxicity

, body we ights or body we i ght gains, food cons umption

, or gross pathology

. Com par ed to th e co ntrol

, abso lu te, adjusted

, and relative (to body) li ve r we i g h ts w ere incr eased (p < 0.05) by 8-10% at 500 mg/kg/day and b y 10-11 % at 1000 m g/kg/day, and relati ve kidn ey we ights were incre ase d ( p < 0

. 05) by 8 and 6 % at 500 and 1000 mg/k g/ day

, respective l y. Alani n e aminotransferase
(ALT) was d ec r eased (p<0.001) b y 38% at 500 mg/kg/day and b y 52% at 1000 m g/ kg/day and

total bilirubin was increa se d (p<0.001) by 1 00% at 500 and 1000 mg/kg / day. A dditionally at
1000 mg/k g/ d ay, alkaline phosphatase (ALP) was increased (p < 0

. 05) by 15 %. MinimalMale Pubertal Assay ( 2012 ) / Page 2 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## increased inflammatory foci with/without single cell necrosis was observed in livers of 5/15 males at 1000 mg/kg/day (NS) compared to 2/15 controls.

There were no effects of treatment on age and body weight at attainment of PPS. All males achieved complete PPS , and s erum testosterone levels were unaffected by treatment. There were

also no treatment

- related changes in weights or microscopic findings for the male reproductive

tissues.

Compared to the controls, s erum T 4 

## levels were de creased (p<0.001) by ≥78% at 500 and 1000 mg/kg/day , with T 4 

## levels being below the method limit of detection (<LOD, 0.82μg/dL) in 6/15

males at 500 mg/kg/day and 12/15 males at 1000 mg/kg/day. Concomitantly, serum TSH levels were increased (not significant [NS]) by 39 and 25% at 500 and 1000 mg/kg/day , respectively. However, no treatment-related changes were noted in thyroid histology.

The high dose (1000 mg/kg/day) was adequate based on increased liver and kidney weights, and changes in clinical chemistry parameters in the study, and considering that 1000 mg/kg/day is the limit dose for the assay

.

The assay satisfies the EDSP Tier 1 Test Order requirement s for a M ale Pubertal Assay (OCSPP

890.150 0).

COMPLIANCE : Signed and dated Data Confidentiality, GLP Compliance, and Quality Assurance statements were provided.Male Pubertal Assay ( 2012 ) / Page 3 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility : Huntingdon Life Sciences

Location: East Millstone, NJ Study Director: G.E. Baxter

Other Personnel: C

. Willard

- Mack (Pathologist), Y

. Wang (Dose Formulation analysis), L

. Ramaih (Clinical Pathologist), S

. Polivy (TSH Hormone analysis), G

. Thomas (Statistics) Study Period: March 30, 2012 to December 19, 2012



## 2

. Test S ubstance : PCNB Technical

Description: O ff

- white to dark tan crystalline solid or powder

Source: AMVAC Chemical Corporation (Los Angeles, CA)

Lot #: 107030L052 (Expiration July 2016) Purity : 95.6% a.i. Stability: 15 days under refrigerated ( 2

- 8 ̊C) or room temperature conditions

CAS #: 82

- 68

- 8

Structure:



## 3

. Vehicle : 1% Aqueous carboxymethyl cellulose (sodium)

4

. Test A nimals : Species: Rat

Strain: Sprague Dawley [Crl:CD ® (SD)IGS BR] Age/ W eight at Allocation : PND 21 / 48.7

- 57.4 g
Source: Charles River Laboratories (Portage, MI) Housing: Adult males were individually housed in plastic shoebox cages with aspen bedding. Selected pups were housed in the same type cage with up to 3/pups/sex/cage.

Diet: Certified Global 18% Protein Rodent Diet, 2018C, in pellet form (Harlan Teklad, Madison, WI), ad libitum . It was stated that the genistein

- equivalent content of the diet was ≤300 μg/g.

Water: Deionized water without chlorine supplementation (made on

- si te), ad libitum

. Environmental

C onditions: Temperature: Humidity: Air changes: Photoperiod: 22.1

- 25.0 ° C

44

- 52% Not provided 14 h light / 10 h dark



## B. ST UDY DESIGN

1. In -L ife D ates : Start: May 2 , 2012 End: June 1, 2012

2. Mating : Time

- mated pregnant dams were received from the supplier on gestation day (GD) 8. The day evidence of mating was observed was designated as GD 0. Litters with fewer than 10 pups were excluded from the study; litters with 10 pups but less than four of a

se x were retained. Litters with more than 10 pups were standardized by culling on PND 4 to 5 pups/sex/litter where possible; culling to 6 males and 4 females or 4 males and 6 females was also acceptable

. NH 2 Cl Cl

Cl Cl

ClMale Pubertal Assay ( 2012 ) / Page 4 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## 3. Animal A ssignment : Offspring were weaned on PND 21, weighed , and ranked by body weight . The 5 heaviest and 5 lightest male pups were then eliminated from use. The remaining males were then assigned to the groups noted in Table 1 starting with the heaviest males by assigning to the groups sequentially (Groups 1, 2 and 3 ) until each group contained

15 males

. It was not stated if placing littermates in the same group was avoided

.

TABLE 1. Study Design a
Test group Dose (mg/kg/day) # of M ales

Control 0 15

Low 500 15 High 1000 15

a Data were obtained from Text Table 2.3

- 1 on page 17 of the study report (MRID 49042103)

.



## 4. Dose S election Rationale : It was stated that the dose levels used in the present study were

selected based on the results of four previously performed studies. In a developmental toxicity study, pregnant females were dosed with PCNB (10 mL/kg) at 0, 250, 750, or

1500 mg/kg/day during GD 6 -15. No clinical signs were noted up to 1500 mg/kg/day; however, decreased body weight gains a nd food consumption were noted during GD 6- 9 at 750 and 1500 mg/kg/day. Food consumption rebounded post-dosing (GD 15-20) at 1500 mg/kg/day. In a 2- year rat oncogenicity study, males and females were dosed with 0, 5, 50, 500, or 1000 mg/kg/day. Body weights were decreased in the 1000 mg/kg/day males and in the 500 and 1000 mg/kg/day females. I n a 2 -generation reproduction toxicity study, rats were dosed with 0, 10, 100, or 1000 mg/kg/day from 10 weeks prior to mating in the P generation through weaning of the F2 generation. No clinical effects were observed. Therefore, doses of 0, 500, and 1000 mg/kg/day were chosen for a non-GLP dose

range -finding pubertal study that also assessed the tolerability of a lower dose volume (5 mL/kg) compared to what was previously used (10 mL/kg). The dose levels and dose volume were acceptably tolerated. The present GLP male pubertal study duplicated the

conditions of the range -finding study.

5. Dose P reparation and Analysis : Dose formulations were prepared every 3 -4 days, and

were stored at room temperature protected from light. An appropriate amount of t he test
substance (not adjusted for purity) was ground with a mortar and pestle into a fine powder

and mixed with a small volume of the vehicle to form a paste. Th e paste was brought up to final volume with additional vehicle, homogenized, and stirred to yield a uniform suspension. Stirring was continuous during sampling and aliquoting. Homogeneity (top, middle, and bottom) and stability analyses were pe rformed prior to study initiation on samples of the same concentrations used in the present study. Stability was determined after storage for up to 15 days at both ambient and refrigerated temperatures. Concentration analyses were performed on all dose levels from the first preparation (administered on Days

1- 4).

Results of D ose Analysis

Homogeneity (%CV) : 0.57-4.01%

Stability (% of time 0) : 97.1-97.7%Male Pubertal Assay ( 2012 ) / Page 5 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## Concentration (% of nominal): 88.1-95.5%

The analytical data indicated that the mixing procedure was adequate and that the variation between nominal and actual dosage to the animals was acceptable

. Concentration analysis

for t he Week 1 (Days 1 -4) 500 mg/kg/day formulation w as 88.1% of nominal, which is outside the protocol- specified acceptance criteria of ±10% . However, this slight deviation did not affect the study results.

6. Dosage A dministration : All doses were administered once daily by gavage, from PND 2 3 through PND 53, in a dose volume of 5 mL/kg. Individual doses were based on the most recently recorded body weights. D osing was performed between 0700 and 0900 hours daily.

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, organ weights, and histopathology. For c ontinuous p arameters

, Bartlett's test for variance homogeneity was applied. I f Bartlett's test was not significant at

the 1% level, parametric methods were applied , using an F1 approximate test for monotonicity. If the F1 test was not significant at the 1% level, Williams' test for a monotonic trend was applied. If the F1 test was significant, suggesting that the doseresponse was not monotonic, Dunnett's test was performed instead. If Bartlett's test was significant at the 1% level, logarithmic and square root transformat ions were tried. If Bartlett's test was still significant, non

- parametric methods were applied to mean ranks

, with

an H1 approximate test for monotonicity. If the H 1 was not significant at the 1% level, Shirley's test for a monotonic trend was applied. If the H 1 test was significant, Steel's test was performed instead. For discrete parameters involving more than two groups, the

Jonckheere- Terpstra test was applied. If the Jonckheere- Terpstra test was significant at the 5% level, the direction of the trend was established and one- tailed step

- down testing in this direction was performed. If the Jonckheere- Terpstra test was not significant at the 5% level,

the Kruskal- Wallis test was applied. If the Kruskal- Wallis test was significant at the 5% level, the treated groups were compared to the control using exact Wilcoxon rank sum tests; otherwise, no further comparisons were made. For b inary p arameters involving more than

two groups, the Cochran

- Armitage test was applied. I f the Cochran

- Armitage test was significant at the 5% level, the direction of the trend was established and one- tailed step

down testing in this direction was performed. If the Cochran

- Armitage test was not significant at the 5% level, the χ 2 

## test (Armitage et al 2002) was applied. If the χ 2 

## test was significant at the 5% level, the test- article treated groups were compared to the control with Fisher's Exact tests, otherwise, no further comparisons were made.

PPS (day of PPS and bodyweight) and organ weight data were also analyzed as follows.

Bartlett's test was applied ; i f this test was not significant at the 1% level, parametric analysis was applied. The bodyweight at PND 21 was used as a covariate in the analyses and comparisons were performed on the adjusted means after the analysis of covariance (ANCOVA)

. The F 1 approximate test was applied ; i f the F 1 test was not significant at the 1% level, Williams' test for a monotonic trend was applied, otherwise Dunnett's test was performed instead. If Bartlett's test was significant at the 1% level, logarithmic and square

root transformations were tried. If Bartlett's test was still significant, non

- parametric testsMale Pubertal Assay ( 2012 ) / Page 6 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## were applied. The H1 approximate test was applied ; i f the H 1 test was not significant a t the

1% leve l, Shirley's test was applied; otherwise Steel's test was performed instead.

For histopathology, t est

- article treated groups were compared to the control with Fis her's

Exact tests

.

Statistical significance was declared at the 5%, 1% and 0.1% levels. The statistical analyses were considered appropriate.

C. METHODS

1. Mortality and C linical Examinations : All animals were observed twice daily for mortality and moribundity beginning on PND 21 and continuing throughout the study.

Individual c linical examinations were conducted daily prior to dosing through the day of

euthanasia

.

2. Body W eight : Animals were weighed at randomization, daily prior to dosing, and on the day of euthanasia

. Mean body weight gains were calculated for each weighing interval, and

for PND 2 3-53.

3. Food Consumption : Food consumption (g/rat/day) was measured by placing a weighed

feeder in each cage, reweighing it after 2 -4 days, and dividing by the number of rats/cage. Food consumption was reported for PND 23-26, 26-30, 30-33, 33-37, 37-40, 40-44, 44-47, 47-51, and 51-53.

4. Preputial Separation ( PPS ) : Each male was observed daily prior to dosing for PPS beginning on PND 30. The age and body weight on the day at which PPS was completed

was recorded for each animal.

5. Sacrifice and Pathology : All animals were euthanized by exsanguination on PND 53 at
least two hours post-dosing. All terminal procedures were completed by 1300 hours.

Unfasted animals were anesthetized with isoflurane and b lood was collected from the aorta. The blood was allowed to clot for at least 30 minutes and centrifuged to obtain serum

. Samples were stored at <−20°C (as required) for subsequent hormone and clinical chemistry

evaluations.

a. Hormone Analysis : Serum T 4 

## and testosterone concentrations were determined by radioimmunoassays; no other details about the radioimmunoassays were provided

. Serum TSH levels were determined by an external laboratory (AniLytics, Inc., Gathersburg, MD); the method used was not reported.Male Pubertal Assay ( 2012 ) / Page 7 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## b. Clinical C hemistry : The following CHECKED (X) parameters were examined.

ELECTROLYTES OTHER

Calcium X Albumin

Chloride X Creatinine*

Magnesium X Urea nitrogen*

Phosphorus Total cholesterol

Potassium X Globulins

Sodium Glucose

ENZYMES X Total bilirubin

X Alkaline phosphatase (AL P ) X Total protein

Cholinesterase (ChE) Triglycerides

Creatine phosphokinase X Albumin/globulin ratio

Lactic acid dehydrogenase (LDH)

X Alanine aminotransferase (ALT/also SGPT)

X Aspartate aminotransferase (AST/also SGOT)

Sorbitol dehydrogenase (SDH)

Gamma glutamyl transferase (GGT)

Glutamate dehydrogenase

* Recommended for the pubertal assay in male rats based on Guideline 890.1 50 0.



## c. Organ W eights and Histopathology : The following CHECKED (X) tissues were collected and weighed. The (XX) organs, in addition, were subjected to histological

examination

.

UROGENITAL OTHER

XX Testes (left and right separately)* + XX Thyroid* +

XX Epididymides (left and right separately)* + XX Liver*

X Seminal vesicle plus coagulating glands (with 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 required based on Guideline 890.1500



## Complete macroscopic examinations were performed on all animals

. All organs collected except the thyroid/trachea were weighed prior to fixation. Th e kidneys, adrenals, and

seminal vesicles were weighed together ; the epididym id es and testes were weighed separately. The seminal vesicles w ere weighed again following removal of the fluid in the lumen (blotted weight).

The testes and epididymides were fixed in Bouin’s fixative for no more than 24 hours, then were rinsed and stored in 70% ethanol. Kidneys were fixed in 10% neutral buffered formalin for no more than 24 hours; the left kidney was retained in 10% neutral bu ffered formalin, the right kidney was rinsed and stored in 70% ethanol. All other tissues were fixed in 10% neutral buffered formalin for no more than 24 hours, then rinsed and stored in

70% ethanol. After fixation , the thyroid w as dissected from the tra chea. The thyroid, left kidney, liver, left epididymis, and left testis were routinely processed, sectioned, stained with hematoxylin and eosin, and examined microscopically.Male Pubertal Assay ( 2012 ) / Page 8 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## Thyroid/parathyroid glands were subjectively graded based on the ratio of folli cular epithelial cell height to colloid area using a five point grading scale , with 1 = shortest epithelium with the most abundant colloid, and 5 = tallest epithelium with the least abundant colloid. A minimum of two sections of each of the two lobes of the thyroid/parathyroid

were evaluated. Testes and epididymides were evaluated as required by US EPA Health Effects Test Guideline OPPTS 870.3800: Reproduction and Fertility Effects. In the testes,

these evaluations were conducted in order to identify treatment

- related effects such as

retained spermatids, missing germ cell layers or types, multinucleated giant cells, or sloughing of spermatogenic cells into the lumen. Examination of the intact epididymis included the caput, corpus, and cauda, accomplished by evaluation of a longitudinal section, and was conducted in order to identify such lesions as sperm granulomas, leukocytic infiltration (inflammation), aberrant cell types within the lumen, or the absence of clear cells

in the cauda epididymal epithelium. The left kidney was evaluated by means of standard histopathology.

II. RESULTS

A. MORTALITY : There was no treatment

- related mortality

.

B. CLINICAL S IGNS OF T OXICITY : No treatment

- related clinical signs of toxicity were observed during the daily examinations. The only findings noted w ere general dermal alopecia of the head/neck in a control male (#1058) during PND 36- 38, general dermal scabs in a control male (#1056) during PND 22-32 and in a 500 mg/kg/day male (#2034) during PND 37-53, and general dermal alopecia of the limbs in a 500 mg/kg/day male (#2035) during PND 48-53.

C. GENERAL G ROWTH

, PREPUTIAL SEPARATION, AND FOOD CONSUMPTION : Body weights, body weight gains, and age and body weight at attainment of PPS are presented in Table 2. There were no effects of treatment on body weights, body weight gains, or age and body weight at attainment of PPS

. All males achieved complete PPS

.

During PND 33-37 and 37-40, food consumption was in creased ( p<0.05 ) by 10 and 20%, respectively, at 1000 mg/kg/day. These transient increases were not considered to have resulted from treatment, and did not affect the outcomes of the study.

The mean s and %CV for age and body weight at PPS and final body weight in the control group were within the recommended range of the performance criteria provided in the Guideline (890.1500) with one exception. The %CV for body weight at PPS was above the top of the recommended range (8.12% control vs. 7.57% top of range).Male Pubertal Assay ( 2012 ) / Page 9 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



### TABLE 2

. General Growth and Preputial Separation ( PPS ) a

Parameter Evaluated Vehicle Control 500 mg/kg/day 1000 mg/kg/day

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Initial body weight (PND 2 3 ; g) U 15 60.5 2.41 3.98 15 61 2.34 3.84% 1 5 61.2 2.33 3.81%

A NA NA NA

Body weight at PPS (g) U 15 221.8 18.0 8.12 15 223.2 20.7 9.27 1 5 236.7 28.2 11.91

A 222 223.2 236.5
Final body weight (g) U 15 310.2 17.87 5.76 15 303.9 24.02 7.90 1 5 309.7 23.2 7.49

A 310.5 303.9 309.4
Final body weight (% of control) U NA 98.0 99.8

A
Body weight gain (final

– initial; g) U 15 249.7 17.89 7.16 15 242.8 22.75 9.37 1 5 248.5 22.49 9.05

A
Age at PPS (PND) U 15 43.2 1.6 3.70 15 44.2 2.8 6.33 1 5 44.5 2 .0 4.49

A
Proportion un separate d (#/N) 0/15 0/15 0/15

a Data were obtained from Table 2 on page s 65-67 , Table 3 on page 72 , Table 5 on page 7 7, and Table 9 on page 87 of the study report (MRID 49042103)

. CV (%) values were calculated by the review ers

. 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

NA Not applicable



## D. ORGAN WEIGHTS : Organ weights at necropsy are presented in Table 3. Absolute, adjusted, and relative (to body) liver weights were increased (p<0.05) at 500 (↑ 8-10 %) and 1000 (↑ 10-11%) mg/kg/day, and relative kidney weights were increased (p<0.05 ) at

500 (↑8%) and 1000 (↑ 6 %) mg/kg/day. All other organ weights were similar to the controls.

The means and %CV of unadjusted values for all organ weights in the control group were

within the recommended range of the performance criteria provided in the Guideline (890.1500) wi th the following exceptions: the mean weight of the kidney was below the

recommended range (2.21 g vs. 2.242-3.050 g); the %CV for the seminal vesicle (without fluid) was above the top of the recommended range (22.55% vs. 21.06%); the left epididymis had a mean weight below the recommended range (235.5 mg vs. 364-528 mg) and a %CV above the top of the recommended range (27.89% vs. 16.39%); the mean weight of the right epididymis was below the recommended range (258.7 mg vs. 364-528 mg); and the %CV for the left testis was above the top of the recommended range (28.68% vs. 17.62%).Male Pubertal Assay ( 2012 ) / Page 10 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



### TABLE 3

. Organ Weights at Necropsy a

Organ Vehicle Control 500 m g/kg/day) 1000 mg /kg/day)

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Liver (g) U 15 13.22 1.008 7.62 15 14.32 * (↑8) 1.729 12.07 15 14.59 ** (↑10) 1.21 8.29

A 13.21 14.32 * (↑8) 14.6 0*** (↑11)

R 15 4.25 9 0.16 4 3.85 15 4.706 *** (↑10) 0.32 8 6.97 15 4.7 20 *** (↑11) 0.327 6.93

Kidneys (g) U 15 2.21 0.106 4.80 15 2.34 0.256 10.94 15 2.33 0.169 7.25

A 2.21 2.33 2.32

R 15 0.715 0.05 1 7.1 3 15 0.7 70 * (↑8) 0.035 4. 55 15 0.75 6 * (↑6) 0.055 7. 28

Pituitary (mg) U 15 10.2 1.39 13.63 15 9.7 1.53 15.77 15 9.3 0.95 10.22

A 10.2 9.7 9.3

R 15 0.0033 0.000 5 15.15 15 0.0032 0.0005 15.63 15 0.003 0 0.000 3 10.00

Adrenals (mg) U 15 44.4 5.33 12.00 15 45 6.78 15.07 15 44.1 7.73 17.53

A 44.4 45 44.1

R 15 0.0143 0.0016 11. 19 15 0.0148 0.0015 10. 14 15 0.0142 0.0021 14. 79

Seminal vesicle + coagulating gland, with fluid (mg) U 15 830.1 178.78 21.54 15 807.9 158.93 19.67 15 856.2 127.56 14.90

A 830.2 807.9 856.1

Seminal vesicle + coagulating gland, without fluid (mg) U 15 590.5 133.17 22.55 15 589.4 101.29 17.19 15 587.3 100.68 17.14

A 589.5 589.4 588.3

Ventral prostate (mg) U 15 250. 0 44.01 17. 60 15 233.5 57.12 24.46 15 243.2 53.83 22.13

A 251 .0 233.6 242.1 Dorsolateral prostate (mg) U 15 104.1 32.07 30.81 15 97.7 43.35 44.37 15 105.5 38.48 36.47

A 104.3 97.7 105.4

LABC (mg) U 15 606 .0 134.63 22.22 15 628.2 139.95 22.28 15 615.6 100.76 16.37

A 605.8 628.1 615.9 Epididymis, left (mg) U 15 235.5 65.67 27.89 15 239.3 25.93 10.84 15 237 .0 31.54 13.31

A NC NC NC Epididymis, right (mg) U 15 258.7 25.33 9.79 15 247 34.78 14.08 15 243.2 23.08 9.49

A 259.4 247 242.5
Testis, left (mg) U 15 1313.8 376.74 28.68 15 1435.7 93.54 6.52 15 1456.4 124.99 8.58

A NC NC NC Testis, right (mg) U 15 1445.4 134.44 9.30 15 1468.4 95.91 6.53 15 1469.8 147.78 10.05

A 1450.1 1468.7 1464.8 Thyroid, fixed (mg) U 15 21.2 2.78 13.11 15 22 .0 3.38 15.36 15 23.1 3.21 13.90

A 21.3 22 .0 23.1

a Data were obtained from Table 9 on page 87

- 90 of the study report (MRID 49042103)

. Percent differences from controls, calculated by the reviewers, are included in parentheses. CV (%) values were calculated by the review ers

. 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

R Organ

- to

- body weight ratio (relative to body weight)

NC Not calculated due to non

- parametric tests

* Significantly different from control; p<0.05

** Significantly different from control; p<0.01

*** Significantly different from control; p<0.001



## E. CLINICAL C HEMISTRY AND H ORMONE L EVELS : Mean hormone and clinical chemistry levels are presented in Table 5. Serum T 4 

## levels were decreased (p<0.001) byMale Pubertal Assay ( 2012 ) / Page 11 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## >78 % at 500 and 1000 mg/kg/day, with values below the method LOD (0.82 μ g/dL) for 6/15 males at 500 mg/kg/day and 12/15 males at 1000 mg/kg/day. Concomitantly, serum TSH levels were increased ( NS ) by 39 % and 25% at 500 and 1000 mg/kg/day , respectively

. Serum testosterone levels were unaffected by treatment. A LT activity was decreased (p<0.001) by 38% at 500 mg/kg/day and by 52% at 1000 mg/kg/day; total bilirubin was increased (p<0.0 0 1) by 100% at 500 and 1000 mg/kg/day. Additionally at 1000 mg/kg/day,

ALP activity was increased (p<0 .05) by 15%, with a trend towards an increase (NS) of 11% at 500 mg/kg/day.

The mean and %CV for serum T 4 

## and testosterone in the control group were within the

recommended range s of the performance criteria provided in the Guideline (890.1500).

TABLE 5

. Hormone Levels and Clinical Chemistry a

Parameter

Evaluated Vehicle Control 500 mg/kg/day 1000 mg/kg/day

N Mean SD CV (%) N Mean SD CV (%) N Mean SD CV (%)

Hormones

Serum T 4 , Total (μg/dL) 15 4.53 0.7 3 16.11 15 b <0.97 *** (↓ > 7 8 ) 0.18 NC 15 b <0.93 *** (↓ > 79 ) 0. 23 NC

Serum TSH (ng/mL) 15 2.81 1.241 44.16 15 3.91 (↑39) 2.341 59.87 15 3.52 (↑25) 1.738 49.38

Serum Testosterone ng/ m L 15 1. 044 0. 577 55.2 7 15 1. 098 1. 19 1 108.4 7 15 1. 394 1.1 50 82.50

Clinical Chemistry

A/G Ratio 15 1.8 0.12 6.67 15 1.7 0.11 6.47 15 1.7 0.11 6.47

A lbumin (g/d L ) 15 3.5 0.08 2.29 15 3.5 0.1 0 2.86 15 3.5 0.14 4.00

ALP ( U / L ) 15 304 44.7 14.70 15 338 (↑1 1 ) 51 .0 15.09 15 350 * ( ↑ 15) 61.6 17.60

ALT ( U / L ) 15 56 6.6 11.79 15 35 *** (↓38) 8.5 24.29 15 27 *** (↓52) 6.7 24.81

AST ( U / L ) 15 119 20 16.81 15 138 46 33.33 15 132 33.1 25.08

C reatinine (mg/d L ) 15 0.2 0.03 15.00 15 0.2 0.03 15.00 15 0.2 0 .00 0.00

G lobulin (g/d L ) 15 2 .0 0.12 6.00 15 2.1 0.15 7.14 15 2.1 0.1 2 5.71

T otal B ili (mg/ dL ) 15 0.06 0.03 0 50.00 15 0.12 *** (↑100) 0.037 30.83 15 0.12 *** (↑100) 0.041 34.17

T otal P rotein (g/ dL ) 15 5.5 0.13 2.36 15 5.5 0.2 0 3.64 15 5.5 0.21 3.82

U rea N itrogen (mg/ dL ) 15 14 1.7 12.14 15 15 2 13.33 15 15 1.8 12.00

a Data were obtained from Table 7 on page 8 1 and Table 8 on page 84 of the study report (MRID 49042103) . Percent differences from controls, calculated by the reviewers, are included in parentheses. CV (%) values were calculated by the

review ers

. b The mean and SD for T 4 were recalculated by the reviewer using data from all 15 animals in the 500 and 1000 mg/kg/day groups. For animals with T 4 values below the method LO D (<0.82 μg/dL), the LO D was used for calculation of the mean

and SD. T 4 va lues were <LO D for 6/16 males at 500 mg/kg/day and 12/15 males at 1000 mg/kg/day

. %CV s were not
calculated for these groups

. N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

NC Not calculated

* Significantly different from control ; p<0.05

** Significantly different from control; p<0.01

*** Significantly different from control; p<0.001



## G. MACROSCOPIC EXAMINATIONS : There were no treatment

- related gross findings reported at necropsy.Male Pubertal Assay ( 2012 ) / Page 12 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## H. HISTOPATHOLOGY : The incidences of histopathological findings of the thyroid gland are presented in Table 6

. No differences were observed in the ratio of follicular cell height

to colloid area between the controls and treatment groups.

TABLE 6

. Incidence of Histopathological

Lesions of the Thyroid Gland a

Treatment Groups Parameter Evaluated
Follicular Cell Height to

Colloidal Area Score

Grade b Incidence

Vehicle Control 1 0

2 1

3 14

4 0

5 0



### 500 mg/kg/day 1 0

2 3

3 12

4 0

5 0



### 1000 mg/kg/day 1 0

2 2

3 1 3

4 0

5 0

a Data were obtained from Table 11 on page 10 0 of the study report (MRID 49042103)

. b Thyroid histopathology is graded 1-5 , with 1 = shortest epithelium with the most abundant colloid, and 5 = tallest epithelium with the

least abundant colloid

.



## The incidence of histopathological findings of the epididymis, kidney, liver, and testis are presented in Table 7. There were no treatment

- related mi croscopic findings , with the exception of the liver. Minimal increased inflammatory foci with/without sin gle cell necrosis was observed in 5/15 males at 1000 mg/kg/day (NS) compared to 2/15 controls. All other microscopic findings were noted in a single animal, were of minimal severity,

and/or occurred in a manner unrelated to dose.Male Pubertal Assay ( 2012 ) / Page 13 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



### TABLE 7

. Incidence of Histopathological Lesions a

Findings Dose L evel

Vehicle Control 500 mg/kg/day 1000 mg/kg/day

Number examined 15 15 14

Epididymis (left)

Cauda: reduced/absent sperm Present 10 11 12 Epithelial vacuolation Minimal 0 0 1
Reduced sperm, sloughed degenerating Moderate

germinal cells and tubular contraction 0 1 0

Epididymis (right) b

Hypospermia Minimal 1 0 0
Kidney (left)

Basophilic tubules Minimal 5 3 4 Mononuclear inflammatory cell infiltrate Minimal 1 0 1 Mineral deposits Minimal 0 1 0 Intratubular eosinophilic material Minimal 0 0 1
Kidney (right) b

Pelvic dilation Minimal 0 1 0

Liver

Increased inflammatory foci with or without Minimal

single cell necrosis 2 1 5

Granuloma Minimal 0 0 1

Testis (left)

Tubular degeneration/atrophy Moderate 0 1 0

a Data were obtained from Table 11 on page s 98

- 100 of the study report (MRID 49042103)

. b Only one animal examined



## III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS’ CONCLUSIONS : PCNB was tested in a male pubertal study at doses up to and including the limit dose (1000 mg/kg/day). There were no test article

related effects on clinical signs, body weights, or feed consumption.

The most consistent, statistically

- significant organ weight changes we re the marginal increases in absolute and relative liver weights at 500 and 1000 mg/kg/day. Microscopic findings in the liver consisted of minimal increased inflammatory foci with or without single cell necrosis, which was slightly greater in 1000 mg/kg/day animals compared to controls. Although these microscopic findings may be related to PCNB exposure , t his change is a common background finding in rats and was not considered to be related to the increased

organ weights as it was present in controls, and was of low incidence and minimal severity. The liver weight increases correlate with significantly decreased ALT activity at >500 mg/kg/day, and may represent systemic hepatic effects from PCNB exposure. The liver weight increases are considered to signify mixed function oxidase induction as has been reported for PCNB previously. Liver weight increases and decreased ALT activity have been reported in previous PCNB chronic toxicity studies. Additionally, decreased ALT has been reported in some cases to be associated with increased Cyp(p450) enzyme induction which is a potential mechanism for the observed decreases in circulating T 4 

## (via enhanced excretion). Overall, the liver weight increases, decreased ALT activity and decreased T 4 

## levels appear ex posure-related and suggest a possible high dose indirect thyroid pathway interaction mediated by hepatic enzyme induction. However, the s ignificant increases in relative kidney weights were not considered test article

- related because they were small inMale Pubertal Assay ( 2012 ) / Page 14 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## ma gnitude, consistent with normal biological variability, and there were no microscopic

correlates.

There were no effects on androgen

- sensitive organ weights, testosterone levels or PPS data, and no exposure-related microscopic findings in reproductive organs. There is no evidence of potential interaction with either the androgen pathways or with the HPG axis. Adrenal and pituitary weights were not affected by PCNB exposures. Decreases in T 4 

## levels were

observed at >500 mg/kg/day and were correlated with marginal, but dose- related increases in TSH. However, these findings were not associated with any differences in thyroid/parathyroid organ weight or histopathology ; therefore, the functional significance of these findings is not clear. As noted abov e, these findings may be associated with enhanced

excretion of T 4 

## mediated by hepatic enzyme induction.

B. AGENCY COMMENTS : There was no treatment

- related mortality , and no treatment

related clinical signs of toxicity were observe d during the daily exami nations. There were no effects of treatment on body weights, body weight gains, or gross findings reported at

necropsy. During PND 33 -37 and 37-40, food consumption was increased (p<0.05) by 10 and 20%, respectively, at 1000 mg/kg/day. These transient increases were not considered to have resulted from treatment, and did not affect the outcomes of the study.

Absolute, adjusted, and relative (to body) liver weights were increased (p<0.05) at by 8 -10%

at 500 mg/kg/day and by 10 -11% at 1000 mg/kg/day, and relative kidney weights were

increased (p<0.05 ) by 8 and 6% at 500 and 1000 mg/kg/day , respectively

. ALT activity was decreased (p<0.001) by 38% at 500 mg/kg/day and by 52% at 1000 mg/kg/day and total bilirubin was increased (p<0.001) by 100% at 500 and 1000 mg/kg/day. Additionally at 1000 mg/kg/day, ALP activity was increased (p<0.05) by 15%. There were no treatment

related microscopic findings, with the exception of the liver. Minimal increased inflammatory foci with/without single cell necrosis wa s observed in livers of 5/15 males at 1000 mg/kg/day (NS) compared to 2/15 controls.

The means and %CV of unadjusted values for all organ weights in the control group were

within the recommended range of the performance criteria provided in the Guidelin e (890.1500) with the following exceptions: the mean weight of the kidney was below the

recommended range (2.21 g vs. 2.242-3.050 g); the %CV for the seminal vesicle (without fluid) was above the top of the recommended range (22.55% vs. 21.06%); the left epididymis had a mean weight below the recommended range (235.5 mg vs. 364-528 mg) and a %CV above the top of the recommended range (27.89% vs. 16.39%); the mean weight of the right epididymis was below the recommended range (258.7 mg vs. 364-528 mg); and the %CV for the left testis was above the top of the recommended range (28.68% vs. 17.62%).

There were no effects of treatment on age and body weight at attainment of PPS. All males achieved complete PPS. Serum testosterone levels were unaffected by treatment. There

were no treatment

- related microscopic findings in the male reproductive tissues.

The mean s and %CV for age and body weight at PPS and final body weight in the control group were within the recommended range of the performance criteria provided in theMale Pubertal Assay ( 2012 ) / Page 15 of 15

PCNB / 056502 O CSPP 89 0. 1 50 0/ OECD None



## Guideline (890.1500) with one exception. The %CV for body weight at PPS was above the top of the recommended range (8.12% control vs. 7.57% top of range).

Serum T 4 

## levels were decreased (p<0.001) by at least 79% at 500 and 1000 mg/kg/day, with

T 4 

## levels being <LO D for 6/15 males at 500 mg/kg/day and 12/15 males at 1000 mg/kg/day. Concomitantly, serum TSH levels were increased (NS) by 39 and 25% at 500 and 1000 mg/kg/day , respectively

. However, no differences were observed in the ratio of follicular cell height to colloid area between the control and treatment groups. The decreased serum

T 4 

## and increased serum TSH concentrations are supportive of a treatment- related effect on the thyroid. This effect may be related to hepatic induction (liver weights were increased up to 11%), but no histopathological effect was observed in the thyroid.

The mean and %CV for serum T 4 

## in the control group were within the recommended range of the performance crite ria provided in the Guideline (890.1500).

The high dose (1000 mg/kg/day) was adequate based on increased liver and kidney weights,

and changes in clinical chemistry parameters

.

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 CV were not presented as a percent , and had to be recalculated by the reviewers

.

• Week 1 (Day 1 -4) dose analysis for 500 mg/kg was 88.1% (< ± 10%).

• Performance criteria data were not reported, but were determined by the reviewers.

• Testosterone data were reported in different units (ng/dL instead of ng/mL), but the conversion yielded acceptable results in the expected range.

# DATA EVALUATION RECORD

PCNB

Study Type: O CSPP 890.1550, Steroidogenesis Assay

EPA Contract No. EP10H001452 Task Assignment No. 3-26-2012 (MRID 48916704)

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: 10 / 0 5 /201 2

Secondary Reviewer Signature: Michelle Sharpe

- Kass, M.S. Date: 10/10/2012

Program Manager: Signature: Jack D. Early, M.S. Date: 10 / 1 8 /2012

Quality Assurance: Signature: Jack D. Early, M.S. Date: 10/1 8 /2012

This Data Evaluation Record may have been altered 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 intended 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 redundancy 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 potential 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).PCN B 

### I 056502



## Primary Reviewer: Stephen C. Dapson. Ph.D.



## Senior Pharmacologist, RAB6, BED (7509P) Secondary Reviewer: John Liccione. Ph.D.



## Health Effects Division Steroidogenesis Assay (201 l) I Pagel of 15

OCSPP 890.1550/ OECD None

## Signature:}e~ 

# JO,.**~e** 

## Date:

## ~

# Signature:~ p 

## r 

## DatC 

## -2

-- 1.>

Template version 081201 l



## DATA EVALUATION RECORD

STUDY TYPE: Steroidogenesis Assay (H295R Ce ll s) ; OCSPP 890.1550



## PC CODE: 056502 

## DP BARCODE: 0405372



## TXR#: 0056474 

## CAS No.: 82-68-8



## TEST MATERIAL (PURITY): PCNB (95.6% a.i.)



## SYNONYMS:

CITATION:

SPONSOR: 1

, 2,3,4,5-pentachloro

- 6-nitrobenzene ; Quintozene

Akhurst

, 

## L. C. (2012) PCNB Technical H295R Steroidogenesis Assay. Huntingdon Life Sciences Ltd.

, Cambridges hir e
, Eng land

. Laboratory Study

No. BDG0126, Jul y 4

, 2012. MRID 489 1 6704. Unpub li shed.

AMV 

## AC Chemical Corporation

, 4695 MacArthur Court

, Suite 1200, Newport Beach, CA



## TEST ORDER#: EDSP-056502-105



## EXECUTIVE SUMMARY: In a steroidogenesis assay (MRID 48916704), H295R cells

cultured 

## in vitro in 24 -well plates were incubated with PCNB (95.6% purity, Lot# 107030L052

at lo g concentrations of 0.0001 to 100 μM for 48 hour s in triplicate for three independent experiments. Dimethyl sulfoxide (DMSO) was used as t h e vehicle, at a final concentration of

0.1%.

Testosterone and estradiol levels were measured with specific EIA kits. 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. The positive

controls included a known inhibitor (prochloraz ) and a known inducer (fo r skolin) of estradiol

and testosterone production.

Precipitation and/or ce ll cytotox i c i ty was n ot observed at PCNB conce n trations of :S 

## 20 μM.

However

, cell viability was reduced to 78% at 30 μM in Run 2 and 31 % at 100 μMin Run 1,

and precipitation was also not ed at 100 μMin Run 1

. Therefore

, th e highest PCNB

concentrations eval u ated were l 0 μMin Runs I and 2 and 20 μM 

## in Run 3.Steroidogenesis Assay (2011) / Page 2 of 15

PCNB / 056502 OCSPP 890.1550/ OECD None



## For the test plates, t he coefficients of variation (% CVs ) ranged from 4.8– 5.8% for ab solute

testosterone concentrations and 1.7–3.2% for absolute estradiol concentrations in the solvent control ( SC ) replicate wells within the test plate s . The between

- plate CVs for hormone

concentrations in the SC wells were 13.6% for testosterone and 50.3% for estradiol. The withinplate CVs were low and met the performance criteria (≤30%), as did the between

- plate CV for testosterone. Although the between plate CVs for estradiol exceeded the guideline performance criteria, the estradiol data is consider ed ac ceptable in light of the low within

- plate CV values.

Basal hormone production in the SC wells was acceptable both in terms of the absolute

concentrat ions and relative to the method’s lower limit of quantitation ( LLQ ). Compared to SC

wells , 10 μM forskolin induced testosterone production on average by 2.26- fold , but induced estradiol by an unknown factor. For estradiol, the fold induction resulting from forskolin could not be confirmed to be above the guideline specified >7.5- fold for the first two assay runs
because the estradiol levels were above the maximum limit of quantitation ( MLQ ); however, based on the MLQ, the minimum levels of induction for estradiol production were greater than 5.12-, 3.12- and 7.70-fold in Runs 1, 2 and 3, respective ly. Compared to the SC, 1 μM prochloraz inhibited the synthesis of testosterone on average to 0.38-fold and estradiol to 0.09- fold. The range of %CV for hormone concentrations for the SC replicates within the QC plate s was 1.5–4.9% for testosterone and 2.5–5.2% for estradiol. The between plate CVs for the SC

wells w as 15.9% for testosterone and 45.0% for estradiol. Similar to the test plates, the withinplate CVs for hormone concentrations on the QC plates were low and met the performance criteria. The performance criteria (≤ 30%) for between

- plate CV s for the QC plates was also met for testosterone, but exceeded for estradiol; as with the between-plate value for estradiol on the test plates, this value is considered acceptable in light of the within

- plate CV values.

There were no significant differences in testosterone concentrations in the PCNB- treated cells

relative to the SC , or in estradiol concentrations at PCNB levels ≤1 μM

. PCNB caused small

, but statistically significant (p ≤ 0.05), i ncreases in estradiol concentrations in the culture medium

at 10 μM in all three runs (1.09 - to 1.21- fold) and at 20 μM in the third run (1.36-fold).

H owever, all significant increases were <1.5

- fold relative to the SC

.

Based on the hormone responses in each of three independent runs, PCNB treatment resulted in statistically significant and reproducible increases in estradiol production, but did not result in statistically significant and reproducible alterations in testosterone production.

Th e assay satisfies the EDSP Tier 1 Test Order requirement s for a Steroidogenesis a ssay (OCSPP 890.1550).

COMPLIANCE : Signed and dated Statement s of Data Confidentiality Claims (no claim of confidentiality was made)

, Compliance with Good Laboratory Practice , Flagging, and Quality Assurance were provided.Steroidogenesis Assay (2011) / Page 3 of 15

PCNB / 056502 OCSPP 890.1550/ OECD None



## I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility : Huntingdon Life Sciences Ltd.

Location: Cambridgeshire, England Study Director: L. C. Akhurst

Other Personnel: J. N. Carter, Head of In Vitro Technologies J. O. Hubbard, Study Manager D. Speechley, Senior Study Manager

S. Bate, Senior S tatistician Study Period: February 2, 2012 through July 4 , 201 2



## 2

. Test S ubstance : PCNB Technical

Description: Light brown powder

Lot # (expiration date): 107030L052 (July 2016 ) Purity: 95.6 % Solubility: Soluble at tested concentrations in DMSO
Vapor pressure : Not provided Stability: Not provided Storage conditions: Room temperature in a sealed container protected from light

CAS #: 82

- 68

- 8 Molecular weight: 295.3

Structure:



### Cl

Cl

Cl Cl Cl NO 2



## 3

. Positive C ontrol : Forskolin

Description (molecular weight) : White powder (410.50)

Source: Sigma

- Aldrich; Cat # F6886

Lot # ( expiration d ate) : 120M5054 V ( January 2016 retest ) Purity: 98% Solubility (in s olvent): Soluble at tested concentrations in DMSO Storage conditions: Room temperature

CAS #: 66575

- 29

- 9



## 4. Negative C ontrol : Prochloraz

Description (molecular weight): White powder (376.67)

Source: Sigma

- Aldrich Fluka Analytical; Cat # 45631

Batch # (expiration date): 6220X ( August 8, 2012 retest ) Purity: 99.1 % Solubility (in solvent): Soluble at tested concentrations in DMSO Storage conditions: Room temperature

CAS #: 6 7747

- 09

- 5Steroidogenesis Assay (2011) / Page 4 of 15

PCNB / 056502 OCSPP 890.1550/ OECD None



## 5

. Solvent/ V ehicle C ontrol : Dimethyl Sulfoxide ( DMSO )

Description (molecular weight) : Clear liquid (78.13)

Source: Sigma

- Aldrich; Cat # 494429

Lot # (expiration date): 22896PMV ( n ot provided ) Purity: 99 .99 % Storage conditions: Not provided

CAS #: 67

- 68

- 5

Justification for choice of

solvent: Not provided. DMSO is a Guideline recommended solvent in which PCNB is reasonably soluble

. Final concentration in assay : 0.1 % v/v



## 6

. Stock Medium : Dulbecco’s modified Eagle’s medium/ Ham’s F12 nutrient

mixture , without phenol red

Source: Sigma

- Aldrich ( St. Louis, MO ) ; Ref # D6434

Lot # (expiration date): RNBB8625 (November 2012)

Sodium bicarbonate : C omponent of stock medium

Nu

- Serum : BD Biosciences ; Ref # 355 1 00 ; Lot # 11268 ; t ested for background hormone concentrations by performing laboratory

ITS+ premix: BD Biosciences; Ref # 354352 ; Lot # 18302 (expiry August 1, 2013), Lot # 22771 (expiry October 14, 2013), and Lot # 09233 (expiry May 1, 2013)



## 7. Test Cells : H295R human adrenocortical carcinoma cells (ATCC CLR -2128; Batch # not provided) at passage 4.5 – 6.5 were incubated in the stock medium at the time of plating, dosing, and harvest. Incubation conditions were 5% CO 2 

## and 37±2°C for approximately 24 hours prior to exposure.

The following performance criteria were met (indicated by an “x”):

x Cell passage identifier . Cell Passage # : 4 .5

– 6 .5

x Cells frozen down at passage 5

x Frozen cells cultured for 4 additional passages

x Total number of passages does not exceed 10



## B. METHODS

1. Pre -T est Information

a. Hormone Assay Interference Test : The protocol for hormone analysis was validated, and the results are presented in a separate Methodology Validation report for study # HLS0809 (data not provided). Hormone assay interference was also evaluated in this study. The fold

difference c ompared to DMSO (SC) was 0.95-1.13 and 89-1.03 for estradiol and testosterone, respectively, indicating a lack of interference.

b. Hormone Extraction : Hormone extraction w as not reported

. The analytical method used for the measurement of testosterone and estradiol in supernatant was validated in study HLS0809 (data not provided).

c. Laboratory Proficiency Test : Limited information was provided in Annex 2 of the study report. The author stated that the proficiency chemicals were tested in accordance with the Endocrine Disrupter Screening Program Test Guidelines OPPTS 890.1550: Steroidogenesis (Human Cell Line H29 5R) (EPA 640 -C-09-003) of October 2009 and that there were noSteroidogenesis Assay (2011) / Page 5 of 15

PCNB / 056502 OCSPP 890.1550/ OECD None



## significant changes in personnel since the conduct of this test. All EC 50 

## values were within the acceptance ranges, e xcept in the first test with forskolin (Table 1). In that case , the

EC 50 

## value for estradiol was 0.28 μM, which fell just outside the range of 0.3 – 3.0 μM. However, the mean value for the three tests, 0.51 μM, was within the acceptable range.

TABLE 1. Results of Laboratory Proficiency Test using Forskolin and Prochloraz

. a



### Compound Concentrations tested ( μ M) Test EC 50 

### ( μ M) b



### Testosterone Estradiol

Forskolin 0.03, 0.1, 0.3, 1, 3

and 10 1 1.34 0.28

2 0.35 0.43

3 0.38 0.81

Mean 0.69 0.51

Prochloraz 0.01, 0.03, 0.1, 0.3, 1, and 3 1 0.05 0.08

2 0.03 0.07

3 0.04 0.07

Mean 0.04 0.07

a Data were obtained from page 75 of the study report.

b The Guideline (890.1550) specified range for EC 50 s for forskolin are 0.2

- 2.0 μ M for testosterone and 0.3

- 3.0 μ M for estradiol, and the specified range for ED 50 s for prochloraz are 0.01

- 0.1 μ M for testosterone and 0.03

- 0.3 μ M for

estradiol.



## 2. Test Solutions : PCNB was dissolved in DMSO to give a concentration of 100 mM. This

solution was diluted in serial ten -fold dilutions in DMSO so that a total of seven concentrations were obtained. All solutions were prepared fresh immediately before

treatment of the cells. Forskolin and prochloraz were dissolved in DMSO to make 10 mM solutions. Dilutions were conducted in DMSO to give a 1 mM solution for forskolin and 1 mM and 0.1 mM solutions for prochloraz. When added to the cell culture plates, these dilutions yie lded final concentrations of 1 μM and 10 μM for forskolin, 0.1 μM and 1 μ M for prochloraz, and 100 μM, 10 μM, 1 μM, 100 nM, 10 nM, 1 nM, and 0.1 nM for P CNB

. The f inal concentration of DMSO in the medium was held constant at 0.1 % (v/v). No precipitation was visible.

3. Cell Plating and P reincubation : Cells were maintained in the Stock Medium described

above. The hormone concentrations in undiluted Nu- Serum were 8.86 ng/mL for testosterone and 1.76 ng/mL for estradiol. H295R cells were grown for five passages, frozen in liquid nitrogen, then thawed and cultured for four to six additional passages prior

to use in the assay. The cells were plated into wells of a 24

- well cell culture plate at a density of approximately 300,000 cells in 1 mL. The cells were then placed into a 5% CO 2 

## incubator at 37±2°C for approximately 24 hours prior to chemical exposure. Prior to dosing, the cells were checked microscopically for degree of confluence, attachment , and proper morphology.

4. Exposure : The medium was removed from the cells and replaced with 1 mL of medium containing concentrations of PCNB (or solvent contro l) in triplicate, according to the schematic presented in Table 2.Steroidogenesis Assay (2011) / Page 6 of 15

PCNB / 056502 OCSPP 890.1550/ OECD None

TABLE 2. Dosing S chematic for the E xposure of H295R C ells to Acephate ( F inal C oncentrations in μ M). a

1 2 3 4 5 6

A DMSO DMSO DMSO 0. 1 0. 1 0. 1

B 100 100 100 0.0 1 0.0 1 0.0 1

C 10 10 10 0.00 1 0.00 1 0.00 1

D 1 1 1 0. 000 1 0. 000 1 0. 000 1

a Data were obtained from page 14 of the study report.



## A concurrent QC plate was included with each of the three independent runs of the test chemical plates to demonstrate the assay’s response to forskolin (an inducer of testosterone and estradiol production) and prochloraz (an inhibitor of testosterone and estradiol production). The QC plate was prepared and dosed in the same manner with either forskolin or prochloraz, according to the schematic presented in Table 3.

TABLE 3. Dosing S chematic for the QC P late for P ositive C ontrols ( F inal C oncentrations). a

1 2 3 4 5 6

A Blank b Blank Blank Blank + methanol Blank + methanol Blank + methanol

B DMSO DMSO DMSO DMSO + methanol DMSO + methanol DMSO + methanol

C Forskolin 1 μM Forskolin 1 μM Forskolin 1 μM Prochloraz 0.1 μM Prochloraz 0.1 μM Prochloraz 0.1 μM

D Forskolin

10 μM Forskolin 10 μM Forskolin 10 μM Prochloraz 1 μM Prochloraz 1 μM Prochloraz 1 μM

a Data were obtained from page 15 of the study report.

b Blank wells received only medium

.



## Following dosing, the plates were incubated for approximately 48 hours under the previously described conditions. After the incubation period, the plates were removed from the incubator and every well checked under the microscope for signs of cytotoxicity (attachment, morphology, etc.) and also as a qualitative assessment of cell density. Two aliquots of medium (490 μ L) were collected and frozen at

− 70°C until further processing.

5. Cell V iability/ Cytotoxicity A ssay : Cytotoxicity was determined by the MTT (3 -(4,5- dimethylthiazol -2- yl)

- 2, 5 -diphenyltetrazolium bromide) assay. Briefly, the medium was removed from the wells, and the wells were washed with DPBS. Methanol was added to

wells A4 -6 and B4-6 of the QC plate to provide controls for cytotoxicity. The QC plate was allowed to stand at room temperature for 30 minutes. After this time, the methanol was

removed , and all wells were rinsed with DPBS. MTT (0.5 mg/mL culture media) was added

in 1 m L per well immediate ly after removal of the DPBS, and the plates were incubated at

37±2°C/5% CO 2 

## for three hours. At the end of three hours, the MTT was removed from the wells, 1

- mL portions of acidic isopropanol were added to each well

, and the plates were shaken for 10 minutes. Portions (200 μ L) were collected, and absorbance was read (along with acidic isopropanol blanks) at 540 nm with a plate reader

.

6. Hormone M easurement S ystem : The concentration of each hormone (testosterone and estradiol) was evaluated in triplicate in the culture medium derived from each well with specific EIA kits supplied by DRG for testosterone (catalog # EIA -1559) and estradiol (catalog # EIA -2693). The lower limits of quantification were 200 pg/m L for testosteroneSteroidogenesis Assay (2011) / Page 7 of 15

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## and 25 pg/mL for estradiol , which are above the guideline specified limits of 100 pg/mL for testosterone and 10 pg/mL for estradiol.

The following performance criteria were met (indicated by an “x”) :

NR Method detection limit (100 pg/mL testosterone; 10 pg/m L estradiol)

NR Spiked sample recovery acceptable for two concentrations of testosterone and estradiol (mean measured amount from triplicate samples within 30% of nominal concentration)

NR Hormone cross

- reactivity (antibody

- based assays only; ≤30% of basal production of the respective hormone)

X Solvent control within 75% range below maximum response on standard curve

X Test compound tested for interference with measurement system



## C. DATA ANALYSIS : Mean values and standard deviations for testosterone and estradiol

concentrations were calculated for each test concentration of PCNB , reference chemicals, the solvent controls, and blanks. The percent CVs were reported for within- plate and

between

- plate variation in hormone concentrations. Relative changes in testosterone and estradiol production were calculated by using the following equation:

Relative Change = Hormone concentration in each well ÷ Hormone concentration of mean

solvent control

A response was considered to be statistically significant if the difference from the solvent

control had a p≤ 0.05. Data were expected to follow a concentration

- related profile.

A parametric analysis was performed if Bartlett's test for variance homogenei ty was not significant at the 1 % level. The F1 approximate test for monotonicity of means was applied.

If the F 1 approximate test for monotonicity of dose-response was not significant at the 1% level, Williams' test for a monotonic trend was applied. If t he F1 approximate test was significant, suggesting that the dose response was not monotonic, Dunnett's test was performed instead.

A non- parametric analysis was perform ed if Bartlett's test was still significant at the

1% level after both logarithmic and square- root transform ations. The H1 approximate test,

the non- parametric equivalent of the Fl test described above, was applied. If the H1 approximate test for monotonicity of dose response was not significant at the 1% level, Shirley's test for a monotonic trend was applied. If the H 1 approximate test was significant, suggesting that the dose-response was not monotonic, Steel's test was perfo rm ed instead. The statistical analysis procedures were considered appropriate.

II. RESULTS

A. TEST COMPOUND : In the first run, PCNB was cytotoxic at the highest concentration (100 μ M), with a viability of 31% relative to the SC. Additionally, a precipitate was

observed at this concentration when the cells were examined by microscopy at 48 hours

after treatment. Based on the viability results from the first run, the highest PCNB

concentration tested in the seco nd assay run was 30 μM. Although no precipitation wasSteroidogenesis Assay (2011) / Page 8 of 15

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## observed at 30 μM of PCNB, viabilit y was 78% of the SC at this concentration. In the third

assay ru n, t he highest concentra tion of PCNB was further reduced to 20 μM, and this concentration was not cytotoxic or associated with precipitation. For the SC replicate wells within the test plate, t he %CVs ranged from 4.8–5.8% for absolute testosterone

concent rations and 1.7–3.2% for absolute estradiol concentrations. The between plate CVs

for the SC w ere 13.6% for testosterone and 50.3 % for estradiol ; the between plate CV for estradiol exceeded the Guideline criteria ( ≤ 30%).

There were no significant differences on testosteron e concentration in the PCNB- treated

cells relative to the SC (Table 4; 0.91- to 1.05-fold change). However, in all three run s, PCNB caused small , but statistically significant

, increases in the concentration of estradiol in the culture medium at the highest analyz able PCNB test concentrations. In all three runs, 10 μM of PCNB resulted in a 1.09- to 1.21-fold increase (p<0.05) estradiol production, and in the third run, 20 μM of PCNB resulted in a 1.36 -fold incre ase (p≤0.001) in estradiol production The effects of PCNB on testosterone and estradiol production are shown in Figures 1 and 2.

TABLE 4. Mean (±SD) Hormone Concentrations Following Treatment with PCNB f or 48 Hours. a

Nominal

Concentration (μM) Run 1 Run 2 Run 3 Run 1 Run 2 Run 3 Mean ± SD Statistical Significance

Testosterone (pg/mL) Fold Difference

DMSO 2150 2000 1640

— — — — — —

20

— — 1560

— — 0.96 0.96 NA

— 10 2230 2030 1690 1.04 1.01 1.03 1.03 0.02

— 1 2220 1990 1680 1.03 0.99 1.03 1.02 0.02

— 0.1 1980 1980 1640 0.92 0.99 1.00 0.97 0.04

— 0.01 2180 1870 1710 1.01 0.94 1.04 1.00 0.05

— 0.001 2270 1810 1650 1.05 0.91 1.01 0.99 0.07

— 0.0001 2200 1920 1620 1.02 0.96 0.99 0.99 0.03

— Estradiol (pg/mL) Fold Difference

DMSO 327.7 618.2 238.1

— — — — — —

20

— — 322.6

— — 1.36 1.36 NA Run 3

10 396.4 675.6 266.6 1.21 1.09 1.12 1.14 0.06 Runs 1 , 2 and 3

1 350.7 613.9 234.6 1.07 0.99 0.99 1.02 0.05

— 0.1 329.9 625.3 234.6 1.01 1.01 0.99 1.00 0.01

— 0.01 318.6 605.3 227.6 0.97 0.98 0.96 0.97 0.01

— 0.001 335.8 603.1 232.1 1.02 0.98 0.97 0.99 0.03

— 0.0001 343.8 644.5 233.2 1.05 1.04 0.98 1.02 0.04

—

a Data were obtained from page s 25 of the study report. The lower limit of quantification (LLQ) was 200 pg/mL for

testosterone and 25 pg/mL for estradiol. NA Not applicable; n=1Steroidogenesis Assay (2011) / Page 9 of 15

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## F IGURE 1. Change in Testosterone P roduction Relative to PCNB C oncentration.Steroidogenesis Assay (2011) / Page 10 of 15

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## FIGURE 2. Change in Estradiol Production Relative to PCNB Concentration.Steroidogenesis Assay (2011) / Page 11 of 15

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## B. CYTOTOXICITY : PCNB was not cytotoxic to the H295R cells at concentrations ≤ 20 μ M (Table 5). Relative to the SC, cell v iab ility in each run ranged from 88-112 % at ≤20 μM

PCNB , but viability was 78% at 30 μ M in Run 2 and 31% at 100 μ M in Run 1. In the quality control plate, viability in each run ranged from 92-111 %, except in the methanoltreated cells (6 -15 % viability).

TABLE 5. Mean (±SD) MTT Cell Viability Results after Treatment with Forskolin, Prochloraz, or PCNB for 48

Hours. a

Compound Concen tration ( μ M) Cell Viability

Mean SD

Blank NA 99.0 5.29
Background NA 106 4.58

SC + Methanol NA 105 4.58

Forskolin 1 98.7 2.52

Forskolin 10 95.3 3.51

Prochloraz 0.1 10.3 4.51

Prochloraz 1 9.67 2.52

PCNB 100 31 NA

PCNB 30 78 NA

PCNB 20 88 NA

PCNB 10 100 5.57

PCNB 1 99 2.00

PCNB 0.1 103.7 4.73

PCNB 0.01 101.7 2.89

PCNB 0.001 102 9.17

PCNB 0.0001 101.3 4.04

a Values were calculated by the reviewers from data obtained from page 24 of the study report.

NA Not applicable; n=1



## C. QC PLATE : The hormone concentrations after exposure to OPP, SC, blank and background samples, as well as the fold-difference change relative to SC (individual and mean ± SD) for the three assay runs, are presented in Table 6. The minimum basal hormone production levels (500 pg/mL for testosterone, 40 pg/mL for estradiol) were met in both blank and SC wells, and basal hormone production in the SC wells wa s > 9.9-fold LLQ for

testosterone and >10.5- fold LLQ for estrogen . Compared to SC, 10 μM forskolin, on

average
, in duced testosterone production by 2.26-fold and estradiol production by an unknown factor. For estradiol, the fold induction resulting from forskolin could not be

confirmed to be above the guideline specified >7.5 for the first two assay runs because the

estradiol levels were above the MLQ (2000 pg/mL) and the basal levels of estradiol production were relatively high in the SC wells for Runs 1 and 2. Based on estradiol level s being >MQL (>2000 pg/mL) , the relative fold induction for 10μM forsk olin was greater than 5.12-fold, 3.12- fold and 7.70-fold for Runs 1, 2 and 3, respectively. Compared to SC

wells , 1 μM prochloraz on average inhibited the synthesis of testosterone to 0.38- fold and

estradiol to 0.09- fold , which are below the guideline specified 0.5-fold reduction.

The r ange for %CV for SC replicates within each plate was 1.5–4.9% for absolute

testosterone concentrations and 2.5-5.2% for absolute estradiol concentrations. The

between

- plate CVs for hormone levels in the S C wells were 15.9% for testosterone andSteroidogenesis Assay (2011) / Page 12 of 15

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## 45.0% for estradiol, which is above the Guideline criteria of ≤ 30%.

The Guideline requirements were generally met indicating that the assay was sensitive to induction and inhibition of testosterone and estradiol. Departu res from the Guideline included: (i) testosterone was only induced by 1.89-fold rather than the Guideline specified
of ≥2 -fold in the second assay run (ii) induction of estradiol production by 10 μM forskolin did not definitively meet the >7.5- fold criteri on in Runs 1 and 2, and (iii) inter- plate viability for estradiol concentrations in the SC wells were above the guideline specified 30% limit.

TABLE 6. Mean (±SD) Hormone Concentrations Following Treatment with Forskolin or Prochloraz for 48 Hours. a

Concentration (μM) Run 1 Run 2 Run 3 Run 1 Run 2 Run 3 Mean ± SD

Testosterone (pg/mL) Fold Difference (Relative to DMSO)

Blank 2590 2300 1990 1.11 1.10 1.18 1.13 0.04

DMSO 2330 2090 1690

— — — — — 1 μM Forskolin 4340 3400 3580 1.86 1.63 2.12 1.87 0.25
10 μM Forskolin 5610 3940 4180 2.40 1.89 2.48 2.26 0.32
0.1 μM Prochloraz 1240 1120 1080 0.53 0.54 0.64 0.57 0.06
1 μM Prochloraz 720 790 760 0.31 0.38 0.45 0.38 0.07
Estradiol (pg/mL) Fold Difference (Relative to DMSO)

Blank 406.9 686.1 264.7 1.05 1.07 1.02 1.05 0.03

DMSO 388.8 640.1 259.9

— — — — — 1 μM Forskolin M LQ M LQ M LQ >5.14 b > 3.12 b >7. 70 b NA NA
10 μM Forskolin M LQ M LQ M LQ >5.14 b > 3.12 b >7. 70 b NA NA
0.1 μM Prochloraz 242.1 314.6 154.1 0.62 0.49 0.59 0.57 0.07
1 μM Prochloraz 35.28 59.34 25.18 0.09 0.09 0.10 0.09 0.01

a Data were obtained from page 26 of the study report. The lower limit of quantification (LLQ) was 200 pg/mL for testosterone and 25 pg/mL for estradiol. ALQ indicates the concentration was above the maximum limit of quantification ( MLQ, >2000 pg/mL).

b The minimum level of the fold induction for estradiol was calculated by dividing the MQL for estradiol by the estradiol concentration in the respectively SC wells.

NA Not applicable



## III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS ’ CONCLUSIONS (from the study report) : The results for the cytotoxicity of PCNB are shown in Table 1 [ of the study report ]. In the first test, PCNB was cytotoxic at the highest concentration of 100 μM; the viability was 31% of the solvent control. Additionally, a precipitate was observed when examining the cells using a microscope 48 hours after treatment at this PCNB concentration. As the viability was < 80% of the solvent control and the test substance was not fully soluble, data from th e highest concentration were not used in the data analysis. In the second test, the highest concentration of PCNB was reduced to 30 μM; however, the viability was 78% of the solvent control at this concentration. No precipitate of the test substance was ob served at this concentration. As the viability was < 80% of the solvent control, data from this highest concentration were not used in the data analysis. In the third test, the highest concentration of PCNB was reduced to 20 μM. This concentration was not cytotoxic or associated with precipitation.Steroidogenesis Assay (2011) / Page 13 of 15

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## The interference assay (Tables 13 and 15 of the Immunoassay phase report, Annex 1) [ of the study report ] demonstrated that PCNB did not interfere with the hormone measurement

assay system. Concentrations determ ined for estradiol and testosterone were similar in the

absence and presence of PCNB. The interference assay for testosterone was repeated as a spurious value was obtained for the blank DMSO (Table 14) [ of the study report ].

The concentrations of estradio l and testosterone observed in the three tests are summari z ed

in Table 2 [ of the study report ] . In all three tests, PCNB caused small statistically significant

increases in the concentration of estradiol in the culture medium at the highest analyz able

PCNB test concentration (10 μM) in the first and second tests (P < 0.001 and P < 0.05, respectively) and at the highest two analy zable PCNB test concentrations (20 and 10 μ M; P < 0.001 and P < 0.01, respectively) in the third test. However, all statistically significant

increases were < 1.5 fold when compared with the solvent control concentrations. The value of 1.5 fold was used as a cutoff for a positive response in the joint EPA/OECD validation program for the steroidogenesis assay (Hecker et al 2011).

In a ll three tests, PCNB caused no statistically significant changes in the concentration of

testosterone in the culture medium.

The concentrations of estradiol and testosterone are detailed in the Immunoassay phase

report, Table 1 to Table 6 and Table 16 (Annex 1) [ of the study report ].

The LOEC for estradiol induction was considered to be 10 μ M in all three tests, with a

NOEC of 1 μ M. The NOEC for testosterone inhibition was considered to be 100 μ M for all

three tests.

A QC plate was run on all three occa sions. Forskolin at 10 μ M caused an increase in the concentrations of both estradiol and testosterone, whereas prochloraz at 1 μ M caused a

decrease in the concentrations of both hormones (see Table 7 to Table 12 and Table 17 of the Immunoassay phase report, Annex 1) [ of the study report ]. The highest measurable fold

increases in estradiol and testosterone by 10 μM forskolin were > 7.5 and 2.48, respectively. The highest measurable fold decreases in estradiol and testosterone by 1 μM prochloraz

were 0. 09 and 0.31, respectively.

The acceptance criteria for forskolin and prochloraz on the QC plate were met on all

occasions with the following exception:

In the 1st and 2nd tests: 10 μM forskolin produced an increase in estradiol concentration

which was ab ove the limit of quantification of 2000 pg/mL and could not be confirmed as > 7.5 times solvent control. This was due to a higher level of basal production of estradiol in

the 1 st and 2nd tests when compared to the 3rd test. In the 3rd test, although the i ncrease in estradiol also lay above the limit of quantitation, it was confirmed as > 7.5 times solvent

control.

All other criteria for CV and basal hormone production were met (Tables 16 and 17 of the Immunoassay phase report, Annex 1) [ of the study report ] with the following exception:Steroidogenesis Assay (2011) / Page 14 of 15

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## The between plate CV for the solvent control values in the test plates was 50.3% for

estradiol instead of < 30%. However, as the CV values for the solvent controls within the plates were all low (< 3.2%), and all fold chan ges were calculated relative to the solvent control on any one plate, the high CV observed between plates was not considered to affect the integrity of the study.

It was concluded that PCNB demonstrated an influence on the steroidogenesis pathway, acting as a very mild inducer of estradiol production. However, the level of induction was below the cutoff value used to determine a positive response in the EPA/OECD joint validation effort (Hecker et al., 2011). The LOEC for the overall study for estradiol induction was 10 μ M, with a NOEC of 1 μ M.

B. AGENCY COMMENTS : G uideline acceptability recommendations were generally met, including adequate production of testosterone and estradiol, acceptable within plate reproducibility (low % CV), and appropriate induction and inhibition with positive controls.

Minor d epartures from the Guideline were observed (see Deficiencies Section below), but these minor departures did not adversely affect the results or conclusions of this study.

Prec ipitation and/or cell cytotoxicity was not observed at PCNB concentration s of ≤ 20 μM. Relative to the SC, cell viability in each run ranged from 88- 112% at ≤ 20 μM PCNB . Cell viability was reduce d to 78% at 30 μM in Run 2 and 31% at 100 μM in Run 1, and precipitation was also noted at 100 μM in Run 1.

For the test plates, t he % CVs ranged from 4.8–5.8% for absolute testosterone concentrations and 1.7–3.2% for absolute estradiol concentrations in the SC replicate wells

within the test plate s. The betw een

- plate CVs for hormone concentrations in the SC wells

were 13.6% for testosterone and 50.3% for estradiol. The within

- plate CVs for both

hormones were low and met the performance criteria , as did the between

- plate CV for

testosterone . The between plate CV for estradiol exceed the specified 30% maximum , but is considered acceptable in light of the within- plate CV values.

There were no significant differences in testosterone concentrations in the PCNB- treated

cells relative to the SC

, or in estradiol concentrations at PCNB concentration ≤ 1 μM

. PCNB caused small statistically significant increases (p ≤ 0.05) in the estradiol

concentration s in the culture medium at 10 μM in all three runs (1.09- to 1.21- fold) and at 20 μM in the third run (1.36-fold). However, all significant increases were < 1.5- fold

relative to SC, which was the proposed cutoff for a positive response in the multi-laboratory validation report and the joint EPA/OECD validation program for the steroidogenesis assay.

Basal hormone production in SC wells was acceptable both in terms of the absolute concentrations and relative to the method LLQ. Compared to the SC well s, 10 μM forskolin induced testosterone production by 2.26-fold and induced estradiol by an unknown factor. For estradiol, the fold induction resulting from forskolin could not be confirmed to be above the guideline specified >7.5 for the first two assay runs because the estradiol levels were above the MLQ; however, based on the MLQ, the minimum levels of induction for estradiolSteroidogenesis Assay (2011) / Page 15 of 15

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## production were greater than 5.12-, 3.12- and 7.70-fold in Runs 1, 2 and 3, respectively. Compared to SC, 1 μM prochloraz on average inhibited the synthesis of testosterone to 0.38-fold and estradiol to 0.09-fold. The ranges for % CV within

- plate and between

- plate SC replicates on the QC plates were of similar magnitude to those from the test plates. All

% CV values for the SC well on the QC plate s met the performance criteria ( ≤ 30%) except

for the betw een

- plate CVs for estradiol (45.0 %).

Based on the results of this study, PCNB wa s not an inhibitor of steroidogenesis, but slightly

induced estradiol production at PCNB concentrations of 10 – 20 μM.

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

• Stability of PCNB in the test system was not reported.

• Departures from the Guideline included: (i) testosterone was only induced by 1.89-fold rather than the Guideline specified of ≥2 -fold in Run 2 and (ii) induction of estradiol production by 10 μM forskolin did not definitively meet the >7.5-fold criterion in Runs

1 and 2.

• The between

- plate CVs for estradiol concentrations in the SC well s exceeded the acceptable 30% limit for both the test and QC plates

.