UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: 6/29/2015 

SUBJECT: Phosmet: Data Evaluation Records (DERs) for EDSP Tier 1 Assays 

PC Code: 059201 

Decision No.: 459049, 463273 

Petition No.: NA 

DP Barcode: D397165, D400672 

Registration No.: NA 

Regulatory Action: NA 

Risk Assessment Type: NA 

TXR No.: 0056199 

MRID No.: See Table 

Case No.: NA 

CAS No.: 732-11-6 

40 CFR: NA 

FROM: Greg Akerman, Ph.D. Do- ff--- - lmmediate Office 

Health Effects Division (7509P) 

THROUGH: J

Deputy 

ess Rowland 

Director 

~-~ 

Health Effects Division 

TO: Jolene Trujillo 

Biologist/Chemical Review Manager 

Risk Management and Implementation Branch V 

Pesticide Re-evaluation Division (7505P) 

I. ACTION REQUESTED 

Ver.Apr. 2010 

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

Division (HED) review the Endocrine Disruptor Screening Program (EDSP) Tier 1 assays 

submitted in response to the agency's Test Order for phosmet: Test Order # EDSP-059201-54. 

Pagel of2 

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Page 2 of 2 

II. RESPONSE

Attached are the EDSP Tier 1 assay DERs for phosmet.

III. MRID Table

Chemical: Phosmet PC Code: 059201

Guideline Assay MRID 

890.1100 Amphibian Metamorphosis Assay (Frog) 48673001

890.1150 Androgen Receptor Binding (Rat Prostate) 48618703

890.1200 Aromatase Assay (Human Recombinant) 48618702

890.1250 Estrogen Receptor Binding 48618704

890.1300 Estrogen Receptor Transcriptional Activation 

(Human Cell Line HeLa-9903) 48618705 

890.1350 Fish Short-Term Reproduction 48673002

890.1400 Hershberger (Rat) 48618706

890.1450 Female Pubertal (Rat) 48673003

890.1500 Male Pubertal (Rat) 48673003

890.1550 Steroidogenesis (Human Cell Line – H295R) 48618701

890.1600 Uterotrophic (Rat) 48618707

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԡԹՌԹԯԽՉՍՁՊԽՅԽՆՌ    ԢԭԞԡԭԟԹՊԻՇԼԽ  

ԬԢԠԡԡԹՌԹԭՇՁՆՌ  

ԢԭԞԪԯԦԡ   

ԢԭԞԤՍՁԼԽՄՁՆԽ   

      ԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԣՊՇԿ

 

ԱԽՋՌԪԹՌԽՊՁԹՄ ԭՀՇՋՅԽՌ          ԭՍՊՁՌՑ
    

ԠՇՅՅՇՆԫԹՅԽԭՀՇՋՅԽՌ

ԠՀԽՅՁԻԹՄԫԹՅԽ  ԦԲԭԞԠ   ԫՇՌԯԽՈՇՊՌԽԼ

 ԠԞ԰ԫԹՅԽ  ԫՇՌԯԽՈՇՊՌԽԼ

ԠԞ԰ԫՇ  

԰ՑՆՇՆՑՅՋ  ԦՅՁԼԹՆնԱԽԻՀՆՁԻԹՄ

ԢԭԞԭԠԠՇԼԽ 

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԧՇՀՆԪԹՊՌՇՆ ԰ՁԿՆԹՌՍՊԽ 

԰ՌԹԾԾ԰ԻՁԽՆՌՁՋՌԠԹՅԺՊՁԼԿԽԢՆՎՁՊՇՆՅԽՆՌԹՄԦՆԻ ԡԹՌԽ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊԱԽՊՁ԰ԪՑԽՊՋ ԰ՁԿՆԹՌՍՊԽ  

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԠԹՅԺՊՁԼԿԽԢՆՎՁՊՇՆՅԽՆՌԹՄԦՆԻ ԡԹՌԽ

 

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊԠԹՌՀԽՊՁՆԽԞՍԺԽԽ ԡԹՌԽ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԲ԰ԢԭԞԬԭԭԢԣԢԡԢԯԟԦԳ ԰ՁԿՆԹՌՍՊԽ

ԡԹՌԽԢՎԹՄՍԹՌՁՇՆԠՇՅՈՄԽՌԽԼ#ԼԼՅՅՅՑՑՑՑ%

ԠԦԱԞԱԦԬԫԩԽԽԪԯԭՀՇՋՅԽՌԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑՏՁՌՀԞԾՊՁԻԹՆԠՄԹՏԽԼԣՊՇԿ
ԵԽՆՇՈՍՋ

ՄԹԽՎՁՋԣՇՄՄՇՏՁՆԿԬԭԭԱ԰ԱԽՋՌԤՍՁԼԽՄՁՆԽԹՆԼԬԢԠԡԱԽՋՌԤՍՁԼԽՄՁՆԽԫՇԲՆՈՍԺՄՁՋՀԽԼՋՌՍԼՑ

ՈԽՊԾՇՊՅԽԼԺՑ԰ՅՁՌՀԽՊՋԳՁՋԻՁԽՆՌԴԹՊԽՀԹՅԪԹՋՋԹԻՀՍՋԽՌՌՋԩԹԺՇՊԹՌՇՊՑՊԽՈՇՊՌՆՍՅԺԽՊ

԰ՌՍԼՑՋՈՇՆՋՇՊԽԼԺՑԤՇՏԹՆԠՇՅՈԹՆՑԶՍՅԹԞՊՁՒՇՆԹ԰ՌՍԼՑԻՇՅՈՄԽՌԽԼԣԽԺՊՍԹՊՑ

ԡՁՋԻՄԹՁՅԽՊԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՁՆՌՀՁՋԡԢԯՌԽՅՈՄԹՌԽԹՊԽՇԾԾԽՊԽԼԹՋԹԿԽՆԽՊԹՄՊԽԾԽՊԽՆԻԽՌՇԹՁԼ

ՁՆՈՊԽՈԹՊԹՌՁՇՆՇԾՌՀԽԡԢԯԱՀԽՈՍՊՈՇՋԽՇԾՌՀԽՋԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՁՋՆՇՌՌՇՋԽՊՎԽԹՋՋՍԺՋՌՁՌՍՌԽԾՇՊՌՀԽԱԽՋՌ

ԤՍՁԼԽՄՁՆԽՋՆՇՊՌՇՈՊՇՎՁԼԽԹՆՑԿՍՁԼԹՆԻԽՇՆՀՇՏՌՀԽՋՌՍԼՑՋՀՇՍՄԼԺԽԻՇՆԼՍԻՌԽԼ

Page 3 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԫՇՌԽԱՀԽԲ԰ԢԭԞԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅ
Ԣԡ԰ԭԱՁԽՊՋԻՊԽԽՆՁՆԿԺԹՌՌԽՊՑՁՋԻՇՅՈՊՁՋԽԼՇԾԽՄԽՎԽՆ

ՋԻՊԽԽՆՁՆԿԹՋՋԹՑՋՁՆՌԽՆԼԽԼՌՇՁԼԽՆՌՁԾՑԹԻՀԽՅՁԻԹՄ0ՋՄՁՃԽՄՑԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՁԽՁՌՋՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀ

ՌՀԽԽՋՌՊՇԿԽՆԹՆԼՊՇԿԽՆՇՊՌՀՑՊՇՁԼ
ԢԞՇՊԱՈԹՌՀՏԹՑՋԱՀԽՊՇԺՍՋՌՆԽՋՋՇԾՌՀԽԱՁԽՊԺԹՌՌԽՊՑՁՋԺԹՋԽԼՇՆ

ՌՀԽՋՌՊԽՆԿՌՀՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՌՇՁԼԽՆՌՁԾՑՈՇՌԽՆՌՁԹՄԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՏՁՌՀԻՇՅՈՄԽՅԽՆՌԹՊՑԽՆԼՈՇՁՆՌՋ

ՏՁՌՀՁՆՌՀԽԹՋՋԹՑՏՀԽՊԽԹՎԹՁՄԹԺՄԽԹՆԼՊԽԼՍՆԼԹՆԻՑԹԻՊՇՋՋՌՀԽԺԹՌՌԽՊՑԱՀՍՋՌՀԽՊԽՋՍՄՌՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄ

ԹՋՋԹՑՋՀՇՍՄԼՆՇՌԺԽԻՇՆՋՁԼԽՊԽԼՁՆՁՋՇՄԹՌՁՇՆԺՍՌՊԹՌՀԽՊՋՀՇՍՄԼԺԽԻՇՆՋՁԼԽՊԽԼՁՆՌՀԽԻՇՆՌԽՐՌՇԾՇՌՀԽՊԹՋՋԹՑՋ

ՁՆՌՀԽԺԹՌՌԽՊՑԹՋՏԽՄՄԹՋԬՌՀԽՊ԰ԻՁԽՆՌՁԾՁԻԹՄՄՑԯԽՄԽՎԹՆՌԦՆԾՇՊՅԹՌՁՇՆ
Ԭ԰ԯԦԦՆՇՊԼԽՊՌՇԼԽՌԽՊՅՁՆԽՁԾԹԻՀԽՅՁԻԹՄ

ՀԹՋՌՀԽՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀՌՀԽԢԞՇՊԱՈԹՌՀՏԹՑՋԹԴԽՁԿՀՌՇԾԢՎՁԼԽՆԻԽ
ԴՇԢԽՎԹՄՍԹՌՁՇՆՇԾԱՁԽՊ

ԹՋՋԹՑՊԽՋՍՄՌՋՁՆԻՇՅԺՁՆԹՌՁՇՆՏՁՌՀՌՀԽԾՁՆԼՁՆԿՋՁՆՌՀԽԬ԰ԯԦՋՀՇՍՄԼԺԽՍՆԼԽՊՌԹՃԽՆ
ՊԽԾԽՊՌՇՌՀԽԴՇԢ

ԡՇԻՍՅԽՆՌ

ԢԵԢԠԲԱԦԳԢ԰ԲԪԪԞԯԶ

ԱՀԽԼԹՑԹՋՋԹՑՇԾՈՀՇՋՅԽՌՇՆԹՅՈՀՁԺՁԹՆՅԽՌԹՅՇՊՈՀՇՋՁՋՇԾԞԾՊՁԻԹՆԠՄԹՏԽԼԣՊՇԿ
ԵԽՆՇՈՍՋՄԹԽՎՁՋՏԹՋ

ԻՇՆԼՍԻՌԽԼ ՍՆԼԽՊԾՄՇՏՌՀՊՇՍԿՀԻՇՆԼՁՌՁՇՆՋԞՅՈՀՁԺՁԹՆՄԹՊՎԹԽ 
ՌԹԼՈՇՄԽՋՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈՊԽՈՄՁԻԹՌԽԹՌ

ԫՁԽՍՏՃՇՇՈԣԹԺԽՊ 
ԫԣՋՌԹԿԽՏԽՊԽ ԽՐՈՇՋԽԼՌՇ ՈՀՇՋՅԽՌ 
 ՈՍՊՁՌՑ ԹՌ ՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՇԾ


ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩԪԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽ
ԩԬԮ

ԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋՅԹՁՆՌԹՁՆԽԼԹՌՌՇոԠԹՆԼԹՈԥՇԾ

ՌՇ

ԭՀՇՋՅԽՌՋՁԿՆՁԾՁԻԹՆՌՄՑԼԽԻՊԽԹՋԽԼՆՇՊՅԹՄՁՒԽԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩՁՆՆՇՆՄԹՌԽՋՌԹԿԽՌԹԼՈՇՄԽՋ
ԫԣՋՌԹԿԽ

ԹՌՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՇՆԡԹՑՋԹՆԼԪԽԼՁԹՆԫՁԽՍՏՃՇՇՈԣԹԺԽՊ


ԫԣՋՌԹԿԽՏԹՋՍՆԹԾԾԽԻՌԽԼՇՆԡԹՑՌՀՇՍԿՀԹՋՁԿՆՁԾՁԻԹՆՌԼԽՄԹՑՏԹՋՇԺՋԽՊՎԽԼԹՌՇՆԡԹՑԹՌՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ

ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋՇԺՋԽՊՎԽԼԪՁՄԼՌՀՑՊՇՁԼԿՄԹՆԼ

ՀՑՈԽՊՌՊՇՈՀՑԾՇՄՄՁԻՍՄԹՊ ԻԽՄՄ ՀՑՈԽՊՈՄԹՋՁԹ ԹՆԼԾՇՄՄՁԻՍՄԹՊ ԻԽՄՄ ՀՑՈԽՊՌՊՇՈՀՑՏԽՊԽ ՇԺՋԽՊՎԽԼ ԹՌ ԹՄՄ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄՋ

ՁՆԻՄՍԼՁՆԿԻՇՆՌՊՇՄՋՌՀԽՊԽՏԹՋՆՇԹՈՈԹՊԽՆՌՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼՈԹՌՌԽՊՆՁՆՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋԱԹԼՈՇՄԽՋՏՁՌՀ

ՋՈՁՆԹՄԻՍՊՎԹՌՍՊԽՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՇՇԾՌԹԼՈՇՄԽՋՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽ

ՊԽՈՇՊՌԽԼԹՄՄԹՆԹՄՑՋԽՋԹՊԽԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԣԢԱԞԵԻՇՆՌՊՇՄԹՆԼԹՆԹՄՑՋԽՋՇԾ԰ԳԩՆՇՊՅԹՄՁՒԽԼ

ԥԩԩԹՆԼԺՇԼՑՏԽՁԿՀՌՏԽՊԽՈԽՊԾՇՊՅԽԼԽՐԻՄՍԼՁՆԿՄԹՌԽՋՌԹԿԽ
ԫԣՋՌԹԿԽ ՌԹԼՈՇՄԽՋ

ԪՁՆՇՊԼԽՎՁԹՌՁՇՆՋԾՊՇՅՌՀԽԿՍՁԼԽՄՁՆԽՏԽՊԽՆՇՌԽԼԺՍՌՌՀԽՑԼՁԼՆՇՌՋՍԺՋՌԹՆՌՁՎԽՄՑԹԾԾԽԻՌՌՀԽՊԽՋՍՄՌՋՇՊՁՆՌԽՊՈՊԽՌԹՌՁՇՆ

ՇԾՌՀԽՋՌՍԼՑԱՀԽԹՋՋԹՑՋԹՌՁՋԾՁԽՋՌՀԽԢԡ԰ԭԱՁԽՊԱԽՋՌԬՊԼԽՊՊԽՉՍՁՊԽՅԽՆՌԾՇՊԹՆԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԹՋՋԹՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ


ԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌՇՊԿԹՆՁՋՅԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

ԱԽՋՌՇՊԿԹՆՁՋՅՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՇՈՌՁՇՆԹՄԫՇՌԯԽՈՇՊՌԽԼ

ԱԽՋՌՌՑՈԽԾՄՇՏՌՀՊՇՍԿՀ

ԱԹԺՄԽ  ԰ՍՅՅԹՊՑ ՇԾ ԡԽՎԽՄՇՈՅԽՆՌԹՄ ԹՆԼ ԱՀՑՊՇՁԼ ԭԹՌՀՇՄՇԿՑԥՁՋՌՇՈԹՌՀՇՄՇԿՑ ԢԾԾԽԻՌՋ ՁՆ ՌՀԽ ԞՅՈՀՁԺՁԹՆ

ԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԞԪԞՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ

԰ՌԹԿԽ

ԥՁՆԼԩՁՅԺ

ԩԽՆԿՌՀ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԡԽՎԽՄՇՈՅԽՆՌ

ԱՀՑՊՇՁԼԤՊՇՋՋ

ԹՆԼ

ԥՁՋՌՇՈԹՌՀՇՄՇԿՑ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

 ԫՇ ԫՇ ԫՇ ԫՇ ԫԞ ԫԞ ԫՇ

 ԫՇ ԶԽՋ ԶԽՋ ԶԽՋ ԫԞ ԫԞ ԫՇ

 ԫՇ ԶԽՋ ԶԽՋ ԶԽՋ ԫԞ ԫԞ ԫՇ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



 Ԟ՟ՑԽՋՠՁՆԼՁԻԹՌԽՋԹՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄՍՆՄԽՋՋ

ՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼ



 ԱՀԽԻՊՁՌԽՊՁԹԾՇՊՋՁԿՆՁԾՁԻԹՆԻԽԹՊԽԼԽՋԻՊՁԺԽԼՁՆՌՀԽԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼ԰ՌԹՌՁՋՌՁԻԹՄԳԽՊՁԾՁԻԹՌՁՇՆՋԽԻՌՁՇՆՋՇԾ

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

ԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ



 ԥՁՆԼՄՁՅԺՄԽՆԿՌՀՁՋՆՇՊՅԹՄՁՒԽԼՌՇՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰Գԩ

Ԧ ԪԞԱԢԯԦԞԩ԰ԞԫԡԪԢԱԥԬԡ԰ 

 ԤՍՁԼԽՄՁՆԽԣՇՄՄՇՏԽԼԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼԾՇՄՄՇՏՁՆԿԿՍՁԼԽՄՁՆԽՋՇՍՌՄՁՆԽԼՁՆՌՀԽԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄ

ԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ0ՋԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅԱԽՋՌԤՍՁԼԽՄՁՆԽՋ

Page 5 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋ
ԣՊՇԿԹՆԼԬԢԠԡԤՍՁԼԽՄՁՆԽԾՇՊԱԽՋՌՁՆԿ

ՇԾԠՀԽՅՁԻԹՄՋԫՇԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑԱՀԽԾՇՄՄՇՏՁՆԿ

ԼԽՎՁԹՌՁՇՆՋՏԽՊԽՆՇՌԽԼ

 ԦՌՏԹՋՆՇՌՋՈԽԻՁԾՁԽԼՇՆՏՀՁԻՀԼԹՑՋԽՅԺՊՑՇՋՏԽՊԽԻՀԽԻՃԽԼԾՇՊՎՁԹԺՁՄՁՌՑ

 ԱՀԽԾՄՇՏՊԹՌԽՊԽՋՍՄՌԽԼՁՆԹՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԽՎԽՊՑՀՇՍՊՋԤՍՁԼԹՆԻԽՊԽԻՇՅՅԽՆԼՋԻՇՅՈՄԽՌԽ

ՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԹՈՈՊՇՐՁՅԹՌԽՄՑԽՎԽՊՑՀՇՍՊՋ

 ԯԽՋՍՄՌՋԾՊՇՅՌՀԽՈԽՊՁՇԼՁԻՋԻՊԽԽՆՁՆԿԹՆԹՄՑՋՁՋՇԾՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊՏԽՊԽՆՇՌՈՊՇՎՁԼԽԼԥՇՏԽՎԽՊՌՀԽ

ՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌՆՇՈԽՋՌՁԻՁԼԽՋԭԠԟՋՇՊՌՇՐՁԻՅԽՌԹՄՋՏԽՊԽԼԽՌԽԻՌԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԻՇՆՋՁԼԽՊԽԼՌՇՐՁԻԹԻԻՇՊԼՁՆԿՌՇԞ԰ԱԪՋՌԹՆԼԹՊԼՋ

 ԱՀԽՄՁԿՀՌՁՆՌԽՆՋՁՌՑ
ԨՄՍՐՏԹՋՄՇՏԽՊՌՀԹՆՊԽԻՇՅՅԽՆԼԽԼ
ԨՄՍՐ

 ԴԹՌԽՊՀԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬԽՐԻԽԽԼԽԼՌՀԽՊԽԻՇՅՅԽՆԼԽԼՀԹՊԼՆԽՋՋ
ՅԿԩ

ԹՋԠԹԠԬ

 ԱՀԽՌԽՅՈԽՊԹՌՍՊԽ
ոԠԾԽՄՄՇՍՌՋՁԼԽՇԾՌՀԽՊԽԻՇՅՅԽՆԼԽԼՊԹՆԿԽ
չոԠ

ԱՀԽՋԽԼԽՎՁԹՌՁՇՆՋԼՇՆՇՌՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌՌՀԽՊԽՋՍՄՌՋՇՊՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽՋՌՍԼՑ

 ԠՇՅՈՄՁԹՆԻԽ  ԰ՁԿՆԽԼԹՆԼԼԹՌԽԼԫՇԡԹՌԹԠՇՆԾՁԼԽՆՌՁԹՄՁՌՑԤԩԭԹՆԼԮՍԹՄՁՌՑԞՋՋՍՊԹՆԻԽՋՌԹՌԽՅԽՆՌՋ

ՏԽՊԽՈՊՇՎՁԼԽԼԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼՁՆԻՇՅՈՄՁԹՆԻԽՏՁՌՀԹՄՄՈԽՊՌՁՆԽՆՌԬԢԠԡ


ԬԢԠԡԹՆԼԲ԰ԢԭԞ
ԠԣԯԭԹՊՌԹՆԼԠԣԯԭԹՊՌԤՇՇԼ

ԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽՊԽԿՍՄԹՌՁՇՆՋՏՁՌՀՌՀԽԾՇՄՄՇՏՁՆԿԽՐԻԽՈՌՁՇՆՊՇՍՌՁՆԽԾՇՇԼԹՆԼ

ՏԹՌԽՊԻՇՆՌԹՅՁՆԹՆՌՋԻՊԽԽՆՁՆԿԹՆԹՄՑՋԽՋՏԽՊԽԻՇՆԼՍԻՌԽԼՍՋՁՆԿՋՌԹՆԼԹՊԼԲ԰

ԢԭԞՈՊՇԻԽԼՍՊԽՋԺՑԤԽՇԩԹԺՋԦՆԻԟՊԹՁՆՌՊԽԽԪԹՋՋԹԻՀՍՋԽՌՌԽՋ

ԞԱԽՋՌԪԹՌԽՊՁԹՄ   ԭՀՇՋՅԽՌ

ԡԽՋԻՊՁՈՌՁՇՆ   ԰ՇՄՁԼ

ԬԢԠԡՊԽԻՇՅՅԽՆԼՋԼԽՋԻՊՁԺՁՆԿՏԹՌԽՊՋՇՄՍԺՁՄՁՌՑՅԽՄՌՁՆԿԺՇՁՄՁՆԿՈՇՁՆՌՋՌԹԺՁՄՁՌՑՁՆՏԹՌԽՊԹՆԼՄՁԿՀՌՈԨԹԭՇՏՇՊԨՇՏ

ՎԹՈՇՊՈՊԽՋՋՍՊԽՇԾՌԽՋՌԻՇՅՈՇՍՆԼԽՐՈՁՊԹՌՁՇՆԼԹՌԽ

ԩՇՌԫՇԟԹՌԻՀԫՇ ԤԮԥ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭՍՊՁՌՑ    

ԦՅՈՍՊՁՌՁԽՋ   ԫՇՆԽԯԽՈՇՊՌԽԼ

԰ՌԹԺՁՄՁՌՑՇԾԠՇՅՈՇՍՆԼԱՀԽԼԹՑՅԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇՆՄՑՑՁԽՄԼԽԼՊԽԻՇՎԽՊՁԽՋՇԾ

ՇԾՆՇՅՁՆԹՄԥՇՏԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՊԽՄԹՌՁՎԽՄՑՋՌԹԺՄԽՏՁՌՀԠԳՋՊԹՆԿՁՆԿ

ԾՊՇՅՌՇ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾ

ԱԽՋՌԠՀԽՅՁԻԹՄՋ  ԰ՌՇՊԽԼԹՌՊՇՇՅՌԽՅՈԽՊԹՌՍՊԽՁՆՌՀԽՇՊՁԿՁՆԹՄԻՇՆՌԹՁՆԽՊՁՆԹԼԹՊՃՎԽՆՌՁՄԹՌԽԼ

ԻԹԺՁՆԽՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԟԱԽՋՌԬՊԿԹՆՁՋՅ

ԱԹԺՄԽԤԽՆԽՊԹՄԦՆԾՇՊՅԹՌՁՇՆԞԺՇՍՌՌՀԽԱԽՋՌ԰ՈԽԻՁԽՋԹՆԼԭԹՊԽՆՌԹՄԠԹՊԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

԰ՈԽԻՁԽՋԻՇՅՅՇՆՆԹՅԽ ԞԾՊՁԻԹՆԠՄԹՏԽԼԣՊՇԿ ԢԭԞՊԽԻՇՅՅԽՆԼՋԞԾՊՁԻԹՆԻՄԹՏԽԼԾՊՇԿ


ԵԽՆՇՈՍՋՄԹԽՎՁՋԴԽՋՌԽՊՆ#ԞԾՊՁԻԹ%ԻՄԹՏԽԼ

ԾՊՇԿ԰ՁՄՍՊԹՆԹ
ԵԽՆՇՈՍՋՌՊՇՈՁԻԹՄՁՋՅԹՑԺԽ

ՍՋԽԼԹՋԹՆԹՄՌԽՊՆԹՌԽՋՈԽԻՁԽՋՀՇՏԽՎԽՊԹՄՁՋՌ

ՇԾԹՄՄՇԾՌՀԽՆԽԻԽՋՋԹՊՑՈՊՇՌՇԻՇՄԼԽՎՁԹՌՁՇՆՋՌՇ

ԹԻԻՇՅՅՇԼԹՌԽՌՀՁՋՋՈԽԻՁԽՋՁՋՊԽԻՇՅՅԽՆԼԽԼ

ԾՇՊՁՆԻՄՍՋՁՇՆՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌԱՀԽԿՍՁԼԽՄՁՆԽ

ՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹ

ՍՋԽԼՌՇՋՍՈՈՇՊՌՌՀԽՊԽՄՁԹԺՁՄՁՌՑՇԾՌՀԽՌԽՋՌԺԽ

ՁԼԽՆՌՁԾՁԽԼ

԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԵԽՆՇՈՍՋՄԹԽՎՁՋ԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼ ԫՇՌԯԽՈՇՊՌԽԼ

Բ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ

԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅԱՁԽՊԞՋՋԹՑՋ
ԬԠ԰ԭԭԱԽՋՌԤՍՁԼԽՄՁՆԽ԰ԽՊՁԽՋԪԹՊԻՀԬԾԾՁԻԽՇԾԠՀԽՅՁԻԹՄ԰ԹԾԽՌՑԹՆԼԭՇՄՄՍՌՁՇՆԭՊԽՎԽՆՌՁՇՆ
ԬԠ԰ԭԭԴԹՋՀՁՆԿՌՇՆԡԠ
ՀՌՌՈՏՏՏԽՈԹԿՇՎԽՆԼՇՈՍԺՋԹՋՋԹՑՎԹՄՁԼԹՌՁՇՆԻՄԹՊՁԾՁԻԹՌՁՇՆԼՇԻՈԼԾ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԽՊԽՈԹՊԽՆՌՋՅԹՁՆՌԹՁՆԽԼԹՋՁՆՀՇՍՋԽՋՌՇԻՃ!

ԶԽՋ ԦՆՀՇՍՋԽԻՍՄՌՍՊԽՏԹՋՇՊՁԿՁՆԹՄՄՑՇԺՌԹՁՆԽԼ

ԾՊՇՅԫԹՋԻՇԣՇՊՌԞՌՃՁՆՋՇՆԴՁՋԻՇՆՋՁՆԹՆԼՏԹՋՅԹՁՆՌԹՁՆԽԼԹՋԺՊԽԽԼԽՊՋԾՇՊԹՈՈՊՇՐՁՅԹՌԽՄՑՇՆԽՑԽԹՊՈՊՁՇՊՌՇՍՋԽԾՇՊԿԽՆԽՊԹՌՁՆԿՌԹԼՈՇՄԽՋՍՋԽԼՁՆՌՀՁՋԽՐՈՇՋՍՊԽ

ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՄԹՊՎԹԽ ՍՋԽԼ ՁՆ ՌՀԽ

ԹՋՋԹՑԺԽԼԽՊՁՎԽԼԾՊՇՅՁՆՀՇՍՋԽԹԼՍՄՌՋ

ԴԽՊԽՈԹՊԽՆՌԹՄԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!

ԶԽՋ

ԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԾՇՊՈԹՊԽՆՌԹՄԾՊՇԿՋ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԠՇՆՌՁՆՍՇՍՋ

ԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄԾԽԽԼՁՆԿ ԡՍՊՁՆԿՌՀԽՈՊԽԽՐՈՇՋՍՊԽ

ՈԽՊՁՇԼՌԹԼՈՇՄԽՋՏԽՊԽԾԽԼՌՏՁԻԽՈԽՊԼԹՑՏՁՌՀՅԿՌԹԼՈՇՄԽՏՁՌՀՁՆԻՊԽԹՋՁՆԿՊԹՌԽՋՌՀՊՇՍԿՀՇՍՌՌՀԽԽՐՈՇՋՍՊԽ

ԱԹԼՈՇՄԽՋՏԽՊԽԾԽԼԵԽՆՇՈՍՋԢՐՈՊԽՋՋԱԹԼՈՇՄԽԣՇՇԼ
ԵԽՆՇՈՍՋԢՐՈՊԽՋՋԟՊՇՇՃՋՎՁՄՄԽԣՄՇՊՁԼԹ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄՀԽԹՄՌՀ ԱՀԽԺՊՇՇԼՋՌՇԻՃԼՁԼՆՇՌ

ՋՀՇՏԹՆՑՋՁԿՆՇԾՋՁԻՃՆԽՋՋԼՁՋԽԹՋԽՁՆՂՍՊՁԽՋՇՊԹԺՆՇՊՅԹՄՁՌՁԽՋԾՊՇՅՌՀԽԼԹՑՇԾՊԽԻԽՁՈՌՌՇՌՀԽԼԹՑՇԾՈՊԽԽՐՈՇՋՍՊԽՁՆՁՌՁԹՌՁՇՆ

ԱԹԺՄԽԩԹՊՎԹՄ԰ԽՄԽԻՌՁՇՆԹՆԼԠԹՊԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԟԽՋՌՋՁՆԿՄԽՋՈԹՏՆ! ԶԽՋ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌՀԽԺԽՋՌ-

ՁՆԼՁՎՁԼՍԹՄՋՈԹՏՆՋՏՁՌՀԹՅՁՆՁՅՍՅՇԾ

ՄԹՊՎԹԽՋՈԹՏՆԺԽԽՎԹՄՍԹՌԽԼՌՇՁԼԽՆՌՁԾՑՌՀԽ

ԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆԹՆԼՌՀԹՌՌՀԽՄԹՊՎԹԽՋԽՄԽԻՌԽԼ

ԾՇՊՌԽՋՌՁՆԿՇՊՁԿՁՆԹՌԽԾՊՇՅՌՀԽԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆ


ՁԽՌՀԽՋՈԹՏՆՋԹՊԽՆՇՌԻՇՅՁՐԽԼ

ԫՍՅԺԽՊՇԾՋՈԹՏՆՋԽՎԹՄՍԹՌԽԼ
ՁԾԹՈՈՄՁԻԹԺՄԽ



ԫՍՅԺԽՊՇԾԽԿԿՋՋԹՅՈՄԽԼՈԽՊՋՈԹՏՆ

ԞՌՄԽԹՋՌ ԦՌՏԹՋՆՇՌՋՈԽԻՁԾՁԽԼՇՆՏՀՁԻՀԼԹՑՋ

ԽՅԺՊՑՇՋՏԽՊԽԻՀԽԻՃԽԼԾՇՊՎՁԹԺՁՄՁՌՑ

ԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ԫԣ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԺԽ

Page 10 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ԼԹՑՋՈՇՋՌԾԽՊՌՁՄՁՒԹՌՁՇՆ


ԼՈԾ

ՁՆՁՌՁԹՌԽԼՏՁՌՀՄԹՊՎԹԽԹՌԫՁԽՍՏՃՇՇՈ-ԣԹԺԽՊ


ԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ
ԼԹՑՋ

ՈՇՋՌԾԽՊՌՁՄՁՒԹՌՁՇՆ

ԪԽԹՆՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՊԽՈՇՊՌԽԼ

ԫՇՌՅԽԹՋՍՊԽԼ

ԯԹՆԿԽՇԾՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՊԽՈՇՊՌԽԼ

ԫՇՌՅԽԹՋՍՊԽԼ

ԴԹՋՌՀԽՇՈՌՁՇՆԹՄՋՁՒԽՋԽՄԽԻՌՁՇՆՅԽՌՀՇԼՍՋԽԼ!

ԫՇ 

ԡԽՌԹՁՄՋՇՆՄԹՊՎԹՄՋԽՄԽԻՌՁՇՆ ԫՁՆԽՀՍՆԼՊԽԼՌԹԼՈՇՄԽՋ

ԾՊՇՅՌՀԽՀՁԿՀԽՋՌՉՍԹՄՁՌՑՋՈԹՏՆՏԽՊԽՌՊԹՆՋԾԽՊՊԽԼՌՇՊԽԹՊՁՆԿՎԽՋՋԽՄՋ
ՌԹԼՈՇՄԽՋԩԬՆԻԽՌԹԼՈՇՄԽՋՊԽԹԻՀԽԼԫԣՋՌԹԿԽՀԽԹՄՌՀՑՌԹԼՈՇՄԽՋՏԽՊԽՊԹՆԼՇՅՄՑՋԽՄԽԻՌԽԼԾՇՊՍՋԽՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽԽՐՈՇՋՍՊԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԩՇԹԼՁՆԿՊԹՌԽ
ՊԽԹՊՁՆԿԼԽՆՋՁՌՑ +ՄԹՊՎԹԽԩ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՊԽԹՊՁՆԿ ԼԽՆՋՁՌՑ


ՄՇԹԼՁՆԿ ՊԹՌԽ ՆՇՌ ԽՐԻԽԽԼ ԹՈՈՊՇՐՁՅԹՌԽՄՑ 

ՄԹՊՎԹԽԩ ԻՍՄՌՍՊՁՆԿ ՋՑՋՌԽՅ ԾՇՊ ԾՄՇՏՌՀՊՇՍԿՀ

ՋՑՋՌԽՅՋ ՇՊ  ՌԹԼՈՇՄԽՋԩ ՁՆ ՋՌԹՌՁԻՊԽՆԽՏԹՄ

ԽՐՈՇՋՍՊԽՋՑՋՌԽՅՋ

ԱՑՈԽՇԾԾՇՇԼ ԵԽՆՇՈՍՋԢՐՈՊԽՋՋ

ԱԹԼՈՇՄԽԣՇՇԼ

ԢԭԞՊԽԻՇՅՅԽՆԼՋ԰ԽՊԹԪՁԻՊՇՆն ՌՀՊՇՍԿՀՇՍՌ

ՈՊԽԽՐՈՇՋՍՊԽ
ԹԾՌԽՊԫԣՋՌԹԿԽԹՆԼ

ԼՍՊՁՆԿՌՀԽԽՆՌՁՊԽԼԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԦԾ

ԹՆՇՌՀԽՊԼՁԽՌՁՋՍՋԽԼՌՀԽՋՌՍԼՑՊԽՈՇՊՌՋՀՇՍՄԼ

ՈՊՇՎՁԼԽԹՆԹՄՑՋՁՋՇԾՁՇԼՁԼԽԻՇՆՌԽՆՌԹՆԼՈՇՌԽՆՌՁԹՄ

ԻՇՆՌԹՅՁՆԹՆՌՋԹՆԼՌՀԽԼՁԽՌՋՀՇՍՄԼ

ԼԽՅՇՆՋՌՊԹՌԽԽՉՍԹՄՈԽՊԾՇՊՅԹՆԻԽՌՇ԰ԽՊԹ

ԪՁԻՊՇՆն 

԰ՇՍՊԻԽՇԾԾՇՇԼ ԵԽՆՇՈՍՋԢՐՈՊԽՋՋ

ԟՊՇՇՃՋՎՁՄՄԽԣԩ

ԦՇԼՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆԼՁԽՌ
ՁԾՃՆՇՏՆ

ԫՇՌՊԽՈՇՊՌԽԼ 

ԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿ ՌՁՅԽՋԼԹՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾԽԽԼՁՆԿՇԻԻՍՊԹՌՄԽԹՋՌ

ՌՏՁԻԽՈԽՊԼԹՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿՊԽԿՁՅԽ ԣԽԽԼՁՆԿՊԽԿՁՅԽԾՇՄՄՇՏԽԼ

ԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋԼՍՊՁՆԿՌՀԽ

ՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԺԽՁՆԻՊԽԹՋԽԼԹՄՇՆԿՏՁՌՀ

ՄԹՊՎԹՄԿՊՇՏՌՀՌՇԹՈՈՊՇՐՁՅԹՌԽՄՑ

ՅԿՄԹՊՎԹԼԹՑԺՑՌԽՋՌՁՆՁՌՁԹՌՁՇՆԢԭԞԹՆԼ

ԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋՁՆԻՊԽԹՋԽ

ԾՊՇՅՅԿՄԹՊՎԹԼԹՑԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
԰ՌՍԼՑ

ԡԹՑՌՇՅԿՄԹՊՎԹԼԹՑՁՆՌՀԽՄԹՋՌՏԽԽՃ

ՇԾՌՀԽՌԽՋՌ
԰ՌՍԼՑԡԹՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԠԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱՑՈԽՇԾԽՐՈՇՋՍՊԽ ԣՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏՌՀՊՇՍԿՀ

ՋՑՋՌԽՅ

ԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋ

ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ

ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ

ՊԽԻՇՅՅԽՆԼԽԼ

ԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ

+ՅԩՅՁՆ ԠԹՄԻՍՄԹՌԽԼԺԹՋԽԼՇՆԩԾՁՄՄՎՇՄՍՅԽԹՆԼ

ՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌՋԽՎԽՊՑՀՇՍՊՋԱՀՁՋՊԽՋՍՄՌԽԼՁՆԹՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԽՎԽՊՑՀՇՍՊՋ

ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋ

ՅԩՅՁՆ
ԻՇՅՈՄԽՌԽՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԻԹ

ԽՎԽՊՑՀՊՋ

ԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋ
ՁԾԹՈՈՄՁԻԹԺՄԽ

԰ՌՇԻՃՋՇՄՍՌՁՇՆՋԾՁՄՄԽԼԻՀԽՅՁԻԹՄԼՁՄՍՌԽՊԻԽՄՄՋՏՀՁԻՀՌՀԽՆՌՊԹՆՋԾԽՊՊԽԼՌՀԽԼՁՄՍՌԽԼՋՌՇԻՃՋՇՄՍՌՁՇՆՋՌՇՌՀԽԹՈՈՊՇՈՊՁԹՌԽՌԽՋՌԻՀԹՅԺԽՊ

ԯԽԻՇՅՅԽՆԼԽԼՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊ

ԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋԪՁՐՁՆԿԻՀԹՅԺԽՊՁՋ

ՊԽԻՇՅՅԽՆԼԽԼԺՍՌՆՇՌՊԽՉՍՁՊԽԼԞԽՊԹՌՁՇՆ

ՁՋՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՅՁՐՁՆԿԞ

ԼԽՅՇՆՋՌՊԹՌՁՇՆՌՀԹՌՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՁՋ

ԻՇՅՈՄԽՌԽՄՑՅՁՐԽԼԺԽԾՇՊԽՁՆՌՊՇԼՍԻԽԼՁՆՌՇՌՀԽ

ՌԽՋՌՋՑՋՌԽՅՁՋՊԽԻՇՅՅԽՆԼԽԼԱՀԽ

ՊԽԻՇՅՅԽՆԼԽԼԾՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑՁՋ

ՏՁՌՀՁՆ

ԯԽՆԽՏԹՄՈԽՊՁՇԼԾՇՊՋՌԹՌՁԻՊԽՆԽՏԹՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ ԦԾՋՌԹՌՁԻՊԽՆԽՏԹՄՁՋՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋ

ՀՊՊԽՆԽՏԹՄՊԽՆԽՏԹՄՈԽՊՁՇԼՁՋ

ՊԽԻՇՅՅԽՆԼԽԼՆՇՌՌՇԽՐԻԽԽԼՀՇՍՊՋ

ԞԽՊԹՌՁՇՆ! ԫՇ ԢԭԞՊԽԻՇՅՅԽՆԼՋՅԹՁՆՌԹՁՆՁՆԿԼՁՋՋՇՄՎԽԼ

ՇՐՑԿԽՆԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԹՁՊՋԹՌՍՊԹՌՁՇՆ


 ՅԿԩԞԽՊԹՌՁՇՆՅԹՑԺԽՅԹՁՆՌԹՁՆԽԼ

ՌՀՊՇՍԿՀԺՍԺԺՄԽՊՋԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՇՋԽՌ

ԺՍԺԺՄԽՊՋԹՌՄԽՎԽՄՋՌՀԹՌԼՇՆՇՌԻԹՍՋԽՋՌՊԽՋՋ

ՇՆՌՀԽՌԹԼՈՇՄԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ ԩԹԺՇՊԹՌՇՊՑՏԽՄՄՏԹՌԽՊ

ՇԺՌԹՁՆԽԼԾՊՇՅԹՆՇՆՋՁՌԽՅԽՌԽՊԺԽԼՊՇԻՃՏԽՄՄՏԹՋԾՇՊՌՁԾՁԽԼՏՁՌՀԣԢԱԞԵՋՇՄՍՌՁՇՆԹԻԻՇՊԼՁՆԿՌՇ

Ԟ԰ԱԪԿՍՁԼԽՄՁՆԽՋ

ԱՀԽՏԹՌԽՊՏԹՋՈՍՅՈԽԼՌՇԹԻՇՆԻՊԽՌԽՊԽՋԽՊՎՇՁՊՏՀԽՊԽՁՌՏԹՋՋՍՈՈՄԽՅԽՆՌԽԼՇՆԼԽՅԹՆԼՏՁՌՀԼԽԻՀՄՇՊՁՆԹՌԽԼԱՇՏՆՇԾԴԹՊԽՀԹՅՏԽՄՄՏԹՌԽՊԴԹՌԽՊՏԹՋԹԽՊԹՌԽԼՈՊՁՇՊՌՇՍՋԽՌՇԽՆՋՍՊԽՈՊՇՈԽՊԽՉՍՁՄՁԺՊԹՌՁՇՆՇԾԼՁՋՋՇՄՎԽԼԿԹՋԽՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼ

ՏԹՌԽՊՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄՏԹՌԽՊ

ԺԽՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊ

ՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊ

ՈՇՋՋՁԺՄԽԻՇՆՌԹՅՁՆԹՆՌՋՁՆԻՄՍԼՁՆԿՃՆՇՏՆ

ՋՍԺՋՌՊԹՌԽՋՇԾՌՀԽՁՇԼՁՆԽՌՊԹՆՋՈՇՊՌԽՊՇԾՌՀԽ

ՌՀՑՊՇՁԼԿՄԹՆԼ
ԽԿԾՄՍՇՊՁԼԽԻՀՄՇՊԹՌԽ

ՈԽՊԻՀՄՇՊԹՌԽԬԢԠԡԹԻԻԽՈՌՋԹՆՑՏԹՌԽՊՁՆ

ՏՀՁԻՀՌՀԽՌԽՋՌՋՈԽԻՁԽՋՋՀՇՏԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄ

ԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌ

ԿՍՁԼԽՄՁՆԽ

ԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!

ԶԽՋ ԫՇՈԽՋՌՁԻՁԼԽՋԭԠԟՋՇՊՌՇՐՁԻՅԽՌԹՄՋՏԽՊԽ

ԼԽՌԽԻՌԽԼԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԻՇՆՋՁԼԽՊԽԼՌՇՐՁԻՁՆԹՆՑՇԾՌՀԽՏԹՌԽՊՋԹՅՈՄԽՋԹՆԹՄՑՒԽԼՁՆԹԿՊԽԽՅԽՆՌՏՁՌՀԞ԰ԱԪՋՌԹՆԼԹՊԼՈՊԹԻՌՁԻԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԦՇԼՁԼԽՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՆՏԹՌԽՊ!

ԫՇ ԱՀԽՅՇՋՌՊԽԻԽՆՌԹՆԹՄՑՋՁՋՇԾՌՀԽՏԽՄՄՏԹՌԽՊ

ԾՇՍՆԼՁՇԼՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾ+սԿԩ

ԦԾՊԽԻՇՆՋՌՁՌՍՌԽԼՏԹՌԽՊՁՋՍՋԽԼՇՊՁԾ

ԺԹԻՃԿՊՇՍՆԼՄԽՎԽՄՋՇԾՁՇԼՁԼԽՁՆՆԹՌՍՊԹՄՏԹՌԽՊ

ԹՊԽՄԽՋՋՌՀԹՆսԿԩՁՇԼՁԼԽ

ՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՋՊԽԻՇՅՅԽՆԼԽԼԱՀՁՋ

ՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՋՁՆԹԼԼՁՌՁՇՆՌՇՌՀԽ

ՊԽԻՇՅՅԽՆԼԽԼԼՁԽՌԹՊՑՋՇՍՊԻԽՇԾՁՇԼՁԼԽ


ԽԿՁՆ԰ԽՊԹԪՁԻՊՇՆ

ԱԽՋՌՎԽՋՋԽՄՌՑՈԽՅԹՌԽՊՁԹՄՋ ԤՄԹՋՋԹՉՍԹՊՁԹ ԢԭԞ ԹՆԼ ԬԢԠԡ ՊԽԻՇՅՅԽՆԼ ՌՀԹՌ

ՏԹՌԽՊԻՇՆՌԹԻՌ ՈՇՊՌՁՇՆՋ ՇԾ ՌՀԽ ՋՑՋՌԽՅ ՆՇՌ

ԻՇՅՈՊՇՅՁՋԽ ՌՀԽ ՋՌՍԼՑ 
ԽԿ ԹՄՄ ԿՄԹՋՋ

ՎԽՋՋԽՄՋՇՊԿՄԹՋՋՎԽՋՋԽՄՋՏՁՌՀՋՌԹՁՆՄԽՋՋՋՌԽԽՄ

ԾՊԹՅԽՋԹՊԽԹԻԻԽՈՌԹԺՄԽԽՐԹՅՈՄԽՋ

ԱԽՋՌՎԽՋՋԽՄՋՁՒԽ ՐՐԻՅԣՁՄՄՎՇՄՍՅԽ +ԩ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽՋՑՋՌԽՅ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ

ԪԽԹՋՍՊԽՅԽՆՌ

ԦՆՌԽՊՎԹՄ

ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԥԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬ  

ԫԞ


ՇՆՄՑՊԹՆԿԽՋ

ՈՊՇՎՁԼԽԼ

ԪԽԹՋՍՊԽԼԹՌՌԽՋՌ

ՁՆՁՌՁԹՌՁՇՆԹՆԼՏԽԽՃՄՑ

ՌՀԽՊԽԹԾՌԽՊ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՀԹՊԼՆԽՋՋՌՇ

ՅԿԩԹՋԠԹԠԬ

Ոԥ   

ԪԽԹՋՍՊԽԼՁՆԹՄՄ

ՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄՋ

ՇՆԡԹՑԹՆԼՁՆ

ԹՄՌԽՊՆԹՌՁՆԿՊԽՈՄՁԻԹՌԽՋ

ԼԹՁՄՑՌՀԽՊԽԹԾՌԽՊ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥչ

ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ

ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼ

ԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ՅԿԩ 
 
 

ԪԽԹՋՍՊԽԼՁՆԹՄՄ

ՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄՋ

ՇՆԡԹՑԹՆԼՁՆ

ԹՄՌԽՊՆԹՌՁՆԿՊԽՈՄՁԻԹՌԽՋ

ԼԹՁՄՑՌՀԽՊԽԹԾՌԽՊ

ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ԡԬ

 ՅԿԩ
 ԹՁՊՋԹՌՍՊԹՌՁՇՆԬԢԠԡ

ՊԽԻՇՅՅԽՆԼՋԡԬԻՇՆԻԽՆՌՊԹՌՁՇՆ ՅԿԩ


 ԹՁՊՋԹՌՍՊԹՌՁՇՆ

Page 18 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ

ԪԽԹՋՍՊԽՅԽՆՌ

ԦՆՌԽՊՎԹՄ

ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱԽՅՈԽՊԹՌՍՊԽ
ոԠ   

ԪԽԹՋՍՊԽԼՁՆԹՄՄ

ՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄՋ

ՇՆԡԹՑԹՆԼՁՆ

ԹՄՌԽՊՆԹՌՁՆԿՊԽՈՄՁԻԹՌԽՋ

ԼԹՁՄՑՌՀԽՊԽԹԾՌԽՊԞՄՋՇ

ՅԽԹՋՍՊԽԼ

ԻՇՆՌՁՆՍՇՍՋՄՑՁՆ

ԯԽՈՄՁԻԹՌԽԞՇԾՌՀԽ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչՇԠ

ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ

ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼՇԠ

ԦՇԼՁԼԽ
սԿԩ ԫԞ ԫԞ 

ԟԹՋԽԼՇՆՅՇՋՌ

ՊԽԻԽՆՌԹՆԹՄՑՋՁՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՉՍԹՌՁԻՁՇԼՁԼԽՊԹՆԿԽ

-սԿԩ
ՋՍՈՈՄԽՅԽՆՌԹՄՁՇԼՁԼԽՋՀՇՍՄԼՆՇՌ

ԽՐԻԽԽԼսԿԩ

Page 19 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ

ԪԽԹՋՍՊԽՅԽՆՌ

ԦՆՌԽՊՎԹՄ

ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞՅՅՇՆՁԹ ԫՇՌԯԽՈՇՊՌԽԼ ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑՇԾ

ՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ

ՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋԺԽՅԽԹՋՍՊԽԼՁՆԹ

ԻՇՆՌՊՇՄԹՆԼԹՌՇՆԽՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԹՌՄԽԹՋՌՏԽԽՃՄՑԦՆՋՌԹՌՁԻՊԽՆԽՏԹՄՋՑՋՌԽՅՋ

ՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋՁՆԻՄՍԼՁՆԿ

ԹՅՅՇՆՁԹՋՀՇՍՄԼԺԽՅԽԹՋՍՊԽԼՂՍՋՌՈՊՁՇՊՌՇ

ՊԽՆԽՏԹՄԦՆԹԼԼՁՌՁՇՆԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ

ԡԬԺԽՅԽԹՋՍՊԽԼԹՌԽԹԻՀԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌ

ՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌՌԽՅՈԽՊԹՌՍՊԽԺԽ

ՅԽԹՋՍՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑԬԢԠԡ

ՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԡԬԹՆԼՌԽՅՈԽՊԹՌՍՊԽԺԽ

ՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌՈԥԹՆԼ

ՀԹՊԼՆԽՋՋԺԽՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌԹՌՌՀԽ

ԺԽԿՁՆՆՁՆԿԹՆԼԽՆԼՇԾՌՀԽՌԽՋՌ

ԣՄՍՇՊՁԼԽ ԫՇՌԯԽՈՇՊՌԽԼԭԽՊԻՀՄՇՊԹՌԽ ԫՇՌԯԽՈՇՊՌԽԼԠՀՄՇՊԹՌԽ ԫՇՌԯԽՈՇՊՌԽԼ

ԞՄՃԹՄՁՆՁՌՑ
ՅԿԩԹՋԠԹԠԬ

ԠՇՆԼՍԻՌՁՎՁՌՑ
սՅՀՇՋԻՅ









ԫԞ


ՇՆՄՑՊԹՆԿԽՋ

ՈՊՇՎՁԼԽԼ

ԪԽԹՋՍՊԽԼԹՌՌԽՋՌ

ՁՆՁՌՁԹՌՁՇՆԹՆԼՏԽԽՃՄՑ

ՌՀԽՊԽԹԾՌԽՊ

 ԡ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ! ԶԽՋԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!

԰ՇՄՍԺՁՄՁՌՑՌՊՁԹՄՋՈՊՁՇՊՌՇՌՀԽՊԹՆԿԽԾՁՆԼԽՊՊԽՎԽԹՄԽԼՌՀԹՌՈՀՇՋՅԽՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՊԽՄԹՌՁՎԽՋՌԹԺՄԽՇՎԽՊՀՇՍՊՋՍՋՁՆԿԹԺՍԾԾԽՊԽԼԹՉՍԽՇՍՋՋՇՄՍՌՁՇՆՇԾՈԥԞՆՁՆՁՌՁԹՄՊԹՆԿԽԾՁՆԼՁՆԿՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼՏՁՌՀՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՍՈՌՇՅԿԩԺՍՌՆՇՌՇՐՁԻՊԽՋՈՇՆՋԽՏԹՋՇԺՋԽՊՎԽԼ

ԞՋԽԻՇՆԼՌՊՁԹՄՏԹՋ

ԻՇՆԼՍԻՌԽԼՏՁՌՀՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՍՈՌՇՅԿԩ

ԱՀԽՋԽԻՇՆԼՊԹՆԿԽԾՁՆԼՁՆԿՋՌՍԼՑՑՁԽՄԼԽԼԹՆԩԠՇԾՅԿԹՁԩԱՀԽՀՁԿՀԽՋՌ

ՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌՏԹՋՋԽՌԹՌԹՈՈՊՇՐՁՅԹՌԽՄՑՇԾՌՀԽԢԠ

ԹՆԼՏՁՌՀԹԼՁՄՍՌՁՇՆԾԹԻՌՇՊՇԾ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ

ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ

ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ

ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ

԰ՈԽԻՁԽՋ ԵԽՆՇՈՍՋՄԹԽՎՁՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԩՁԾԽՋՌԹԿԽ ԫԣԱԽՋՌԼՍՊԹՌՁՇՆ ՀՇՍՊՋ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋ ԱՀԽՁՆՁՌՁԹՄՊԹՆԿԽԾՁՆԼԽՊ

ՏԹՋԻՇՆԼՍԻՌԽԼՍՆԼԽՊԾՄՇՏՌՀՊՇՍԿՀԻՇՆԼՁՌՁՇՆՋՏՁՌՀՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩԱՀԽՋԽԻՇՆԼՏԹՋԻՇՆԼՍԻՌԽԼՍՆԼԽՊԾՄՇՏՌՀՊՇՍԿՀԻՇՆԼՁՌՁՇՆՋՏՁՌՀՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩ

ԱՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՋԽԻՇՆԼՊԹՆԿԽԾՁՆԼԽՊՏԹՋՌՀԽՀՁԿՀԽՋՌԹՌՌԹՁՆԹԺՄԽԻՇՆԻԽՆՌՊԹՌՁՇՆՏՁՌՀՌՀԽՍՋԽՇԾԹԺՍԾԾԽՊԽԼԹՉՍԽՇՍՋՋՇՄՍՌՁՇՆՏՁՌՀՈԥ

ԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱԽՋՌԼՍՊԹՌՁՇՆ ԼԹՑՋ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ԼՍՊԹՌՁՇՆ ՇԾ ՌՀԽ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԼԹՑՋ

ԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԯԹՆԿԽԾՁՆԼԽՊՇԾՌՀԽԢԠՏՁՌՀԹԼՁՄՍՌՁՇՆ

ԾԹԻՌՇՊՇԾԾՇՊՌՀԽՌՏՇՄՇՏԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ

ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ

ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ

ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ

ԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫՇՌԹՈՈՄՁԻԹԺՄԽ

԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ՅԹՐՁՅՍՅ

ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՋԽՈԹՊԹՌՁՇՆ ԺԽ  ԹՆԼ ՌՀԽ

ՅՁՆՁՅՍՅԺԽ

ԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄՁԾԹՈՈՊՇՈՊՁԹՌԽ

ԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!

ԶԽՋ 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԪԽԹՆՅԽԹՋՍՊԽԼ 

ԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿԹՁԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ

ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋ

ԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡ ԫՇՌԯԽՈՇՊՌԽԼԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԡԹՑՋԹՆԼ ԱՀԽՊԽՋՍՄՌՋԾՊՇՅՌՀԽԡԹՑՋԹՅՈՄՁՆԿ

ԼԽՅՇՆՋՌՊԹՌԽԼՈՇՇՊԮԠՊԽԻՇՎԽՊՁԽՋՊԹՆԿՁՆԿԾՊՇՅՌՇՇԾՆՇՅՁՆԹՄԾՇՊՌՁԾՁԽԼՄԽՎԽՄՋԡՍԽՌՇՌՀԽՈՇՇՊՊԽԻՇՎԽՊՁԽՋՌՀԽՈՊԽԻՁՋՁՇՆԹՆԼՉՍԹՄՁՌՑԻՇՆՌՊՇՄԾՇՊՌՀՁՋԹՆԹՄՑՋՁՋՏԽՊԽԼԽԽՅԽԼՉՍԽՋՌՁՇՆԹԺՄԽԱՀԽՊԽԾՇՊԽՌՀԽԽՐՈՇՋՍՊԽՋՑՋՌԽՅՏԹՋՊԽՋԹՅՈՄԽԼՇՆԡԹՑԱՀԽՋԽՊԽԻՇՎԽՊՁԽՋՏԽՊԽՏՁՌՀՁՆԽՐՈԽԻՌԹՌՁՇՆՋԹՆԼՏԽՊԽՍՋԽԼԾՇՊԻԹՄԻՍՄԹՌՁՇՆՇԾՅԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ
ԡԹՑՎԹՄՍԽՋՏԽՊԽԽՐԻՄՍԼԽԼ

ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԺԽՅԽԹՋՍՊԽԼՁՆՇՆԽՌԹՆՃԹՌԽԹԻՀՌՊԽԹՌՅԽՆՌ

ՄԽՎԽՄԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԹՆԼԽՎԽՊՑՏԽԽՃ

ՌՀԽՊԽԹԾՌԽՊ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ  ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԽՍՋԽՇԾԹ

ԻՇՆԻՍՊՊԽՆՌՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿ

ԹԿԽՆՌՁՋՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՄԹՊՎԹԽՈԽՊՌՊԽԹՌՅԽՆՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

 

ԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ! ԫՇ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌԽՐԻԽԽԼ

ՅՄԩԬԢԠԡՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՇՄՎԽՆՌ

ՀԹՎԽՆՇԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊՈՊՇԼՍԻԽԹՆՑ

ՇՌՀԽՊԹԼՎԽՊՋԽԽԾԾԽԻՌՋԹՆԼՌՀԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆ

ՆՇՌԺԽԿՊԽԹՌԽՊՌՀԹՆՅՄԩ

ԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏԞՉՍԹՌՁԻ

ԱՇՐՁԻՇՄՇԿՑՈՈ-

ԬԢԠԡ
ԤՍՁԼԹՆԻԽԡՇԻՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋՇՆ

Page 25 of 260
ԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

          ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ՋԽԼ! ԫՇ

ԹԺՄԽ ԫԞ

ԹՌՁՇՆ
Ջ ԫԞ

ՀՊՋՄՁԿՀՌՀՊՋԼԹՊՃ

ԞՅՁՆՍՌԽՄՇՏՄՁԿՀՌՌՊԹՆՋՁՌՁՇՆՈԽՊՁՇԼ

ՏԹՋՍՋԽԼԺԽՌՏԽԽՆՌՀԽՄՁԿՀՌԹՆԼԼԹՊՃՈՀԹՋԽՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ


ՄՁԿՀՌԼԹՊՃ

ՋՍՊԾԹԻԽ ԨՄՍՐ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑ-ԨՄՍՐ


ԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ

ԱՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋՏԽՊԽՊԽՈՇՊՌԽԼԹՋԻՄԽԹՊ

ԹՆԼԻՇՄՇՊՄԽՋՋ

ԭԹՊՁՋԣՊԹՆԻԽ

Page 26 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱՊԽԹՌՅԽՆՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌԦԡ

ԫՇՅՁՆԹՄ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԪԽԹՋՍՊԽԼ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԪԽԹՆԠԳ
 ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ  ԩԬԮ ԫԞ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌԽՋՌՁՌԽՅ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՅԹՁՆՌԹՁՆԽԼԹՌԹԻՇԽԾԾՁԻՁԽՆՌՇԾ

ՎԹՊՁԹՌՁՇՆ
ԠԳ

ԱՊԽԹՌՅԽՆՌ   ԱՊԽԹՌՅԽՆՌ   ԱՊԽԹՌՅԽՆՌ   

ԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ      

 ԢԬԺՋԽՊՎԹՌՁՇՆՋ

ԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋ ԡԹՑԫԣՋՌԹԿԽՏԽՌՏԽՁԿՀՌՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩՆՇՊՅԹՄՁՒԽԼԥԩԩ

        ԡԹՑԫԣՋՌԹԿԽՏԽՌՏԽՁԿՀՌՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩՆՇՊՅԹՄՁՒԽԼԥԩԩՌՀՑՊՇՁԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑ        ԡԹՁՄՑՅՇՊՌԹՄՁՌՑՋՍԺՄԽՌՀԹՄԽԾԾԽԻՌՋ

ԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ!ԶԽՋ

Page 27 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՅՇՊՌԹՄՁՌՑԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋՇԻԻՍՊԼԹՁՄՑԹՌԹՅՁՆՁՅՍՅՇՌՀԽՊՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽՊԽԻՇՅՅԽՆԼԽԼԹՋԾՇՄՄՇՏՋԫԣ

ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ
ԼԹՑՋԹՆԼԹՆՑԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՁՆԼՁԻԹՌԽԼԺՑՌԹԼՈՇՄԽՋՌՀԹՌԻԹՆՆՇՌԺԽԹՋՋՁԿՆԽԼԹՆԫԣՋՌԹԿԽ
ԼԹՑՋԹՆԼ

ՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԼԹՑՋԹՆԼՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
ԼԹՑՋԹՆԼԺՇԼՑՏԽՁԿՀՌ
ՌԽՋՌՁՆՁՌՁԹՌՁՇՆԾՇՊՇՈՌՁՇՆԹՄՋՁՒԽԺԹՋԽԼՄԹՊՎԹՄՋԽՄԽԻՌՁՇՆԹՆԼՌՀՑՊՇՁԼ

ԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑ
ԼԹՑԫՇՌԽՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՑՋԽԻՌՁՇՆՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԹՄՋՇՁՆԻՄՍԼԽՋՌՀՑՊՇՁԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑՇԺՋԽՊՎԹՌՁՇՆՋ

Page 28 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԦԦ ԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫ

Ԟ ԯԽՋՍՄՌՋ

ԡԹՁՄՑՄԹՊՎԹՄՋՍՊՎՁՎԹՄՏԹՋՆՇՌՈՊՇՎՁԼԽԼԯԹՌՀԽՊՌՇՌԹՄՋՍՊՎՁՎԹՄՇՎԽՊՌՀԽԼԹՑԽՐՈՇՋՍՊԽՈԽՊՁՇԼՏԹՋՊԽՈՇՊՌԽԼ

ԟՑՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՋՍՊՎՁՎԹՄԹՎԽՊԹԿԽԼՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼԹՆԼ
ՄՇՋՋՇԾ

ՌԹԼՈՇՄԽՇՎԽՊԼՍՊԹՌՁՇՆՇԾՌԽՋՌՌՁՅԽՈՇՁՆՌՍՆՃՆՇՏՆՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿ

ԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

ԱԹԺՄԽԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑ

ԡԹՑ ԡԹՑ

Ն ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ Ն ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ  ԫԯ ԫԯ ԫԯ ԫԯ 

  ԫԯ ԫԯ ԫԯ ԫԯ 

  ԫԯ ԫԯ ԫԯ ԫԯ 

  ԫԯ ԫԯ ԫԯ ԫԯ 

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



԰ԹՅՈՄԽՋՁՒԽԹՆԼԻՍՅՍՄԹՌՁՎԽՅՇՊՌԹՄՁՌՑՎԹՄՍԽՋԹՌԡԹՑՈՊՁՇՊՌՇՁՆՌԽՊՁՅՋԹԻՊՁԾՁԻԽ

ԪԽԼՁԹՆԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋՇՆԡԹՑՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ
ԱԹԺՄԽ

ԟՑՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՅԽԼՁԹՆԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՅԽԹՆՅԽԹՋՍՊԽԼ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈՋ
ԱԹԺՄԽԱՀԽՌՀԹՆԼՌՀՈԽՊԻԽՆՌՁՄԽՋՇՆԡԹՑԼՁԼՆՇՌԼՁԾԾԽՊԺՑՅՇՊԽՌՀԹՆՋՌԹԿԽՋԫՇ

ԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋՊԽՈՇՊՌԽԼ

ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ-ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽԹՆԼԞՋՑՆԻՀՊՇՆՇՍՋԡԽՎԽՄՇՈՅԽՆՌ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽ

Page 29 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

#ՅԽԹՆՅԽԹՋՍՊԽԼ% ԡԹՑ ԡԹՑ

Ն

ԪԽԼՁԹՆ

԰ՌԹԿԽ

ԞՋՑՆԻՀՊՇՆՇՍՋ Ն

ԪԽԼՁԹՆ

԰ՌԹԿԽ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ      

      

      

      

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ

ԪԽԹՆՆՇՊՅԹՄՁՒԽԼԥԩԩՊԹՆԿԽԼԾՊՇՅՌՇՇՆԡԹՑԹՆԼԾՊՇՅՌՇՇՆԡԹՑ
ԱԹԺՄԽ



ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ-ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ
ԥԩԩ

ԡԹՑ ԡԹՑ

Ն ԪԽԹՆ


ՅՅ

չ԰ԡ

ԥԩԩ

԰Գԩ Ն ԪԽԹՆ
ՅՅ

չ԰ԡ

ԥԩԩ

԰Գԩ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ        

        

        

        

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ



 ԰ՍՅՅԹՊՑՊԽՋՍՄՌՋԾՇՊՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩԹՊԽՈՊԽՋԽՆՌԽԼՁՆՌՀԽՆԽՐՌՌԹԺՄԽ
ԱԹԺՄԽ

ԴՀՇՄԽԺՇԼՑՏԽՌՏԽՁԿՀՌՇՆԡԹՑԹՎԽՊԹԿԽԼԿՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՊԹՆԿԽԼԾՊՇՅՌՇ

ԿՁՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ
ԱԹԺՄԽԬՆԡԹՑԺՇԼՑՏԽՁԿՀՌԹՎԽՊԹԿԽԼԿՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԹՆԼՊԹՆԿԽԼԾՊՇՅՌՇԿՁՆՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ

ԱԹԺՄԽԩԹՊՎԹՄԤՊՇՏՌՀՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

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

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ            

            

            

            

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ



ԞՄՋՇՊԽԾԽՊՊԽԼՌՇԹՋ՟ՏԽՌՏԽՁԿՀՌՠՁՆՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽ

ԱՀՑՊՇՁԼԿՄԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՊԽՎԽԹՄԽԼՌՀՑՊՇՁԼԿՄԹՆԼՀՑՈԽՊՌՊՇՈՀՑԾՇՄՄՁԻՍՄԹՊԻԽՄՄՀՑՈԽՊՈՄԹՋՁԹԹՆԼԾՇՄՄՁԻՍՄԹՊ

ԻԽՄՄՀՑՈԽՊՌՊՇՈՀՑԥՇՏԽՎԽՊՌՀԽՋԽԾՁՆԼՁՆԿՋՏԽՊԽԻՇՆՋՁԼԽՊԽԼՍՆՊԽՄԹՌԽԼՌՇՌՊԽԹՌՅԽՆՌԺԽԻԹՍՋԽՌՀԽՑՏԽՊԽ

ՇՆՄՑՇԾՅՁՄԼՋԽՎԽՊՁՌՑԹՆԼՇԻԻՍՊՊԽԼՁՆԹՄՄՌՊԽԹՌԽԼԿՊՇՍՈՋԹՆԼԻՇՆՌՊՇՄՋՁՆԹՅԹՆՆԽՊՍՆՊԽՄԹՌԽԼՌՇԻՇՆԻԽՆՌՊԹՌՁՇՆ


ԱԹԺՄԽՋԹՆԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՊՇՋՋԭԹՌՀՇՄՇԿՑԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑՇԾՌՀԽԱՀՑՊՇՁԼԤՄԹՆԼՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԱՀՑՊՇՁԼԤՄԹՆԼ

ԥՑՈԽՊՌՊՇՈՀՑ

ԱՀՑՊՇՁԼԤՄԹՆԼ

ԞՌՊՇՈՀՑ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՌՊՇՈՀՑ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԫԽԿԹՌՁՎԽ

ԠՇՆՌՊՇՄ

        

        

        

        

         

        

        

        

         

        

        

        

         

        

        

        



 ԱՀՑՊՇՁԼԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՄԼ

ԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԬԢԠԡԫՇԾՇՊՊԽԾԽՊԽՆԻԽ



 ԪՁՋՋՁՆԿՌՁՋՋՍԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԱՀՑՊՇՁԼԤՄԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԮՍԹՄՁՌԹՌՁՎԽԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆ

ԞՊԽԹ
ԦՆԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆ

ԞՊԽԹ
ԡԽԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥԽՁԿՀՌ
ԦՆԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥԽՁԿՀՌ


ԡԽԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

԰ՀԹՈԽ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ      ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

      ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

      ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԮՍԹՄՁՌԹՌՁՎԽԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆ

ԞՊԽԹ
ԦՆԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԩՍՅԽՆ

ԞՊԽԹ
ԡԽԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥԽՁԿՀՌ
ԦՆԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄԥԽՁԿՀՌ


ԡԽԻՊԽԹՋԽ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

԰ՀԹՈԽ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

      ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ     ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԱՀՑՊՇՁԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՁՋԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԬԢԠԡԫՇԾՇՊՊԽԾԽՊԽՆԻԽ ԱՀԽՊԽՏԹՋՅՁՋՋՁՆԿՌՁՋՋՍԽԾՊՇՅՇՆԽՌԹԼՈՇՄԽ

ԟԽԿՁՆՆՁՆԿՇՆԡԹՑԹՆԼԻՇՆՌՁՆՍՁՆԿՌՀՊՇՍԿՀՇՍՌՌՀԽԼՍՊԹՌՁՇՆՇԾՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼՋՈՁՆԹՄԻՍՊՎԹՌՍՊԽՏԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԟՑՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՁՆԻՁԼԽՆԻԽՇԾՋՈՁՆԹՄԻՍՊՎԹՌՍՊԽԹՎԽՊԹԿԽԼՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼԹՆԼՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

Page 34 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԠՄՁՆՁԻԹՄ԰ՁԿՆՋՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԠՄՁՆՁԻԹՄ԰ՁԿՆՋ

ԱՑՈԽ Ն ԦՆԻՁԼԽՆԻԽ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ   ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ   ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ   ԰ՈՁՆԹՄԻՍՊՎԹՌՍՊԽ  

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԟ ԰ՌՍԼՑԞՍՌՀՇՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

ԞՆԹՄՑՒԽԼԽՆԼՈՇՁՆՌՋՁՆԻՄՍԼԽԼԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ԰ԳԩԥԩԩԹՆԼՏԽՌՏԽՁԿՀՌԞՄՄՋՌԹՌՁՋՌՁԻԹՄԻՇՆԻՄՍՋՁՇՆՋ

ՏԽՊԽՅԹԼԽԹՌՌՀԽՄԽՎԽՄՇԾԻԽՊՌԹՁՆՌՑԽՐԻԽՈՌՁՆՌՀԽԻԹՋԽՇԾՌՀԽԺԹՋՁԻԹՋՋՍՅՈՌՁՇՆՌԽՋՌՋ
԰ՀԹՈՁՊՇԴՁՄՃՋ0

ԱԽՋՌԹՆԼԟԹՊՌՄԽՌՌ0ՋԱԽՋՌՁՆՏՀՁԻՀՌՀԽՄԽՎԽՄՇԾԻԽՊՌԹՁՆՌՑՏԹՋԹՈՈՄՁԽԼ

ԪՇՊՌԹՄՁՌՑՏԹՋԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԣՁՋՀԽՊ0ՋԢՐԹԻՌԱԽՋՌՏՁՌՀԟՇՆԾԽՊՊՇՆՁԥՇՄՅԹԼՂՍՋՌՅԽՆՌԡԽՎԽՄՇՈՅԽՆՌԹՄ

ՋՌԹԿԽՏԹՋԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌԽՋՌԥԩԩ԰ԳԩԹՆԼՏԽՌՏԽՁԿՀՌՏԽՊԽ

ԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌՏՀԽՆԹՅՇՆՇՌՇՆՁԻՌՊԽՆԼՏԹՋՈՊԽՋԽՆՌԴՀԽՆԹՅՇՆՇՌՇՆՁԻ

ՌՊԽՆԼՏԹՋՆՇՌԹՈՈԹՊԽՆՌՌՀԽՋԽԽՆԼՈՇՁՆՌՋՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԡՍՆՆԽՌՌ0ՋԪՍՄՌՁՈՄԽԠՇՅՈԹՊՁՋՇՆՌԽՋՌ

ՏՀԽՆՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՈԹՊԹՅԽՌՊՁԻՋՌԹՌՁՋՌՁԻՋՏԽՊԽՅԽՌՇՊՌՀԽԪԹՆՆԴՀՁՌՆԽՑՌԽՋՌՏՁՌՀԟՇՆԾԽՊՊՇՆՁԥՇՄՅ

ԹԼՂՍՋՌՅԽՆՌ ՏՀԽՆ ՌՀԽ ԼԹՌԹ ԼՁԼ ՆՇՌ ՅԽԽՌ ՌՀԽ ԹՋՋՍՅՈՌՁՇՆՋ ՇԾ ՆՇՊՅԹՄՁՌՑ ԹՆԼ ՀՇՅՇՋՃԽԼԹՋՌՁԻՁՌՑ

ԠԢԱԦ԰ԠՇՅՈՊԽՀԽՆՋՁՎԽԢՆՎՁՊՇՆՅԽՆՌԹՄԱՇՐՁԻՁՌՑԦՆԾՇՊՅԹՌՁՇՆ԰ՑՋՌԽՅԱԪԳԽՊՋՁՇՆՋՇԾՌՏԹՊԽՏԹՋՍՋԽԼ

ՌՇՈԽՊԾՇՊՅԹՄՄՋՌԹՌՁՋՌՁԻԹՄԻՇՅՈՍՌԹՌՁՇՆՋ

ԟՑՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆՆՇԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽԾՇՍՆԼՁՆՄԹՊՎԹՄՋՍՊՎՁՎԹՄԺԽՌՏԽԽՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ

ԬՆԡԹՑՆՇՋՁԿՆՁԾՁԻԹՆՌՁՆՀՁԺՁՌՁՇՆՋՇՊՈՊՇՅՇՌՁՇՆՋՏԽՊԽՇԺՋԽՊՎԽԼԾՇՊԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՇՊՏԽՌՏԽՁԿՀՌ

ԹՌԹՆՑՌՊԽԹՌՅԽՆՌԿՊՇՍՈ԰ԳԩՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՏՀԽՊԽԹՋԺՇՌՀԥԩԩ

ԹՆԼՆՇՊՅԹՄՁՒԽԼԥԩԩՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԬՆԡԹՑ

ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽԥԩԩԹՆԼՆՇՊՅԹՄՁՒԽԼԥԩԩՏԽՊԽԹՄՄՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼՁՆՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԽՋՌ

ՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈՋ ՊԽՄԹՌՁՎԽՌՇՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄԥՇՏԽՎԽՊ ՇՆԡԹՑ ՏԽՌՏԽՁԿՀՌ ԹՆԼ԰ԳԩՏԽՊԽ

ՍՆԹԾԾԽԻՌԽԼԹՌԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԱՀԽՊԽՏԽՊԽՆՇԹՈՈԹՊԽՆՌՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼՌՊԽՆԼՋՁՆՌՀՑՊՇՁԼԿՄԹՆԼ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄՇԺՋԽՊՎԹՌՁՇՆՋ

ԦՆՊԽԿԹՊԼՋՌՇՋՈՁՆԹՄԻՍՊՎԹՌՍՊԽՌՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌՌՀԽՁՆԻՁԼԽՆԻԽՇԾՋՈՁՆԹՄԼԽԾՇՊՅՁՌՁԽՋՁՆՌՀԽ

ԻՍՊՊԽՆՌԹՋՋԹՑՏԽՊԽՍՆՊԽՄԹՌԽԼՌՇՌՊԽԹՌՅԽՆՌՏՁՌՀՈՀՇՋՅԽՌԣՍՊՌՀԽՊՁՌՏԹՋՊԽՈՇՊՌԽԼՌՀԹՌԺԹՋԽԼՇՆՀՁՋՌՇՊՁԻԹՄ

ԻՇՆՌՊՇՄԼԹՌԹԻՇՄՄԽԻՌԽԼԹՌ԰ՅՁՌՀԽՊՋԳՁՋԻՁԽՆՌՌՀԽՋԽԼԽԾՇՊՅՁՌՁԽՋԼՁԼՆՇՌՀԹՎԽԹՆԽԿԹՌՁՎԽՁՅՈԹԻՌՇՆՌՀԽ

ՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀՁՋՋՌՍԼՑԱՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌԾՇՊՌՀԽՈՊԽՎՁՇՍՋՄՑԻՇՆԼՍԻՌԽԼՋՌՍԼՁԽՋՌՀԽՊԽՏԹՋ

ՆՇԻՇՊՊԽՄԹՌՁՇՆԺԽՌՏԽԽՆՌՀԽՈՊԽՋԽՆԻԽՇԾՋՈՁՆԹՄԼԽԾՇՊՅՁՌՁԽՋԹՆԼՌՀԽՁՆԻՊԽԹՋԽՁՆԠԳԾՇՊՈՇՌԽՆՌՁԹՄՄՑԹԾԾԽԻՌԽԼ

ԽՆԼՈՇՁՆՌՋ
ԽԿ԰ԳԩԥԩԩՏԽՌԺՇԼՑՏԽՁԿՀՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 ԠԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋ԰ՍՊՎՁՎԹՄՊԹՆԿԽԼԾՊՇՅՌՇԱՀԽՊԽԾՇՊԽՌՀԽՊԽՎՁԽՏԽՊՎՁՋՍԹՄՄՑԼԽՌԽՊՅՁՆԽԼՌՀԹՌ

ՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄՀԹԼՆՇԽԾԾԽԻՌՇՆՄԹՊՎԹՄՅՇՊՌԹՄՁՌՑԡԹՑԹՆԼԡԹՑԿՊՇՏՌՀՈԹՊԹՅԽՌԽՊՋ
԰ԳԩԹՆԼԺՇԼՑ

ՏԽՁԿՀՌԼՁԼՆՇՌԽՐՀՁԺՁՌՅՇՆՇՌՇՆՁԻՌՊԽՆԼՋԺՍՌՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՈԹՊԹՅԽՌՊՁԻՋՌԹՌՁՋՌՁԻՋԹՆԼՏԽՊԽ

ՌՀԽՊԽԾՇՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՌՏՇՋՁԼԽԼԡՍՆՆԽՌՌ0ՋՌԽՋՌԡԹՑԹՆԼԡԹՑԼԽՎԽՄՇՈՅԽՆՌԹՄՈԹՊԹՅԽՌԽՊՋ


ԫԣՋՌԹԿԽԹՆԼՆՇՊՅԹՄՁՒԽԼԥԩԩԼՁԼՆՇՌԽՐՀՁԺՁՌՋՍԺՋՌԹՆՌՁՎԽԼԽՈԹՊՌՍՊԽՋԾՊՇՅՅՇՆՇՌՇՆՁԻՁՌՑՌՀԽՊԽԾՇՊԽ

ԻՇՆՋՁՋՌԽՆՌՏՁՌՀՌՀԽԬԠ԰ԭԭԿՍՁԼԽՄՁՆԽՌՀԽՋԽԽՆԼՈՇՁՆՌՋՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՇՆԽՋՁԼԽԼ

ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌՊԽՆԼՌԽՋՌԞՄՄԹՆԹՄՑՋԽՋՏԽՊԽԻՇՆԼՍԻՌԽԼԺՑԻՇՅՈԹՊՁՆԿՌՊԽԹՌՅԽՆՌԼԹՌԹՌՇ

ՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՍՋՁՆԿԹՆĮՇԾՍՆՄԽՋՋՋՈԽԻՁԾՁԽԼՇՌՀԽՊՏՁՋԽԯԽՋՍՄՌՋԾՊՇՅՇՆԽՋՁԼԽԼՌՊԽՆԼՌԽՋՌՋ


ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՏԽՊԽԻՇՅՈԹՊԽԼՌՇԹՋԽԻՇՆԼԹՊՑĮՌՇՁՄՄՍՋՌՊԹՌԽՏՀԽՌՀԽՊՌՀԽԽԾԾԽԻՌՏՇՍՄԼՋՌՁՄՄ

ԺԽԻՇՆՋՁԼԽՊԽԼՋՁԿՆՁԾՁԻԹՆՌՁԾԹՌՏՇՋՁԼԽԼ
ՎԽՊՋՍՋՇՆԽՋՁԼԽԼՌՊԽՆԼՌԽՋՌՏԽՊԽՍՋԽԼ

ԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋՊԽՈՇՊՌԽԼ

 ԠՇՆԻՄՍՋՁՇՆՋ

ԱՀԽՊԽՎՁԽՏԽՊԾՇՍՆԼՆՇՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋՁՆԡԹՑՏԽՌՏԽՁԿՀՌՇՊՅԽԼՁԹՆԫԣՋՌԹԿԽ
ԡՍՆՆԽՌՌ0ՋՌԽՋՌ

Ո ԡԹՑ԰ԳԩՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈ
ՊԽԼՍԻՌՁՇՆԡՍՆՆԽՌՌ0Ջ

ՈԣՍՊՌՀԽՊԡԹՑԥԩԩՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼ
ՁՆՀՁԺՁՌՁՇՆՋԹՌԹՄՄՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ


ԧՇՆԻՃՀԽԽՊԽՈ = ՏՀԽՊԽԹՋՆՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼ
ԹՌՌՀԽՅՁԼԼՄԽԹՆԼ

ՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋ
ԧՇՆԻՃՀԽԽՊԽՈ 

ԡԹՑԼԽՎԽՄՇՈՅԽՆՌԹՄՈԹՊԹՅԽՌԽՊՋ
ՁԽԫԣՋՌԹԿԽՆՇՊՅԹՄՁՒԽԼԥԩԩՏԽՊԽԺՇՌՀՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌ

ՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ԧՇՆԻՃՀԽԽՊԽՈ =ԬԾՌՀԽ

ՌՀՊԽԽԿՊՇՏՌՀՈԹՊԹՅԽՌԽՊՋՇՆԡԹՑ
ՁԽ԰ԳԩԥԩԩԹՆԼՏԽՌՏԽՁԿՀՌՇՆՄՑԥԩԩՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼ

ԹՌՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈ
ՊԽԼՍԻՌՁՇՆԧՇՆԻՃՀԽԽՊԽՈ ԡԹՑ԰ԳԩԹՆԼ

ՏԽՌՏԽՁԿՀՌՏԽՊԽՍՆԹԾԾԽԻՌԽԼ
ԡՍՆՆԽՌՌ0ՋՈ 

ԞՄՄԽԾԾԽԻՌՋՁԼԽՆՌՁԾՁԽԼԹՋՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌՊԽՅԹՁՆՋՁԿՆՁԾՁԻԹՆՌՏՀԽՆ

ԻՇՅՈԹՊԽԼՌՇՌՀԽԹԼՂՍՋՌԽԼĮՏՀՁԻՀԹԻԻՇՍՆՌՋԾՇՊՌՀԽԻՇՆՋԽՊՎԹՌՁՋՅՇԾՌՀԽՇՆԽՋՁԼԽԼՌՊԽՆԼՌԽՋՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽ  ԡԽՎԽՄՇՈՅԽՆՌԹՄ ԹՆԼ ԱՀՑՊՇՁԼ ԤՊՇՋՋ ԭԹՌՀՇՄՇԿՑԥՁՋՌՇՈԹՌՀՇՄՇԿՑ ԢՆԼՈՇՁՆՌՋ ՁՆ ՌՀԽ ԞԪԞ ՏՁՌՀ

ԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽ ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ

ԱՀՑՊՇՁԼԤՊՇՋՋ

ԹՆԼԥՁՋՌՇ

ՈԹՌՀՇՄՇԿՑ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

ԪԽԼՁԹՆ Ո ԪԽԼՁԹՆ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԱՊԽԹՌՅԽՆՌ

ԯԽՄԹՌԽԼ

ԢԾԾԽԻՌՋ!


ԶԽՋԫՇ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ  ԫԞ  ԫԞ  ԫԞ  ԫԞ ԫՇ

         ԫՇ

         ԫՇ

         ԫՇ

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ

ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ

ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ

ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ

ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋ

ՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ



 ԥՁՆԼՄՁՅԺՄԽՆԿՌՀՁՋՆՇՊՅԹՄՁՒԽԼՌՇՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰Գԩ



Page 38 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋՁՆՌՀԽԞԪԞՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

԰ՆՇՍՌԳԽՆՌԩԽՆԿՌՀ ԟՇԼՑԴԽՁԿՀՌ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ ԫԞ ԫԞ  ԫԞ  ԫԞ  ԫԞ

        

        

        

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ



ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ

Ԣ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

ԱՀԽՌԽՅՈԽՊԹՌՍՊԽՎԹՊՁԹՆԻԽ
ոԠՏԹՋՋՄՁԿՀՌՄՑՇՍՌՋՁԼԽՌՀԽՊԹՆԿԽՊԽԻՇՅՅԽՆԼԽԼՁՆՌՀԽՈԽՊԾՇՊՅԹՆԻԽ

ԻՊՁՌԽՊՁԹ
չոԠԞՄՌՀՇՍԿՀՌՀԽՊԽՏԽՊԽՇՌՀԽՊԼԽՎՁԹՌՁՇՆՋԾՊՇՅՌՀԽԿՍՁԼԽՄՁՆԽՁՆԻՄՍԼՁՆԿՏԹՌԽՊՀԹՊԼՆԽՋՋՌՀԹՌ

ՏԹՋՀՁԿՀԽՊՌՀԹՆՊԽԻՇՅՅԽՆԼԽԼՌՀԽՋՌՍԼՑՅԽՌԹՄՄՊԽՅԹՁՆՁՆԿՎԹՄՁԼՁՌՑԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹ

ԣԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋ

ԱՀԽՊԽՎՁԽՏԽՊ0ՋՊԽՋՍՄՌՋՏԽՊԽԻՇՅՈԹՊԹԺՄԽՌՇՌՀՇՋԽՇԾՌՀԽՋՌՍԼՑԹՍՌՀՇՊՏՁՌՀՌՀԽԽՐԻԽՈՌՁՇՆՌՀԹՌՌՀԽՊԽՎՁԽՏԽՊ

ԾՇՍՆԼՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻՌՁՇՆՋՁՆԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩԹՌԹՄՄՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՏՀԽՊԽԹՋՌՀԽՋՌՍԼՑԹՍՌՀՇՊ

ՇՆՄՑԾՇՍՆԼՊԽԼՍԻՌՁՇՆՋՁՆՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈԱՀԽՋՌՍԼՑԹՍՌՀՇՊԹՄՋՇՅՁՋՁԼԽՆՌՁԾՁԽԼ

ՇՆԽՌԹԼՈՇՄԽՁՆՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ԱԹԼՈՇՄԽԦԡԡԫԣՋՌԹԿԽԹՋԺԽՁՆԿՄԹՌԽՋՌԹԿԽ
ԫԣՋՌԹԿԽ

 ՀՇՏԽՎԽՊԺԹՋԽԼՇՆՌՀԽԼԽՋԻՊՁՈՌՁՎԽՋՌԹՌՁՋՌՁԻՋՁՆՌՀԽՊԽՈՇՊՌՁՌԼՁԼՆՇՌԹՈՈԽԹՊՌՇԺԽԽՐԻՄՍԼԽԼԾՊՇՅ

ԹՆԹՄՑՋՁՋ

Page 39 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԦԦԦ ԯԢԣԢԯԢԫԠԢ԰

ԦՎԽՋԪՁԻՀԹԽՄԠԢԱԦ԰ԠՇՅՈՊԽՀԽՆՋՁՎԽԢՆՎՁՊՇՆՅԽՆՌԹՄԱՇՐՁԻՁՌՑԦՆԾՇՊՅԹՌՁՇՆ԰ՑՋՌԽՅԱԪԲՋԽՊ0ՋԤՍՁԼԽ

ԱՁԼԽՈՇՇՄ԰ԻՁԽՆՌՁԾՁԻ԰ՇԾՌՏԹՊԽԪԻԨՁՆՄԽՑՎՁՄՄԽԠԹՄՁԾՇՊՆՁԹ

ԩՇՈԽՒԞԥՑԼՊՇՄՑՋՁՋՇԾ#Ԡ%ԭՀՇՋՅԽՌԹՌԳԹՊՁՇՍՋՈԥԩԽՎԽՄՋԹՆԼԱԽՅՈԽՊԹՌՍՊԽՋԭԱԯԩԯԽՈՇՊՌԫՍՅԺԽՊ

Դ԰ՈՇՆՋՇՊԽԼԹՆԼՋՍԺՅՁՌՌԽԼԺՑԤՇՏԹՆԠՇՅՈԹՆՑՈՈԪԯԦԡ

ԪՇՍՆՌԡԦ ԹՆԼԴԞԟՊՍՆԿՋ ԞՋՁՅՈՄՁԾՁԽԼ ԼՇՋՁՆԿ ԹՈՈԹՊԹՌՍՋԾՇՊԾՁՋՀՌՇՐՁԻՇՄՇԿՁԻԹՄ ՋՌՍԼՁԽՋԴԹՌԽՊ

ԯԽՋԽԹՊԻՀ

ԫՁԽՍՏՃՇՇՈԭԡԹՆԼԣԹԺԽՊԧԫՇՊՅԹՄԱԹԺՄԽՇԾԵԽՆՇՈՍՋՄԹԽՎՁՋԤԹՊՄԹՆԼԭՍԺՄՁՋՀՁՆԿԫԽՏԶՇՊՃ

԰ՈՊԹԿՍԽԧԟԪԽԹՋՍՊԽՅԽՆՌՇԾՈՇՄՄՍՌԹՆՌՌՇՐՁԻՁՌՑՌՇԾՁՋՀԟՁՇԹՋՋԹՑՅԽՌՀՇԼՋԾՇՊԹԻՍՌԽՌՇՐՁԻՁՌՑԴԹՌԽՊ

ԯԽՋԽԹՊԻՀ

Page 40 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԞԭԭԢԫԡԦԵԦԬԲԱԭԲԱԬԣԯԢԳԦԢԴԢԯ0԰԰ԱԞԱԦ԰ԱԦԠԞԩԳԢԯԦԣԦԠԞԱԦԬԫ

test for amphib metamorph screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR01 ( 7-d wet weight (g) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.915 0.142 1.571 0.248 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 0.51 0.04 0.02 7.47 0.45, 0.57 

 Dose1 4 0.45 0.02 0.01 3.54 0.42, 0.47 

 Dose2 4 0.48 0.05 0.03 10.86 0.40, 0.56 

 Dose3 4 0.44 0.07 0.04 16.03 0.33, 0.56 

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

 Ctrl 0.52 0.46 0.54 . . 

 Dose1 0.44 0.43 0.47 87.96 12.04 

 Dose2 0.46 0.44 0.56 94.50 5.50 

 Dose3 0.42 0.39 0.55 87.13 12.87 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 1.60 0.241 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 0.51 . 0.51 . . . . . . 

 Dose1 0.45 0.228 0.46 0.130 . . . . . 

 Dose2 0.48 0.758 0.46 0.138 0.771 . . . . 

 Dose3 0.44 0.188 0.44 0.051 0.999 0.702 . . . 

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.768 0.001 1.000 0.426 USE NON-PARAMETRIC TESTS 

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

Page 41 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 53.50 0.58 0.29 1.08 52.58, 54.42 

 Dose1 4 53.50 0.58 0.29 1.08 52.58, 54.42 

 Dose2 4 53.75 0.50 0.25 0.93 52.95, 54.55 

 Dose3 4 53.50 0.58 0.29 1.08 52.58, 54.42 

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

 Ctrl 53.50 53.00 54.00 . . 

 Dose1 53.50 53.00 54.00 100.00 0.00 

 Dose2 54.00 53.00 54.00 100.47 -0.47 

 Dose3 53.50 53.00 54.00 100.00 0.00 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 0.71 0.870 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 53.50 . . 

 Dose1 53.50 1.000 0.500 

 Dose2 54.00 0.624 0.754 

 Dose3 53.50 1.000 0.586 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.960 0.653 1.293 0.322 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 20.25 0.67 0.33 3.29 19.19, 21.31 

 Dose1 4 19.38 0.28 0.14 1.42 18.94, 19.81 

 Dose2 4 19.73 0.65 0.32 3.30 18.69, 20.76 

 Dose3 4 18.90 1.02 0.51 5.41 17.27, 20.53 

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

 Ctrl 20.45 19.30 20.80 . . 

 Dose1 19.35 19.10 19.70 95.68 4.32 

 Dose2 19.60 19.10 20.60 97.41 2.59 

 Dose3 18.50 18.20 20.40 93.33 6.67 

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

Page 42 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 2.61 0.100 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 20.25 . 20.25 . . . . . . 

 Dose1 19.38 0.237 19.55 0.110 . . . . . 

 Dose2 19.73 0.603 19.55 0.117 0.894 . . . . 

 Dose3 18.90 0.048 18.90 0.012 0.778 0.387 . . . 

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

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.971 0.859 2.971 0.074 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 2.48 0.16 0.08 6.45 2.22, 2.73 

 Dose1 4 2.26 0.07 0.04 3.13 2.14, 2.37 

 Dose2 4 2.13 0.09 0.05 4.32 1.98, 2.28 

 Dose3 4 2.10 0.23 0.11 10.90 1.73, 2.46 

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

 Ctrl 2.45 2.31 2.69 . . 

 Dose1 2.23 2.21 2.36 91.11 8.89 

 Dose2 2.14 2.02 2.22 86.06 13.94 

 Dose3 2.07 1.87 2.37 84.65 15.35 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 5.19 0.016 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 2.48 . 2.48 . . . . . . 

Page 43 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Dose1 2.26 0.146 2.26 0.036 . . . . . 

 Dose2 2.13 0.019 2.13 0.004 0.655 . . . . 

 Dose3 2.10 0.010 2.10 0.002 0.467 0.987 . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 9.09 0.028 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 2.45 . . 

 Dose1 2.23 0.103 0.022 

 Dose2 2.14 0.067 <.001 

 Dose3 2.07 0.103 <.001 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose1 

 Jonckheere Dose1 

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.953 0.540 3.268 0.059 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 0.12 0.01 0.00 6.75 0.11, 0.14 

 Dose1 4 0.12 0.00 0.00 3.85 0.11, 0.12 

 Dose2 4 0.11 0.00 0.00 3.05 0.10, 0.11 

 Dose3 4 0.11 0.01 0.00 7.20 0.10, 0.12 

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

 Ctrl 0.12 0.11 0.13 . . 

 Dose1 0.12 0.11 0.12 95.31 4.69 

 Dose2 0.11 0.11 0.11 88.37 11.63 

 Dose3 0.11 0.10 0.12 90.41 9.59 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 4.00 0.035 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Page 44 of 260
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Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 0.12 . 0.12 . . . . . . 

 Dose1 0.12 0.467 0.12 0.135 . . . . . 

 Dose2 0.11 0.021 0.11 0.008 0.285 . . . . 

 Dose3 0.11 0.058 0.11 0.008 0.563 0.944 . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 7.19 0.066 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 0.12 . . 

 Dose1 0.12 0.413 0.155 

 Dose2 0.11 0.080 0.003 

 Dose3 0.11 0.156 0.007 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere Dose2 

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.936 0.305 1.220 0.345 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 59.13 0.85 0.43 1.44 57.77, 60.48 

 Dose1 4 59.13 0.63 0.31 1.06 58.12, 60.13 

 Dose2 4 58.13 0.25 0.13 0.43 57.73, 58.52 

 Dose3 4 57.75 0.50 0.25 0.87 56.95, 58.55 

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

 Ctrl 59.25 58.00 60.00 . . 

 Dose1 59.00 58.50 60.00 100.00 0.00 

 Dose2 58.00 58.00 58.50 98.31 1.69 

 Dose3 58.00 57.00 58.00 97.67 2.33 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 9.65 0.022 

Page 45 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՀՇՋՅԽՌՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

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MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 59.25 . . 

 Dose1 59.00 1.000 0.441 

 Dose2 58.00 0.168 0.021 

 Dose3 58.00 0.107 <.001 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere Dose2 

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.961 0.682 3.150 0.065 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 1.66 0.03 0.02 1.89 1.61, 1.71 

 Dose1 4 1.72 0.09 0.04 5.24 1.57, 1.86 

 Dose2 4 1.71 0.04 0.02 2.06 1.65, 1.76 

 Dose3 4 1.61 0.12 0.06 7.39 1.42, 1.80 

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

 Ctrl 1.67 1.61 1.68 . . 

 Dose1 1.71 1.63 1.81 103.56 -3.56 

 Dose2 1.70 1.67 1.75 103.11 -3.11 

 Dose3 1.58 1.50 1.78 97.45 2.55 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 1.47 0.273 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 1.66 . 1.69 . . . . . . 

 Dose1 1.72 0.596 1.69 0.822 . . . . . 

 Dose2 1.71 0.684 1.69 0.851 0.999 . . . . 

 Dose3 1.61 0.789 1.61 0.305 0.308 0.369 . . . 

Page 46 of 260
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                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

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test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.961 0.689 0.816 0.510 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 29.18 0.50 0.25 1.71 28.38, 29.97 

 Dose1 4 29.90 0.63 0.32 2.12 28.89, 30.91 

 Dose2 4 29.93 0.26 0.13 0.88 29.51, 30.34 

 Dose3 4 29.65 0.58 0.29 1.96 28.73, 30.57 

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

 Ctrl 29.30 28.50 29.60 . . 

 Dose1 30.00 29.10 30.50 102.49 -2.49 

 Dose2 29.90 29.70 30.20 102.57 -2.57 

 Dose3 29.60 29.00 30.40 101.63 -1.63 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 1.84 0.194 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 29.18 . 29.67 . . . . . . 

 Dose1 29.90 0.162 29.67 0.947 . . . . . 

 Dose2 29.93 0.145 29.67 0.961 1.000 . . . . 

 Dose3 29.65 0.447 29.65 0.964 0.900 0.872 . . . 

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.950 0.482 5.729 0.011 USE NON-PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

Page 47 of 260
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 Ctrl 4 15.93 1.23 0.61 7.70 13.97, 17.88 

 Dose1 4 15.43 0.95 0.48 6.18 13.91, 16.94 

 Dose2 4 13.98 0.39 0.20 2.82 13.35, 14.60 

 Dose3 4 11.95 2.16 1.08 18.11 8.51, 15.39 

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

 Ctrl 16.35 14.20 16.80 . . 

 Dose1 15.85 14.00 16.00 96.86 3.14 

 Dose2 14.05 13.50 14.30 87.76 12.24 

 Dose3 11.80 9.80 14.40 75.04 24.96 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 7.01 0.006 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 15.93 . 15.93 . . . . . . 

 Dose1 15.43 0.913 15.43 0.363 . . . . . 

 Dose2 13.98 0.149 13.98 0.039 0.455 . . . . 

 Dose3 11.95 0.003 11.95 <.001 0.015 0.200 . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 8.31 0.040 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 16.35 . . 

 Dose1 15.85 0.410 0.153 

 Dose2 14.05 0.152 0.011 

 Dose3 11.80 0.101 <.001 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere Dose2 

test for amphib metamorph screen study - Phosmet 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals N/A alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) N/A alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.929 0.231 3.947 0.036 USE NON-PARAMETRIC TESTS 

Page 48 of 260
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                  ԢԭԞԪԯԦԡԫՍՅԺԽՊ

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 0.55 0.05 0.02 8.53 0.48, 0.62 

 Dose1 4 0.53 0.04 0.02 7.21 0.46, 0.59 

 Dose2 4 0.47 0.02 0.01 3.21 0.44, 0.49 

 Dose3 4 0.40 0.07 0.03 17.26 0.29, 0.51 

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

 Ctrl 0.57 0.48 0.58 . . 

 Dose1 0.54 0.47 0.55 95.45 4.55 

 Dose2 0.47 0.45 0.48 85.00 15.00 

 Dose3 0.40 0.33 0.48 73.18 26.82 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 3 12 7.94 0.003 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 0.55 . 0.55 . . . . . . 

 Dose1 0.53 0.791 0.53 0.276 . . . . . 

 Dose2 0.47 0.069 0.47 0.017 0.344 . . . . 

 Dose3 0.40 0.002 0.40 <.001 0.014 0.251 . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 9.98 0.019 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 0.57 . . 

 Dose1 0.54 0.230 0.072 

 Dose2 0.47 0.094 0.004 

 Dose3 0.40 0.080 <.001 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere Dose2 

Page 49 of 260
DATA EVALUATION RECORD

PHOSMET

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

EPA Contract No. EP10H001452 

Task Assignment No. 2-4-2012 (MRID 48618703) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

David A. McEwen, B.S. Date: 11/30/2011

Secondary Reviewer Signature:

Michelle J. Sharpe-Kass, M.S. Date: 12/01/2011

Program Manager: Signature:

Jack D. Early, M.S. Date: 12/05/2011

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 12/05/2011

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by Dynamac Corporation personnel. 

Page 50 of 260
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).

Page 51 of 260
PHOSMET/059201 

Androgen Receptor Binding (Rat Prostate Cytosol) (2011) I Page I of 14 

OCSPP 890.1150/ OECD None 

Primary Reviewer: Jessica Ryman. Ph.D .. D.A.B.T. 

Health Effects Division 

Secondary Reviewer: __ G=---re.,.g"'"'Ak-=--e=rm=an~, "'""" P..... h =D ...... ___ _ 

Health Effects Division 

Sign" Date: ~~ / 

Signature: 

Date: G It 2 /,~ 

Template version 0812011 

DATA EVALUATION RECORD 

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

PC CODE: 059201 DP BARCODE: D397 I 65 

TXR#: 0056199 CAS No.: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8% a.i.) 

SYNONYMS: 2-( dimethoxyphosphinothioylsulfanylmethyl)isoindole-1,3-dione; Imidan 

technical 

CITATION: Willoughby, J.A (2011). Phosmet: Androgen Receptor Binding (Rat Prostate 

Cytosol). CeeTox, Kalamazoo, Ml. Laboratory Study #: 9142V-l 00348ARB, 

November 2, 2011. MRID 48618703. Unpublished. 

SPONSOR: Gowan, 370 Main Street, Yuma, AZ 85364 

TEST ORDER#: EDSP-059201-54 

EXECUTIVE SUMMARY: In an androgen receptor (AR) binding assay (MRIO 48618703), 

ventral prostate cytosol from Sprague Dawtey rats was used as the source of the AR. The 

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 (RI 881). 

Saturation binding data were not originally provided in the study report; however, summarized 

saturation binding data (MRID 48843501 ) from the performing laboratory were submitted 

following a request by the Agency. The mean dissociation constant (K-0) for [3H]-Rl 881 was 

1.080±0.690 nM, and the estimated Bma.x was l.071±0.167 fmol/100 μg protein for the single 

batch of prostate cytosol that was used in the assay. Only one of the three Kd values was within 

the range reported in the EPA validation program (0.685 to 1.57 nM), and all Bmax values were 

below the recommended range (7 to 16 fmol/ I 00 μg protein). Although the goodness of fit for 

individual runs was acceptable (R2 = 0.880-0.986), confidence in these numbers is low based on 

the large variation in l<d estimates among runs. 

The competitive binding experiment was conducted to measure the binding of a single 

concentration of [3H]-Rl 881 (10 nM) in the presence of increasing concentrations of phosmet 

(96.8% purity; logarithmic increase from 10·

10 to 10·3 M). Dimethyl sulfoxide (DMSO) was 

used as a vehicle at a final assay concentration of approximately 3.2%. The assay included 

dexamethasone as a weak positive control, and RI 881 as the ligand reference standard. Three 

Page 52 of 260
Androgen Receptor Binding (Rat Prostate Cytosol) (2011) / Page 2 of 14

PHOSMET/059201 OCSPP 890.1150/ OECD None

independent runs were conducted with 3 replicates per concentration per run. The estimated log 

IC50s for R1881 and the weak positive control (dexamethasone) were in the ranges of -9.0 to -9.9 

M and -4.3 to -4.6 M, respectively. Phosmet displaced more than 50% of the radiolabeled R1181 

from the AR in all three competitive binding runs. The estimated log IC50 was -5.0 M in each 

run and averaged -5.0 M; therefore, phosmet is classified as an AR “binder”. The mean relative 

binding affinity (RBA) for the positive control dexamethasone was 0.0013%. The RBA for 

phosmet was calculated to be 0.0050%, indicating a stronger affinity for the AR than the weak 

positive control. Confidence in these numbers is high due to the small variation. The solvent 

control responses indicated no drift in the study assay. All performance criteria were met, with 

the exception of the bottom (% binding) of dexamethasone in Assay #1, and the bottom plateau 

level could not be accurately calculated because of a deviation where the concentration range for 

dexamethasone was prepared slightly different than that specified in the guideline. This was 

considered a minor deviation. 

Based on the results of the three competitive binding runs, phosmet is classified as a Binder in 

the Androgen Receptor Binding Assay. 

The assay satisfies the EDSP Tier 1 Test Order requirements for an Androgen Receptor Binding 

assay (OCSPP 890.1150). 

COMPLIANCE: Signed and dated Data Confidentiality, GLP Compliance and Quality 

Assurance statements were provided. 

Page 53 of 260
Androgen Receptor Binding (Rat Prostate Cytosol) (2011) / Page 3 of 14

PHOSMET/059201 OCSPP 890.1150/ OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test facility: CeeTox, Inc.

Location: 4717 Campus Drive, Kalamazoo, MI 49008

Study Director: J.A. Willoughby, Sr.

Other Personnel: D. Blakeman, C. Haines, and S. McColley

Study Period: September 10, 2011 to September 17, 2011

2. Test substance: Phosmet

Description: White crystalline solid

Source: Gowan Company

Batch #: GQH9118000

Purity: 96.8%

Solubility: Not reported

Volatility: Not reported

Stability: Not reported

Storage conditions: Ambient

CAS #: 732-11-6

Molecular weight: 317.32

Structure: O

O

S

P

S

OCH3

N OCH3

3. Non-labeled ligand: R1881

Supplier: Sigma Aldrich, St. Louis, MO

Catalog #: R0908

Batch #: 060M4638

Purity: 98%

CAS #: 965-93-5

4. Radioactive ligand: [

3

H]-R1881

Supplier: Perkin-Elmer, Boston, MA

Catalog and Batch #: NET590; Lot # 653698

Date of production: February 24, 2011

Date of use: September 10, 2011 to September 18, 2011

Radiochemical purity: >97%

Specific activity: 85.1 Ci/mmol*

*The SAadjusted was 82.6 Ci/mol (10-Sept-2011), 82.5 Ci/mol (13-Sept-2011), and 92.5 

Ci/mol (17-Sept-2011). 

Concentration in stock: 1.0 nM

5. Positive control: Dexamethasone

Supplier: Sigma Aldrich, St. Louis, MO

Catalog #: D1756

Lot #: 077K1050

Purity: 99%

CAS # : 50-02-2

6. Solvent/vehicle control: DMSO

Justification for choice of solvent: Not provided

Final concentration: 3.2%

Page 54 of 260
Androgen Receptor Binding (Rat Prostate Cytosol) (2011) / Page 4 of 14

PHOSMET/059201 OCSPP 890.1150/ OECD None

B. METHODS

1. Preparation of Rat Ventral Prostate Cytosol: The rat ventral prostate tissue was 

purchased from Charles River Laboratories (location not reported). Male Sprague Dawley 

rats (number not reported) were castrated at 90 days of age and were euthanized the 

following day. The ventral prostate tissues were collected and stored at 

approximately -80°C until use, and were processed as a batch and used for multiple studies.

The cytosol was prepared by adding low-salt TEDG buffer (10 mM Tris, 1 mM sodium 

molybdate, 1.5 mM EDTA, 10% glycerol and 1 mM DTT, 0.5% protease inhibitor) at pH 

7.4 to the ventral prostate tissues at 10 mL/g of tissue. The tissues were minced, 

homogenized at 4°C, and centrifuged for 30 min at 30,000 × g at 4°C. The supernatant was

aliquoted (2-4 mL) in tubes and stored at -80°C until used. Protein concentration of the 

cytosol prepared for this study was determined to be 6.2 mg/mL using the Bradford method 

(Bio-Rad). 

2. Saturation Radioligand Binding Experiment: A saturation binding experiment measuring 

total and non-specific binding of [3H]-R1881 was performed to demonstrate that the AR was 

present in reasonable concentrations and had the appropriate affinity for the R1881 ligand 

(MRID 48843501). The conditions for the saturation binding experiment are summarized in 

Table 1.

TABLE 1. Summary of Conditions for Saturation Binding Experiment a

Source of receptor Rat ventral prostate cytosol 

Concentration of radioligand (as serial dilutions) 0.25 to 10 nM

Concentration of non-labeled ligand (100X [radioligand]) 2 to 1000 nM

Optimization of receptor concentration Sufficient to bind 25 to 35% of 

radioligand at 0.25 nM

Temperature 4o C 

Incubation time 16 to 20 hours 

Composition of assay buffer 

(TEDG)

Tris 10 mM (pH 7.4)

EDTA 1.5 mM 

Glycerol 10% 

Phenylmethylsulfonyl fluoride (PMSF) 1 mM 

DTT 1 mM 

Sodium Molybdate 1 mM

a Data were obtained from page 2 of the study report (MRID 48843501).

On the day of each assay, the specific activity of the stock solution [3H]-R1881 (originally 

85.1 Ci/mmol as manufactured on February 24, 2011) was adjusted for decay over time 

(adjusted specific activities were not reported), and serial dilutions in low-salt 

TEDG+PMSF buffer were prepared to achieve the final concentrations in cytosol of 0.25, 

0.50, 0.70, 1.0, 1.5, 2.5, 5.0, and 10 nM to determine total binding. To determine nonspecific binding, solutions of non-labeled R1881 were prepared in a similar manner to 

achieve concentrations that were 100-fold greater than each respective radiolabeled 

concentration, resulting in final concentrations in cytosol of 25, 50, 70, 100, 150, 250, 500, 

and 1000 nM. In the absence of cytosol, the radiation found in 7.5, 15, 21, 30, or 45 μL of 

10 nM [3

H]-R1881 and 7.5, 15, or 30 μL of 100 nM [3H]-R1881 was measured. 

Page 55 of 260
Androgen Receptor Binding (Rat Prostate Cytosol) (2011) / Page 5 of 14

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For each batch of cytosol, the optimal protein concentration was determined by calculating 

specific binding to differing amounts of protein per tube with 0.25 nM radiolabeled R1881. 

The optimal protein concentration was determined to be 1.86 mg protein/assay tube, which 

resulted in the binding of approximately 25-35% of the total radioactivity added. Cytosolic 

protein used in this assay was thawed fresh for this experiment at 4°C, and maintained at 

4°C during the binding assay. Each saturation binding experiment consisted of three noncurrent runs (conducted on September 9, 11, and 16, 2011, respectively), and each run 

contained three replicates at each concentration, resulting in the 72 samples depicted in 

Table 2.

TABLE 2. Saturation Binding Experiment Runa,b

Total Binding Non-Specific Binding Radioligand alone

Tubes 1-24c Tubes 25-48d Tubes 49-72e

[

3

H]-R1881

Final conc. (nM)

[

3

H]-R1881

Final conc. (nM)

R1881

Final conc. (nM)

[

3

H]-R1881

Initial conc. (nM)

[

3

H]-R1881

(μL)

0.25 0.25 25 10 7.5

0.50 0.50 50 10 15

0.70 0.70 70 10 21

1.0 1.0 100 10 30

1.5 1.5 150 10 45

2.5 2.5 250 100 7.5

5.0 5.0 500 100 15

10 10 1000 100 30

a Data were obtained from page 3 of the study report (MRID 48843501).

b Each concentration was run in triplicate for a total of 72 samples.

c Tubes 1-24 contained 50 μL of triamcinolone acetonide and 7.5-45 μL [3

H]-R1881. Samples were dried, 

and 300 μl of prostate cytosol were added.

d Tubes 25-48 contained 50 μL of triamcinolone acetonide and 7.5-45 μL [3

H]-R1881. R1881 was added in a 

100-fold molar excess of [3

H]-R1881 in a volume of 7.5-45 μL. Samples were dried, and 300 μl of prostate 

cytosol were added.

e Tubes 49-72 contained only 7.5, 15, 21, 30, or 45 μL of 10 nM [3

H]-R1881 or 7.5, 15, or 30 μL of 100 nM 

[

3

H]-R1881 without cytosol or other components to determine the total counts added.

Following addition of triamcinolone acetonide, [3

H]-R1881, and/or R1881, the tubes were 

dried, dissolved in diluted prostate cytosol (300 μL), and incubated in a rotor for 20 hours at 

approximately 4°C. Samples were maintained at temperatures of approximately 4°C except 

during whole rack vortexing. To separate bound from free R1881, hydroxyapatite (HAP) 

slurry was added to each tube and vortexed 5 times with 4-minute intervals over 20 minutes. 

The samples were then centrifuged, and the supernatant was aspirated and discarded. The 

samples were washed 4 times in 2 mL of ice cold TEDG+PMSF buffer, followed by 

vortexing and centrifugation for 3 minutes at 700 x g. Following the last wash and 

decanting of the Tris buffer pellets were then extracted by additional of 2 mL of ethanol. 

The samples were vortexed and centrifuged for 10 minutes at 1000 x g. Samples were 

maintained on ice at all times between vortexing. After the final centrifugation, the ethanol 

supernatants were decanted into scintillation vials that each contained 14-mL portions of 

scintillation cocktail, and the radiation was quantified by liquid scintillation counting. A 

total of three runs were performed.

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3. Competitive Binding Experiment: A summary of the assay conditions for the competitive 

binding experiment is presented in Table 3. 

TABLE 3. Summary of Conditions for Competitive Binding Experiment a

Source of receptor Rat prostate cytosol

Concentration of radioligand 1 nM

Optimization of receptor concentration Sufficient to bind 10-15% of radioligand b

Concentration of test substance (as serial dilutions) 10-10 to 10-3 M

Incubation Temperature 4±2°C

Incubation time 16-20 hours 

Composition of assay buffer Tris 10 mM (pH 7.4)

EDTA 1.5 mM 

Glycerol 10% (v/v)

Protease inhibitor 0.5% (v/v)

DTT 1 mM 

Sodium Molybdate 1 mM 

a

 Data were obtained from page 15 of the study report.

b Obtained in Study Report on page 15. 

The competitive binding experiment was performed according to the protocol provided in 

the EPA Test Guidelines OCSPP 890.1150. The competitive binding experiment measures 

the binding of a single concentration of [3

H]-R1881 (adjusted specific activity of 85.1

Ci/mmol) to the AR in the presence of increasing concentrations of a test substance.

DMSO was used as the vehicle, and the solubility of the test material at the top 

concentrations of 10-3 and 10-4 M in 100% DMSO was determined by visual observation. 

Additionally, all test material solutions were examined for precipitation following the 

overnight incubation period. Due to precipitation being observed at 10-3 M, the suitable top 

concentration of Phosmet for use in all independent runs was 10-4 M.

Dilutions of the test substance, reference standard (R1881), weak positive control 

(dexamethasone), and solvent control (DMSO) were prepared to achieve the concentrations 

shown in Table 4. Each assay consisted of three independent runs on three different days, 

and each run contained three replicates at each concentration, resulting in a total of 81 

samples per run. 

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

Solvent Control Reference standard c Weak positive control d Test Chemical e

None DMSO R1881 Dexamethasone Phosmet

Tubes 7-12 Tubes 13-18 and 19-33 f Tubes 37-60 Tubes 61-84 Tubes 1-6

1×10-7.48 1×10-6 1×10-3 1×10-4 1×10-3 1×10-4

1×10-8.48 1×10-7 1×10-4 1×10-5 1×10-4 1×10-5

1×10-9.48 1×10-8 1×10-5 1×10-6 1×10-5 1×10-6

1×10-10.48 1×10-9 1×10-6 1×10-7 1×10-6 1×10-7

1×10-11.48 1×10-10 1×10-7 1×10-8 1×10-7 1×10-8

1×10-12.48 1×10-11 1×10-8 1×10-9 1×10-8 1×10-9

-- 1×10-9 1×10-10 1×10-9 1×10-10

-- 1×10-10 1×10-11 1×10-10 1×10-11

a Data were obtained from pages 53-58 of the study report.

b Each concentration of each chemical was run in triplicate for a total of 81 tubes per run. Tubes 7-84 contained 

50 μL of triamcinolone acetonide and 30 μL [3

H]-R1881. Samples were dried, and 300 μl of prostate cytosol 

were added. Tubes 7-84 also contained 10 μL of the solvent control, reference standard (non-radiolabeled R1881), weak positive control, or test substance, with the exception of Tubes 13-18 that contained 30 μL of nonradiolabeled R1881 (used to evaluate non-specific binding). Tubes 1-6 contained only 30 μl of [3

H]-R1881.

c The concentrations of R1881 used in the 1st competitive binding assay ranged from 1x10-7.48 to 1x10-12.48, while 

the standard concentrations of 1x10-6 to 1x10-11 were used in the 2nd and 3rd assays.

d The concentrations of dexamethasone used in the 1st competitive binding assay ranged from 1x10-3 to 1x10-10, 

while the standard concentrations of 1x10-4 to 1x10-11 were used in the 2nd and 3rd assays.

e The concentrations of phosmet used in the 1st competitive binding assay ranged from 1x10-3 to 1x10-10, while 

concentrations of 1x10-4 to 1x10-11 were used in the 2nd and 3rd assays.

f Tubes 13-18 were used to evaluate non-specific binding by adding 100X of cold (non-radiolabeled) R1881

4. Data Analysis: The maximal binding capacity (Bmax), dissociation constant (Kd), the top 

and bottom of the curve, Hill slope, inhibition concentration (IC50), and standard deviations 

were assessed using GraphPad PRISM (GraphPad Software, Inc., San Diego, CA). 

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 (i.e. a Log IC50 was obtained). 

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. 

Equivocal: The average lowest portion of curves across runs is between 50% and 75% 

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).

b. Descriptors for receptor binding

Bmax: maximal binding capacity

Kd: dissociation constants 

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IC50: Concentration of the test substance at which 50% of radioligand is displaced from the AR 

by the competitor

Relative Binding Affinity (RBA): IC50 of R1881 × 100 ÷ IC50 of test substance 

II. RESULTS

A. SATURATION BINDING EXPERIMENT: Saturation binding experiment parameters 

are presented in Table 5. The mean Kd for [3H]-R1881 was 1.080±0.690 nM, and the 

estimated Bmax was 1.071±0.167 fmol/100 μg protein for the single batch of prostate cytosol 

that was used in the assay. Only one of the three individual Kd values was within the range 

reported in the EPA validation program (0.685 to 1.57 nM); the mean value was above the 

acceptable range. Although the goodness of fit (R2 = 0.880-0.986) was acceptable, 

confidence in these numbers is low based on the large variation in Kd estimates among runs.

TABLE 5. Saturation Binding Experiment of [3H]-R1881 with Androgen Receptor from Rat Prostate 

Cytosola

Parameter Run 1 Run 2 Run 3 Mean ± SEb

R2 (unweighted) 0.880 0.986 0.893 0.880-0.986

Bmax (nM) 0.010 0.008 0.011 0.010±0.002

Bmax (fmol/100 μg protein) 1.087 0.896 1.229 1.071±0.167

Kd (nM) 0.855 0.531 1.855 1.080±0.690

a Data were obtained from supplemental information provided by the laboratory (MRID 48843501).

b The range of R2 is reported and the mean ± SE is reported for the other parameters.

R2 Goodness of fit for curve calculated for specific binding.

Figure 1 illustrates the non-specific, specific, and total binding curves for [3

H]-R1881 to the 

androgen receptor for the three independent runs. The specific binding reached a plateau in 

each run, and non-specific binding was less than 20% of total binding. Figure 2 contains the 

Scatchard plots that illustrate the binding of [

3

H]-R1881 to the androgen receptor. 

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FIGURE 1. Binding of [3H]-R1881 to the Androgen Receptor during the Saturation 

Binding Experiment.

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FIGURE 2. Scatchard Plots of the Binding of [3H]-R1881 to the Androgen Receptor.

Page 61 of 260
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B. COMPETITIVE BINDING EXPERIMENT: The results from the three competitive 

binding experiments are summarized in Table 6 and shown graphically in Figures 3 – 5. 

Non-specific binding values were 8.9%, 10.3%, and 14.0%. Phosmet reduced the 

radiolabeled R1881 binding to the AR by more than 50% in each of the three runs. The 

estimated log IC50s for R-1881 and the weak positive control (dexamethasone) were in the 

ranges of -9.0 to -9.9 M and -4.3 to -4.6 M, respectively. The estimated log IC50 for 

phosmet was -5.0 M in each run which resulted in the mean log IC50 of -5.0 M for the test 

material. The mean RBA for the positive control was 0.0013%. Phosmet was classified as a 

“binder” in all three runs, as the RBA was calculated to be 0.0050%, indicating a stronger 

affinity for the androgen receptor than the positive control, dexamethasone. Confidence in 

these numbers is high due to the small variation. The solvent control responses indicated no 

drift in the study assay. 

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

Parameter Assay 1 Assay 2 Assay 3 Mean

r

2 (unweighted) R1881 NR NR NR NR

Dexamethasone NR NR NR NR

Phosmet NR NR NR NR

Log IC50 (M) R1881 -9.9 -9.0 -9.0 -9.3b

Dexamethasone -4.3 -4.4 -4.6 -4.4b

Phosmet -5.0 -5.0 -5.0 -5.0

IC50 (M)b R1881 1.3 x 10-10 10-9 10-9 1.1 x 10-10

Dexamethasone 5.0 x 10 -5 4.0 x 10 -5 2.5 x 10 -5 4.0 x 10 -5

Phosmet 10 -5 10 -5 10 -5 10 -5

RBA (as % IC50) c R1881 

Dexamethasone

100

0.0003

100

0.0025

100

0.0040

100

0.0013

Phosmet 0.0013 0.0100 0.0100 0.0050

a Data were obtained from page 20 of the study report.

b Calculated by reviewer

c Calculated by reviewer: [IC50 (in M) Dexamethasone or Phosmet / IC50 (in M) R1881] x 100% 

NA Not applicable

NR Not reported 

RBA (%) relative binding affinity

FIGURE 3. Binding of Phosmet, R1881 and Dexamethasone in Assay 1. 

 

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FIGURE 4. Binding of Phosmet, R1881 and Dexamethasone in Assay 2. 

FIGURE 5. Binding of Phosmet, R1881 and Dexamethasone in Assay 3. 

C. PERFORMANCE CRITERIA: To ensure that the competitive binding assay was 

functioning properly, each run was evaluated using the following criteria in Table 7: 

TABLE 7. Criterion a Tolerance 

Limit(s) b Value Yes No

Ligand depletion is minimal. The recommended ratio of total 

binding in the absence of competitor to total amount of [

3

H]-

R1881 added per assay tube (% binding)

≤15 10.5 to 12.6 X 

Test chemical Top (% binding) 80 to 115 102.3 to 107.5 X

R1881 fitted curve parameters

Top (% binding) 82 to 114 96 to 103 X

Bottom (% binding) -2.0 to 2.0 0 X

Hill Slope -1.2 to -0.8 -1.0 X

Weak positive control (dexamethasone) fitted curve parameters

Top (% binding) 87 to 106 101 to 105 X

Bottom (% binding) -12 to 12 -1 to 7 X

Hill Slope -1.4 to -0.6 -1.0 to -0.6 X

Saturation Binding Experiment Kd (nM) 0.685 to 1.57 nM 0.531 to 1.855d Xd

Non-specific binding (%)c 8.1-10.0 <20% X

a Data were obtained from pages 23-28 of the study report.

b These values represent ranges from the validation study. 

c MRID 48843501

d One value was below the limit, one value was within the limit, and one value was above the limit.

Additionally, the curve for the reference material showed that increasing concentrations of 

unlabeled R1881 displaced [3

H]-R1881 in a manner consistent with one-site binding, as 

Page 63 of 260
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indicated by a Hill slope of -1.0 to -0.6. Examination across the runs indicated consistency 

of the Hill slope, placement along the X-axis, and top and bottom plateaus. 

The percentage of the total specific binding in the solvent controls was approximately 10%. 

This was within the less than the ≤ 20% recommended in the guideline. Ligand depletion 

was also minimal. Sufficient optimization of the number of specific binding sites is 

supported by curves for controls of acceptable steepness, low non-specific binding, and low 

variability. 

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: All three assays achieved the binder criterion 

described in the guideline (<50% radioligand binding). There were no apparent alterations 

in radiolabeled R1881 binding at any of the lower concentrations tested. Phosmet was 

classified as binding based on the average of the three valid assays with a mean value of 

“2”. The mean RBA (calculated by dividing the log IC50 of the control/test material by the 

log IC50 of the positive control R1881) was 0.5 for both dexamethasone and phosmet. 

B. AGENCY COMMENTS: In the saturation binding experiment, the mean Kd for [3H]-

R1881 was 1.080 nM, and the mean estimated Bmax was 1.071 fmol/100 μg protein for the 

single batch of prostate cytosol that was used in the assay. Only one of the three individual 

Kd values was within the range reported in the EPA validation program (0.685 to 1.57 nM); 

the mean value was above the acceptable range. 

In the competitive binding experiment, the estimated log IC50s for R-1881 and the weak 

positive control (dexamethasone) were in the ranges of -9.0 to -9.9 M and -4.3 to -4.6 M, 

respectively. The estimated log IC50 for phosmet was -5.0 M in each run, and the mean log 

IC50 for phosmet was -5.0 M, classifying it as an AR binder. The mean RBA for the 

positive control was 0.0013%, and the mean RBA for phosmet was 0.0050%, indicating a 

stronger affinity for the androgen receptor compared to dexamethasone. Confidence in 

these numbers is high due to the small variation. The solvent control responses indicated no 

drift in the study assay. All performance criteria were met, with the exception of the bottom 

(% binding) of dexamethasone in Assay #1, the bottom plateau level could not be accurately 

calculated because of a deviation where the concentration range for dexamethasone was 

prepared slightly different than that specified in the guideline. As this was a minor 

deviation, the reviewers concluded that the performance criteria were met. Phosmet is 

classified as a binder in the androgen receptor assay.

 

C. STUDY DEFICIENCIES: The following deficiencies were noted that are not considered 

to have had an adverse impact on the results, interpretation or conclusions of this study: 

• The required r2

 value for the competitive binding assay was not reported. 

• Non-specific binding exceeded the tolerance limits for Assays 2 and 3. This was not 

considered to have a negative impact on the study because there was still enough of a 

dynamic range in which to detect changes in binding with concentration for control and 

test chemicals. 

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APPENDIX 1 (from page 49 of the Study Report) 

Page 65 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1200; Aromatase Assay

EPA Contract No. EP10H001452 

Task Assignment No. 2-4-2012 (MRID 48616302) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

Ronnie J. Bever Jr., Ph.D., D.A.B.T. Date: 12/15/2011

Secondary Reviewer Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 12/15/2011

Program Manager: Signature:

Jack D. Early, M.S. Date: 12/15/2011

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 12/15/2011

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by Dynamac Corporation personnel. 

Page 66 of 260
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).

Page 67 of 260
PHOSMET I 059201 

Primary Reviewer: Vincent Chen, M.S 

Health Effects Division 

Secondary Reviewer: Greg Akerman, Ph.D. 

Health Effects Division 

Aromatase (Human Recombinant) Assay (2011) I Page I of 13 

OCSPP 890.1200 I OECD None 

/-- Signature:~ c--

Date: z_y -sv Al W ...LS 

Signature: 

Date: 

,4 

Gb.:r 

~ 

/1 ) 

Template version 08/2011 

DATA EV ALU A TI ON RECORD 

STUDY TYPE: Aromatase (Human Recombinant); OCSPP 890.1200 

PC CODE: 059201 DP BARCODE: D397165 

TXR: 0056199 CAS: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8% a.i.) 

SYNONYMS: 

IUPAC: 0,0-dimethyl S-phthalimidomethyl phosphorodithioate 

CAS: S-[(l ,3-dihydro-l ,3-dioxo-2H-isoindol-2-yl)methyl] 0 ,0-dimethyl 

phosphorodithioate 

CITATION: Wilga, P.C. (2011). Phosmet: Human Recombinant Aromatase Assay. CeeTox, 

Inc (4717 Campus Drive, Kalamazoo, MI 49009, US]. Laboratory Study 

Number: 9142V-100348AROM. 03 November 2011. MRID 48618702. 

Unpublished. 

SPONSOR: Gowan Co., 370 Main Street, Yuma, AZ 85364, US 

TEST ORDER: EDSP-059201-54 

EXECUTIVE SUMMARY: In an in vitro aromatase (CYP 19) assay (MRJD 48618702), 

phosmet (96.8% a.i., batch # GQH9 11 8000) in dimethyl sulfoxide (DMSO) was incubated with 

human recombinant aromatase and tritiated androstenedione ([ 1P-3H(N)]-androst-4-ene-3,17-

dione; [3H]-ASDN) at concentrations of 0, 10-3, 10-3.s,10-4, 10-s, 10-6, 10-1, 10-8, 10-9, or 

10-10 M for 15 minutes at 37°C to assess the effect on aromatase activity. Due to slight 

precipitation that was observed at the high concentration in the first two runs, the high 

concentration was decreased to l 0·3.s M for the third run. 

Aromatase activity was determined by measuring the amount of tritiated water produced at the 

end of a 15-minute incubation period for each concentration of chemical. Tritiated water was 

quantified using liquid scintillation counting (LSC). Three independent runs were conducted, 

and each run included a full activity control, a background activity control, a positive control 

series (10- 10 to 10-5 M) using a known inhibitor (4-hydroxyandrostenedione; 4-0H ASDN), and 

the test chemical series (10- 10 to 10-3) with 3 replicates per concentration. 

Aromatase activity in the full activity controls ranged from 0.150 to 0.376 nmol·mgprotein- 1·min- 1 for the 3 test runs, with a mean and standard deviation of0.268±0.081 nmol·mgprotein- 1·min- 1. Activity in the background controls ranged from 0.37% to 0.97% and averaged 

0.56% of the full control activity. The response of the full activity controls and background 

Page 68 of 260
Aromatase (Human Recombinant) Assay (2011) / Page 2 of 13

PHOSMET / 059201 OCSPP 890.1200 / OECD None

controls were acceptable for each run. However, each full activity control was not generally 

within 10% of the average for the full activity controls, as recommended by the EPA. Run 1 had 

roughly half the activity of the other runs and the 0.5 mL count for total activity was roughly half 

that of the other runs. This discrepancy was not explained in the methods of the study report, 

and applies to both the controls and phosmet in run 1 compared to runs 2 and 3. 

For the positive control substance (4-OH ASDN), aromatase activity averaged 0.257±0.078 

nmol∙mg-protein−1∙min−1 at the lowest tested concentration (10−10 M) and 0.002±0.001 nmol∙mgprotein−1∙min−1 at the highest tested concentration (10−5 M). The results were generally within 

the recommended ranges for the top of the curve, bottom curve, Hill slope, log IC50, and 

coefficient of variation for replicates of each concentration.

For phosmet, aromatase activity averaged 0.231±0.059 nmol∙mg-protein−1∙min−1 at the lowest 

tested concentration of 10-10 M and 0.033±0.002 nmol∙mg-protein-1∙min−1 at the highest tested 

concentration of 10−3

 M. The lowest portion of the response curve across runs for phosmet was 

less than 50% activity, indicating that phosmet is an inhibitor of aromatase activity at the highest 

soluble concentration. Phosmet decreased aromatase activity to 34% at 10−4 M. 

The estimated log IC50 ranged from -4.37 to -4.89 M for phosmet and averaged -4.54 M 

compared to 4OH-ASDN, which averaged -7.21 M. The average slope of the concentration 

response curve was -1.20 for phosmet and -0.97 for 4OH-ASDN. Confidence in the mean log 

IC50 for both chemicals and the Hill slope for the positive control is high due to the small 

variation, but the variation was moderate (22.5% CV) for the slope value of phosmet. At 10-10 M 

in Run 2, aromatase activity was only 69-73% of control, as compared to 95-101% of control in 

the other runs; no explanation was provided. 

Based on the data from the average response curve, phosmet is classified as an Inhibitor of 

aromatase activity in this assay

The assay satisfies the EDSP Tier 1 Test Order requirements for an Aromatase assay (OCSPP 

890.1200).

COMPLIANCE: Signed and dated GLP Compliance and Quality Assurance statements were

provided. 

Page 69 of 260
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I. MATERIALS AND METHODS

A. MATERIALS: 

1. Test Substance: Phosmet

Description: Off-white crystals

Source: Gowan

Batch # (Expiration Date): GQH9118000 (January 31, 2013)

Purity: 96.8% a.i.

Vapor Pressure at 25°C: 0.065 mPa

Storage Conditions: Room temperature

Stability: Not reported

Solvent: DMSO

Solubility (in Test Solvent): Approximately 10−3.5M

Highest Concentration Tested: 10−3M

Stock Solution Preparation Methodology: Not provided; serial dilutions assumed

Molecular Weight: 317.3

CAS #: 732-11-6

Structure:

2. Non-Labeled Substrate: Androstenedione (ASDN)

CAS # : 63-05-8

Source: Steraloids, Inc. (Cat. # L1712)

Batch # (Expiration Date): L1712 (April 2016)

Purity: 99.8%

3. Radiolabeled Substrate: [1β-3H(N)]-Androst-4-ene-3,17-dione; ([3H]-ASDN)

Source: Perkin Elmer (Cat. # NET-926)

Batch # (Expiration Date): 619344 (10 January 2012)

Radiochemical Purity (Supplier): 97%

Specific Activity: 26.3 Ci/mmol

Radiochemical Purity (In-Lab Determination): Not provided

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

CAS # 566-48-3

Source: Sigma-Aldrich (Cat. # F2552)

Batch # (Expiration Date): 081K2133 (March 2015)

Purity: 99.6%

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

Source: Sigma-Aldrich (Cat. # D2650)

Lot # (Expiration Date): RNBB7617 (February 2013)

Justification for Choice of Solvent: Acceptable vehicle by OCSPP guideline 890.1200

Concentration (% of Total Volume in Assays): 1%

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

Source: BD GentestTM (Woburn, MA; Cat. # 456260)

Lot # (Expiration Date): 03897 (February 2014)

Protein Concentration: 7.4 mg/mL

Cytochrome C Reductase Activity: 290 nmol/min/mg

Aromatase Activity: 6.0 pmol/min/pmol P450

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B. METHODS

1. Assay Components 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 ASDN, and the amount of tritium added to each incubation tube was 

approximately 0.1 μCi. 

Test chemical stock solutions were prepared such that the total volume of each test chemical 

formulation used per assay was 1% (20 μL in 2 mL) of the total assay volume to minimize 

the potential for the solvent to inhibit the enzyme. Selection of the solvent, DMSO, was 

based on the following reasons: i) DMSO was listed as an acceptable vehicle in the OCSPP 

890.1200 Guidelines; ii) DMSO was less volatile than ethanol; and iii) DMSO was more 

accurate to pipette because of its density and viscosity. 

A stock solution of the positive control substance, 4-OH ASDN, was formulated in DMSO. 

Fresh dilutions of the stock solution were prepared in the same solvent on the day of use. 

Dilutions were prepared such that the target concentrations of the positive control substance 

(0.1–10,000 nM; Table 4) were achieved by the addition of 20 μL of the dilution for a final 

assay volume of 2 mL.

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

−80±10oC for no longer than 7 months. Microsomes were portioned into individual vials 

based on the protein concentration of the batch (approximately 0.004 mg/ml microsomal 

protein/tube) and stored at −80±10oC until used to minimize freeze-thaw cycles to no more 

than one. 

Other assay components, such as sodium phosphate buffer, propylene glycol, and NADPH, 

are reported in Table 1.

TABLE 1. Assay Components and Conditions

Assay Factor Values

Sodium phosphate buffer (pH 7.4) 0.1M

Microsomal protein 0.004 mg/mL

NADPH 0.3 mM

[

3H]ASDN 100 nM

Propylene glycol 5%

Temperature 37±2°C

Incubation time 15 min

2. Suitability Assessments: The protein concentration of the microsomes was supplied by the 

vendor as 7.4 mg/mL. Aromatase activity of the microsomes was also provided by the 

vendor as 6.0 pmol/min/pmole P450. The minimum mean aromatase activity in the full 

activity control samples was determined to be 0.150 nmol/mg-protein/min, which was 

greater than the minimum recommended aromatase activity of 0.1 nmol/mg-protein/min.

3. Aromatase Assay: Each assay run contained 4 tubes for the full enzyme activity and 4 

tubes for background activity controls. Two tubes of each control were run at the beginning 

of the assay, and two of each control were run at the end of the assay. A full concentration 

curve in duplicate for the positive control, and a full concentration curve in triplicate for the 

Page 71 of 260
Aromatase (Human Recombinant) Assay (2011) / Page 5 of 13

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test substance were established. The aromatase assay was generally conducted according to 

the procedures described in OCSPP 890.1200 (Section h, pp. 9-10). 

The amount of 3H2O in the aqueous fraction was quantified for each assay tube by LSC, and 

aromatase activity was reported in units of nmol∙mg-protein-1∙min-1. 

4. Demonstration of Proficiency: It was stated that prior to conducting this assay, a full-scale 

assay consisting of three independent runs was conducted using the positive control (4-OH 

ASDN) and the four proficiency chemicals (econazole, fenarimol, nitrofen, and atrazine) 

listed in the OCSPP 890.1200 guideline. Proficiency was demonstrated when the positive 

control met the performance criteria stated in the guideline and by the correct classification 

of the proficiency chemicals. It was stated that the data were generated and maintained at 

the Performing Laboratory; however, chemical proficiency data were not provided. 

a. Positive Control: 

Initial Demonstration of Laboratory Proficiency: Prior to conducting the aromatase activity 

assay, positive control assays were conducted with three independent runs. These data were 

not provided. However, positive controls were run concurrently with the test compound in 

the aromatase activity assay. These positive control data met the following criteria:

• Mean aromatase activity in the absence of an inhibitor was at least 0.1 nmol/mgprotein/min.

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

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

4-OH ASDN was <15%.

• Performance criteria (Table 2) were met, and served as guidance in identifying runs that 

provided parameters in the preferred ranges.

Demonstration of Proficiency of New Technician for Conducting Assay (when applicable): 

The positive control data met the criteria as listed in section (i) of OCSPP 890.1200. 

TABLE 2. Performance Criteria for the Positive Control

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

Slope -1.2 -0.8 -1.02 -0.94

Top (%) 90 110 85.58 100.53

Bottom (%) -5 +6 -0.28 0.69

Log IC50 (M) -7.3 -7.0 -7.35 -7.09

b. Proficiency Chemicals: Data was not provided. 

TABLE 3. Proficiency Chemicals

Compound CAS# Class Concentrations

Econazole 24169-02-6 Inhibitor ---

Fenarimol 60168-88-9 Inhibitor ---

Nitrofen 1836-75-5 Inhibitor ---

Atrazine 1912-24-9 Non-inhibitor ---

5. Determination of Aromatase Activity with Test Chemical: The response of aromatase 

activity to the presence of eight concentrations of the test chemical per run, in triplicate, was 

tested during three independent runs. After completion of the first run, the data were 

Page 72 of 260
Aromatase (Human Recombinant) Assay (2011) / Page 6 of 13

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reviewed and solubility was visually assessed (presence of cloudiness or a precipitate). No 

data adjustments were necessary. The full enzymatic activity was obtained at the two lowest 

concentrations of the test chemical in two runs but not the third, defining the top of the 

concentration-response curve.

TABLE 4. Test Chemical Study Design for Each Test Run

Sample Type Repetitions (Tubes) Description Reference or Chemical (M)

Full Activity Control 4 All test componentsa 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

Phosmet Conc 1a b 3 All test components plus phosmet 1×10-3

Phosmet Conc 1b c 3 All test components plus phosmet 1×10-3.5

Phosmet Conc 2 3 All test components plus phosmet 1×10-4

Phosmet Conc 3 3 All test components plus phosmet 1×10-5

Phosmet Conc 4 3 All test components plus phosmet 1×10-6

Phosmet Conc 5 3 All test components plus phosmet 1×10-7

Phosmet Conc 6 3 All test components plus phosmet 1×10-8

Phosmet Conc 7 3 All test components plus phosmet 1×10-9

Phosmet Conc 8 3 All test components plus phosmet 1×10-10

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

b The high dose for runs 1 and 2. Slight precipitation was observed at this dose.

c The high dose for run 3. No precipitation was observed at this dose.

C. DATA ANALYSIS

1. Raw Data: Raw data were converted to aromatase activity (nmol/mg protein/min) and 

percent control for the positive control and test chemical. The following raw data and 

calculated endpoints for each run were included in the report (Table 5). 

TABLE 5. Raw and Calculated Data

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/min X

Average aromatase activity in the full activity control tubes X

Percentage of control activity remaining in the presence of various inhibitor concentrations X

DPM Disintegrations per minute

2. Statistical Methods: Statistical analyses and graphical displays were conducted using 

XLfit, v5.2.0.0 (IDBS, Guildford, UK). Basic statistical analyses were performed on the 

data, which included means of replicates, standard deviation of the mean, standard error of 

the mean, and coefficient of variation. 

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The response curve was fitted by weighted least squares nonlinear regression analysis with

weights equal to 1/Y. Model fits were carried out using a 4-parameter regression model 

(XLfit; IDBS; v5.2.0.0; Fit Model 208,) and Tukey’s Bi-Weight statistical analysis for 

outlier analysis. For each run, the individual percent of control values were plotted versus 

the logarithm (base 10) of the test chemical concentration. The fitted concentration

response curve was superimposed on the plot, with individual plots prepared for each run. 

The average percent of control values versus the logarithm of test chemical concentration 

for the individual runs were included on the same graph with their respective fitted response 

curves. In addition, the average percent of control values for each run versus the logarithm 

of test chemical concentration were plotted on a separate graph along with the average 

concentration response curve across runs were superimposed on the same plot. 

3. Interpretation of Results: Interpretation of the assay results was based 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% Inhibitor

Average lowest portion of curves across runs is between 50% and 75% activityb Equivocal

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

Data do not fit model ---

II. RESULTS

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

0.150 to 0.376 nmol∙mg-protein−1∙min−1 for the 3 test runs, with a mean and standard 

deviation of 0.268±0.081 nmol∙mg-protein−1∙min−1. Activity in the background controls 

ranged from 0.37% to 0.97% and averaged 0.56% of the full control activity. The response 

of the full activity controls and background controls were acceptable within each run. 

However, Run 1 had roughly half the activity of the other runs, and the 0.5 mL count for 

total activity was roughly half that of the other runs. This discrepancy was not explained in 

the methods of the study report, and applies to both the controls and phosmet in run 1 

compared to runs 2 and 3. 

B. POSITIVE CONTROL: For the positive control substance (4-OH ASDN), aromatase 

activity averaged 0.257±0.078 nmol∙mg-protein−1∙min−1 at the lowest tested concentration 

(10−10 M) and 0.002±0.001 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 3 runs is presented in Table 7, along with 

the overall standard deviation and %CV. The inhibition response curves for the positive 

control are shown in Figure 1. These results were generally within the recommended ranges 

for the top of the curve, bottom curve, Hill slope, log IC50, and coefficient of variation for 

replicates of each concentration.

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Aromatase (Human Recombinant) Assay (2011) / Page 8 of 13

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TABLE 7. Effect of Phosmet on Aromatase Activity (as Percent of Control) from Independent Runs a

Chemical Conc. Log M # Runs Overall Mean Overall SD Overall SEM Overall %CV

4-OH ASDN

(positive control)

-5 3 0.82 0.12 0.05 14.14

-6 3 6.44 1.07 0.43 16.54

-6.5 3 16.66 2.81 1.15 16.89

-7 3 36.05 3.52 1.44 9.76

-7.5 3 63.50 4.18 1.71 6.59

-8 3 79.85 6.57 2.68 8.23

-9 3 92.27 10.27 4.19 11.13

-10 3 96.78 8.58 3.50 8.87

Phosmet -3 3 14.79 5.23 2.14 35.36

-3.5 3 29.49 1.22 0.50 4.14

-4 3 34.08 5.16 2.11 15.13

-5 3 72.43 10.38 4.24 14.33

-6 3 89.94 9.27 3.79 10.31

-7 3 91.36 9.99 4.08 10.93

-8 3 90.40 9.16 3.74 10.13

-9 3 90.63 11.04 4.51 12.18

-10 3 88.53 12.70 5.18 14.34

a Calculated by the reviewers using the information presented on pages 29-31 of the study report. 

SD Standard Deviation

SEM Standard Error of the Mean

CV Coefficient of Variance

Page 75 of 260
Aromatase (Human Recombinant) Assay (2011) / Page 9 of 13

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FIGURE 1. Inhibition Response Curves for 4-OH ASDN. 

C. TEST SUBSTANCE: For phosmet, aromatase activity averaged 0.231±0.059 

nmol∙mg-protein−1∙min−1 at the lowest tested concentration of 10-10 M and 0.033±0.002 

nmol∙mg-protein-1∙min−1 at the highest tested concentration of 10−3 M. The mean aromatase 

Page 76 of 260
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activity of phosmet (expressed as % full control activity) for each concentration tested 

across all 3 runs is presented in Table 7, along with the overall standard deviation and %CV. 

Inhibition response curves for phosmet from each run are shown in Figure 2, and the 

average inhibition response curve across all runs is shown in Figure 3. 

Page 77 of 260
Aromatase (Human Recombinant) Assay (2011) / Page 11 of 13

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FIGURE 2. Inhibition Response Curves for Phosmet.

A slight amount of the compound was 

observed in the miniscus, near the 

surface for the highest concentration.

A slight amount of the compound was 

observed in the miniscus, near the 

surface for the highest concentration.

Page 78 of 260
Aromatase (Human Recombinant) Assay (2011) / Page 12 of 13

PHOSMET / 059201 OCSPP 890.1200 / OECD None

FIGURE 3. Mean Inhibition Response Curve for Phosmet

A slight amount of the 

compound was observed in the 

meniscus, near the surface for 

the highest concentration.

The effect of phosmet on inhibition of aromatase activity is presented in Table 8. The 

estimated log IC50 ranged from -4.37 to -4.89 M for phosmet and averaged -4.54 M 

compared to 4OH-ASDN, which averaged -7.21 M. The average slope of the concentration 

response curve was -1.20 for phosmet and -0.97 for 4OH-ASDN. Confidence in the mean 

log IC50 for both chemicals and the Hill slope for the positive control is high due to the 

small variation, but the variation was moderate (22.5% CV) for the slope value of phosmet. 

TABLE 8. Effect of Phosmet and 4OH-ASDN on Aromatase Activity (as Percent of Control) from Independent Runs a

Chemical Run 1 Run 2 Run 3 Mean SD %CV

Log IC50 (M)

Phosmet -4.37 -4.37 -4.89 -4.54 0.30 6.62

4-OH ASDN -7.19 -7.09 -7.35 -7.21 0.13 1.82

Slope

Phosmet -1.16 -0.95 -1.48 -1.20 0.27 22.48

4-OH ASDN -0.94 -1.02 -0.95 -0.97 0.04 4.49

a Data for individual control runs were obtained from page 27 of the study report. IC50 and slope values for phosmet were 

calculated by the reviewers using Graphpad Prism based on data provided on pages 44, 49 and 54. Mean, SD, and %CV for 

phosmet and control were calculated by the reviewers.

SD Standard Deviation

CV Coefficient of Variance

NA Not applicable

At 10-10 M in Run 2, aromatase activity was only 69-73% of control, as compared to 

95-101% of control in the other runs. No explanation was provided in the study report 

concerning this observation. Based on the data from the average response curve and the 

criteria listed above in Table 6, the results support the conclusion that phosmet inhibits 

aromatase. 

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Aromatase (Human Recombinant) Assay (2011) / Page 13 of 13

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III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS CONCLUSIONS: A decrease in aromatase activity was identified at 

the very highest concentration of phosmet tested (e.g., 10−3 M), but solubility issues were 

observed. Phosmet reduced aromatase to 34.1% of control activity at 10−4 M and thus was 

classified as an inhibitor, per OPPTS 890.1200 guideline, under the conditions of this assay. 

Phosmet at lower exposures of 10–10 M to 10–5 M showed essentially no effect (e.g., 

non-inhibitor). 

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

0.150 to 0.376 nmol∙mg-protein−1∙min−1 for the 3 test runs, with a mean and standard 

deviation of 0.268±0.081 nmol∙mg-protein−1∙min−1. Activity in the background controls 

ranged from 0.37% to 0.97% and averaged 0.56% of the full control activity. The response 

of the full activity controls and background controls were acceptable for each run. 

However, each full activity control was not generally within 10% of the average for the full 

activity controls as recommended by the EPA. Run 1 had roughly half the activity of the 

other runs and the 0.5 mL count for total activity was roughly half that of the other runs. 

This discrepancy was not explained in the methods of the study report, and applies to both 

the controls and phosmet in run 1 compared to runs 2 and 3. For the positive control 

substance (4-OH ASDN), aromatase activity averaged 0.257±0.078 nmol∙mgprotein−1∙min−1 at the lowest tested concentration (10−10 M) and 0.002±0.001 nmol∙mgprotein−1∙min−1 at the highest tested concentration (10−5 M). The estimated log IC50 ranged 

from -4.37 to -4.89 M for phosmet and averaged -4.54 M compared to 4OH-ASDN, which 

averaged −7.21 M. The average slope of the concentration response curve was -1.20 for 

phosmet and -0.97 for 4OH-ASDN. Confidence in the mean log IC50 for both chemicals 

and the Hill slope for the positive control is high due to the small variation, but the variation 

was moderate (22.5% CV) for the slope value of phosmet. At 10-10 M in Run 2, aromatase 

activity was only 69-73% of control, as compared to 95-101% of control in the other runs; 

an explanation was not provided. 

 The lowest portion of the response curve across runs for phosmet was less than 50% activity, 

indicating that phosmet is an inhibitor of aromatase activity at the highest soluble 

concentration (phosmet decreased aromatase activity to 34% at 10−4

 M). Based on the data 

from the average response curve, the results indicate the phosmet is an inhibitor of 

aromatase activity in this assay

C. STUDY DEFICIENCIES: The following deficiencies were noted that are not considered 

to have had an adverse impact on the results, interpretation or conclusions of this study: 

• Proficiency chemical data were not provided.

• Different counts for total activity in 0.5 mL and full activity controls (nmol/mg/min) were 

observed in Run 1 compared to Runs 2 and 3, but no explanation was provided. 

• At 10-10 M in Run 2, aromatase activity was only 69-73% of control, as compared to 95-

101% of control in the other runs. No explanation was provided in the study report 

concerning this observation. 

• Information on the stability of the stock solution was not reported. 

Page 80 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1250, Estrogen Receptor Binding Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 2-4-2012 (MRID 48618704) 

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:

Michelle J. Sharpe-Kass, M.S. Date: 12/12/2011

Secondary Reviewer Signature:

David A. McEwen, B.S. Date: 12/19/2011

Program Manager: Signature:

Jack D. Early, M.S. Date: 12/23/2011

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 12/23/2011

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by Dynamac Corporation personnel. 

Page 81 of 260
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).

Page 82 of 260
PRONAMIDE/ 101701 

Androgen Receptor Binding (Rat Prostate Cytosol) (2012) I Page J of 13 

OCSPP 890.1150/ OECD None 

Primary Reviewer: Patience Browne, Ph.D. 

Health Effects Division,. Office of Pesticide Progra.ms 

Secondary Reviewer: Greg Akerman, Ph.D . . 

Health Effects Division; Office of Pesticide Programs 

Signatu~ e__ 

Signature: l>ate: ~~ ~ 

· Date: \:20of 2 

Template version 08/2011 

DATA EVALUATION RECORD 

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

OCSPP 890.1250 

PC CODE: 059201 DP BARCODE: D397 l 65 

TXR#: 0056199 CAS No.: 732-11-6 

TEST MATERIAL CPURIT\'): Phosmet (96.8%) 

SYNONYMS: Imidan Technical; 2-( dimethoxyphosphinothioylsulfanylmethyl)isoindole-1 ,3-

dione 

CITATION: Willoughby, J.A. Sr. (2011). Phosmet: Estrogen Receptor Binding (Rat Uterine 

Cytosol). CeeTox, Kalamazoo, MI. 9142V-100348ERB, November 2, 2011. 

MRID 48618704 Unpublished. 

SPONSOR: Gowan Company, 370 Main Street, Yuma, AZ 85364 

TEST ORDER#: EDSP-059201-54 

EXECUTIVE SUMMARY: In an estrogen receptor (ER) binding assay (MRID 48618704), 

uterine cytosol from Sprague-Dawley rats was used as the source of ER to conduct saturation 

and competitive binding experiments. A saturation binding experiment was conducted to 

demonstrate that the ER in the rat uterine cytosol was present in reasonable numbers and was 

functioning with appropriate affinity for the radiolabeled reference estrogen prior to routinely 

conducting ER competitive binding experiments. The competitive binding experiment was 

conducted to measure the binding of a single concentration of [3H]-17P-estradiol (1 nM) in the 

presence of increasing concentrations of phosmet (96.8% purity; logarithmic increase from I 0-10 

to 10-3 M). DMSO was used as a vehicle at a final concentration of <4%. The assay included 

19-norethindrone as a weak positive control, octyltriethoxysilane as a negative control, and l 7Pestradiol as the natural ligand reference material. 

Saturation binding data were not provided in the study report; however, summarized saturation 

binding data (MRID 48843501) from the perfor,ming laboratory were submitted following a 

request by the Agency. 

For the Competitive Binding Experiment, a log ICso could not be calculated for phosmet. The 

mean log ICso for l 7P-estradiol was -9.0 Mand the average log ICso for 19-norethindrone was 

- 5.5 M. The mean RBA was 0.03% for 19-norethindrone compared to the positive control (I 

nM I 7P-estradiol), but a RBA could not be calculated for phosmet. 

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Based on the top % binding for 19-norethindrone at 49%, Run 2 should not be considered for 

evaluation of phosmet for binding to the ER. The Hill slope for 17β-estradiol in Run 3 (−1.7) 

was outside of parameter limits. Precipitation was observed at 10-4M (but not 10-3 M) in Run 1 

and at the 10-3 M in Runs 2 and 3. In these instances, data for those concentrations were 

disregarded by the study author despite indications of potential interaction with the estrogen 

receptor. The investigators failed to follow assay guidelines that recommend testing solubility of 

test substances in increasing solvent concentrations (up to 10% DMSO) and including half log 

concentrations at the limit of solubility. Because of insufficient attempts to resolve issues with 

solubility of the test substance at concentrations that suggested an ER interaction, there is lack of 

confidence in the results of the three runs; therefore the assay is considered to be technically 

inadequate.

The assay does not satisfy does not satisfy the EDSP Tier 1 Test Order requirements for an 

Estrogen Receptor Binding assay (OCSPP 890.1250). This assay is not satisfied due to issues with 

test chemical solubility. However a repeat of this assay is not required since negative results were 

seen in the Tier 1 ERTA and OSRI which evaluated potential interaction of phosmet with the ER. 

For additional information see the EDSP Tier 1 Weight of Evidence Analysis for Phosmet (TXR 

0057145). 

COMPLIANCE: Signed and dated GLP and Quality Assurance statements were provided. 

Page 84 of 260
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I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: CeeTox

Location: Kalamazoo, MI

Study Director: Jamin A. Willoughby, Ph.D.

Other Personnel: Karen Rutherford, Director of Laboratory Operations

David Blakeman, Senior Scientiet/Endocrine Group Leader

Cameron Haines, Scientist

Steven McColley, Scientist

Biranna Wallace, Lead Cell Culture Scientist

Colleen Toole, Ph.D., Director of Project Management

Study Period: May 25- Nov 2, 2011

2. Test substance: Phosmet

Description: White crystalline solid

Source: Gowan Company (Yuma, AZ)

Lot/Batch #: GQH9118000, Exp Jan 31, 2013

Purity: 96.8% a.i.

Solubility: Not reported

Volatility: Not reported

Stability: Not reported

Storage conditions: Ambient

CAS #: 732-11-6

Molecular weight: 317.32 g/mol

Structure: O

O

S

P

S

OCH3

N OCH3

3. Non-labeled ligand: 17β-estradiol

Supplier: Sigma-Aldrich (St Louis, MO)

Catalog # E8875

Batch #: 110M0138V

Purity: 100% a.i.

CAS #: 50-28-2

4. Radioactive ligand: [

3

H]-17β-estradiol

Supplier: Perkin-Elmer (Boston, MA)

Catalog #: NET517

Batch#: 650702

Radiochemical purity: Not reported

Specific activity: 130.2 Ci/mol 

Concentration of stock: 1 nM

5. Positive control: 19-norethindrone

Supplier: Sigma-Aldrich (St Louis, MO)

Catalog # N4128

Batch #: 030M1359V

Purity: 99% a.i.

CAS # : 66-22-4

6. Negative control: Octyltriethoxysilane

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PHOSMET / 059201 OCSPP 890.1250/ OECD None

Supplier: Sigma-Aldrich (St Louis, MO)

Catalog # 440213

Batch #: 2499KK

Purity: 99.34% a.i.

CAS # : 2943-75-1

7. Solvent/vehicle control: DMSO

Justification for choice of solvent: None reported

Final Concentration 4% v/v

B. METHODS 

1. Preparation of Rat Uterine Cytosol (RUC): Rat uteri from female Sprague-Dawley rats 

(number not reported) aged 12-13 weeks were obtained from Harlan Laboratories. Rats were 

ovariectomized 7 days prior to being euthanized. Upon receipt, the uterine tissue was 

inspected for signs of residual ovarian tissue after ovariectomy, and compromised tissue was 

discarded. The uteri were weighed, placed in ice-cold TEDG (Tris, EDTA, DTT, glycerol) +

Protease inhibitor (PI) buffer and used immediately. Uteri were homogenized in buffer, 

centrifuged for 10 min at 2500 × g at 4oC. Supernatant was transferred and centrifuged for 

60 minutes at 105,000 × g, discarding the resulting pellets. Protein concentration of the 

cytosol was determined to be 3.22 mg/mL using a BioRad Protein Assay Kit (compatible 

with DTT in the TEDG buffer). Cytosol was divided into aliquots (1-6 mL) for either 

immediate use or storage at -80oC until use.

2. Saturation (radioligand) Binding Experiment: It was stated that proficiency records for 

this assay are archived and maintained at CeeTox, Inc. Saturation binding data were not 

provided in the study report; however, summarized saturation binding data (MRID 

48843501) from the performing laboratory were submitted following a request by the 

Agency (Tables 1 and 2). 

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3. Competitive Binding Experiment: A summary of the experiment conditions for the 

Competitive Binding Experiment is included in Table 3. 

TABLE 3. Summary of Conditions for Competitive Binding Experiment a

Source of receptor Rat Uterine Cytosol 

Concentration of radioligand 1 nM 

Concentration of receptor Sufficient to bind 11-12% of radioligand b

Concentration of test substance (as serial dilutions) 10-10 to 10-3 mM

Temperature 4±2 °C 

Incubation time 16-20 hours 

Composition of assay buffer Tris 10 mM (pH 7.4)

EDTA 1.5 mM 

Glycerol 10% v/v

Protease Inhibitor 0.5% v/v

DTT 1 mM 

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

b Calculated by reviewer. Data obtained from pages 35, 40 and 45 of the study report. 

A solubility test was performed to determine the appropriate solvent (DMSO) using visual 

observation (it was not stated if magnification was used). On the day of the assay, the 

specific activity of the stock solution [3H]-17β-estradiol was adjusted for decay over time, 

and diluted in TEDG + PI buffer to achieve a final concentration of 1 nM. No details were 

provided on the determination of the optimal protein concentration, but the amount used was 

sufficient to bind 11-12% of the radioligand, based on the data provided for total binding and 

total activity. The amount of protein used in each tube was 80.0 μg protein per tube. Serial 

dilutions of the phosmet, positive control (19-norethindrone), negative control 

(octyltriethoxysilane), and reference material (non-labeled 17β-estradiol) were prepared to 

achieve the concentrations shown in Table 4. Each assay consisted of three runs, and each 

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run contained three replicates at each concentration, plus six tubes to determine total activity 

(master mix) resulting in a total of 102 tubes/assay run. 

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

Phosmet Positive control Negative control Reference Chemical

19-Norethindrone Octyltriethoxysilane Non-labeled

17β-estradiol

Tubes 79-102 c Tubes 31-54 c Tubes 55-78 c Tubes 7-30 c

10-10 10-8.5 10-10 Solvent control d

10-9 10-7.5 10-9 10-11

10-8 10-7 10-8 10-10

10-7 10-6.5 10-7 10-9.5

10-6 10-6 10-6 10-9

10-5 10-5.5 10-5 10-8.5

10-4 10-4.5 10-4 10-8

10-3 10-4 10-3 10-7

a Data were obtained from pages 35-49 of the study report. 

b Each tube contains: 10μL of either the test substance, positive control, negative control, solvent control, or 

non-labeled 17β-estradiol; 390 μL of TEDG + PI buffer with [3

H]-17β-estradiol; and 100 μL of uterine 

cytosol (with ER), for a total of 500 μL.

c Each concentration of each chemical was run in triplicate, for a total of 93 tubes per run plus 9 tubes to 

determine total activity and total binding. 

d Solvent is DMSO (4%) in Tubes 7-9.

Tubes were incubated with gentle vortexing for 16-20 hours at 4°C. To separate bound from 

free estradiol, hydroxyapatite (HAP) slurry was added to each tube and vortexed for 

approximately 10 seconds at 5 minute intervals for a total of 15 minutes. Subsequently, the 

contents of each tube were washed three times as follows: TEDG + PMSF buffer was added, 

vortexed, centrifuged for 10 min at 1000 x g, and the supernatant decanted and discarded. 

Ethanol was added to the HAP pellet remaining in each tube to extract the [

3

H]-17β-estradiol, 

followed by vortexing, and centrifugation for 10 min at 1000 x g. An aliquot of supernatant 

was radioassayed by scintillation counting. The temperature was maintained at 4oC 

throughout the assay prior to extraction with ethanol. 

C. DATA ANALYSIS: For the saturation binding experiment (data not reported), total binding 

and non-specific binding data were modeled via non-linear regression using Graph Pad Prism 

(version not reported; GraphPad Software, Inc., La Jolla, CA) or XLfit, no method was 

reported for outlier exclusion. It was not reported if receptor binding data plots were 

corrected for ligand depletion. For the competitive binding assay, similar methods of 

nonlinear regression were used to fit a curve (for 17β-estradiol, the positive control, and the 

test substance) to the Hill equation formula which incorporated log IC50 as a parameter to be 

estimated. 

1. Definitions

a. Classification of test material: Classification of the test material is based on the average of 

three runs. Each run was first individually classified as follows:

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Interactive = lowest point on the fitted curve within the range of the data is less than 50% 

(i.e., >50% of the radiolabeled estradiol has been displaced from the ER).

Not interactive = there are usable data points at or above 10-6M and either the lowest point 

on the fitted response curve within the range of the data is above75% (i.e., 

<25% of the radiolabeled estradiol has been displaced from the ER) or a 

binding curve cannot be fitted and the lowest average percent binding among 

concentration groups in the data is above 75%. 

Equivocal up to the limit of concentrations tested = there are no data points at or above a 

test chemical concentration of 10-6M and either a binding curve can be fit but 

≤50% of the radiolabeled estradiol has been displaced from the ER or a binding 

curve cannot be fit and the lowest average percent binding among 

concentration groups in the data is >50%. 

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

above. 

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

Run Classification Numerical Value

Interactive 2

Equivocal 1

Not interactive 0

Equivocal up to the limit of concentrations tested “missing”

The values for each run were then averaged across runs and the chemical classified using the 

following ranges: 

Test Material Classification Numerical Range

Interactive average ≥1.5

Equivocal 0.5≥ average <1.5

Not interactive average <0.5

Equivocal up to the limit of concentrations tested “missing”

b. Descriptors for receptor binding: 

Bmax: maximum specific binding number (fmol ER/100 μg cytosol protein) measures the 

concentration of active receptor sites

Kd: dissociation constant (nM), measures the affinity of the receptor for its natural ligand

IC50: concentration of the test substance at which 50% of the radioligand is displaced from 

the receptor

Relative Binding Affinity (RBA %): IC50 of 17β-estradiol ÷ IC50 of test substance × 100) 

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II. RESULTS

A. SATURATION BINDING EXPERIMENT: Saturation binding data were not provided in 

the study report; however, summarized saturation binding data (MRID 48843501) from the 

performing laboratory were submitted following a request by the Agency. Saturation binding 

experiment parameters are presented in Table 5. Figures 1-6 show the specific, non-specific, 

and total binding curves for [3H]-17β-estradiol to the estrogen receptor for saturation binding 

and the Scatchard plots for runs 1-3.

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B. COMPETITIVE BINDING EXPERIMENT: The results from the three Competitive 

Binding Assays are summarized in Table 6 and shown graphically in Figures 7, 8 and 9. The 

estimated mean log IC50 was not calculated for phosmet, as the percent binding did not cross 

the 50% mark. The estimated mean log IC50s for 17β-estradiol and the positive control were 

−9.0 M and −5.5M, respectively. The mean RBA was 0.03% for the positive control. 

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

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

r

2 (unweighted), 17β-estradiol NR NR NR NA

 19-norethindrone NR NR NR NA

Phosmet NR NR NR NA

Log IC50 (M), 17β-estradiol -9 -9.1 -9 -9.0

 19-norethindrone -5.6 -5.4 -5.5 -5.5

Phosmet NA NA NA NA

IC50 (M), 17β-estradiol 1.00 x 10-9 7.94 x 10-10 1.00 x 10-9 9.26 x 10-10

 19-norethindrone 2.51 x 10-6 3.98 x 10-6 3.16 x 10-6 3.16 x 10-6

Phosmet NA NA NA NA

Log RBA (%), 19-norethindrone -3.40 -3.70 -3.50 -3.53

Phosmet NA NA NA NA

RBA (%), 19-norethindrone 0.04 0.02 0.03 0.03

Phosmet NA NA NA NA

a Data were obtained from pages 21-22 of the study report.

b The mean and standard deviation are reported for the concurrent replicates within each run.

r

2 Goodness of fit

RBA (%) Relative binding affinity

NA Not applicable

NR Not reported

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FIGURE 71. Percentage E2 Bound to the Estrogen Receptor in the Presence of Phosmet, 

Unlabeled EW, 19-norethindrone or Octyltriethoxysilane. Run 1

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FIGURE 8. Percentage E2 Bound to the Estrogen Receptor in the Presence of Phosmet, 

Unlabeled EW, 19-norethindrone or Octyltriethoxysilane. Run 2

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FIGURE 9. Percentage E2 Bound to the Estrogen Receptor in the Presence of Phosmet, 

Unlabeled EW, 19-norethindrone or Octyltriethoxysilane. Run 3

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The classification of the test material is based on the average of three runs. Each run was 

individually classified as shown in Table 7.

TABLE 7. Binding Classification of Phosmet with Estrogen Receptor a

Run 1 2 3 Mean Binding Classificationc

Classification category value b NA NA NA NA NA

a Technical deficiencies noted in all three runs.

b Classification category value: Interactive = 2; Equivocal = 1; Not interactive = 0; Equivocal up to the limit of 

concentrations tested (“missing”, i.e., not included in calculation of mean).

c Interactive = mean ≥1.5; Equivocal = 0.5≤ mean <1.5; Not interactive = mean <0.5

C. PERFORMANCE CRITERIA: To ensure that the competitive binding assay functioned

properly, each run was evaluated using the following criteria: 

TABLE 8. Criterion a Tolerance 

Limit(s) Value Yes No

17β-estradiol fitted curve parameters

Loge residual SD ≤2.35 1.20 to 1.95 X

Top (% binding) b 94 to 111 95 to 109 X

Bottom (% binding) -4 to 1 -1 to 5 X

Hill Slope (log10(M)-1) -1.1 to -0.7 -1.7 to -1 X

Weak Positive control (19-norethindrone) fitted curve parameters

Loge residual SD` NA 0.91 to 1.59

Top (% binding) b NA 49 to 100

Bottom (% binding) NA -9 to 0

Hill Slope (log10(M)-1) -1.1 to -0.7 -2.5 to -0.9

Solvent concentration

DMSO ≤10% 4% X

Negative control (octyltriethoxysilane) does not displace more than 

25% of [

3

H]-17β-estradiol from the ER on average across all 

concentrations

≤25% <11% X

a Data were obtained from pages 25, 27 and 29 of the study report. 

b The EPA Guideline does not define a set of tolerance limits for 19-norethindrone. Acceptance criteria were only 

defined for norethynodrel, which cannot be obtained commercially. The values reported were considered 

acceptable as they show 19-norethindrone to be an acceptable weak positive control.

NA Not applicable

Additionally, the curve for the reference material showed that increasing concentrations of 

unlabeled 17β-estradiol displaced [3H]-17β-estradiol in a manner consistent with one-site 

binding, as indicated by a Hill slope of -1.0 for the first run. The second and third runs 

showed Hill slopes of −1.4 and −1.7. 

The weak positive control, 19-norethindrone had a Hill Slope of -1.4 in the third assay, and 

the second assay showed a top plateau level of 49% binding, a bottom plateau level of −9% 

and a hill slope of −2.5. These data are consistent with a weak positive control and therefore, 

invalidate the run. 

Phosmet was tested over a concentration range that fully defined the top of the curve. The 

maximum percent binding 105.7% was within 25 percentage points of the value for the 

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PHOSMET / 059201 OCSPP 890.1250/ OECD None

lowest concentration of the estradiol standard 95.1%. Examination across the runs indicated 

consistency of placement along the X-axis, and a top plateau for phosmet. 

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: In all three independent runs, the mean specific 

binding was >80% for the negative control octyltriethoxysilane. The data for 17β-estradiol 

and 17-norethyndrone were within the acceptable ranges, with deviations which were minor 

and not considered to reflect true deviation from the suggested ranges outlined in the 

OPPTS guideline. The data for 19-norethindrone were outside the acceptance criteria in 

Run 1. However, the positive and negative controls both were within acceptance criteria. 

This suggests that the problem with the 19-norethindrone data in the second run was most 

likely in the preparation of the compound. 

The mean RBA (calculated by dividing the log IC50 of the test material by the log IC50 of 

17β-estradiol) [sic] was 0.6 for 19-norethindrone. There was no RBA to be calculated for 

phosmet.

Phosmet solubilized in DMSO was classified as "non-interacting" in all three independent 

runs and thus had a final classification of "non-interacting" under the conditions of this study. 

B. AGENCY COMMENTS: The saturation binding experiment demonstrated that the ER 

isolated from rat uterine cytosol was present in reasonable numbers and was functioning 

with appropriate affinity for the radio-labeled reference estrogen prior to routinely 

conducting ER Competitive Binding Experiments. The mean Kd for [3

H]-17β-estradiol was 

0.331 ± 0.061 nM and the mean Bmax was 0.549 ± 0.100 nM (74.55 ± 3.03 fmol/100μg) 

protein for the prepared rat uterine cytosol Precipitation was observed at 10-4 M (but not 

10-3 M) in Run 1 and 10-3 M concentrations in Runs 2 and 3. In these instances, data for 

those concentrations were disregarded by the study author despite indications of potential 

interaction with the estrogen receptor. The investigators failed to follow assay guidelines 

that recommend testing solubility of test substances in increasing solvent concentrations (up 

to 10% DMSO) and including half log concentrations at the limit of solubility. Because of 

insufficient attempts to resolve solubility of test substance at concentrations where there 

were indications of potential ER interactions, there is lack of in all the 3 runs; therefore the 

assay is considered to be technically inadequate. In addition, the intra assay weak positive 

control (19-norethindrone) did not show an acceptable response for run 2, and the Hill slope 

for 17β-estradiol in the third run (−1.7) did not fall within parameter limits specified in the 

guidelines. 

C. STUDY DEFICIENCIES: The following deficiencies were noted that are considered to 

have had an adverse impact on the results, interpretation or conclusions of this study: 

• Hill slopes for 17β-estradiol outside guideline criteria. The weak positive control, 19-

norethindrone showed a top plateau level of 49% binding in the second run, a bottom 

plateau level of −9% and a hill slope of −2.5. The Investigator noted that the weak 

positive control data were well outside the guidelines for acceptance, however, in the 

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same run the positive and negative controls were within the acceptable criteria. They 

suggest that the problem was not due to the system but the preparation of the compound. 

• Higher concentrations (<10%) of DMSO were not tested to resolve solubility issues, nor 

was EtOH tried as an alternative solvent (as instructed by guidelines).

• No logical physicochemical rationale for precipitate at 10-4 M and not at 10-3 M; either 

precipitate was overlooked or technical differences in treatment of assay tubes at different 

concentrations. Insufficient attempts to resolve issues with solubility of the test 

substance at concentrations that suggested an ER interaction. 

Page 100 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1300, Estrogen Receptor Transcriptional Activation 

EPA Contract No. EP10H001452 

Task Assignment No. 2-4-2012 (MRID 48618705) 

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 J. Sharpe-Kass, M.S. Date: 12/05/2011

Secondary Reviewer Signature:

Rebecca Bryan, B.S. Date: 12/07/2011

Program Manager: Signature:

Jack D. Early, M.S. Date: 12/15/2011

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 12/15/2011

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by CSS-Dynamac Corporation personnel. 

Page 101 of 260
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).

Page 102 of 260
PHOSMET /059201 

Estrogen Receptor Transcriptional Activation (2011) I Page 1 of2 

OCSPP 890.1300/ OECD 455 

Primary Reviewer: Sheila Healy. Ph.D. 

Health Effects Division 

Secondary Reviewer: Minerva Mercado, Ph.D., DABT 

Health Effects Division 

Signa{~ . ~_........""""......q.. __ _ 

Date: -c~~-7':~-:::?-

Template version 08/2011 

DATA EV ALU A TI ON RECORD 

STUDY TYPE: Estrogen Receptor Transcriptional Activation (Human cell Line, HeLa-9903); 

OCSPP 890.1300; OECD 455. 

PC CODE: 059201 DP BARCODE: 0397165 

TXR#: 0056 199 CAS No.: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8% a.i.) 

SYNONYMS: 2-( dimethoxyphosphinothioylsulfanylmethyl)isoindole-1 ,3-dione; Imidan 

technical 

CITATION: Willoughby, J.A. Sr. (2011). Phosmet: Estrogen Receptor Transcriptional 

Activation (Human cell Line, HeLa-9903). CeeTox, Kalamazoo, Ml. Laboratory 

Study#: 9142V-l 00348ERT A, November 2, 2011. MRID 48618705. 

Unpublished. 

SPONSOR: Gowan, 370 Main Street, Yuma, AZ 85364 

TEST ORDER#: EDSP-059201-54 

EXECUTIVE SUMMARY: In an estrogen receptor transcriptional activation assay (ERTA; 

MRID 48618705) conducted by CeeTox, hERa.-HeLa-9903 cells cultured in vitro were exposed 

to phosmet (96.8% a.i., lot# GQH9 l 800) at concentrations increasing logarithmically from I 0-11 

to 10-4 M mg/mL in DMSO (0. 1 %) for approximately 24 hours. The assay was performed twice 

using 96-well plates and each phosmet concentration was tested in 6 wells/plate in each as·say. 

Cells were exposed to the phosmet for 24 ± 2 hours to induce reporter (luciferase) gene products. 

Luciferase expression in response to activation of the estrogen receptor by phosmet was 

measured using a proprietary CeeTox Standard Operating Protocol (SOP), which was not 

included in the report. 

Phosmet was tested up to the limit of cytotoxicity, 10-4 M. The mean RPCMax for phosmet was 

1.6-3.9%, the PCMax was 10·

7 Mand the PC10 could not be calculated as the RPCMax was less 

than 10%. Cytotoxicity of 20.1 % was observed in the highest concentration in the first run. A 

similar trend of cytotoxicity was observed in the second run, with the highest concentration 

having cell viability of only 81. 7%. 

In the main assays, the responsiveness of the cells to the very weak positive control 17a.-

methyltestosterone was lower than the expected values, indicating a decreased sensitivity of the 

assay to very weak agonists. The PC10 for 17a.-methyltestosterone should have been reached by 

Page 103 of 260
Estrogen Receptor Transcriptional Activation (2011) / Page 2 of 2 

PHOSMET /059201 OCSPP 890.1300/ OECD 455

10-6 M but its maximum RPC was 8.8%, at that concentration. A higher concentration (10-5 M) 

reached 47% RPC but in the presence of cytotoxicity. Cytotoxicity was also observed at the 

highest concentrations of 17α-estradiol and corticosterone. Although the conditions of this assay 

were not optimal to detect very weak activity, phosmet responses were similar to those of the 

negative control corticosterone and not comparable to the responses of 17α-methyltestosterone, 

which was able to reach a maximum of 6.8-8.8% PC. Phosmet was only able to reach a 

maximum of 1.6-3.9% PC when tested up to the highest concentration possible based on 

cytotoxicity. Because the RPCMax < PC10 in both assay runs, phosmet was considered negative 

for estrogen receptor transcriptional activation in this test system.

This assay satisfies the EDSP Tier 1 Test Order requirement for an Estrogen Receptor 

Transcriptional Activation assay (OCSPP 890.1300). 

COMPLIANCE: Signed and dated GLP, Quality Assurance and Data Confidentiality 

statements were provided. 

Page 104 of 260
Estrogen Receptor Transcriptional Activation (2011) / Page 3 of 9 

PHOSMET /059201 OCSPP 890.1300/ OECD 455

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Substance: Phosmet

Description: Technical, white crystalline solid, MW 317.32 g/mol

Source: Gowan Company (no catalog#)

Lot/Batch #: GQH91800; Exp 1/31/2013

Purity: 96.8%

Solubility: Not reported (NR)

Volatility: NR

Stability: NR

Storage conditions: Ambient

Vapor pressure: NR

CAS #: 732-11-6

Structure:

2. Reference substances

17β-estradiol (strong estrogen; positive control)

Supplier: NR

Catalogue and Batch #: NR

Purity: NR

CAS # : 50-28-2

17α-estradiol (weak estrogen)

Supplier: NR

Catalogue and Batch #: NR

Purity: NR

CAS # : 57-91-0

Corticosterone (negative compound)

Supplier: NR

Catalogue and Batch #: NR

Purity: NR

CAS # : 50-22-6

17α-methyltestosterone (very weak agonist)

Supplier: NR

Catalogue and Batch #: NR

Purity: NR

CAS # : 58-18-4

3. Vehicle(s)

Solvent: DMSO. Supplier, lot and purity not reported 

Solvent control 

(final concentration):

0.1%

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PHOSMET /059201 OCSPP 890.1300/ OECD 455

B. METHODS

1. Cell Culture: Stably-transfected hERα-HeLa-9903 cells were obtained from the Japanese 

Collection of Research Bioresources Cell Bank and were verified to be free of mycoplasma 

infection using DNA Fluorochrome analysis by Bionique Testing Laboratories. Cells were 

maintained in Eagles Minimum Essential Medium without phenol red, supplemented with 60 

mg/L kanamycin and 10% dextran-coated charcoal-treated fetal bovine serum (source not 

reported), in an incubator under 5% CO2 at 37oC. Cells used in the range-finding study 

(7/5/2011) were from Passage 21. For the main study new cells were brought up from 

cryopreservation and were Passages 19 and 20 for the experimental runs (8/23/2011 and 

8/25/2011). Upon reaching 75-90% confluence, cells were subcultured into test plates. 

2. Transcriptional Activation Assays: For each run, cells were plated in 96-well culture 

plates at a density of 1×104 cells/100 μL medium/well and allowed to attach for at least 3 

hours. The growth media was replaced with media containing serial log dilutions of phosmet 

in DMSO. Cells were incubated for 24 ± 2 hours at 37 ± 1°C. All concentrations were tested 

in replicates of 6/plate. Additionally, for each concentration 2 replicates/plate were prepared 

with hERα antagonist ICI 182,780 co-treatment, to allow for the identification of nonspecific induction of the luciferase gene. The total final concentration of DMSO was 0.1%. 

Transcriptional activation of the estrogen receptor was determined using a proprietary 

CeeTox SOP, which was not provided. A list of reagents was provided, but ingredients of 

the luciferase assay reagent were identified as proprietary information. 

a. Preliminary Test: A preliminary test evaluating concentrations ranging from10-6.5 to 10-3 M 

was conducted to determine the appropriate concentration range and to determine 

concentrations resulting in insolubility and/or cytotoxicity. Cytotoxicity was determined by a 

two-read propidium iodide (PI) uptake assay. Cells were seeded into black-walled 96-well 

plate and exposed to phosmet at logarithmic concentrations of 10-6.5 to 10-3 M; digitonin was 

also used as a positive control for cytotoxicity. Following exposure, growth medium was 

removed and cells were exposed to PI. Background-corrected fluorescence was calculated 

for each well. Limit of solubility was determined by visual inspection of the test materials 

and controls after preparation of the final 1X dosing solutions in culture media. A sample of 

the 1x dosing solution was placed into wells of a clear 96-well plate and an endoscope was 

used to assess precipitation. 

b. Proficiency Chemicals: Prior to testing unknown chemicals, each laboratory must confirm 

the responsiveness of the test system, at least once for each newly prepared batch of cell 

stocks taken from the frozen stock by independent testing of the 10 proficiency chemicals 

listed below. Proficiency records were not provided in the study report; however, proficiency 

data for the performing laboratory was submitted following a request by the Agency (MRID 

48843501). The responsiveness of the test system was evaluated on March 5, 2010 and April 

12 and April 28, 2011. Cells used for the proficiency tests were at passage 15, 25 and 28, 

respectively. It is not clear if the cells used in the proficiency tests are from the same frozen 

stock as cells used in the current assay. 

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Compound CAS No. Concentration

Range (M)

Expected

Response a Notes

Diethylstilbestrol (DES) 56-53-1 10−14 to 10−8 Positive ---

17α-Ethynyl estradiol (EE) 57-63-6 10−14 to 10−8 Positive ---

Hexestrol 84-16-2 10−13 to 10−7 Positive ---

Genistein 446-72-0 10−12 to 10−5 Positive Cytotoxic at 0.01b, 0.1, and 1 mM

Estrone 53-16-7 10−12 to 10−6 Positive ---

Butyl paraben 94-26-8 10−11 to 10−4 Positive Cytotoxic at 0.1b and 1 mM

1,3,5-Tris(4-

hydroxyphenyl)benzene c

15797-52-1 10−12 to 10−5 Positive Cytotoxic at 100 μM. PCmax approx. 50% 

PC. Binds hERα and has ER antagonistic 

activity

Dibutyl phthalate (DBP) 84-74-2 10−11 to 10−4 Negative d Cytotoxic at 1 mM

Atrazine 1912-24-9 10−11 to 10−4 Negative Cytotoxic at 1 mM b

Corticosterone 50-22-6 10−10 to 10−4 Negative If not cytotoxic at 1 mM, then that should be 

the highest tested concentration

a Positive = RPCMax ≥10% of the response of the positive control in at least 2 of 2 (or 2 of 3) runs

Negative = RPCMax fails to achieve at least 10% of the response of the positive control in 2 of 2 (or 2 of 3) runs

b Cytotoxicity is expected to be close to 80% at this concentration.

c Compound selected to challenge solubility and cytotoxicity

d DBP is negative for ERα mediated transcriptional activation, but may not be negative for non-ERβ mediated transcriptional 

activation. A positive result would indicate that the system is detecting activity other than that due to pure ERα, and is 

therefore unacceptable.

c. Reference Chemicals: To ensure the stability of the response from the cell line, six 

concentrations of each of the following reference chemicals were included in each plate in 

the current assay, along with the test chemical: 

Reference Chemical CAS No. Concentration Range Class

17β-estradiol 50-28-2 10-14 to 10-8 Strong estrogen

17α-estradiol 57-91-0 10-12 to 10-6 Weak estrogen

Corticosterone 50-22-6 10-10 to 10-4 Negative compound

17α-methyltestosterone 58-18-4 10-11 to 10-5 Very weak agonist

3. Data analysis: To obtain the transcriptional activity relative to 1 nM E2 positive control 

(PC), luminescence signals from the concurrent plate were analyzed by subtracting the mean 

vehicle control value from each well value to normalize the data. Normalized values were

then divided by the mean normalized PC value and multiplied by 100 to express relative 

transcriptional activity as a percentage of the PC (RPC) (software used to calculate RPCMax

not reported). The test material was defined as negative for inducing estrogen receptor 

transcriptional activation if the RPCMax < PC10 in 2 of 2 (or 2 of 3) runs. Log EC50 and Hill 

slop values are calculated only if a positive response is observed. Coefficients of variation 

(CV) were calculated for the luminescence data triplicates. Concentrations showing >20% 

cytotoxicity or evidence of insolubility were excluded from analyses. 

4. Definitions

EC50 = concentration of agonist that induces a response halfway between the baseline 

(bottom) and maximum (top) response 

PC10 = concentration of a test chemical at which the response is 10% of the response induced 

by the positive control (E2 at 1 nM) in each plate 

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Estrogen Receptor Transcriptional Activation (2011) / Page 6 of 9 

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PC50 = concentration of a test chemical at which the response is 50% of the response induced 

by the positive control (E2 at 1 nM) in each plate 

RPCMax = maximum level of response induced by a test chemical, expressed as a percentage 

of the response induced by the positive control (1 nM E2) on the same plate 

PCMax = concentration of a test chemical inducing the RPCMax

II. RESULTS

A. PRELIMINARY TEST: Percent cell viability is reported in Table 1. Cytotoxicity was 

observed with phosmet at 10-3 M in the rangefinder (7/5/2011). Based on these results,

logarithmic concentrations of phosmet from 10-11 to 10-4 M were selected for the assay. 

However, cytotoxicity was observed at 10-4 M in the first run (8/23/2011) only. 

TABLE 1. Preliminary Test for Solubility, Cytotoxicity, and Concentration-Selection for Phosmeta

Concentration (M) % Viability Comments

10-6.5 104

10-6 101

10-5.5 100

10-5 96

10-4.5 98

10-4 86

10-3.5 80

10-3 15 Cytotoxicity of >20% was observed

E2 1nM NR

VC NR

a Data were obtained from page 19 of the study report.

VC = Vehicle control

B. Positive and Negative Reference Chemicals

1. Proficiency Chemicals: Responsiveness of cells to proficiency chemicals was tested in 

duplicate on different days. Results are reported in Table 2. In general, the responses 

demonstrate proficiency; however some deviations from validated ranges were noted. Mean 

activity of the PC (1 nM 17β-estradiol) was > 4-fold VC activity on each plate, for all runs. 

The reference compounds 17β-estradiol, 17α-estradiol and 17α-methyltestosterone were 

within the acceptable ranges with a few exceptions in runs 1 and 3, as noted in Appendix 1. 

TABLE 2. Proficiency Chemicals a

Compound Expected Response Lab Response

Diethylstilbestrol Positive Positive

17α-Ethynyl estradiol Positive Positive

Hexestrol Positive Positive

Genistein Positive Positive

Estrone Positive Positive

Butyl paraben Positive Positive

1, 3, 5-Tris(4-hydroxyphenyl)benzene Positive Positive

Dibutyl phthalate Negative Negative

Atrazine Negative Negative

Corticosterone Negative Negative

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2. Reference Chemicals: Values derived from the concentration response curve (e.g., log

PC50, log PC10, log EC50, Hill slope) for the four concurrently run reference materials are 

included in Table 3. The transcriptional responsiveness of 17α-estradiol and 17β-estradiol 

were within the acceptable range. The log PC50 and log PC 10 for the very weak agonist 17αmethyltestosterone were not reported. The study author indicated that the PC10 was not 

reached due to cytotoxicity at the highest concentration. Inspection of the raw data by the 

reviewer indicated that 17α-methyltestosterone did not attain transcriptional activation equal 

to 10% of the positive control; therefore a PC10 or PC 50 could not be calculated. A doseresponsive trend was observed starting at approximately at 10-8 M. Maximum RPC of 17αmethyltestosterone was 8.8% at 10-6 M, and cytotoxicity occurred at the next higher 

concentration tested (10-5 M testosterone) in both experimental runs. 

TABLE 3. Performance Criteria for Reference Chemicalsa

Reference Chemical 

Parameter

Acceptable Range Values Acceptable

Run 1 Run 2 Yes No

17β-estradiol

Log PC50 -11.4 to -10.1 -10.3 -10.4 X

Log PC10 <-11 -11.5 -11.3 X

Log EC50 -11.3 to -10.1 -10.3 -10.3 X

Hill Slope 0.7 to 1.5 0.9 1.2 X

Test range 10-14 to 10-8 M 10-15 to 10-8 M 10-15 to 10-8 M X

17α-estradiol

Log PC50 -9.6 to -8.1 -8.5 -8.6 X

Log PC10 -10.7 to -9.3 -9.6 -9.6 X

Log EC50 -9.6 to -8.4 -8.5 -8.6 X

Hill Slope 0.9 to 2.0 1.2 1.4 X

Test range 10-12 to 10-6 M 10-13 to 10-6 M 10-13 to 10-6 M X

Corticosterone

Test range 10-10 to 10-4 M 10-11 to 10-4 M 10-11 to 10-4 M X

17α-methyltestosterone

Log PC50 -6.0 to -5.1 NC NC X

Log PC10 -8.0 to -6.2 NC NC X

Test range 10-11 to 10-5 M 10-12 to 10-5 M 10-12 to 10-5 M X

a Data were obtained from pages 11 and 22 of the study report. 

NC = not calculated

C. DEFINITIVE ASSAY

1. Vehicle and Positive Controls: Data for the vehicle and positive controls are included in 

Table 4. The overall mean response values (Light units) for the vehicle control were 10892 

for the first run and 9933 for the second run. The mean normalized value for the positive 

control was 253542 for the first run and 167033 for the second run. Light units 

corresponding to the PC50 (50% of the maximum response) for E2 in this assay is 132217 for 

the first run and 88483 for the second run; the PC10 (10% of the maximum response) is 

35157 for the first run and 25643 for the second run.

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

Sample Vehicle Control Positive Control b

Runs Mean SD Mean SD Fold Induction c 

1 10892 2749 253542 142342 23

2 9933 1246 167033 34868 17

a Data were obtained from pages 30 and 31 of the study report. Values were calculated by the reviewer. 

b Positive control was 17β-estradiol (E2) at 1 nM.

c Fold-induction = (mean TA of PC)/(mean TA of VC)

2. Test Material: Relative (to the PC) transcriptional activation at each concentration of 

phosmet during the two assay runs is presented in Table 5. The concentration-response 

curves depicting fold induction of relative transcriptional activation is presented in Figure 1 

below. The mean RPCMax for phosmet was 1.6% for the first run and 3.9% for the second 

run, and the associated PCMax was 10-7 M. Cytotoxicity of 20.1% was observed in the 

highest concentration in the first run, and a similar trend of cytotoxicity (18.3%) was 

observed in the second run at the highest concentration. 

Due to the failed responsiveness of these cells to the very weak agonist 17αmethyltestosterone, the possibility that phosmet is a very weak estrogen agonist could not be 

evaluated

TABLE 5. Relative Transcriptional Activation (RTA) of Phosmeta 

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

Run 1 Run 2

Conc. (M) Mean SD Mean SD

10-4 --b --b 2.6 0.9

10-5 0.5 0.8 2.5 1.2

10-6 1.6 0.8 3.0 1.2

10-7 1.6 0.8 3.9 0.8

10-8 -0.1 0.8 1.7 1.0

10-9 0.8 1.0 1.4 1.3

10-10 -0.1 0.7 0.9 1.2

10-11 0.0 1.8 0.8 1.1

Log EC50 NA NA

Hill Slope NA NA

RPCMax 1.6% 3.9%

PCMax 10-6 - 10-7 10-7

PC50 NA NA

PC10 NA NA

a Data were obtained from pages 20 and 21 of the study report. 

b Not reported due to cytotoxicity >20%

NA= Not Applicable

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FIGURE 1. Fold Induction of Relative Transcription Activation (RTA) of phosmet compared to the 

Positive Control.

VC= Vehicle Control

PC= Positive Control (1 nM E2)

3. Performance Criteria: Proficiency chemicals were tested in duplicate on different days, 

with appropriate responses (Table 2). The transcriptional responsiveness of 17α-estradiol 

and 17β-estradiol were within the acceptable range. However, 17α-methyltestosterone did 

not induce transcriptional activation equal to 50% or 10% of the positive control; therefore a 

PC10 and PC 50 could not be calculated for this very weak agonist. Based on calculations 

conducted by the reviewer on the raw data provided, the fold-induction corresponding to 

PC10 of concurrent PC was greater than 1+2 standard deviations of the fold-induction value 

of the concurrent VC as expected. The CV of the luminescence data was not reported. 

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III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS’ CONCLUSIONS: The suitable top concentration of phosmet for use 

in the transcriptional activation assays was 10-4 M. Cytotoxicity was observed in the highest 

concentration tested (10-3 M) in the range finding test and at 10-4 M in the first valid run. 

Cytotoxicity was <20% at all of the exposure concentrations tested in the second valid run. 

Phosmet did not result in in an increase in luciferase activity at any of the viable 

concentrations tested in either run; phosmet is not an agonist of hERα in the HeLa-9903 

model system. 

B. AGENCY COMMENTS: Phosmet was tested up to the limit of cytotoxicity, 10-4 M. 

Cytotoxicity of 20.1% was observed in the highest concentration in the first run. A similar 

trend of cytotoxicity was observed in the second run, with the highest concentration having 

cell viability of only 81.7%. 

The mean RPCMax for phosmet was 1.6-3.9%, the PCMax was 10-7 M and the PC 10 could not 

be calculated as the RPCMax was less than 10%. 

Although the conditions of this assay were not optimal to detect very weak activity, phosmet 

responses were similar to those of the negative control corticosterone and not comparable to 

the responses of 17α-methyltestosterone, which was able to reach a maximum of 6.8-8.8% 

PC. Phosmet was only able to reach a maximum of 1.6-3.9% PC when tested up to the 

highest concentration possible based on cytotoxicity. Because the RPCMax < PC10 in both 

assay runs, phosmet was considered negative for estrogen receptor transcriptional activation 

in this test system.

C. STUDY DEFICIENCIES: The following deficiencies were noted: 

• 17α-methyltestosterone did not induced transcriptional activation equal to 50% or 10% of 

the positive control; therefore a PC10 and PC50 could not be calculated. 

• Cytotoxicity observed at the highest concentrations of 17α-estradiol, 17αmethyltestosterone and corticosterone. 

• The source for the fetal bovine serum was not provided. 

Page 112 of 260
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APPENDIX 1. Performance Criteria for Reference Chemicals in Proficiency 

Test (MRID 48843501)

Reference Chemical 

 Parameter Acceptable Range Values Acceptable

Run 1 Run 2 Run 3 Yes No

PC Fold Induction 21.1-24.6 75.1-84.7 17.9-20.2

17β-estradiol

Log PC50 −11.4 to −10.1 -9.6 -11.3 -10.6 Run 1

Log PC10 <−11 -11.5 -12.5 -12.1 Run 1

Log EC50 −11.3 to −10.1 -9.0 -11.3 -10.6 Run 1

Hill Slope 0.7 to 1.5 1.2 0.9 0.8 X

Test range 10−14 to 10−8 M 10-13 to 10-7 10-15 to 10-7 M 10-15 to 10-7 M Run 1

17α-estradiol

Log PC50 −9.6 to −8.1 -8.3 -9.4 -8.7 X

Log PC10 −10.7 to −9.3 -9.3 -10.5 -9.9 X

Log EC50 −9.6 to −8.4 -8.2 -9.3 -8.9 Run 1

Hill Slope 0.9 to 2.0 0.9 0.9 2.9 Run 3

Test range 10−12 to 10−6 M 10-15 to 10-7 M 10-13 to 10-5 M 10-13 to 10-5 M Run 1

17α-methyltestosterone

Log PC50 −6.0 to −5.1 -6.2 NR -5.2 Run 1,2

Log PC10 −8.0 to −6.2 -8.1 -6.3 -7.7 Run 1

Log EC50 NA -6.2 NR -5.1 NA

Hill Slope NA 0.7 0.3 0.4 NA

Test range 10−11 to 10−5 M 10-12 to 10-4 M 10-12 to 10-4 M 10-12 to 10-4 M X

NA = not applicable

NR = not reported

Page 113 of 260
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ԭՁՅԽՈՀԹՄԽՋ ՈՊՇՅԽՄԹՋ ՏԹՋ

ԻՇՆԼՍԻՌԽԼ ՍՆԼԽՊԾՄՇՏՌՀՊՇՍԿՀ ԻՇՆԼՁՌՁՇՆՋ԰ՁՐՌԽԽՆ ԿՊՇՍՈՋ ՇԾ ՅՇՆՌՀ ՇՄԼԾՁՋՀ 
ՅԹՄԽՋ ԹՆԼ ԾԽՅԹՄԽՋ ՈԽՊ

ԿՊՇՍՈ  ԿՊՇՍՈՋ ՈԽՊ ՌՊԽԹՌՅԽՆՌ ՏԽՊԽ ԽՐՈՇՋԽԼ ՌՇ ՈՀՇՋՅԽՌ 
 ՈՍՊՁՌՑ ԹՌ ՆՇՅՁՆԹՄ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՇԾ 


ԻՇՆՌՊՇՄ   ԹՆԼ  ՅԿ ԹՁԩ ՅԽԹՆՅԽԹՋՍՊԽԼ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՏԽՊԽ ԩԬԮ 


ԹՆԼՅԿԹՁԩԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋՅԹՁՆՌԹՁՆԽԼԹՌՌՇՇ

ԠԹՆԼԹՈԥՇԾՌՇ



԰ՍՊՎՁՎԹՄՏԹՋ ՄՇՏ ԹՌՌՀԽ ՀՁԿՀՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ 
ՏՁՌՀ ՇՆՄՑ ՇՆԽՅԹՄԽ ԹՆԼ ՇՆԽԾԽՅԹՄԽ ՋՍՊՎՁՎՁՆԿՌՇ ՋՌՍԼՑ

ՌԽՊՅՁՆԹՌՁՇՆԽՆԼՈՇՁՆՌՋԹՌՌՀՁՋՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏԽՊԽՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼՇՊՁՆԻՄՍԼԽԼՁՆՌՀԽՊԽՋՍՄՌՋԞՌՌՀԽ

ՁՆՌԽՊՅԽԼՁԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆՌՀԽՊԽՏԹՋԹԼԽԻՊԽԹՋԽՁՆՋՍՊՎՁՎԹՄԻՇՅՈԹՊԽԼՌՇԻՇՆՌՊՇՄԹՆԼԿԽՆԽՊԹՄՁՒԽԼՇՎԽՊՌ

ՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑՁՆԺՇՌՀՅԹՄԽՋԹՆԼԾԽՅԹՄԽՋՁՆԻՄՍԼՁՆԿՄԽՌՀԹՊԿՑՁՆԹՄՄՋՍՊՎՁՎՁՆԿԾՁՋՀԹՆԼՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅՁՆ

ԾԽՅԹՄԽՋԞՌՌՀԽՄՇՏԻՇՆԻԽՆՌՊԹՌՁՇՆՋՍՊՎՁՎԹՄՏԹՋՊԽԼՍԻԽԼԺՑԻՇՅՈԹՊԽԼՌՇԻՇՆՌՊՇՄԟՇԼՑՏԽՁԿՀՌԹՆԼՄԽՆԿՌՀ

ՏԽՊԽՆՇՌՋՁԿՆՁԾՁԻԹՆՌՄՑԼՁԾԾԽՊԽՆՌՁՆՅԹՄԽՇՊԾԽՅԹՄԽԾՁՋՀԹՌԹՆՑՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԦՆՌՀԽԻՇՆՌՊՇՄԿՊՇՍՈՋՈԹՏՆՁՆԿՇԻԻՍՊՊԽԼԹՌՄԽԹՋՌԽՎԽՊՑԼԹՑՋՁՆՌՏՇՇԾՌՀԽԾՇՍՊՊԽՈՄՁԻԹՌԽՋԹՆԼԾԽԻՍՆԼՁՌՑՏԹՋ

 ԽԿԿՋԾԽՅԹՄԽԼԹՑՊԽՈՄՁԻԹՌԽ ԾԽԻՍՆԼՁՌՑ ՏԹՋ  ԽԿԿՋԾԽՅԹՄԽԼԹՑ ԾՇՊ ՌՀՊԽԽ ՊԽՈՄՁԻԹՌԽՋ ԹՆԼ 

ԽԿԿՋԾԽՅԹՄԽԼԹՑ ԾՇՊ ՇՆԽ ՊԽՈՄՁԻԹՌԽ ԣԽՊՌՁՄՁՒԹՌՁՇՆ ՋՍԻԻԽՋՋ ՁՆ ՌՀԽ ԻՇՆՌՊՇՄ ԿՊՇՍՈ ԹՎԽՊԹԿԽԼ  ԞՌ ՌՀԽ

ՁՆՌԽՊՅԽԼՁԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆՈՀՇՋՅԽՌՋՁԿՆՁԾՁԻԹՆՌՄՑ ՊԽԼՍԻԽԼԾԽՊՌՁՄՁՌՑ
ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՈԺՑԹՆԼ

ԾԽԻՍՆԼՁՌՑ
ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՈԺՑԻՇՅՈԹՊԽԼՌՇՌՀԽԻՇՆՌՊՇՄ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԣԽՅԹՄԽ ԿՇՆԹԼՇՋՇՅԹՌՁԻ ՁՆԼԽՐ 
Ԥ԰Ԧ ՏԹՋ ՋՁԿՆՁԾՁԻԹՆՌՄՑ ՊԽԼՍԻԽԼ ԺՑ  ԹՌ ՌՀԽ ՁՆՌԽՊՅԽԼՁԹՌԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆ


ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ Ո ՊԽՄԹՌՁՎԽ ՌՇ ԻՇՆՌՊՇՄ ՅԹՄԽ Ԥ԰Ԧ ՏԹՋ ՍՆԹԾԾԽԻՌԽԼ ԺՑ ՈՀՇՋՅԽՌ ՌՊԽԹՌՅԽՆՌ


Ո ԴՀՁՄԽ ՆՇՌ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌ 
ԪԹՆՆԴՀՁՌՆԽՑ Ո ՅԽԼՁԹՆ ՅԹՄԽ ՆՍՈՌՁԹՄ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽՋ

ՏԽՊԽՊԽԼՍԻԽԼԺՑԹՌՌՀԽՁՆՌԽՊՅԽԼՁԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆԻՇՅՈԹՊԽԼՌՇՌՀԽԻՇՆՌՊՇՄՆՇՌՍԺԽՊԻՄԽՋՏԽՊԽՇԺՋԽՊՎԽԼ

ԾՇՊ ԾԽՅԹՄԽՋ ԪԹՄԽ ԹՆԼ ԾԽՅԹՄԽ ՎՁՌԽՄՄՇԿԽՆՁՆ 
ԳԱԤ ՄԽՎԽՄՋ ՏԽՊԽ ՆՇՌ ՋՁԿՆՁԾՁԻԹՆՌՄՑ ԼՁԾԾԽՊԽՆՌ ԾՊՇՅ ՌՀԽ ԻՇՆՌՊՇՄ

ԹՄՌՀՇՍԿՀՌՀԽՊԽՏԹՋԹՆԹՈՈԹՊԽՆՌՁՆԻՊԽԹՋԽՁՆՅԹՄԽԳԱԤԹՌՌՀԽՁՆՌԽՊՅԽԼՁԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆԼՍԽՋՇՄԽՄՑՌՇ

ՀՁԿՀՄԽՎԽՄՋՁՆՌՏՇՅԹՄԽՋՁՆՌՀՁՋԿՊՇՍՈԭՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋՏԽՊԽՆՇՌՅԽԹՋՍՊԽԼ

ԤՇՆԹԼԹՄՋՌԹԿՁՆԿԽԾԾԽԻՌՋՏԽՊԽՁՆԼՁԻԹՌԽԼԾՇՊԾԽՅԹՄԽԾՁՋՀԹՌՌՀԽՄՇՏՌՊԽԹՌՅԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆԹՆԼԾՇՊՅԹՄԽՋԹՆԼ

ԾԽՅԹՄԽՋ ԹՌ ՌՀԽ ՁՆՌԽՊՅԽԼՁԹՌԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ԢԾԾԽԻՌՋ ՇՆ ԿՇՆԹԼԹՄ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ ՁՆ ՅԹՄԽ ԾՁՋՀ ՁՆԻՄՍԼԽԼ ԹՆ

ՁՆԻՊԽԹՋԽԼՈԽՊԻԽՆՌԹԿԽՇԾՋՈԽՊՅԹՌՇԿՇՆՁԹ
ԹՆԼՅՁՄԼԼՁԾԾՍՋԽՌՀՁԻՃԽՆՁՆԿՇԾՌՀԽԿԽՊՅՁՆԹՄԽՈՁՌՀԽՄՁՍՅՄՁՆՁՆԿԺՑ

ՋՈԽՊՅԹՌՇԿՇՆՁԹԹՌՌՀԽՁՆՌԽՊՅԽԼՁԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆԾԽՅԹՄԽԾՁՋՀՁՆԻՁԼԽՆԻԽՋՇԾԼԽԻՊԽԹՋԽԼՑՇՄՃՋՑՆՌՀԽՋՁՋՏԽՊԽ

ՇԺՋԽՊՎԽԼ ԹՌ ԺՇՌՀ ՄՇՏ 
 ԹՆԼ ՁՆՌԽՊՅԽԼՁԹՌԽ 
 ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՊԽՄԹՌՁՎԽ ՌՇ ՌՀԽ ԻՇՆՌՊՇՄՋ 


ԬԻԻԹՋՁՇՆԹՄ ԼՁՋՊՍՈՌՁՇՆՋ ՇԾ ԳԱԤ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՏԽՊԽ ՆՇՌԽԼ ՁՆ ՌՀԽ ԾՇՄՄՁԻՄԽՋ ՇԾ ՋՇՅԽ ԾԽՅԹՄԽՋ ԹՆԼ ՅՁՆՁՅԹՄ

ՁՆՌԽՊՋՌՁՌՁԹՄԾՁԺՊՇՋՁՋՏԹՋՇԺՋԽՊՎԽԼԹՌՌՀԽՁՆՌԽՊՅԽԼՁԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆԦՆԹԼԼՁՌՁՇՆՁՆԻՁԼԽՆԻԽՋՇԾՁՆԻՊԽԹՋԽԼՇՇԻՑՌԽ

ԹՌՊԽՋՁԹՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՏՁՌՀԹՆԼՇԾՌՀԽԾՁՋՀԽՐՀՁԺՁՌՁՆԿ

ՌՀՁՋԾՁՆԼՁՆԿՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼՄՇՏԹՆԼՅՁԼՌՊԽԹՌՅԽՆՌՋ ՊԽՋՈԽԻՌՁՎԽՄՑԦՆՇԾՌՀԽՋԽԻԹՋԽՋԿՊԹՆՍՄՇՅԹՌՇՍՋ

ՁՆԾՄԹՅՅԹՌՁՇՆՏԹՋՇԺՋԽՊՎԽԼԽՎՁԼԽՆԻԽՇԾՅՁԻՊՇՋՈՇՊՁԼՁԹՁՆԾԽԻՌՁՇՆՏԹՋԹՄՋՇՇԺՋԽՊՎԽԼ

ԦՆՋՍՅՅԹՊՑԹՌՌՀԽՅՁԼԻՇՆԻԽՆՌՊԹՌՁՇՆԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՒԹՌՁՇՆԹՆԼԾԽՅԹՄԽՏԽՊԽԤ԰ԦՏԽՊԽԼԽԻՊԽԹՋԽԼԻՇՅՈԹՊԽԼ

ՌՇԻՇՆՌՊՇՄՋԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑՏԹՋԹԾԾԽԻՌԽԼԹՋՋՀՇՏՆԺՑԼԽԻՊԽԹՋԽԼՑՇՄՃՋՑՆՌՀԽՋՁՋՁՆՌՀԽՄՇՏԹՆԼՅՁԼ

ԻՇՆԻԽՆՌՊԹՌՁՇՆ ԾԽՅԹՄԽՋ ԹՆԼ ՇԻԻԹՋՁՇՆԹՄ ԼՁՋՊՍՈՌՁՇՆՋ ՇԾ ԾՇՄՄՁԻՍՄԹՊ ԳԱԤ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ԱՀԽ ՈՊՇՈՇՊՌՁՇՆ ՇԾ

ՋՈԽՊՅԹՌՇԿՇՆՁԹ ՁՆ ՌՀԽ ՌԽՋՌԽՋ ՏԹՋ ՁՆԻՊԽԹՋԽԼ ԹՌ ՌՀԽ ՀՁԿՀ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ԥՁԿՀ ՅՇՊՌԹՄՁՌՑ ԹՆԼ ԻՄՁՆՁԻԹՄ ՋՁԿՆՋ ՇԾ

ՌՇՐՁԻՁՌՑՁՆՌՀՁՋՋՌՍԼՑՅԹՑԻՇՆԾՇՍՆԼՌՀԽՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽՋԽՈԹՊԹՅԽՌԽՊՋ

ԞՄՄ ՌՀԽ ՈԽՊԾՇՊՅԹՆԻԽ ԹՆԼ ՎԹՄՁԼՁՌՑ ԻՊՁՌԽՊՁԹ ՏԽՊԽ ՅԽՌ ԾՇՊ ՌՀՁՋ ՋՌՍԼՑ ԽՐԻԽՈՌ ԾՇՊ ՇՆԽ ԣՇՊ ՇՆԽ ՊԽՈՄՁԻԹՌԽ ՁՆ ՌՀԽ

ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ ՌՀԽ ԾԽԻՍՆԼՁՌՑ ՏԹՋ  ԽԿԿՋԾԽՅԹՄԽԼԹՑ ԹՆԼ ՁՌ ԼՁԼ ՆՇՌ ՋՈԹՏՆ ԹՌ ՄԽԹՋՌ ԽՎԽՊՑ  ԼԹՑՋ

ՅԽԽՌՁՆԿ ՇՆԽ ՇԾ ՌՀԽՋԽ ԻՊՁՌԽՊՁԹ ՁՋ ՍՋԽԼ ՌՇ ԼԽՅՇՆՋՌՊԹՌԽ ԹԻՌՁՎԽ ՋՈԹՏՆՁՆԿ ԞՄՌՀՇՍԿՀ ՆՇՌ Թ ՎԹՄՁԼՁՌՑ ԻՊՁՌԽՊՁԹ ՌՀԽ

ԽՆԼՈՇՁՆՌՋ ԹՌ ՌՀԽ ՀՁԿՀ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ 
 ՅԿ ԹՁԩ ՏԽՊԽ ՆՇՌ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ԹՆԹՄՑՒԽԼ ԼՍԽ ՌՇ ՅՇՊՌԹՄՁՌՑ


ԱՀԽՊԽԾՇՊԽՇՆՄՑՌԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՏԽՊԽԹՆԹՄՑՒԽԼՁՆՌՀՁՋՋՌՍԼՑԞԼԼՁՌՁՇՆԹՄՄՑՌՀԽՋՍՊՎՁՎԹՄ ՊԹՌԽՁՆ

ՌՀԽ ՄՇՏԽՋՌ ՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈ ՏԹՋ  ԹՆԼ ՁՆ ՇՆԽ ՊԽՈՄՁԻԹՌԽ ՌՀՊԽԽ ՇԾ ՌՀԽ ԾՇՍՊ ԹՎԹՁՄԹԺՄԽ ԾԽՅԹՄԽՋ ԼՁԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԽՋՋԽՆՌՁԹՄՄՑՄԽԹՎՁՆԿՇՆՄՑՌՀՊԽԽՎՁԹԺՄԽՊԽՈՄՁԻԹՌԽՋՁՆՌՀԽՄՇՏԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԹՎԹՁՄԹԺՄԽԾՇՊԹՆԹՄՑՋՁՋՁՆՌԽՊՈՊԽՌԹՌՁՇՆ

ԞՄՌՀՇՍԿՀ ՁՆԼՁՎՁԼՍԹՄՋ ԼՁՋՈՄԹՑՁՆԿ ԻՄՁՆՁԻԹՄ ՋՁԿՆՋ ՇԾ ՌՇՐՁԻՁՌՑ ՏԽՊԽ ՆՇՌ ԽՐԻՄՍԼԽԼ ԾՊՇՅ ՋՌԹՌՁՋՌՁԻԹՄ ԹՆԹՄՑՋԽՋ ՌՀԽ

ՈՊԽՋԽՆԻԽՇԾՌՀԽՋԽԻՄՁՆՁԻԹՄՋՁԿՆՋԹՄՇՆԿՏՁՌՀՌՀԽՀՁԿՀՊԹՌԽՇԾՁՆԻՊԽԹՋԽԼՇՇԻՑՌԽԹՌՊԽՋՁԹՁՆՌՀԽԻՇՆՌՊՇՄՋՅԹՃԽՋՁՌ

ՅՇՊԽԼՁԾԾՁԻՍՄՌՌՇՁՆՌԽՊՈՊԽՌՌՀԽՊԽՋՍՄՌՋՇԾՌՀԽՋՌՍԼՑ

ԞՄՌՀՇՍԿՀՌՀԽՅՇՊՌԹՄՁՌՑՁՆՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄԻՄՁՆՁԻԹՄՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑՁՆՌՀԽՁՆՌԽՊՅԽԼՁԹՌԽՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԹՆԼ ՆՇՌԽՏՇՊՌՀՑ ՊԹՌԽ ՇԾ ՇՇԻՑՌԽ ԹՌՊԽՋՁԹ ՁՆ ԻՇՆՌՊՇՄ ԾԽՅԹՄԽՋ ՅԹՃԽ ՌՀԽ ՊԽՋՍՄՌՋ ԼՁԾԾՁԻՍՄՌ ՌՇ ՁՆՌԽՊՈՊԽՌ ՏՀԽՆ

ԻՇՆՋՁԼԽՊԽԼՁՆԻՇՆՌԽՐՌՇԾՇՌՀԽՊԹՎԹՁՄԹԺՄԽԱՁԽՊԢԡ԰ԭԼԹՌԹԾՇՊՈՀՇՋՅԽՌՌՀՁՋՋՌՍԼՑՋԹՌՁՋԾՁԽՋՌՀԽԢԡ԰ԭԱՁԽՊ

ԱԽՋՌԬՊԼԽՊՊԽՉՍՁՊԽՅԽՆՌԾՇՊԹԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌԬՊԿԹՆՁՋՅԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՅՇՆՌՀՋ

ԪԽԹՆԺՇԼՑՏԽՁԿՀՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՅԽԹՋՍՊԽԼԪԹՄԽԿԾԽՅԹՄԽԿ

ԪԽԹՆՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՅԽԹՋՍՊԽԼԫՇՌՊԽՈՇՊՌԽԼ



ԱԽՋՌԱՑՈԽ
ԣՄՇՏՌՀՊՇՍԿՀ԰ՌԹՌՁԻ԰ՌԹՌՁԻԯԽՆԽՏԹՄԣՄՇՏՌՀՊՇՍԿՀ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢԾԾԽԻՌՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ


ԣ԰ԱԯԞՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԣԽԻՍՆԼՁՌՑ

ԣԽՊՌ

԰ՍԻԻԽՋՋ

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ Ԥ԰Ԧ ԤՇՆԹԼԹՄԥՁՋՌՇ ԭՄԹՋՅԹԳԱԤ

Ԫ ԣ Ԫ ԣ Ԫ ԣ Ԫ ԣ

 ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԶԽՋ ԫՇ ԫՇ

 ԶԽՋ ԶԽՋ ԫՇ ԫՇ ԫՇ ԶԽՋ ԶԽՋ ԶԽՋ ԫՇ ԫՇ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԠՇՆԻԠՇՆԻԽՆՌՊԹՌՁՇՆԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԣԣԽՅԹՄԽԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ

԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑ

ԪԪԹՄԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱ

ԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ



 Ԟ՟ՑԽՋՠՁՆԼՁԻԹՌԽՋԹՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄՍՆՄԽՋՋ

ՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼ



 ԱՀԽԻՊՁՌԽՊՁԹԾՇՊՋՁԿՆՁԾՁԻԹՆԻԽԹՊԽԼԽՋԻՊՁԺԽԼՁՆՌՀԽԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼ԰ՌԹՌՁՋՌՁԻԹՄԳԽՊՁԾՁԻԹՌՁՇՆՋԽԻՌՁՇՆՋՇԾ

ՌՀԽԡԢԯԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼ

ԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՀՁԿՀՅՇՊՌԹՄՁՌՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԦԪԞԱԢԯԦԞԩ԰ԞԫԡԪԢԱԥԬԡ԰

ԤԲԦԡԢԩԦԫԢԣԬԩԩԬԴԢԡ  ԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼԹԻԻՇՊԼՁՆԿՌՇՌՀԽԲ԰ԢԭԞԬԠ԰ԭԭ

՟ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՎԽԞՋՋԹՑՠԹՆԼԬԢԠԡ


ԱՀԽԾՇՄՄՇՏՁՆԿԼԽՎՁԹՌՁՇՆՋՏԽՊԽՆՇՌԽԼ



 ԱՀԽ ԾԽԻՍՆԼՁՌՑ ՁՆ ՇՆԽ ՊԽՈՄՁԻԹՌԽ ՇԾ ՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ ՏԹՋ 

ԽԿԿՋԾԽՅԹՄԽԼԹՑ ՆՇՊ ԼՁԼՌՀԽ ՊԽՈՄՁԻԹՌԽ ՋՈԹՏՆ ԹՌ ՄԽԹՋՌ ԽՎԽՊՑ  ԼԹՑՋ ԪԽԽՌՁՆԿ

ՇՆԽՇԾՌՀԽՋԽԻՊՁՌԽՊՁԹՁՋՆԽԽԼԽԼՌՇԼԽՅՇՆՋՌՊԹՌԽԹԻՌՁՎԽՋՈԹՏՆՁՆԿ

 ԱՀԽ ԽՆԼՈՇՁՆՌՋ ԹՌ ՌՀԽ ՀՁԿՀ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ 
 ՅԿ ԹՁԩ ՏԽՊԽ ՆՇՌ

ՋՌԹՌՁՋՌՁԻԹՄՄՑ ԹՆԹՄՑՒԽԼ ԼՍԽՌՇՅՇՊՌԹՄՁՌՑ ՇՆՄՑ ՇՆԽՅԹՄԽ ԹՆԼ ՇՆԽԾԽՅԹՄԽՋՍՊՎՁՎԽԼ

ԹՌ ՋՌՍԼՑ ՌԽՊՅՁՆԹՌՁՇՆ ԞՄՋՇ ԻՄՁՆՁԻԹՄ ՋՁԿՆՋ ՇԾ ՌՇՐՁԻՁՌՑ ԹՌ ՌՀԽ  ՅԿ ԹՁԩ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՅԹՃԽՊԽՋՍՄՌՋԹՌՌՀՁՋՌՊԽԹՌՅԽՆՌՄԽՎԽՄԼՁԾԾՁԻՍՄՌՌՇՁՆՌԽՊՈՊԽՌ

 ԱՀԽՈՀՑՋՁԻՇԻՀԽՅՁԻԹՄՈՊՇՈԽՊՌՁԽՋՇԾՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ

 ԱՀԽ ՍՆՁՇՆՁՒԽԼ ԹՅՅՇՆՁԹ ԹՆԼ ՊԽՋՁԼՍԹՄ ԻՀՄՇՊՁՆԽ ՁՆ ՌՀԽ ՌԽՋՌ ՏԹՌԽՊ ՏԽՊԽ ՆՇՌ

ՊԽՈՇՊՌԽԼԱՀԽԬԠ԰ԭԭՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԽՋՌԹԺՄՁՋՀՅԹՐՁՅՍՅՄԽՎԽՄՋ

ԾՇՊ ՌՀԽՋԽ ՎԹՄՍԽՋ ԹՆԼ ՁՌ ՁՋ ՍՆԻՄԽԹՊ ՁԾ ՌՀԽ ՅԹՐՁՅՍՅ ՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋ ՏԽՊԽ

ԽՐԻԽԽԼԽԼ

ԱՀԽՀՁԿՀՁՆԻՁԼԽՆԻԽՇԾՅՇՊՌԹՄՁՌՑԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋՅԹՃԽՌՀԽՊԽՋՍՄՌՋՇԾՌՀՁՋՋՌՍԼՑԼՁԾԾՁԻՍՄՌՌՇՁՆՌԽՊՈՊԽՌ

ԥՇՏԽՎԽՊԾԽՏԽԾԾԽԻՌՋՏԽՊԽՋԽԽՆՁՆՌՀԽԹԺՋԽՆԻԽՇԾՇՎԽՊՌՌՇՐՁԻՁՌՑՁՆՌՀԽԹՎԹՁՄԹԺՄԽՊԽՈՄՁԻԹՌԽՋՇԾՌՀԽՄՇՏ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄԹՆԼՁՌՁՋԻՇՆՋՁԼԽՊԽԼՍՆՄՁՃԽՄՑՌՀԹՌՊԽՈԽՌՁՌՁՇՆՇԾՌՀԽՋՌՍԼՑԹՌՄՇՏԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՏՇՍՄԼՑՁԽՄԼ

ՋՌՊՇՆԿԽՊՊԽՋՍՄՌՋ

 ԠԬԪԭԩԦԞԫԠԢ   ԰ՁԿՆԽԼ ԹՆԼ ԼԹՌԽԼ Ԥԩԭ ԮՍԹՄՁՌՑ ԞՋՋՍՊԹՆԻԽ ԹՆԼ ԡԹՌԹ ԠՇՆԾՁԼԽՆՌՁԹՄՁՌՑ ԻՄԹՁՅՋ

ՋՌԹՌԽՅԽՆՌՋՏԽՊԽ ՈՊՇՎՁԼԽԼ ԱՀՁՋ ՋՌՍԼՑՏԹՋ ԻՇՆԼՍԻՌԽԼ ՁՆ ԹԻԻՇՊԼԹՆԻԽՏՁՌՀԤԩԭ

԰ՌԹՆԼԹՊԼՋ ԹՋ ՈՍԺՄՁՋՀԽԼ ԺՑ ՌՀԽ Բ԰ ԢԭԞ 
 Ԡԣԯ ԭԹՊՌՋ  ԹՆԼ ԬԢԠԡ

ԭՊՁՆԻՁՈՄԽՋՇԾԤԩԭ#ԢԫԳԪԠԠԥԢԪ
%

ԞԱԢ԰ԱԪԞԱԢԯԦԞԩ  ԭՀՇՋՅԽՌԠԞ԰ԫՇ

ԡԽՋԻՊՁՈՌՁՇՆ    ԫՇՆԽՊԽՈՇՊՌԽԼԢՐՈՁՊԹՌՁՇՆԼԹՌԽԧԹՆՍԹՊՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԬԢԠԡ ՊԽԻՇՅՅԽՆԼՋ ԼԽՋԻՊՁԺՁՆԿՏԹՌԽՊ ՋՇՄՍԺՁՄՁՌՑ ՅԽՄՌՁՆԿԺՇՁՄՁՆԿ ՈՇՁՆՌ ՋՌԹԺՁՄՁՌՑ ՁՆՏԹՌԽՊ ԹՆԼ ՄՁԿՀՌ ՈԨԹԭՇՏ ՇՊ

ԨՇՏՎԹՈՇՊՈՊԽՋՋՍՊԽՇԾՌԽՋՌԻՇՅՈՇՍՆԼԽՐՈՁՊԹՌՁՇՆԼԹՌԽ

ԩՇՌԫՇԟԹՌԻՀԫՇ  ԤԮԥ

ԭՍՊՁՌՑ     

ԦՅՈՍՊՁՌՁԽՋ     ԫՇՆԽՊԽՈՇՊՌԽԼ

԰ՌԹԺՁՄՁՌՑ ՇԾ ԠՇՅՈՇՍՆԼ  ԞՆԹՄՑՌՁԻԹՄ ՎԽՊՁԾՁԻԹՌՁՇՆ ՇԾ ՌՀԽ ՌԽՋՌ ՅԹՌԽՊՁԹՄ ԾՊՇՅ ՌՁՅԽ   ԹՆԼ  ԼԹՑՋ

ՑՁԽՄԼԽԼՊԽԻՇՎԽՊՁԽՋՇԾՌՇՇԾՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԱԽՋՌՋՇՄՍՌՁՇՆԾՇՊՌՁԾՁԽԼՏՁՌՀՈՀՇՋՅԽՌ

ԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩՑՁԽՄԼԽԼՊԽԻՇՎԽՊՁԽՋՇԾՌՇՏՁՌՀ

ՇՆԽ ՇՍՌՄՁԽՊ ՊԽԻՇՎԽՊՑ ՇԾ ՈՇՋՋՁԺՄՑ ԼՍԽՌՇՋՈՁՃՁՆԿ ՀԹՆԼՄՁՆԿ ՇՊ ՁՆՋՌՊՍՅԽՆՌ ԽՊՊՇՊՋԱՀԽԠԳ0ՋԾՇՊ

ՌՀԽՁՆԼՁՎՁԼՍԹՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԹՆԿԽԼԾՊՇՅԾՇՊՌՀԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԱՀԽՋԽԼԹՌԹՁՆԼՁԻԹՌԽ

ՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄՏԹՋՋՌԹԺՄԽՍՆԼԽՊՌՀԽՌԽՋՌԻՇՆԼՁՌՁՇՆՋ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾ

ԱԽՋՌԠՀԽՅՁԻԹՄՋ   ԱՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽՏԹՋՋՌՇՊԽԼԹՌՊՇՇՅՌԽՅՈԽՊԹՌՍՊԽՁՆԼԹՊՃՎԽՆՌՁՄԹՌԽԼ

ԻԹԺՁՆԽՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԟԱԽՋՌՇՊԿԹՆՁՋՅ

ԱԹԺՄԽԤԽՆԽՊԹՄԦՆԾՇՊՅԹՌՁՇՆԞԺՇՍՌՌՀԽԱԽՋՌ԰ՈԽԻՁԽՋԹՆԼԞԻԻՄՁՅԹՌՁՇՆ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

԰ՈԽԻՁԽՋԻՇՅՅՇՆՆԹՅԽ ԣԹՌՀԽԹԼԪՁՆՆՇՏ ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԹՌՀԽԹԼՅՁՆՆՇՏ


ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ ԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼԴԽՊԽԾՁՋՀՇԺՌԹՁՆԽԼԾՊՇՅԹՋՁՆԿՄԽՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃ!

ԶԽՋ ԰ՇՍՊԻԽՆՇՌՊԽՈՇՊՌԽԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԾՊՇՅԹՋՁՆԿՄԽ

ՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃ

ԴԽՊԽԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!

ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԹԻԻՄՁՅԹՌԽԼ

ՍՆԼԽՊՏԹՌԽՊՉՍԹՄՁՌՑԹՆԼՁՄՄՍՅՁՆԹՌՁՇՆ

ԻՇՆԼՁՌՁՇՆՋՌՀԹՌԹՊԽՋՁՅՁՄԹՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽ

ՌԽՋՌ

ԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼ ԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՌՏՇՏԽԽՃ

ԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԫՇՌԽՌՀԹՌՌՀԽԹԻԻՄՁՅԹՌՁՇՆ

ՈԽՊՁՇԼՁՋԼՁԾԾԽՊԽՆՌԾՊՇՅՌՀԽՋՍԺՋԽՉՍԽՆՌՁՆ

ՋՁՌՍՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆՀԽԹՄՌՀ ԪՇՊՌԹՄՁՌՁԽՋԼՍՊՁՆԿԼԹՑՋՈՊՁՇՊՌՇՈՊԽ

ԽՐՈՇՋՍՊԽՈԽՊՁՇԼՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼԣՁՋՀԼՁԼՆՇՌՊԽԻԽՁՎԽԹՆՑՌՊԽԹՌՅԽՆՌԾՇՊԼՁՋԽԹՋԽԼՍՊՁՆԿԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԟԽՀԹՎՁՇՊԹՄԹԺՆՇՊՅԹՄՁՌՁԽՋՇՊԻՄՁՆՁԻԹՄՋՁԿՆՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽ

ԼԹՑՋՈՊՁՇՊՌՇՌՀԽՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽԺԽ

ՄԽՋՋՌՀԹՆՇԾՌՀԽԻՍՄՌՍՊԽՈՇՈՍՄԹՌՁՇՆԦԾ

ՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽՋԽԼԹՑՋՁՋԿՊԽԹՌԽՊՌՀԹՆ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԾՁՋՀԺԽ

ՊԽՂԽԻՌԽԼԦԾՅՇՊՌԹՄՁՌՑՁՋԺԽՌՏԽԽՆԢԭԞ

ՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽՀԽՄԼԹՆՇՌՀԽՊ

ԼԹՑՋԦԾՅՇՊՌԹՄՁՌՁԽՋԿՊԽԹՌԽՊՌՀԹՆՇԻԻՍՊ

ԼՍՊՁՆԿՌՀՁՋԽՐՌԽՆԼԽԼԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԾՁՋՀՆՇՌԺԽՍՋԽԼ

ԱՑՈԽՇԾԾՇՇԼ ԩՁՎԽԺՊՁՆԽՋՀՊՁՅՈ

ՆԹՍՈՄՁՁ
ԞՊՌԽՅՁԹ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԾԽԼԾՊՇՒԽՆ

ԺՊՁՆԽՋՀՊՁՅՈՌՏՁԻԽՈԽՊԼԹՑՌՇՈՊՇՅՇՌԽ

ԹԻՌՁՎԽՊԽՈՊՇԼՍԻՌՁՇՆԹՆԼՅԹՁՆՌԹՁՆԺՇԼՑ

ԻՇՆԼՁՌՁՇՆ

԰ՇՍՊԻԽՇԾԾՇՇԼ ԫՇՌՊԽՈՇՊՌԽԼԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿ ՌՁՅԽՋԼԹՑԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿ ԫՇՆԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԣՁՋՀ԰ԽՄԽԻՌՁՇՆԹՆԼԭՊԽԢՐՈՇՋՍՊԽԭԽՊԾՇՊՅԹՆԻԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ՅՇՆՌՀՋ ԯԽՈՇՊՌԽԼԹՋՏԽԽՃՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՊՇԼՍԻՌՁՎԽՄՑՅԹՌՍՊԽ


ՋԽՐՍԹՄՄՑԼՁՅՇՊՈՀՁԻԾՁՋՀՅՇՆՌՀՋ

ՇՄԼ

ԪԽԹՆՏԽՁԿՀՌՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

Կ ԟԹՋԽԼՇՆՅԹՄԽՋՍՋԽԼՌՇՋՌՇԻՃ

ԹՉՍԹՊՁԹԾՇՊՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԹՋՍԺՋԹՅՈՄԽ

ՇԾԾՁՋՀԺԽՏԽՁԿՀԽԼԺԽԾՇՊԽՌՀԽՌԽՋՌՌՇ

ԽՋՌՁՅԹՌԽՌՀԽՅԽԹՆՏԽՁԿՀՌԾՇՊԽԹԻՀՋԽՐԦՌՁՋ

ՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌՀԽՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՇԾ

ԽԹԻՀԾՁՋՀՋԽՄԽԻՌԽԼԾՇՊՌՀԽՌԽՋՌԺԽՏՁՌՀՁՆ

չՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԾՇՊԽԹԻՀՋԽՐ

ԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋ
ՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

ՌՇԿ ԦՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋՏՁՌՀՁՆչՇԾՌՀԽ

ԽՋՌՁՅԹՌԽԼՅԽԹՆ

ԪԽԹՆՏԽՁԿՀՌՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

Կ ԟԹՋԽԼՇՆԾԽՅԹՄԽՋՍՋԽԼՌՇՋՌՇԻՃ

ԹՉՍԹՊՁԹԾՇՊՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ

ԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋ
ԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

ՌՇԿ ԦՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋՏՁՌՀՁՆչՇԾՌՀԽ

ԽՋՌՁՅԹՌԽԼՅԽԹՆ

ԪԽԹՆՄԽՆԿՌՀՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԪԽԹՆՄԽՆԿՌՀՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ

ԡՍՊԹՌՁՇՆՇԾՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ ԼԹՑՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾԼԹՑՋԴԽՊԽՈՊԽԽՐՈՇՋՍՊԽԻՇՆԼՁՌՁՇՆՋՁԼԽՆՌՁԻԹՄՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!

ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽ

ԻՇՆԼՁՌՁՇՆՋՁՆԻՄՍԼՁՆԿՌԽՅՈԽՊԹՌՍՊԽ

ՈՀՇՌՇՈԽՊՁՇԼԾԽԽԼՁՆԿԽՌԻԺԽՁԼԽՆՌՁԻԹՄՌՇ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԻՇՆԼՁՌՁՇՆՋ

ԫՍՅԺԽՊՇԾՈՊԽԽՐՈՇՋՍՊԽՌԹՆՃՋ  ԢՐՌՊԹՊԽՈՄՁԻԹՌԽՋՏԽՊԽԽՋՌԹԺՄՁՋՀԽԼՌՇ

ԹԻԻՇՍՆՌԾՇՊԹՈՇՌԽՆՌՁԹՄՄԹԻՃՇԾՋՈԹՏՆՁՆԿՁՆՋՇՅԽԻՀԹՅԺԽՊՋԹՆԼՇՊՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀՁՋՈՀԹՋԽ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹԼԼՁՌՁՇՆԹՄՌԹՆՃՋՋԽՌ

ՍՈԹՌՌՀԽԺԽԿՁՆՆՁՆԿՇԾՈՊԽԽՐՈՇՋՍՊԽՏՁՄՄ

ԽՆՋՍՊԽՌՀԹՌՋՍԾԾՁԻՁԽՆՌՊԽՈՄՁԻԹՌԽՋՏՁՌՀՌՀԽ

ԻՇՊՊԽԻՌՋԽՐՊԹՌՁՇԹՊԽԹՎԹՁՄԹԺՄԽԾՇՊՌՀԽ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԫՍՅԺԽՊՇԾՅԹՄԽՋՈԽՊՌԹՆՃ ԫՍՅԺԽՊՇԾԾԽՅԹՄԽՋՈԽՊՌԹՆՃ 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԭՊԽԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑ ԽԿԿՋԾԽՅԹՄԽ

ՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑ

ՊԽՈՄՁԻԹՌԽ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽ

ԾԽԻՍՆԼՁՌՑՁՆԽԹԻՀՊԽՈՄՁԻԹՌԽ
ՌԹՆՃՋԽՄԽԻՌԽԼ

ԾՇՊՍՋԽՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԹՌՄԽԹՋՌ

ԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՊԽՈՄՁԻԹՌԽ

ԼՍՊՁՆԿՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԫՍՅԺԽՊՇԾՋՈԹՏՆՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽ

 ՌՏՇՌՁՅԽՋՁՆԼԹՑՋ ԰ՈԹՏՆՁՆԿՇԻԻՍՊՊԽԼԹՌՄԽԹՋՌԽՎԽՊՑ

ԼԹՑՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՈԹՏՆՁՆԿՇԻԻՍՊԹՌ

ՄԽԹՋՌՌՏՁԻԽՁՆՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԡԽՌԹՁՄՋՇՆՈՊԽԽՐՈՇՋՍՊԽ  ԫՇՆԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԠԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱՑՈԽՇԾԽՐՈՇՋՍՊԽ ԣՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏ

ՌՀՊՇՍԿՀՋՑՋՌԽՅԞՋՆՇՌԽԼՁՆՌՀԽ

ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋԼՇԻՍՅԽՆՌ 

ՌՀԽՍՋԽՇԾԹՋՌԹՌՁԻՊԽՆԽՏԹՄՋՑՋՌԽՅՁՋՆՇՌ

ՊԽԻՇՅՅԽՆԼԽԼԾՇՊՌՀՁՋԹՋՋԹՑ

ԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅ

ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊ

ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ

ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ

ՊԽԻՇՅՅԽՆԼԽԼ

ԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽ ԠԹԩՀՊ


ԽՉՍՁՎԹՄԽՆՌՌՇՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌՋԼԹՑ

ԠԹՄԻՍՄԹՌԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊԺԹՋԽԼՇՆԩԻՑԻՄԽԹՌԹՊԹՌԽՇԾԻՑԻՄԽՋՀՊՋ

ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋ

ՅԩՅՁՆ
ԩՀՊՇՊԹՌՄԽԹՋՌՌՇՌԹՄ

ՎՇՄՍՅԽԽՐԻՀԹՆԿԽՋՈԽՊԼԹՑ

 Բ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿ

ԭՊՇԿՊԹՅԱՁԽՊԞՋՋԹՑՋ
ԬԠ԰ԭԭԱԽՋՌԤՍՁԼԽՄՁՆԽ԰ԽՊՁԽՋԪԹՊԻՀԬԾԾՁԻԽՇԾԠՀԽՅՁԻԹՄ԰ԹԾԽՌՑԹՆԼԭՇՄՄՍՌՁՇՆԭՊԽՎԽՆՌՁՇՆ
ԬԠ԰ԭԭԴԹՋՀՁՆԿՌՇՆԡԠ
ՀՌՌՈՏՏՏԽՈԹԿՇՎԽՆԼՇՈՍԺՋԹՋՋԹՑՎԹՄՁԼԹՌՁՇՆԻՄԹՊՁԾՁԻԹՌՁՇՆԼՇԻՈԼԾ

 ԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋ

ԣՄՇՏՋՈՄՁՌՌՁՆԿԻՀԹՅԺԽՊՋՏԽՊԽՍՋԽԼԺԽՌՏԽԽՆԼՁՄՍՌԽՊԻԽՄՄՋԹՆԼՌՀԽՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄՋԱՊԽԹՌՅԽՆՌՊԽԻՇՎԽՊՁԽՋՏԽՊԽՆՇՌՅԽԹՋՍՊԽԼՈՊՁՇՊՌՇՌԽՋՌՁՆՁՌՁԹՌՁՇՆՌՇՁՆԼՁԻԹՌԽՁԾԼՁՄՍՌԽՊՀԹԼՊԽԹԻՀԽԼԽՉՍՁՄՁԺՊՁՍՅԣՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑՏԹՋՆՇՌՊԽՈՇՊՌԽԼ

ԯԽԻՇՅՅԽՆԼԽԼՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏ

ՌՀՊՇՍԿՀՋՑՋՌԽՅՋԪՁՐՁՆԿԻՀԹՅԺԽՊՁՋ

ՊԽԻՇՅՅԽՆԼԽԼԺՍՌՆՇՌՊԽՉՍՁՊԽԼ

ԞԽՊԹՌՁՇՆՁՋՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՅՁՐՁՆԿ

ԞԼԽՅՇՆՋՌՊԹՌՁՇՆՌՀԹՌՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆ

ՁՋԻՇՅՈՄԽՌԽՄՑՅՁՐԽԼԺԽԾՇՊԽՁՆՌՊՇԼՍԻԽԼ

ՁՆՌՇՌՀԽՌԽՋՌՋՑՋՌԽՅՁՋՊԽԻՇՅՅԽՆԼԽԼ

ԱՀԽՊԽԻՇՅՅԽՆԼԽԼԾՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑ

ՁՋՏՁՌՀՁՆ

ԞԽՊԹՌՁՇՆ! ԫՇ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹԽՊԹՌՁՇՆՁԾԼՁՋՋՇՄՎԽԼ

ՇՐՑԿԽՆՊԽԹԻՀԽՋՅԿԩ


ՋԹՌՍՊԹՌՁՇՆ

԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ ԴԽՄՄՏԹՌԽՊ ԡՁՄՍՌՁՇՆՏԹՌԽՊՏԹՋԹԽՊԹՌԽԼՈՊՁՇՊՌՇՍՋԽ ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼ

ՏԹՌԽՊՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄ

ՏԹՌԽՊԺԽՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊ

ՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊ

ՈՇՋՋՁԺՄԽԻՇՆՌԹՅՁՆԹՆՌՋԬԢԠԡԹԻԻԽՈՌՋ

ԹՆՑՏԹՌԽՊՁՆՏՀՁԻՀՌՀԽՌԽՋՌՋՈԽԻՁԽՋՋՀՇՏ

ԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋ

ՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!

ԶԽՋ 

ԱԽՋՌՎԽՋՋԽՄՌՑՈԽՅԹՌԽՊՁԹՄՋ ԤՄԹՋՋԹՉՍԹՊՁԹՏՁՌՀ

ՋՁՄՁԻՇՆԽՋԽԹՄԹՆՌԹՆԼՆՑՄՇՆ

ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՏԹՌԽՊ

ԻՇՆՌԹԻՌՈՇՊՌՁՇՆՋՇԾՌՀԽՋՑՋՌԽՅՆՇՌ

ԻՇՅՈՊՇՅՁՋԽՌՀԽՋՌՍԼՑ
ԽԿԹՄՄԿՄԹՋՋ

ՎԽՋՋԽՄՋՇՊԿՄԹՋՋՎԽՋՋԽՄՋՏՁՌՀՋՌԹՁՆՄԽՋՋ

ՋՌԽԽՄԾՊԹՅԽՋԹՊԽԹԻԻԽՈՌԹԺՄԽԽՐԹՅՈՄԽՋ

ԱԽՋՌՎԽՋՋԽՄՋՁՒԽ ԻՅՏՁԼԽՐԻՅ

ՄՇՆԿՐԻՅՀՁԿՀՋՇՄՍՌՁՇՆԼԽՈՌՀԻՅ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԩՌԽՋՌ

ԻՀԹՅԺԽՊՋ
ԽԿՐՐԻՅ

ԣՁՄՄՎՇՄՍՅԽ ԩ ԢԭԞՊԽԻՇՅՅԽՆԼՋԩՋՇՄՍՌՁՇՆՈԽՊՌԹՆՃ԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՅԹՌԽՊՁԹՄ ՁՆԻՀԼՁԹՅԽՌԽՊԹԿԽԼ

ԭԳԠԻՍՌՁՆՀԹՄԾ
ԹՊԻՀԽՋԹՆԼՁՆՌՇԻՅՋԽԻՌՁՇՆՋԹՆԼՈՇՋՁՌՁՇՆԽԼՁՆԹՋԻՊԽԽՆԽԼԿՄԹՋՋԻՇՄՄԽԻՌՁՇՆՌՊԹՑ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԽԹԻՀՌԹՆՃԻՇՆՌԹՁՆ

ՌՀՊԽԽՋԽՅՁԻՁՊԻՍՄԹՊՋՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋ

ԽԿԹԿԽԼԭԳԠՈՁՈԽԻՅՁՆ

ՄԽՆԿՌՀՋՈՄՁՌՄԽՆԿՌՀՏՁՋԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋՁՒԽ

ԭԳԠԻՍՌՁՆՀԹՄԾ
ԹՊԻՀԽՋԹՆԼՁՆՌՇԻՅՋԽԻՌՁՇՆՋ

ԢԹԻՀՋՍԺՋՌՊԹՌԽՈՄԹԻԽԼՇՆՋԻՊԽԽՆԽԼԿՄԹՋՋԻՇՄՄԽԻՌՁՇՆՌՊԹՑ
ՐՐԻՅԩՐԴՐԥԻՇՎԽՊԽԼՏՁՌՀԻՅՋՌԹՁՆՄԽՋՋՋՌԽԽՄ

ՅԽՋՀ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽՋՑՋՌԽՅ

 ԫՇՆԽ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ

ԪԽԹՋՍՊԽՅԽՆՌ

ԦՆՌԽՊՎԹՄ

ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱԽՅՈԽՊԹՌՍՊԽ
ոԠ    ԠՇՆՌՁՆՍՇՍՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչՇԠ

ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ

ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼՇԠ

Ոԥ    ԡԹՁՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥՌՇԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ՅԿԩ 
 
 
 ԡԹՁՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ 
ԡԬ ՅԿԩ
 ԹՁՊՋԹՌՍՊԹՌՁՇՆԱՇՌԹՄԹՄՃԹՄՁՆՁՌՑ
ՅԿԩԹՋԠԹԠԬ

   ԴԽԽՃՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՇՌԹՄԹՄՃԹՄՁՆՁՌՑ 

ՅԿԩԹՋԠԹԠԬ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ

ԪԽԹՋՍՊԽՅԽՆՌ

ԦՆՌԽՊՎԹՄ

ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԥԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬ    ԴԽԽՃՄՑԱՇՌԹՄՇՊԿԹՆՁԻԻԹՊԺՇՆ
ՅԿԩ   ԫԞ ԫՇՎԡԽԻ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՇՌԹՄՇՊԿԹՆՁԻ

ԻԹՊԺՇՆՁՆԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽՅԿԩ

ԲՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹ
μԿԩ ԫՇՌՊԽՈՇՊՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՍՆՁՇՆՁՒԽԼ

ԹՅՅՇՆՁԹՁՆՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ

μԿԩ

ԯԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽ
μԿԩ ԫՇՌՊԽՈՇՊՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽ

ՁՆԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽμԿԩ

ԠՇՆԼՍԻՌՁՎՁՌՑ
μՅՀՇՋԻՅ    ԴԽԽՃՄՑ

ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑ

ՇԾՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ

ՌԽՅՈԽՊԹՌՍՊԽՈԥԹՆԼԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ

ԺԽՅԽԹՋՍՊԽԼՁՆԹՄՄՌԽՋՌՌԹՆՃՋԹՌՄԽԹՋՌ

ՏԽԽՃՄՑԹՆԼՌՀԹՌՀԹՊԼՆԽՋՋԹՆԼԹՄՃԹՄՁՆՁՌՑ

ԺԽՅԽԹՋՍՊԽԼՁՆԻՇՆՌՊՇՄՋԹՆԼՁՆՇՆԽՌԹՆՃ

ԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՄԽԹՋՌ

ՏԽԽՃՄՑԦՆԹԼԼՁՌՁՇՆԻՇՆՌՁՆՍՇՍՋ

ՌԽՅՈԽՊԹՌՍՊԽՅՇՆՁՌՇՊՁՆԿՇԾԹՌՄԽԹՋՌՇՆԽ

ՌԹՆՃՁՋԽՆԻՇՍՊԹԿԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ

 ԪԽԹՆՋՏԽՊԽԻԹՄԻՍՄԹՌԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊԹՋՌՀԽԹՎԽՊԹԿԽՇԾՌՀԽՅՁՆՁՅԹԹՆԼՅԹՐՁՅԹԾՇՊՌՀԽՊԹՆԿԽՋՈՊՇՎՁԼԽԼԹԻՊՇՋՋԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌԽԼՄԽՎԽՄՋԡ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋ

ԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ! ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊ

ՁԾՀՇՍՊԩԠԼԹՌԹԾՇՊՌՀԽԾԹՌՀԽԹԼՅՁՆՆՇՏ

ԹՊԽՍՆԹՎԹՁՄԹԺՄԽ

ԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!

ԟԹՋԽԼՇՆՌՀԽՊԽՋՍՄՌՋՇԾՀՊՊԹՆԿԽԾՁՆԼՁՆԿՌԽՋՌԹՆԼՁՆԻՇՆՋՍՄՌԹՌՁՇՆՏՁՌՀՌՀԽՋՌՍԼՑՋՈՇՆՋՇՊ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽՋԽՄԽԻՌԽԼԺԹՋԽԼՇՆՌՇՐՁԻՁՌՑ

ԼԹՌԹԾՇՊՇՌՀԽՊԾՁՋՀՋՌՍԼՁԽՋՇՊՋՈԽԻՁԽՋՁԾ

ԹՎԹՁՄԹԺՄԽԬՌՀԽՊՏՁՋԽԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑ

ՄՁՅՁՌՇԾՌՀԽՌԽՋՌԻՇՅՈՇՍՆԼՇՊՅԿԩ


ՏՀՁԻՀԽՎԽՊՁՋՄՇՏԽՊՁՋԹՈՈՊՇՈՊՁԹՌԽ

԰ՈԽԻՁԽՋ ԣԹՌՀԽԹԼԪՁՆՆՇՏ 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԩՁԾԽՋՌԹԿԽ ԫՇՌՊԽՈՇՊՌԽԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԹՆԿԽԾՁՆԼՁՆԿՌԽՋՌՋ

ԺԽՈԽՊԾՇՊՅԽԼՏՁՌՀԾՁՋՀՇԾՋՁՅՁՄԹՊԹԿԽԹՆԼ

ՋՁՒԽՌՇՌՀՇՋԽՌՀԹՌՏՇՍՄԼԺԽՍՌՁՄՁՒԽԼՁՆՌՀԽ

ՌԽՋՌ

ԱԽՋՌԼՍՊԹՌՁՇՆ ՀՊՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՀՇՍՊԽՐՈՇՋՍՊԽ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋ ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊ

ՏՁՌՀԾՁՎԽՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՈՄՍՋԹԻՇՆՌՊՇՄ


ՋՁՐՌՇՌԹՄՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՏՁՌՀԾՇՍՊ

ԾԽՅԹՄԽՋԹՆԼՌՏՇՅԹՄԽՋՈԽՊԽՐՈՇՋՍՊԽՌԹՆՃ


ԾՁՋՀՌՇՌԹՄԱՀԽՆՍՅԺԽՊՇԾՅՇՊՌԹՄՁՌՁԽՋ

ՌՀԹՌՇԻԻՍՊՅԹՑԺԽՍՋԽԼՌՇԼԽՎԽՄՇՈԹ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԻՍՊՎԽ

ԟԹՋԽԼՍՈՇՆՌՀԽՊԽՋՍՄՌՋՌՀԽՀՁԿՀԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՌՀԹՌԼՇԽՋՆՇՌՊԽՋՍՄՌՁՆ

ՁՆԻՊԽԹՋԽԼՅՇՊՌԹՄՁՌՑՇՊՋՁԿՆՋՇԾՇՎԽՊՌ

ՅՇՊԺՁԼՁՌՑԻՇՅՈԹՊԽԼՌՇԻՇՆՌՊՇՄՋՇՊՌՀԽ

ԼԽՊՁՎԽԼՀՊԩԠՅԹՑԺԽՋԽՄԽԻՌԽԼԹՋՌՀԽ

ՀՁԿՀԽՋՌԽՐՈՇՋՍՊԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽ

ԼԹՑՌԽՋՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱԽՋՌԼՍՊԹՌՁՇՆ ԼԹՑՋ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ԼՍՊԹՌՁՇՆ ՇԾ ՌՀԽ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԼԹՑՋ

ԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԱՀԽԹԻՍՌԽՌՇՐՁԻՁՌՑ

ՀՇՍՊԩԠԾՇՊՈՀՇՋՅԽՌ

ՏՁՌՀԾԹՌՀԽԹԼՅՁՆՆՇՏՁՋ

ՅԿԩ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾ

ՌՀԽՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊ

ԼԽՅՇՆՋՌՊԹՌԽՋԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ


ԽԿՌՀԽՀՇՍՊԩԠՏՀՁԻՀԽՎԽՊ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ

ԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ

԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԱԽՆԾՇՄԼ


ԻՇՆՌՊՇՄ

ԹՆԼՅԿ

ԹՁԩ

ԢԭԞՋՍԿԿԽՋՌՋՌՀԹՌԹԻՇՆԻԽՆՌՊԹՌՁՇՆ

ՋԽՈԹՊԹՌՁՇՆՇԾԺԽՌՏԽԽՆ
ՇՊՌՀՊԽԽԾՇՄԼ

ԹՆԼ
ՇՊՌԽՆԾՇՄԼՁՋՋԻՁԽՆՌՁԾՁԻԹՄՄՑ

ԹԻԻԽՈՌԹԺՄԽ 

ԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄՁԾԹՈՈՊՇՈՊՁԹՌԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!

ԶԽՋ 

ԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԪԽԹՆՅԽԹՋՍՊԽԼ 

ԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿԹՁԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ

ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋ

ԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡ ԫՇՌՊԽՈՇՊՌԽԼ ԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԹՆԼԼԹՑՋ  ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅ

ԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽՅԽԹՋՍՊԽԼՈՊՁՇՊՌՇՌՀԽ

ԹԼԼՁՌՁՇՆՇԾԾՁՋՀՁՆԹՄՄՌԹՆՃՋԹՆԼԹՌՄԽԹՋՌ

ՏԽԽՃՄՑՌՀԽՊԽԹԾՌԽՊՁՆՌՏՇՊԽՈՄՁԻԹՌԽՋՈԽՊ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԹՋՌՀԽՊԹՆԼՇՅՁՒԽԼԻՇՅՈՄԽՌԽԺՄՇԻՃԼԽՋՁԿՆՍՋԽԼ!

ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹՄՄԾՁՋՀԺԽՊԹՆԼՇՅՄՑ

ԹՋՋՁԿՆԽԼՌՇՌԹՆՃՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽ

ԱԹՆՃՋԹՊԽՌՀԽՆՊԹՆՃԽԼԹԻԻՇՊԼՁՆԿՌՇՈՊԽ

ԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑԹՆԼՌՀԽՌԹՆՃՋՏՁՌՀՌՀԽ

ՀՁԿՀԽՋՌԾԽԻՍՆԼՁՌՑԹՊԽՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇ

ԹԼԽԾՁՆՁՌՁՎԽՌԽՋՌՌՊԽԹՌՅԽՆՌԹՆԼԺՄՇԻՃԾՁՊՋՌ

ԢԹԻՀԺՄՇԻՃԻՇՆՌԹՁՆՋՇՆԽՊԽՈՄՁԻԹՌԽՇԾԽԹԻՀ

ՌՊԽԹՌՅԽՆՌՁՆԻՄՍԼՁՆԿԻՇՆՌՊՇՄՋ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԻՇՆԻՍՊՊԽՆՌ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿԹԿԽՆՌՁՋ

ՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

  ԢԭԞՊԽԻՇՅՅԽՆԼՋՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽ 

ԫՍՅԺԽՊՇԾԾԽՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

  ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԽՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ! ԫՇ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌ

ԽՐԻԽԽԼՅՄԩԬԢԠԡՊԽԻՇՅՅԽՆԼՋ

ՌՀԹՌՋՇՄՎԽՆՌՀԹՎԽՆՇԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊ

ՈՊՇԼՍԻԽԹՆՑՇՌՀԽՊԹԼՎԽՊՋԽԽԾԾԽԻՌՋԹՆԼՌՀԹՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՆՇՌԺԽԿՊԽԹՌԽՊՌՀԹՆՅՄԩ

ԴԹՋԹՈՇՋՁՌՁՎԽԻՇՆՌՊՇՄՍՋԽԼ! ԫՇԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄԻՇՆԻԽՆՌՊԹՌՁՇՆ
Ջ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ 

ԭՀՇՌՇՈԽՊՁՇԼ ՀՊՋՄՁԿՀՌ

ՀՊՋԼԹՊՃ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ


ՄՁԿՀՌԼԹՊՃ

ԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏԞՉՍԹՌՁԻ

ԱՇՐՁԻՇՄՇԿՑՈՈ-

ԬԢԠԡ
ԤՍՁԼԹՆԻԽԡՇԻՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋՇՆԱԽՋՌՁՆԿԹՆԼ

ԞՋՋԽՋՋՅԽՆՌԫՇԭԹՊՁՋԣՊԹՆԻԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԩՁԿՀՌՁՆՌԽՆՋՁՌՑԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ

ՄՍՐ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑ-

ՄՍՐ
ԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋ ԱԽՋՌՋՇՄՍՌՁՇՆՋՏԽՊԽՊԽՈՇՊՌԽԼՌՇԺԽԻՄԽԹՊ

ԹՆԼԻՇՄՇՊՄԽՋՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱՊԽԹՌՅԽՆՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌԦԡ

ԫՇՅՁՆԹՄ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԪԽԹՆԪԽԹՋՍՊԽԼ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԪԽԹՆԠԳ
 ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑ

 ԩԬԮ ԫԞ 

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌԽՋՌ

ՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽ

ՅԹՁՆՌԹՁՆԽԼԹՌԹԻՇԽԾԾՁԻՁԽՆՌՇԾ

ՎԹՊՁԹՌՁՇՆ
ԠԳ

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ ԫԞ ԫԞ 

ԱՊԽԹՌՅԽՆՌ   

ԯԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼչ

ԠԳ

ԱՊԽԹՌՅԽՆՌ   

ԯԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼչ



ԠԳ

ԱՊԽԹՌՅԽՆՌ   

ԯԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼչ

ԠԳ

ԡՁՄՍՌԽՊ԰ՌՇԻՃ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ 

ԩԬԮՅԿԹՁԩ

ԢԬԺՋԽՊՎԹՌՁՇՆՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋ ԰ՍՊՎՁՎԹՄԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋՏԽՊԽՇԺՋԽՊՎԽԼԼԹՁՄՑԞՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ
ԡԹՑՋԽԻՇՆԼԹՊՑ

ՋԽՐ ԻՀԹՊԹԻՌԽՊՁՒԹՌՁՇՆ 
ԺՇԼՑ ԻՇՄՇՊ ՈԹՌՌԽՊՆ ԺՇԼՑ ՋՀԹՈԽ ԺՇԼՑ ՏԽՁԿՀՌ ՄԽՆԿՌՀ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽ ԿՇՆԹԼԹՄ ՋՌԹԿՁՆԿ ԹՆԼ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՑԹՆԼՈՄԹՋՅԹՎՁՌԽՄՄՇԿԽՆՁՆՏԽՊԽԽՎԹՄՍԹՌԽԼԭՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋՏԽՊԽՆՇՌՅԽԹՋՍՊԽԼ

ԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ!ԶԽՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՋՍՊՎՁՎԹՄԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋՋԽԻՇՆԼԹՊՑՋԽՐԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼՇՌՀԽՊԻՄՁՆՁԻԹՄՋՁԿՆՋՇԻԻՍՊԹՌՄԽԹՋՌԼԹՁՄՑԞՌ

ՌԽՋՌ ՌԽՊՅՁՆԹՌՁՇՆ 
ԼԹՑ  ԹԼԼՁՌՁՇՆԹՄ ՇԺՋԽՊՎԹՌՁՇՆՋ ՁՆԻՄՍԼԽ ԺՇԼՑ ՏԽՁԿՀՌ ԹՆԼ ՄԽՆԿՌՀ ՆՍՈՌՁԹՄ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽ ԿՇՆԹԼԹՄ ՋՌԹԿՁՆԿ ԹՆԼ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ ՈՄԹՋՅԹ

ՎՁՌԽՄՄՇԿԽՆՁՆԹՆԼՈՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋ
ՌԽՋՌՇՋՌԽՊՇՆԽԹՆԼȕԽՋՌՊԹԼՁՇՄՁԾՅԽԹՋՍՊԽԼԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
Ԥ԰ԦՁՋԻԹՄԻՍՄԹՌԽԼՍՋՁՆԿԹՊԹՌՁՇՇԾԿՇՆԹԼՏԽՁԿՀՌ

ՌՇԺՇԼՑՏԽՁԿՀՌ
ԿՇՆԹԼՏԽՁԿՀՌՌՇՌՀԽՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌՁՆՅԿՐԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ

ԠՄՁՆՁԻԹՄՋՁԿՆՋՇԾՇՎԽՊՌՌՇՐՁԻՁՌՑՅԹՑՁՆԻՄՍԼԽ
ԺՍՌԹՊԽՆՇՌՄՁՅՁՌԽԼՌՇՀԽՅՇՊՊՀԹԿԽԻԽՋՋԹՌՁՇՆՇԾԾԽԽԼՁՆԿԹՆԼՇՌՀԽՊԹԺՆՇՊՅԹՄԺԽՀԹՎՁՇՊ

ԦԦԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫ

ԣՇՊ ԹՄՄ ՋՌՍԼՑ ԹՍՌՀՇՊ ՊԽՋՍՄՌՋ ՌՀԽ ԽՆԼՈՇՁՆՌՋ ԹՌ ՌՀԽ ՀՁԿՀ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ 
 ՅԿ ԹՁԩ ՏԽՊԽ ՆՇՌ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ԹՆԹՄՑՒԽԼ ԼՍԽ ՌՇ ՅՇՊՌԹՄՁՌՑԞԼԼՁՌՁՇՆԹՄՄՑՌՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋԹՌՌՀԽՅԿԹՁԩԻՇՆԻԽՆՌՊԹՌՁՇՆՅԽՌՌՀԽԿՍՁԼԽՄՁՆԽԼԽԾՁՆՁՌՁՇՆՇԾՇՎԽՊՌՅՇՊԺՁԼՁՌՑ

ԥՇՏԽՎԽՊՁՆԼՁՎՁԼՍԹՄՋԾՊՇՅՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏԽՊԽՆՇՌԽՐԻՄՍԼԽԼԾՊՇՅՌՀԽՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋՁՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

Ԟ ԯԽՋՍՄՌՋ

ԱՀԽՊԽՏԹՋՋՍՊՎՁՎԹՄՁՆՌՀԽԻՇՆՌՊՇՄԿՊՇՍՈԞՌՌՀԽՄՇՏԻՇՆԻԽՆՌՊԹՌՁՇՆԾՇՍՊԾԽՅԹՄԽՋԼՁԽԼԹՆԼՌՀՊԽԽՇԾՌՀԽՋԽԾԽՅԹՄԽՋՏԽՊԽԾՊՇՅՇՆԽՊԽՈՄՁԻԹՌԽԞՌ

ՌՀԽ ՁՆՌԽՊՅԽԼՁԹՌԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՌՏՇ ՅԹՄԽՋ ԹՆԼ ԾՇՍՊԾԽՅԹՄԽՋ ԼՁԽԼ ԼՍՊՁՆԿ ՌՀԽ ՋՌՍԼՑ ԞՄՄ ԺՍՌ ՇՆԽ ՅԹՄԽ ԹՆԼ ԾԽՅԹՄԽ ԼՁԽԼ ԹՌ ՌՀԽ ՀՁԿՀ ԻՇՆԻԽՆՌՊԹՌՁՇՆԬՎԽՊԹՄՄՅԽԹՆՋՍՊՎՁՎԹՄՎԹՄՍԽՋՏԽՊԽԹՆԼՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ

ՊԽՋՈԽԻՌՁՎԽՄՑ

ԱԹԺՄԽԞԼՍՄՌԣՁՋՀ԰ՍՊՎՁՎԹՄՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԰ՍՊՎՁՎՁՆԿ ԰ՍՊՎՁՎԹՄ Ն ԰ՍՊՎՁՎՁՆԿ ԰ՍՊՎՁՎԹՄ

ԠՇՆՌՊՇՄ
ԩԬԮ      

      

      

      

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ

 ԦՆՌՀՁՋՌԹԺՄԽ՟ՆՠՊԽԾԽՊՋՌՇՌՀԽՌՇՌԹՄՆՍՅԺԽՊՇԾԾՁՋՀՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

ԩԬԮՅԿԹՁԩ

Page 140 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԪԽԹՆՅԹՄԽԺՇԼՑՏԽՁԿՀՌՎԹՄՍԽՋՏԽՊԽԹՆԼԿԹՆԼԾԽՅԹՄԽԺՇԼՑՏԽՁԿՀՌՎԹՄՍԽՋՏԽՊԽԹՆԼԿՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ


ԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

ԱԹԺՄԽ԰ՁՒԽԹՌԱԽՋՌԱԽՊՅՁՆԹՌՁՇՆՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԟՇԼՑԴԽՁԿՀՌ ԩԽՆԿՌՀ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն

ԪԽԹՆ


Կ

չ԰ԡ Ն

ԪԽԹՆ


Կ

չ԰ԡ Ն

ԪԽԹՆ


ՅՅ

չ԰ԡ Ն

ԪԽԹՆ


ՅՅ

չ԰ԡ

ԠՇՆՌՊՇՄ
ԩԬԮ            

            

            

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

 ԦՆՌՀՁՋՌԹԺՄԽ՟ՆՠՊԽԾԽՊՋՌՇՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋ
ՌԹՆՃՋՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄ ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՀՁԿՀՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

Page 141 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԪԽԹՆԾԽԻՍՆԼՁՌՑՎԹՄՍԽՋՏԽՊԽԹՆԼԹՆԼԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋՏԹՋԹՆԼՁՆՌՀԽՅԽԹՆ

ՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

ԱԹԺՄԽԣԽԻՍՆԼՁՌՑԹՆԼԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԣԽԻՍՆԼՁՌՑ ԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋ


ԪԽԹՆ չ԰ԡ ԪԽԹՆ չ԰ԡ

ԠՇՆՌՊՇՄ
ԩԬԮ    

    

    

 ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ

 ԣԽԻՍՆԼՁՌՑՁՋԻԹՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋՈԽՊՋՍՊՎՁՎՁՆԿԾԽՅԹՄԽՈԽՊՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՈԽՊՊԽՈՄՁԻԹՌԽ



 ԣԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋ
ՁՋԻԹՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽՅԺՊՑՇՋԼՁՎՁԼԽԼԺՑՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋՅՍՄՌՁՈՄՁԽԼ

ԺՑ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

ԪԽԼՁԹՆՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՋՏԽՊԽԹՆԼՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄԹՆԼ

ՅԿ ԹՁԩ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄՋ ՊԽՋՈԽԻՌՁՎԽՄՑ 
ԱԹԺՄԽ ԫՇՆԽ ՇԾ ՌՀԽ ՋՍՊՎՁՎՁՆԿ ԾԽՅԹՄԽՋՏԽՊԽ ԾՇՍՆԼ ՌՇ ՀԹՎԽ

ՌՍԺԽՊԻՄԽՋ

Page 142 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԫՍՈՌՁԹՄԱՍԺԽՊԻՄԽ԰ԻՇՊԽՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆ

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ

Ն ԪԽԼՁԹՆ

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ

ԠՇՆՌՊՇՄ
ԩԬԮ    

    

    

 ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ



 ԦՆՌՀՁՋՌԹԺՄԽ՟ՆՠՊԽԾԽՊՋՌՇՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋ
ՌԹՆՃՋՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

ԪԽԹՆ ՅԹՄԽ Ԥ԰Ԧ ՏԹՋ   ԹՆԼ  ԹՆԼ ՅԽԹՆ ԾԽՅԹՄԽ Ԥ԰Ԧ ՏԹՋ   ԹՆԼ  ՁՆ ՌՀԽ ՅԽԹՆ

ՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

Page 143 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐ
Ԥ԰ԦՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն

ԪԽԹՆԤ԰Ԧ




չ԰ԡ Ն

ԪԽԹՆԤ԰Ԧ




չ԰ԡ

ԠՇՆՌՊՇՄ
ԩԬԮ      

      

      

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ

ԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
ՁՋԻԹՄԻՍՄԹՌԽԼԹՋԿՇՆԹԼՏԽՁԿՀՌ
ՌՇՌՀԽՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌ
ՅԿՐ





 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

ԪԽԼՁԹՆ ՅԹՄԽ ԿՇՆԹԼԹՄ ՋՌԹԿԽՏԹՋ   ԹՆԼ  ԹՆԼ ՅԽԼՁԹՆ ԾԽՅԹՄԽ ԿՇՆԹԼԹՄ ՋՌԹԿԽՏԹՋ   ԹՆԼ  ՁՆ ՌՀԽ

ՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ

Page 144 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆ԰ՌԹԿԽ Ն ԪԽԼՁԹՆ԰ՌԹԿԽ

ԠՇՆՌՊՇՄ
ԩԬԮ    

    

    

 ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԧԧՍՎԽՆՁՄԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼԲԱ԰ԲՆԹԺՄԽՌՇՋՌԹԿԽ

 ԦՆՌՀՁՋՌԹԺՄԽ՟ՆՠՊԽԾԽՊՋՌՇՌՀԽՌՇՌԹՄՆՍՅԺԽՊՇԾՁՆԼՁՎՁԼՍԹՄՋՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄՍՈՇՆՏՀՁԻՀՇԺՋԽՊՎԹՌՁՇՆՋՏԽՊԽՅԹԼԽԹՌ

ՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ



 ԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼՋՌՀԽԾՇՄՄՇՏՁՆԿԿՇՆԹԼԹՄՋՌԹԿՁՆԿՋԻԹՄԽԾՇՊՅԹՄԽԾԹՌՀԽԹԼՅՁՆՆՇՏՍՆԼԽՎԽՄՇՈԽԼԽԹՊՄՑ

ՋՈԽՊՅԹՌՇԿԽՆՁԻՅՁԼՋՈԽՊՅԹՌՇԿԽՆՁԻՄԹՌԽՋՈԽՊՅԹՌՇԿԽՆՁԻՋՈԽՆՌ



 ԱՀԽԿՍՁԼԽՄՁՆԽՊԽԻՇՅՅԽՆԼՋՌՀԽԾՇՄՄՇՏՁՆԿԿՇՆԹԼԹՄՋՌԹԿՁՆԿՋԻԹՄԽԾՇՊԾԽՅԹՄԽԾԹՌՀԽԹԼՅՁՆՆՇՏՍՆԼԽՎԽՄՇՈԽԼԽԹՊՄՑ

ԼԽՎԽՄՇՈՅԽՆՌՅՁԼԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՀՑԼՊԹՌԽԼՈՇՋՌՇՎՍՄԹՌՇՊՑ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

ԞԻԻՇՊԼՁՆԿՌՇՌՀԽՋՌՍԼՑՊԽՈՇՊՌՁՆՅԹՄԽԾՁՋՀՌՀԽՊԽՏԽՊԽԹՆՁՆԻՊԽԹՋԽԼՈԽՊԻԽՆՌԹԿԽՇԾՋՈԽՊՅԹՌՇԿՇՆՁԹ
ԱԹԺՄԽ

ՁՆՌՀԽՅԿ ԹՁԩ ԿՊՇՍՈՏՁՌՀԾՇՍՊՅՁՆՁՅԹՄՌՇՅՁՄԼ ՁՆԻՁԼԽՆԻԽՋ ՇՍՌ ՇԾ ՁՆԼՁՎՁԼՍԹՄՋԱՏՇՅԹՄԽՋ ԹՄՋՇ

ՀԹԼՅՁՄԼԼՁԾԾՍՋԽՌՀՁԻՃԽՆՁՆԿՇԾՌՀԽԿԽՊՅՁՆԹՄԽՈՁՌՀԽՄՁՍՅՄՁՆՁՆԿԺՑՋՈԽՊՅԹՌՇԿՇՆՁԹԱՀԽՊԽՏԽՊԽՌՏՇՁՆԻՁԼԽՆԻԽՋՇԾ

ՅՁՆՁՅԹՄՁՆԻՊԽԹՋԽԼՌԽՋՌՁԻՍՄԹՊԼԽԿԽՆԽՊԹՌՁՇՆՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՋՏՁՌՀԻՇՆԻՍՊՊԽՆՌ

ՅՁՆՁՅԹՄՁՆՌԽՊՋՌՁՌՁԹՄԻԽՄՄՀՑՈԽՊՈՄԹՋՁԹՁՆՌՀԽԻՇՆՌՊՇՄՅԹՄԽԹՆԼՅՁՆՁՅԹՄՄՑՁՆԻՊԽԹՋԽԼՈՊՇՈՇՊՌՁՇՆՇԾՋՈԽՊՅԹՌՇԿՇՆՁԹՁՆ

ՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԱՀԽՊԽՏԽՊԽՌՀՊԽԽՁՆԻՁԼԽՆԻԽՋՇԾՅՁՆՁՅԹՄՁՆՌԽՊՋՌՁՌՁԹՄԻԽՄՄՀՑՈԽՊՈՄԹՋՁԹՇՆԽՁՆՌՀԽ

ԻՇՆՌՊՇՄԹՆԼՌՏՇՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԱՀԽՊԽՏԽՊԽԹՄՋՇՇՆԽԻՇՆՌՊՇՄԹՆԼՇՆԽՅԹՄԽԾՊՇՅՌՀԽ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌՏՁՌՀՅՁՆՁՅԹՄԹՋՑՆԻՀՊՇՆՇՍՋԿՇՆԹԼԼԽՎԽՄՇՈՅԽՆՌ
ԱԹԺՄԽ

ԞՄՋՇԹԻԻՇՊԼՁՆԿՌՇՌՀԽՋՌՍԼՑՊԽՈՇՊՌՁՆԾԽՅԹՄԽՋՌՀԽՊԽՏԽՊԽՅՁՄԼԹՆԼՋԽՎԽՊԽՁՆԻՁԼԽՆԻԽՋՇԾԼԽԻՊԽԹՋԽԼՑՇՄՃ

ՋՑՆՌՀԽՋՁՋՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՅՁՆՁՅԹՄՅՁՄԼՅՇԼԽՊԹՌԽԹՆԼՋԽՎԽՊԽՁՆԻՁԼԽՆԻԽ

ՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ
ԱԹԺՄԽԱՀԽՇՆԽԾԽՅԹՄԽՅՇԼԽՊԹՌԽՄՑԹԾԾԽԻՌԽԼԹՄՋՇՀԹԼԹԺՍՆԼԹՆՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԳԱԤՁՆՇՆՄՑԹԾԽՏԾՇՄՄՁԻՄԽՋՏՁՌՀՌՏՇԾԽՅԹՄԽՋՋԽՎԽՊԽՄՑԹԾԾԽԻՌԽԼ
ՇՆԽԽԹԻՀՁՆՌՀԽԹՆԼՅԿԹՁԩ

ԿՊՇՍՈՋ ՏՁՌՀ ՄՁՌՌՄԽ ԳԱԤ ԾՇՊՅԹՌՁՇՆ ԱՀԽ ԾԽՅԹՄԽ ՏՁՌՀ ՌՀԽ ՋԽՎԽՊԽ ԼԽԻՊԽԹՋԽԼ ՑՇՄՃ ՋՑՆՌՀԽՋՁՋ ՁՆ ՌՀԽ  ՅԿ

ԹՁԩ ԿՊՇՍՈ ԹՄՋՇ ՀԹԼ ՋԽՎԽՊԽ ԿՊԹՆՍՄՇՅԹՌՇՍՋ ՁՆԾՄԹՅՅԹՌՁՇՆ ՏՁՌՀՁՆ ՌՀԽ ՇՎԹՊՑ 
ԱԹԺՄԽ  ԤՊԹՆՍՄՇՅԹՌՇՍՋ

ՁՆԾՄԹՅՅԹՌՁՇՆ ՏԹՋ ՆՇՌ ՈՊԽՋԽՆՌ ՁՆ ՌՀԽ ՋԽՎԽՊԽՄՑ ԹԾԾԽԻՌԽԼ ԾԽՅԹՄԽ ԾՊՇՅ ՌՀԽ  ՅԿ ԹՁԩ ԿՊՇՍՈ ԺՍՌ ՏԹՋ

ԻՇՅՅՇՆՏՁՌՀՋԽՎԽՆԾԽՅԹՄԽՋՁՆՌՀԽԻՇՆՌՊՇՄՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԹՆԼՁՆՌՀԽՅԿ

ԹՁԩ 
ՅՁՆՁՅԹՄ ՌՇ ՅՁՄԼ ԹՆԼ ԹՋՋՇԻՁԹՌԽԼ ՏՁՌՀ ՁՆԻՊԽԹՋԽԼ ՇՇԻՑՌԽ ԹՌՊԽՋՁԹ ԽՁԿՀՌ ԻԹՋԽՋ ՀԹԼ ՈՊՇՌՇՒՇԹՄ ՋՈՇՊԽՋ

ՏՁՌՀՁՆԿՊԹՆՍՄՇՅԹՋԞՆՁՆԻՊԽԹՋԽՁՆՇՇԻՑՌԽԹՌՊԽՋՁԹՏԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՏՁՌՀ

ԹՆԼՇԾՌՀԽԾՁՋՀԽՐՀՁԺՁՌՁՆԿՌՀՁՋԾՁՆԼՁՆԿՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼՄՇՏԹՆԼՅՁԼՌՊԽԹՌՅԽՆՌՋՊԽՋՈԽԻՌՁՎԽՄՑԱՀԽՊԽ

ՏԹՋ ՇՆԽ ՁՆԻՁԼԽՆԻԽ ՇԾ ՄՑՅՈՀՇԻՑՌՁԻ ՁՆԾՁՄՌՊԹՌԽՋՏՁՌՀՁՆՌՀԽ ՇՎՁԼՍԻՌ ՁՆ ՌՀԽ ՅԿ ԹՁԩ ԿՊՇՍՈ ԹՆԼ  ՁՆՌՀԽ

 ՅԿ ԹՁԩ ԱՀԽՊԽ ՏԹՋ ՅՁՆՁՅԹՄ ՁՆՌԽՊՋՌՁՌՁԹՄ ԾՁԺՊՇՋՁՋ ՁՆ ՌՀԽ  ՅԿ ԹՁԩ ԿՊՇՍՈ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ

ԭՊԽՋԽՆԻԽՇԾ

ԱԽՋՌՁՋԬՎԹ

ԦՆԻՊԽԹՋԽԼ

ԱԽՋՌՁԻՍՄԹՊ

ԡԽԿԽՆԽՊԹՌՁՇՆ

ԦՆՌԽՊՋՌՁՌՁԹՄԠԽՄՄ


ԩԽՑԼՁԿ

ՀՑՈԽՊՌՊՇՈՀՑ

ՀՑՈԽՊՈՄԹՋՁԹ

ԤԽՊՅՁՆԹՄ

ԢՈՁՌՀԽՄՁՍՅ

ԞՌՊՇՈՀՑ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ


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 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ



 ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄ

ԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԡԽԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ

ԦՆԻՊԽԹՋԽԼԳԹՋԻՍՄԹՊ

ՇՊԦՆՌԽՊՋՌՁՌՁԹՄ

ԭՊՇՌԽՁՆԹԻԽՇՍՋԣՄՍՁԼ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԤՇՆԹԼ

ԡԽՎԽՄՇՈՅԽՆՌ

ԞՄՌԽՊԽԼԭՊՇՈՇՊՌՁՇՆՋ

ՇԾ԰ՈԽՊՅԹՌՇԻՑՌԽՋ

ՇՊ԰ՈԽՊՅԹՌՁԼՋ

ԤՊԹՆՍՄՇՅԹՌՇՍՋ

ԦՆԾՄԹՅՅԹՌՁՇՆ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԩԬԮ           

          

                              

           

          

                              

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԡԽԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ

ԦՆԻՊԽԹՋԽԼԳԹՋԻՍՄԹՊ

ՇՊԦՆՌԽՊՋՌՁՌՁԹՄ

ԭՊՇՌԽՁՆԹԻԽՇՍՋԣՄՍՁԼ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԤՇՆԹԼ

ԡԽՎԽՄՇՈՅԽՆՌ

ԞՄՌԽՊԽԼԭՊՇՈՇՊՌՁՇՆՋ

ՇԾ԰ՈԽՊՅԹՌՇԻՑՌԽՋ

ՇՊ԰ՈԽՊՅԹՌՁԼՋ

ԤՊԹՆՍՄՇՅԹՌՇՍՋ

ԦՆԾՄԹՅՅԹՌՁՇՆ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

           

          

                              

  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾ

ՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽ

ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆԻՊԽԹՋԽԼԬՇԻՑՌԽ

ԞՌՊԽՋՁԹ

ԭԽՊՁԾՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

ԥՑՈԽՊՌՊՇՈՀՑ

ԡԽԻՊԽԹՋԽԼԶՇՄՃ

ԣՇՊՅԹՌՁՇՆ

ԦՆԾԽԻՌՁՇՆ

ԪՁԻՊՇՋՈՇՊՁԼՁԹ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
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

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆԻՊԽԹՋԽԼԬՇԻՑՌԽ

ԞՌՊԽՋՁԹ

ԭԽՊՁԾՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

ԥՑՈԽՊՌՊՇՈՀՑ

ԡԽԻՊԽԹՋԽԼԶՇՄՃ

ԣՇՊՅԹՌՁՇՆ

ԦՆԾԽԻՌՁՇՆ

ԪՁԻՊՇՋՈՇՊՁԼՁԹ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ



 ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄ

ԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋ

ՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆՌԽՊՋՌՁՌՁԹՄԣՁԺՊՇՋՁՋ

ԢԿԿԡԽԺՊՁՋՁՆ

ԬՎՁԼՍԻՌ

ԤՊԹՆՍՄՇՅԹՌՇՍՋ

ԦՆԾՄԹՅՅԹՌՁՇՆ

ԡԽԻՊԽԹՋԽԼԭՇՋՌ

ԬՎՍՄԹՌՇՊՑԣՇՄՄՁԻՄԽՋ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
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 ԫԞ

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ



 ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄ

ԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԪԽԹՆՅԹՄԽԳԱԤՏԹՋՐ

ՐԹՆԼՐԹՆԼԾԽՅԹՄԽԳԱԤՏԹՋՐՐԹՆԼՐ

ՁՆՌՀԽՅԽԹՆՅԽԹՋՍՊԽԼ
ԻՇՆՌՊՇՄԹՆԼՅԿԹՁՅԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ
ԱԹԺՄԽ



ԱԹԺՄԽԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆ
ԳԱԤ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն

ԪԽԹՆ


ՆԿՅԩՈՄԹՋՅԹ

չ԰ԡ Ն

ԪԽԹՆ


ՆԿՅԩՈՄԹՋՅԹ

չ԰ԡ

ԠՇՆՌՊՇՄ
ԩԬԮ  Ր Ր  Ր Ր

  Ր Ր  Ր Ր

  Ր Ր  Ր Ր

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԫԡԫՇՌԼԽՌԽՊՅՁՆԽԼ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ



 ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆՋԻԹՄԻՍՄԹՌԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊ



 ԫՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑ

ԩԬԮՅԿԹՁԩ

ԱԹԺՄԽԭՄԹՋՅԹ԰ԽՐ԰ՌԽՊՇՁԼՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԫՇՌՅԽԹՋՍՊԽԼ

ԱՀՁՋՌԹԺՄԽՁՋՇՅՁՌՌԽԼԺԽԻԹՍՋԽՋԽՐՋՌԽՊՇՁԼՋՏԽՊԽՆՇՌՅԽԹՋՍՊԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱՀԽՊԽՏԽՊԽՆՇՆՇՌԹԺՄԽՇԺՋԽՊՎԹՌՁՇՆՋՏՁՌՀՊԽԿԹՊԼՋՌՇԻՇՄՇՊԹՌՁՇՆԺԹՆԼՁՆԿԻՀԹՆԿԽՋՁՆՇՎՁՈՇՋՁՌՇՊԹՈՈԽԹՊԹՆԻԽՇՊՋՁՒԽՇԾԼՇՊՋԹՄՆԹՈԽՈԹԼԱՀԽՈՊԽՋԽՆԻԽ

ՇԾԻՇՄՇՊԽԼԺԹՊՋ
ԺԹՆԼՁՆԿՁՆՅԹՄԽԾՁՋՀԺՍՌՆՇՌԾԽՅԹՄԽԾՁՋՀ
ԱԹԺՄԽՁՋԻՇՆՋՁԼԽՊԽԼՆՇՊՅԹՄՋԽՐՍԹՄԼՁՅՇՊՈՀՁՋՅԾՇՊՌՀՁՋՋՈԽԻՁԽՋԥՇՏԽՎԽՊՋՁԿՆՋՇԾ

ՅՇՊԺՁԼՁՌՑՁՆԻՄՍԼՁՆԿՄԽՌՀԹՊԿՑԹՆԼՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅՏԽՊԽՇԺՋԽՊՎԽԼՁՆԾՁՋՀԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ԱԹԺՄԽ

ԱԹԺՄԽ԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԹՌԱԽՋՌԱԽՊՅՁՆԹՌՁՇՆ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

ԱՑՈԽ Ն ԦՆԻՁԼԽՆԻԽ ԱՑՈԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԩԬԮ ԠՇՄՇՊԺԹՊՋ   ԫՇՆԽ  

 ԠՇՄՇՊԺԹՊՋ   ԫՇՆԽ  

 ԡԽԾՇՊՅԽԼՄԽՌՀԹՊԿՁԻ   ԩԽՌՀԹՊԿՁԻՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅ  

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

 ԫՇՌԽՌՀԹՌՆՍՈՌՁԹՄՌՍԺԽՊԻՄԽՋԻՇՊԽՁՋՊԽՈՇՊՌԽԼՈՊԽՎՁՇՍՋՄՑՁՆԱԹԺՄԽ ԦՆՌՀՁՋՌԹԺՄԽ՟ՆՠՊԽԾԽՊՋՌՇՌՀԽՆՍՅԺԽՊՇԾՁՆԼՁՎՁԼՍԹՄՋՍՈՇՆՏՀՁԻՀՇԺՋԽՊՎԹՌՁՇՆՋՏԽՊԽՅԹԼԽԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆԩԬԮՅԿԹՁԩ

Page 154 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԟ ԰ՌՍԼՑԞՍՌՀՇՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

ԱՀԽՋՌՍԼՑԹՍՌՀՇՊԹՆԹՄՑՒԽԼՋՍՊՎՁՎԹՄՏԽՁԿՀՌՄԽՆԿՌՀՌՍԺԽՊԻՄԽՋԻՇՊԽԤ԰ԦԾԽՊՌՁՄՁՌՑԾԽԻՍՆԼՁՌՑԹՆԼԳԱԤ

ԡԹՌԹՏԽՊԽԿԽՆԼԽՊՋՈԽԻՁԾՁԻԹՆԼԹՆԹՄՑՒԽԼՁՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋ

ԡԽՋԻՊՁՈՌՁՎԽՋՌԹՌՁՋՌՁԻՋ
ՅԽԹՆՋՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆԽՌԻՏԽՊԽԼԽՌԽՊՅՁՆԽԼԾՇՊԽԹԻՀԽՆԼՈՇՁՆՌ԰ՁԿՆՁԾՁԻԹՆՌ

ԽԾԾԽԻՌՋՏԽՊԽ ԼԽՌԽԻՌԽԼ ԾՇՊ ՈՏՁՌՀ ՌՀԽ ԽՐԻԽՈՌՁՇՆ ՇԾ ԰ՀԹՈՁՊՇԴՁՄՃ0Ջ ԹՆԼ ԟԹՊՌՄԽՌՌ0Ջ ԱԽՋՌՋՏՀՁԻՀ

ՏԽՊԽԺԹՋԽԼՇՆՈ
ԠԢԱԦ԰ԳԽՊՋՁՇՆ԰ՍՊՎՁՎԹՄԼԹՌԹՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿԹԣՁՋՀԽՊ0ՋԽՐԹԻՌ

ՌԽՋՌ
ՏՁՌՀԟՇՆԾԽՊՊՇՆՁԥՇՄՅԹԼՂՍՋՌՅԽՆՌԪԹՄԽԤ԰ԦԾԽԻՍՆԼՁՌՑԹՆԼԳԱԤՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿԞԫԬԳԞ

ԹՆԼ Թ ՇՆԽՌԹՁՄԽԼ ԡՍՆՆԽՌՌ0Ջ ՌԽՋՌ ԣԽՊՌՁՄՁՌՑ ՅԹՄԽ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽ ՅԹՄԽ ՏԽՁԿՀՌ ԹՆԼ ԾԽՅԹՄԽ Ԥ԰Ԧ ԼԹՌԹ

ՏԽՊԽԹՆԹՄՑՒԽԼԺՑԞԫԬԳԞԹՆԼԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԭՊՁՇՊՌՇԡՍՆՆԽՌՌ0ՋԼԹՌԹՏԽՊԽԹՆԹՄՑՒԽԼԺՑ

԰ՀԹՈՁՊՇԴՁՄՃ0ՋՌԽՋՌԹՆԼԩԽՎԽՆԽ0ՋՌՇՌԽՋՌԾՇՊՆՇՊՅԹՄՁՌՑԹՆԼՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՋՊԽՋՈԽԻՌՁՎԽՄՑԦԾ

ՆՇՊՅԹՄՁՌՑ ԹՆԼ ՀՇՅՇԿԽՆԽՁՌՑ ՌԽՋՌՋ ՏԽՊԽ ՈԹՋՋԽԼ 
Ո  Թ ՈԹՊԹՅԽՌՊՁԻ ԹՆԹՄՑՋՁՋ ՏԹՋ ՈԽՊԾՇՊՅԽԼ ԦԾ

ՆՇՆՆՇՊՅԹՄՁՌՑ ՇՊ ՍՆԽՉՍԹՄ ՎԹՊՁԹՆԻԽ ՏԽՊԽ ՁՆԼՁԻԹՌԽԼ 
Ո Թ ՆՇՆՈԹՊԹՅԽՌՊՁԻ ԹՆԹՄՑՋՁՋ ՏԹՋ

ՈԽՊԾՇՊՅԽԼ ՇՆ ՌՀԽ ՊԹՆՃՋ ՇԾ ՌՀԽ ԼԹՌԹ ԱՀԽՋԽ ՅԽՌՀՇԼՋ ԹՈՈԽԹՊ ՌՇ ԺԽ ԻՇՆՋՁՋՌԽՆՌ ՏՁՌՀ ՌՀԽ ՅԽՌՀՇԼՋ

ՊԽԻՇՅՅԽՆԼԽԼՁՆՌՀԽԿՍՁԼԽՄՁՆԽ

ԣՇՊ ԹՄՄ ՋՌՍԼՑ ԹՍՌՀՇՊ ՊԽՋՍՄՌՋՌՀԽ ԽՆԼՈՇՁՆՌՋ ԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ 
ՅԿ ԹՁԩՏԽՊԽ ՆՇՌ

ՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼԼՍԽՌՇՅՇՊՌԹՄՁՌՑԱՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋԹՌՌՀԽՅԿ

ԹՁԩԻՇՆԻԽՆՌՊԹՌՁՇՆՅԽՌՌՀԽԿՍՁԼԽՄՁՆԽԼԽԾՁՆՁՌՁՇՆՇԾՇՎԽՊՌՅՇՊԺՁԼՁՌՑՌՀԽՊԽԾՇՊԽՊԽԼՍԻՌՁՇՆՋԾՇՊԽՆԼՈՇՁՆՌՋ

ԹՌՌՀՁՋԻՇՆԻԽՆՌՊԹՌՁՇՆԻԹՆԺԽ՟ԹՌՌՊՁԺՍՌԽԼՌՇԿԽՆԽՊԹՄՌՇՐՁԻՁՌՑԹՋՇՈՈՇՋԽԼՌՇԽԾԾԽԻՌՋՊԽՄԹՌԽԼՌՇԽՆԼՇԻՊՁՆԽ

ԹԻՌՁՎՁՌՑՠ ԞԼՍՄՌ ՋՍՊՎՁՎԹՄ 
ԻՇՅԺՁՆԽԼ ՋԽՐԽՋ ԹՌ ՌՀԽ  ՅԿ ԹՁԩ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ 
 ՏԹՋ

ՋՁԿՆՁԾՁԻԹՆՌՄՑ ԼՁԾԾԽՊԽՆՌ ԻՇՅՈԹՊԽԼՌՇՌՀԽԻՇՆՌՊՇՄՋ 
 ՈԣՁՋՀԽՊԢՐԹԻՌԟՇՆԾԽՊՊՇՆՁԥՇՄՅՌԽՋՌ

ԱԹԺՄԽԱՀԽՊԽՏԹՋԹՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼԽԻՊԽԹՋԽՁՆԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋԹՌՅԿԹՁԩ

ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄՋ ԻՇՅՈԹՊԽԼ ՌՇ ՌՀԽ ԻՇՆՌՊՇՄ 
Ո ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ՌԽՋՌ ԱԹԺՄԽ ԴՀՁՄԽ ՆՇՌ

ՋՌԹՌՁՋՌՁԻԹՄՄՑԼՁԾԾԽՊԽՆՌԾՊՇՅՌՀԽԻՇՆՌՊՇՄՌՀԽՋՍՈՈՊԽՋՋՁՇՆՇԾԾԽԻՍՆԼՁՌՑՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌ

ՏԹՋԻՇՆՋՁԼԽՊԽԼԺՁՇՄՇԿՁԻԹՄՄՑՊԽՄԽՎԹՆՌ
Ո ԡՍՆՆԽՌՌ0ՋԣՇՊՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽԹՆԼԺՇԼՑՏԽՁԿՀՌ

ՌՀԽՋՌՍԼՑԹՍՌՀՇՊՆՇՌԽԼ ՊԽԼՍԻՌՁՇՆՋՁՆԽՆԼՈՇՁՆՌՋՇԺՋԽՊՎԽԼԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ՌՀԹՌՅԽՌԿՍՁԼԽՄՁՆԽԼԽԾՁՆՁՌՁՇՆՇԾՇՎԽՊՌՅՇՊԺՁԼՁՌՑՌՀԽՊԽԾՇՊԽՌՀԽՋԽՊԽԼՍԻՌՁՇՆՋՏԽՊԽԹՌՌՊՁԺՍՌԽԼՌՇԿԽՆԽՊԹՄ

ՌՇՐՁԻՁՌՑ ԹՋ ՇՈՈՇՋԽԼ ՌՇ ԽԾԾԽԻՌՋ ՊԽՄԹՌԽԼ ՌՇ ԽՆԼՇԻՊՁՆԽ ԹԻՌՁՎՁՌՑ 
ԱԹԺՄԽՋ  ԹՆԼ  ԱՀԽՊԽ ՏԹՋ Թ

ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌ ԼԽԻՊԽԹՋԽ ՁՆ ՅԽԼՁԹՆ ԾԽՅԹՄԽ Ԥ԰Ԧ ՁՆ ՌՀԽ  ՅԿ ԹՁԩ ՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈ

ԻՇՅՈԹՊԽԼՌՇՌՀԽԻՇՆՌՊՇՄ
ՈԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԱԹԺՄԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԞՄՌՀՇՍԿՀՆՇՌԹՆԹՄՑՒԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՌՀԽՊԽՏԽՊԽԿԽՆԽՊԹՄՁՒԽԼՇՎԽՊՌՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑՁՆԺՇՌՀՅԹՄԽՋԹՆԼ

ԾԽՅԹՄԽՋՁՆԻՄՍԼՁՆԿԹՄՄՋՍՊՎՁՎՁՆԿԾՁՋՀԹՌՌՀԽՅԿ ԹՁԩՌՊԽԹՌՅԽՆՌՏՀՁԻՀՏԽՊԽՇԺՋԽՊՎԽԼՌՇԺԽ

ՄԽՌՀԹՊԿՁԻ
ԱԹԺՄԽԦՆՅԹՄԽԾՁՋՀՌՀԽՊԽՏԹՋԹՄՋՇԹՆՁՆԻՊԽԹՋԽԼՈԽՊԻԽՆՌԹԿԽՇԾՋՈԽՊՅԹՌՇԿՇՆՁԹՁՆՌՀԽ

ՅԿԹՁԩԿՊՇՍՈԹՆԼՁՆԾԽՅԹՄԽԾՁՋՀԼԽԻՊԽԹՋԽԼՑՇՄՃՋՑՆՌՀԽՋՁՋՁՆԺՇՌՀՌՀԽԹՆԼ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌՋՊԽՄԹՌՁՎԽՌՇՌՀԽԻՇՆՌՊՇՄՋ
ԱԹԺՄԽՋԹՆԼ

ԠԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄ ԪԽՌՀՇԼՋ  ԱՀԽ ՊԽՎՁԽՏԽՊ ԹՆԹՄՑՒԽԼ ՋՍՊՎՁՎԹՄ 
ՅՇՊՌԹՄՁՌՑ ԼԹՌԹ ԾՇՊ ՅԹՄԽ ԹՆԼ ԾԽՅԹՄԽ ԾՁՋՀ

ԻՇՅԺՁՆԽԼՍՋՁՆԿԣՁՋՀԽՊ0ՋԢՐԹԻՌՌԽՋՌՎՁԹԱՇՐՋՌԹՌԣԽՅԹՄԽԺՇԼՑՏԽՁԿՀՌԹՆԼՄԽՆԿՌՀՅԹՄԽՄԽՆԿՌՀ

ՅԹՄԽ ԿՇՆԹԼՇՋՇՅԹՌՁԻ ՁՆԼԽՐ 
Ԥ԰Ԧ ԹՆԼ ԾԽՅԹՄԽ ՎՁՌԽՄՄՇԿԽՆՁՆ 
ԳԱԤ ՏԽՊԽ ՆՇՌ ԻՇՆՋՁՋՌԽՆՌ ՏՁՌՀ Թ

ՅՇՆՇՌՇՆՁԻ ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ ԞՄՄ ԼԹՌԹՏԽՊԽ ՌԽՋՌԽԼ ԾՇՊ ՆՇՊՅԹՄՁՌՑ ՍՋՁՆԿ ԰ՀԹՈՁՊՇԴՁՄՃՋ ՌԽՋՌ ԹՆԼ

ԾՇՊՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՍՋՁՆԿԩԽՎԽՆԽ0ՋՌԽՋՌԱՀԽՋԽԼԹՌԹՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՆՇՊՅԹՄՁՌՑԹՆԼ

ՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽԹՆԼՏԽՊԽՌՀԽՆԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՈԹՊԹՅԽՌՊՁԻՌՏՇՋՁԼԽԼԡՍՆՆԽՌՌ0ՋՌԽՋՌ

ԪԹՄԽՅԽԼՁԹՆՌՍԺԽՊԻՄԽՋԻՇՊԽԼՁԼՆՇՌԽՐՀՁԺՁՌԹԻՄԽԹՊՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽԹՆԼՌՀԽՊԽԾՇՊԽՏԹՋԹՆԹՄՑՒԽԼ

ՍՋՁՆԿՌՀԽՌՏՇՋՁԼԽԪԹՆՆԴՀՁՌՆԽՑՌԽՋՌ

ԣԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋՅԹՄԽՈՄԹՋՅԹԳԱԤԹՆԼՅԹՄԽԺՇԼՑՏԽՁԿՀՌԽԹԻՀԽՐՀՁԺՁՌԽԼԹՆԹՈՈԹՊԽՆՌ

ՅՇՆՇՌՇՆՁԻԹՄՄՑ ԼԽԻՊԽԹՋՁՆԿ ՌՊԽՆԼ ՏՀԽՆ ԻՇՅՈԹՊԽԼ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ ՌՀԽՋԽ ԽՆԼՈՇՁՆՌՋ ՏԽՊԽ

ԹՆԹՄՑՒԽԼԾՇՊՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌԽՋՌ

ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՁՆԼՁԻԹՌԽԼ ԽԾԾԽԻՌՋ ՏԽՊԽ ԻՇՆՋՁԼԽՊԽԼ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ՋՁԿՆՁԾՁԻԹՆՌ ԹՌ Ո ԴՁՌՀ ՌՀԽ

ԽՐԻԽՈՌՁՇՆ ՇԾ ԣՁՋՀԽՊ0Ջ ԢՐԹԻՌ ԱԽՋՌ ԹՄՄ ԹՆԹՄՑՋԽՋՏԽՊԽ ԻՇՆԼՍԻՌԽԼ ՍՋՁՆԿ ՌՀԽ ԣԦ԰ԥ ՈՊՇԻԽԼՍՊԽ ՁՆ ԰Ԟ԰ն


԰Ԟ԰ԦՆՋՌՁՌՍՌԽԠԹՊՑԫԠՎԽՊՋՁՇՆ

ԫՇՆԽՇԾՌՀԽՋՍՊՎՁՎՁՆԿԾԽՅԹՄԽՋՏԽՊԽԾՇՍՆԼՌՇՀԹՎԽՌՍԺԽՊԻՄԽՋԱՀԽՊԽԾՇՊԽԾԽՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՏԹՋ

ՆՇՌ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ԹՆԹՄՑՒԽԼ ԥՁՋՌՇՈԹՌՀՇՄՇԿՑ ՇԺՋԽՊՎԹՌՁՇՆՋ ՏԽՊԽ ԽՎԹՄՍԹՌԽԼ ՁՆ ԻՇՆՂՍՆԻՌՁՇՆ ՏՁՌՀ ՌՀԽ

ՈԹՌՀՇՄՇԿՁՋՌ0ՋՊԽՈՇՊՌԺՍՌՋԽՎԽՊՁՌՑԹՆԼՁՆԻՁԼԽՆԻԽԼԹՌԹՏԽՊԽՆՇՌՋՍԺՂԽԻՌԽԼՌՇԾՇՊՅԹՄՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 ԠՇՆԻՄՍՋՁՇՆՋ

԰ՍՊՎՁՎԹՄՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼ
ՈՌՇՇԾՌՀԽԻՇՆՌՊՇՄԹՌՌՀԽՁՆՌԽՊՅԽԼՁԹՌԽՌՊԽԹՌՅԽՆՌՄԽՎԽՄ


ԱԹԺՄԽ  ԹՆԼ ԾՍՊՌՀԽՊ ՊԽԼՍԻԽԼ ՌՇ  
ՌՀՇՍԿՀ ՆՇՌ ՋՌԹՌՁՋՌՁԻԹՄՄՑ ԹՆԹՄՑՒԽԼ ԹՌ ՌՀԽ ՀՁԿՀԽՋՌ ՌՊԽԹՌՅԽՆՌ

ՄԽՎԽՄՅԿԹՁԩՏՀՁԻՀՏԹՋԽՐԻՄՍԼԽԼԾՊՇՅԹՆԹՄՑՋԽՋԣՁՋՀՁՆՌՀԽՁՆՌԽՊՅԽԼՁԹՌԽՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԼՁՋՈՄԹՑԽԼ ՋՁԿՆՋ ՇԾ ՅՇՊԺՁԼՁՌՑ ՁՆԻՄՍԼՁՆԿ ՄԽՌՀԹՊԿՑ ԹՆԼ ՄՇՋՋ ՇԾ ԽՉՍՁՄՁԺՊՁՍՅ ԞՄՌՀՇՍԿՀ ՌՀԽ ՁՆՌԽՊՅԽԼՁԹՌԽ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏԹՋՆՇՌԽՐԻՄՍԼԽԼԾՊՇՅՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋՌՀԽՈՊԽՋԽՆԻԽՇԾԻՄՁՆՁԻԹՄՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑԹՌ

ՌՀՁՋ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ ՋՀՇՍՄԼ ԺԽ ԻՇՆՋՁԼԽՊԽԼ ՏՀԽՆ ՁՆՌԽՊՈՊԽՌՁՆԿ ՌՀԽ ՊԽՋՍՄՌՋ ԞԼԼՁՌՁՇՆԹՄՄՑ ՌՀԽ ՇՎԽՊԹՄՄ

ՋՍՊՎՁՎԹՄՁՆՌՀԽՄՇՏԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈ
ՅԿԹՁԩՏԹՋՏՁՌՀՌՀՊԽԽՇԾՌՀԽԾՇՍՊԾԽՅԹՄԽՋՁՆ

ՇՆԽ ՊԽՈՄՁԻԹՌԽ ԼԽԹԼ ԹԿԹՁՆ ՌՀՁՋ ՊԽՈՄՁԻԹՌԽ ՏԹՋ ՆՇՌ ԽՐԻՄՍԼԽԼ ԾՊՇՅ ՌՀԽ ԹՆԹՄՑՋԽՋ ԺՍՌ ՋՀՇՍՄԼ ԺԽ

ԻՇՆՋՁԼԽՊԽԼՏՀԽՆՁՆՌԽՊՈՊԽՌՁՆԿՌՀԽՊԽՋՍՄՌՋ

ԣԽԻՍՆԼՁՌՑ 
Ո ԹՆԼ ԾԽՊՌՁՄՁՌՑ 
Ո ԹՌ ՌՀԽ ՁՆՌԽՊՅԽԼՁԹՌԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՏԽՊԽ ՋՁԿՆՁԾՁԻԹՆՌՄՑ

ԼԽԻՊԽԹՋԽԼ ՏՀԽՆ ԻՇՅՈԹՊԽԼ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ ԢԾԾԽԻՌՋ ՇՆ ԾԽՅԹՄԽ ԿՇՆԹԼԹՄ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑ

ՁՆԻՄՍԼՁՆԿ ԼԽԻՊԽԹՋԽԼ ՑՇՄՃ ՋՑՆՌՀԽՋՁՋ ՏԽՊԽ ՇԺՋԽՊՎԽԼ ԹՌ ՌՀԽ ՄՇՏ ԹՆԼ ՁՆՌԽՊՅԽԼՁԹՌԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԣԽՅԹՄԽ Ԥ԰Ԧ 
Ո ՏԹՋ ՋՁԿՆՁԾՁԻԹՆՌՄՑ ԼԽԻՊԽԹՋԽԼ ԹՌ ՁՆՌԽՊՅԽԼՁԹՌԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ԴՀՁՄԽ ՆՇՌ

ՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՏԽՊԽ ՊԽԼՍԻԽԼԺՑԹՌՌՀԽ ՁՆՌԽՊՅԽԼՁԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆ


ԪԹՆՆԴՀՁՌՆԽՑՈԦՆՅԹՄԽԾՁՋՀՌՀԽՊԽՏԹՋԹՄՋՇԹՆՁՆԻՊԽԹՋԽԼՈԽՊԻԽՆՌԹԿԽՇԾՋՈԽՊՅԹՌՇԿՇՆՁԹԹՌ

ՌՀՁՋՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԴՀՁՄԽ ՆՇՌ ՋՁԿՆՁԾՁԻԹՆՌՄՑ ԼՁԾԾԽՊԽՆՌ ՌՀԽՊԽ ՏԹՋ Թ  ՁՆԻՊԽԹՋԽ ՁՆ ՅԹՄԽ ԳԱԤ ԹՌ ՌՀԽ ՁՆՌԽՊՅԽԼՁԹՌԽ

ԻՇՆԻԽՆՌՊԹՌՁՇՆԿՊՇՍՈԻՇՅՈԹՊԽԼՌՇՌՀԽԻՇՆՌՊՇՄՌՀՁՋԼՁԾԾԽՊԽՆԻԽՁՋԼՍԽՌՇՌՏՇՅԹՄԽՋՁՆՌՀՁՋԿՊՇՍՈՏՁՌՀ

ՀՁԿՀԽՊԳԱԤՄԽՎԽՄՋԻՇՅՈԹՊԽԼՌՇՌՀԽԻՇՆՌՊՇՄ

ԟՇԼՑՏԽՁԿՀՌԹՆԼՄԽՆԿՌՀՏԽՊԽՆՇՌՋՁԿՆՁԾՁԻԹՆՌՄՑԼՁԾԾԽՊԽՆՌՁՆՅԹՄԽՇՊԾԽՅԹՄԽԾՁՋՀԹՌԹՆՑՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ Ԥ԰Ԧ

ԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿ

ԹՆԼԥՁՋՌՇ

ԭՄԹՋՅԹԳԱԤ

ԪԽԼՁԹՆ Ո ԡՁԾԾ Ո ԢԾԾԽԻՌ!
ԶԽՋԫՇ ԡՁԾԾ ԭ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮ  ԫԞ  ԫԞ ԫՇ  ԫԞ

     ԫՇ  

     ԶԽՋ  

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԪԹՆՆԴՀՁՌՆԽՑ ԡՍՆՆԽՌՌ0Ջ ԫԞ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԠՇՆԻԠՇՆԻԽՆՌՊԹՌՁՇՆԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢԽՋՌՊԹԼՁՇՄԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ

 ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՁՆԼՁԻԹՌԽԼ ԽԾԾԽԻՌՋ ԹՆԼ ՈԽՊԻԽՆՌ 
 ԼՁԾԾԽՊԽՆԻԽՋ ԹՊԽ ՊԽՈՇՊՌԽԼ ԺԹՋԽԼ ՇՆ ԻՇՅՈԹՊՁՋՇՆ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ 
ԻՄԽԹՆ ՏԹՌԽՊ ԻՇՆՌՊՇՄ ԠՇՆԻՄՍՋՁՇՆՋ ՊԽԿԹՊԼՁՆԿ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԱՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌԽՋՌՏԹՋՍՋԽԼՌՇԹՆԹՄՑՒԽՅԹՄԽՎՁՌԽՄՄՇԿԽՆՁՆ
ԳԱԤՊԽՋՈՇՆՋԽԼԹՌԹԺԽԻԹՍՋԽՌՀԽՊԽՎՁԽՏԽՊՎՁՋՍԹՄՄՑԼԽՌԽՊՅՁՆԽԼԹՅՇՆՇՌՇՆՁԻԹՄՄՑԼԽԻՊԽԹՋՁՆԿ

ՌՊԽՆԼՁՆՌՀԽՌՊԽԹՌՅԽՆՌՅԽԼՁԹՆՎԹՄՍԽՋ
 ԹՆԼ ՆԿՅԩ ՈՄԹՋՅԹ ԹՌՌՀԽ ԹՆԼՅԿԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ ՊԽՋՈԽԻՌՁՎԽՄՑՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽ ՆԽԿԹՌՁՎԽ

ԻՇՆՌՊՇՄ
ՆԿՅԩՈՄԹՋՅԹԥՇՏԽՎԽՊՌՀԽՇՎԽՊԹՄՄՅԽԹՆԾՇՊՌՀՁՋՌՊԽԹՌՅԽՆՌՏԹՋԿՊԽԹՌԽՊՌՀԹՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՀՁՋՏԹՋԼՍԽՌՇՌՏՇՅԹՄԽԾՁՋՀՁՆՌՀՁՋՌՊԽԹՌՅԽՆՌՏՁՌՀՊԽՈՇՊՌԽԼ

ԳԱԤՄԽՎԽՄՋՌՀԹՌՏԽՊԽՋՍԺՋՌԹՆՌՁԹՄՄՑԿՊԽԹՌԽՊՌՀԹՆՌՀԽԻՇՆՌՊՇՄՋԭՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋՏԽՊԽՆՇՌՅԽԹՋՍՊԽԼ

ԩԬԮՅԿԹՁԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԣԽԻՍՆԼՁՌՑ ԣԽՊՌ԰ՍԻԻԽՋՋ ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ Ԥ԰Ԧ

ԤՇՆԹԼԹՄ

԰ՌԹԿՁՆԿԹՆԼ

ԥՁՋՌՇ

ԭՄԹՋՅԹԳԱԤ

ԡՁԾԾ Ո ԡՁԾԾ ԭ ԪԽԼՁԹՆ Ո ԡՁԾԾ Ո

ԢԾԾԽԻՌ!


ԶԽՋԫՇ

ԡՁԾԾ Ո

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ
ԩԬԮԩԬԮ

 ԫԞ  ԫԞ  ԫԞ  ԫԞ ԫՇ  ԫԞ

      ԫԞ   ԶԽՋ  

      ԫԞ   ԶԽՋ  

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԫԞ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԫԞ ԡՍՆՆԽՌՌ0Ջ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԠՇՆԻԠՇՆԻԽՆՌՊԹՌՁՇՆԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢԽՋՌՊԹԼՁՇՄԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽ

ԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ

 ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՁՆԼՁԻԹՌԽԼ ԽԾԾԽԻՌՋ ԹՆԼ ՈԽՊԻԽՆՌ 
 ԼՁԾԾԽՊԽՆԻԽՋ ԹՊԽ ՊԽՈՇՊՌԽԼ ԺԹՋԽԼ ՇՆ ԻՇՅՈԹՊՁՋՇՆ ՌՇ ՌՀԽ ՆԽԿԹՌՁՎԽ 
ԻՄԽԹՆ ՏԹՌԽՊ ԻՇՆՌՊՇՄ ԠՇՆԻՄՍՋՁՇՆՋ ՊԽԿԹՊԼՁՆԿ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԱՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՋՌԽՈԼՇՏՆՌԽՋՌՏԹՋՍՋԽԼՌՇԹՆԹՄՑՒԽԾԽԻՍՆԼՁՌՑ ՊԽՋՈՇՆՋԽԼԹՌԹԺԽԻԹՍՋԽՌՀԽ ՊԽՎՁԽՏԽՊՎՁՋՍԹՄՄՑԼԽՌԽՊՅՁՆԽԼԹՅՇՆՇՌՇՆՁԻԹՄՄՑԼԽԻՊԽԹՋՁՆԿՌՊԽՆԼՁՆՌՀԽ

ՌՊԽԹՌՅԽՆՌՅԽԼՁԹՆՎԹՄՍԽՋ
ԹՆԼԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑԹՌՌՀԽԹՆԼՅԿԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ


ԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑ

ԩԬԮՅԿԹՁԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԣ԰ԱԯԞՏՁՌՀԭՀՇՋՅԽՌ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԟՇԼՑԴԽՁԿՀՌ ԩԽՆԿՌՀ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ ԪԹՄԽՋ ԣԽՅԹՄԽՋ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԠՇՆՌՊՇՄ
ԩԬԮ  ԫԞ  ԫԞ  ԫԞ  ԫԞ

        

        

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ

ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ

ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽ ՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊ

ԻՇՆՌՊՇՄ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ

ԩԬԮՅԿԹՁԩ

Ԣ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

ԱՀԽՊԽՏԽՊԽՅՁՆՇՊԼԽՎՁԹՌՁՇՆՋԼԽՋԻՊՁԺԽԼՁՆ԰ԽԻՌՁՇՆԦԪԹՌԽՊՁԹՄՋԹՆԼԪԽՌՀՇԼՋՇԾՌՀՁՋԡԢԯՊԽԿԹՊԼՁՆԿԾԹՁՄՍՊԽՌՇ

ՊԽՈՇՊՌ ԻԽՊՌԹՁՆ ՏԹՌԽՊ ԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋ ԪՇՊԽ ՁՅՈՇՊՌԹՆՌՄՑ ՌՀԽ ՋՌՍԼՑ ԼՁԼ ՆՇՌ ՅԽԽՌ ՌՀԽ ՅՁՆՁՅՍՅ ՇԾ  ՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՌՀԹՌԼՁԼՆՇՌԽՐՀՁԺՁՌՌՇՐՁԻՁՌՑԹՋՊԽԻՇՅՅԽՆԼԽԼԺՑՌՀԽԬԠ԰ԭԭԿՍՁԼԽՄՁՆԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 ԱՀԽԾԽԻՍՆԼՁՌՑ ՁՆ ՇՆԽ ՊԽՈՄՁԻԹՌԽ ՇԾՌՀԽ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄՏԹՋԽԿԿՋԾԽՅԹՄԽԼԹՑ ՆՇՊ ԼՁԼ

ՌՀԽ ՊԽՈՄՁԻԹՌԽ ՋՈԹՏՆ ԹՌ ՄԽԹՋՌ ԽՎԽՊՑ  ԼԹՑՋ ԪԽԽՌՁՆԿ ՇՆԽ ՇԾ ՌՀԽՋԽ ԻՊՁՌԽՊՁԹ ՁՆ ՆԽԽԼԽԼ ՌՇ

ԼԽՅՇՆՋՌՊԹՌԽԹԻՌՁՎԽՋՈԹՏՆՁՆԿ

 ԱՀԽԽՆԼՈՇՁՆՌՋԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ՅԿԹՁԩՏԽՊԽՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑԹՆԹՄՑՒԽԼ

ԼՍԽ ՌՇ ՅՇՊՌԹՄՁՌՑ ՇՆՄՑ ՇՆԽ ՅԹՄԽ ԹՆԼ ՇՆԽ ԾԽՅԹՄԽ ՋՍՊՎՁՎԽԼ ԹՌ ՋՌՍԼՑ ՌԽՊՅՁՆԹՌՁՇՆ ԱՀԽՊԽԾՇՊԽ

ՇՆՄՑ  ՌԽՋՌ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄՋ ՏԽՊԽ ԹՆԹՄՑՒԽԼ ՁՆ ՌՀՁՋ ՋՌՍԼՑ ԬԠ԰ԭԭ ԤՍՁԼԽՄՁՆԽ 

ՊԽԻՇՅՅԽՆԼՋ Թ ՅՁՆՁՅՍՅ ՇԾ  ՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՈՄՍՋ Թ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ ԞՄՋՇ ՌՀԽ ՋՌՍԼՑ

ԹՍՌՀՇՊ ՊԽՈՇՊՌԽԼՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋԹՌՌՀԽՅԿԹՁԩԻՇՆԻԽՆՌՊԹՌՁՇՆՅԽՌՌՀԽԿՍՁԼԽՄՁՆԽ

ԼԽԾՁՆՁՌՁՇՆՇԾՇՎԽՊՌՅՇՊԺՁԼՁՌՑՅԹՃՁՆԿՊԽՋՍՄՌՋԾՇՊՌՀՁՋՌՊԽԹՌՅԽՆՌՄԽՎԽՄԼՁԾԾՁԻՍՄՌՌՇՁՆՌԽՊՈՊԽՌ

 ԱՀԽՌՇՌԹՄ ՇՊԿԹՆՁԻ ԻԹՊԺՇՆ ՍՆՁՇՆՁՒԽԼ ԹՅՅՇՆՁԹ ԹՆԼ ՊԽՋՁԼՍԹՄ ԻՀՄՇՊՁՆԽ ՁՆՌՀԽ ՌԽՋՌՏԹՌԽՊՏԽՊԽ

ՆՇՌ ՊԽՈՇՊՌԽԼ ԱՀԽ ԬԠ԰ԭԭ  ՈԽՊԾՇՊՅԹՆԻԽ ԻՊՁՌԽՊՁԹ ԽՋՌԹԺՄՁՋՀ ՅԹՐՁՅՍՅ ՄԽՎԽՄՋ ԾՇՊ

ՌՀԽՋԽՎԹՄՍԽՋԹՆԼՁՌՁՋՍՆԻՄԽԹՊՁԾՌՀԽՅԹՐՁՅՍՅՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՏԽՊԽԽՐԻԽԽԼԽԼ

   ԱՀԽՊԽՅԹՁՆՁՆԿՎԹՄՁԼՁՌՑԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԾՇՊԬԠ԰ԭԭՏԽՊԽՅԽՌ

ԣԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋ

ԱՀԽ ՊԽՎՁԽՏԽՊ0Ջ ԹՆԼ ՌՀԽ ՋՌՍԼՑ ԹՍՌՀՇՊՋ0 ՊԽՋՍՄՌՋ ՏԽՊԽ ՁՆ ԹԿՊԽԽՅԽՆՌ ՊԽԿԹՊԼՁՆԿ ԽԾԾԽԻՌՋ ՇՆ ՋՍՊՎՁՎԹՄ

ԾԽՊՌՁՄՁՒԹՌՁՇՆԹՆԼԾԽՅԹՄԽԤ԰ԦԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿԾԽԻՍՆԼՁՌՑՏԽՊԽԹՄՋՇՋՁՅՁՄԹՊՁՆՌՀԹՌՌՀԽՋՍՈՈՊԽՋՋՁՇՆԹՌ

ՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏԹՋԻՇՆՋՁԼԽՊԽԼԺՁՇՄՇԿՁԻԹՄՄՑՊԽՄԽՎԹՆՌԟՇՌՀՌՀԽՋՌՍԼՑԹՍՌՀՇՊ0ՋԹՆԼ

ՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋՁՋԼԽՌԽԻՌԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻՌՁՇՆՋ
ՈՁՆԾԽՊՌՁՄՁՌՑԹՆԼԾԽՅԹՄԽԤ԰ԦԹՌՌՀԽ

 ՅԿ ԹՁԩ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ ԻՇՆՋՁՋՌԽՆՌ ՏՁՌՀ ՌՀԽ ԻՇՆԻՄՍՋՁՇՆՋ ԾՇՄՄՇՏՁՆԿ ՌՀԽ ԬԠ԰ԭԭ 

ՅԽՌՀՇԼՇՄՇԿՑ
ՍՋՁՆԿՌՀԽՊԽՋՍՄՌՋՇԾԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԦԾՌՀԽՊԽՎՁԽՏԽՊԾՇՄՄՇՏՋՌՀԽՋՍԿԿԽՋՌՁՇՆՇԾՌՀԽ

ՌՊԹԼՁՌՁՇՆԹՄ ԢԣԢԡ ՅԽՌՀՇԼՇՄՇԿՑ ՏՀՁԻՀ ՊԽԻՇՅՅԽՆԼՋ ԴՁՄՄՁԹՅ0Ջ ՌԽՋՌ ԾՇՊ ԻՇՆԻԽՆՌՊԹՌՁՇՆԼԽՈԽՆԼԽՆՌ ՈԹՌՌԽՊՆՋ

ՋԹՌՁՋԾՑՁՆԿ ՈԹՊԹՅԽՌՊՁԻ ԹՋՋՍՅՈՌՁՇՆՋ ՋՁԿՆՁԾՁԻԹՆՌ ՊԽԼՍԻՌՁՇՆՋ ՏԽՊԽ ԹՄՋՇ ԼԽՌԽԻՌԽԼ ԹՌ ՌՀԽ  ՅԿ ԹՁԩ

ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄ 
Ո ԱՀԽ ՇԺՋԽՊՎԹՌՁՇՆՋ ՇԾ ԻՄՁՆՁԻԹՄ ՋՁԿՆՋ ԹՌ  ՅԿ ԹՁԩ ՅԽՌ ՌՀԽ ԿՍՁԼԽՄՁՆԽ

ԼԽԾՁՆՁՌՁՇՆՇԾՇՎԽՊՌՅՇՊԺՁԼՁՌՑՏՀՁԻՀՄԽՆԼՋՍՆԻԽՊՌԹՁՆՌՑՌՇՌՀԽՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՊԽՋՍՄՌՋԹՌՌՀՁՋՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԱՀԽ ՊԽՎՁԽՏԽՊ0Ջ ԻՇՆԻՄՍՋՁՇՆՋ ԺԹՋԽԼ ՇՆ ՌՀԽ ԬԠ԰ԭԭ  ԾՄՇՏԻՀԹՊՌ ԹՊԽ ՈՊԽՋԽՆՌԽԼ ՁՆ ՌՀԽ ԢՐԽԻՍՌՁՎԽ

԰ՍՅՅԹՊՑԹՆԼԠՇՆԻՄՍՋՁՇՆՋՋԽԻՌՁՇՆՋՇԾՌՀՁՋԡԢԯ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱՀԽՋՌՍԼՑԹՍՌՀՇՊՋՊԽՈՇՊՌԽԼՅԽԹՆՅԽԹՋՍՊԽԼՊԽԻՇՎԽՊՁԽՋՇԾՈՀՇՋՅԽՌԹՋՅԿԹՁԩԺԹՋԽԼՇՆՆՇՅՁՆԹՄ

ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՇԾ  ՅԿ ԹՁԩ ՏԹՋ ՁՆԻՇՊՊԽԻՌ ՌՀԽ ՊԽՎՁԽՏԽՊ ՅԽԹՆ ՅԽԹՋՍՊԽԼ ՏԹՋ  ՅԿ ԹՁԩ

ԺԹՋԽԼՇՆՌՀԽԼԹՌԹՈՊՇՎՁԼԽԼԱՀԽՅԽՌՀՇԼ ՊԽԻՇՎԽՊՁԽՋՇԾՈՀՇՋՅԽՌՁՆԣՊՇԿԢՅԺՊՑՇԱԽՊԹՌՇԿԽՆԽՋՁՋԞՋՋԹՑ

ԵԽՆՇՈՍՋ
ԣԢԱԞԵՋՇՄՍՌՁՇՆԾՇՊՌՁԾՁԽԼԹՌԹՆԼՅԿԹՁԩՏԽՊԽչ
Ն

ՍՋՁՆԿԹՆԞԿՁՄԽՆՌ԰ԩԻՇՄՍՅՆՀՇՏԽՎԽՊԣԢԱԞԵՋՇՄՍՌՁՇՆՏԹՋՆՇՌՍՋԽԼԹՋՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊՋՇՍՊԻԽ

ՁՆՌՀՁՋԹՋՋԹՑ

ԦԦ ԯԢԣԢԯԢԫԠԢ԰

ԞՆՃՄԽՑԤԱԧԽՆՋԽՆԨԪԨԹՀՄԪԡԨՇՊՌԽԧԧԹՆԼԪԹՃՑՆԽՆԢԞԡԽՋԻՊՁՈՌՁՇՆԹՆԼԽՎԹՄՍԹՌՁՇՆ

ՇԾԹՋՀՇՊՌՌԽՊՅՊԽՈՊՇԼՍԻՌՁՇՆՌԽՋՌՏՁՌՀՌՀԽԾԹՌՀԽԹԼՅՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԢՆՎՁՊՇՆԱՇՐՁԻՇՄԠՀԽՅ



ԞԭԥԞ ԞԴԴԞ ԴԭԠԣ  ԰ՌԹՆԼԹՊԼ ԪԽՌՀՇԼՋ ԾՇՊ ՌՀԽ ԢՐԹՅՁՆԹՌՁՇՆ ՇԾ ԴԹՌԽՊ ԹՆԼ ԴԹՋՌԽՏԹՌԽՊ ՌՀ

ԢԼՁՌՁՇՆԴԹՋՀՁՆԿՌՇՆԡԠ

Ԟ԰ԱԪ  ԠՇՅՅՁՌՌԽԽ Ԣ ՇՆ ԟՁՇՄՇԿՁԻԹՄ ԢԾԾԽԻՌՋ ԹՆԼ ԢՆՎՁՊՇՆՅԽՆՌԹՄ ԣԹՌԽ ԰ՌԹՆԼԹՊԼ ԤՍՁԼԽ ԾՇՊ

ԠՇՆԼՍԻՌՁՆԿԢԹՊՄՑԩՁԾԽ԰ՌԹԿԽԱՇՐՁԻՁՌՑԱԽՋՌՋՏՁՌՀԣՁՋՀԽՋԞ԰ԱԪԡԽՋՁԿՆԹՌՁՇՆԢԞՅԽՊՁԻԹՆ԰ՇԻՁԽՌՑ

ԾՇՊԱԽՋՌՁՆԿԹՆԼԪԹՌԽՊՁԹՄՋԟԹՊՊԥԹՊԺՇՊԡՊՁՎԽԭԬԟՇՐԠԴԽՋՌԠՇՆՋՀՇՀՇԻՃԽՆԭԽՆՆՋՑՄՎԹՆՁԹ

ԦՎԽՋԪՁԻՀԹԽՄԠԢԱԦ԰ԠՇՅՈՊԽՀԽՆՋՁՎԽԢՆՎՁՊՇՆՅԽՆՌԹՄԱՇՐՁԻՁՌՑԦՆԾՇՊՅԹՌՁՇՆ԰ՑՋՌԽՅգԲՋԽՊ	ՋԤՍՁԼԽ

ԱՁԼԽՈՇՇՄ԰ԻՁԽՆՌՁԾՁԻ԰ՇԾՌՏԹՊԽԪԻԨՁՆՄԽՑՎՁՄՄԽԠԹՄՁԾՇՊՆՁԹԪՇՍՆՌԡԦԹՆԼԴԞԟՊՍՆԿՋԞՋՁՅՈՄՁԾՁԽԼ

ԼՇՋՁՆԿԹՈՈԹՊԹՌՍՋԾՇՊԾՁՋՀՌՇՐՁԻՇՄՇԿՑՋՌՍԼՁԽՋԴԹՌԽՊԯԽՋԽԹՊԻՀ

԰ՈՊԹԿՍԽ ԧԟ  ԪԽԹՋՍՊԽՅԽՆՌ ՇԾ ՈՇՄՄՍՌԹՆՌ ՌՇՐՁԻՁՌՑ ՌՇ ԾՁՋՀ  ԟՁՇԹՋՋԹՑ ՅԽՌՀՇԼՋ ԾՇՊ ԹԻՍՌԽ ՌՇՐՁԻՁՌՑ

ԴԹՌԽՊԯԽՋ

ԬԢԠԡ 
ԣՁՋՀ԰ՀՇՊՌ ԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑԬԢԠԡԤՍՁԼԽՄՁՆԽԾՇՊՌՀԽՌԽՋՌՁՆԿԠՀԽՅՁԻԹՄՋԱԽՋՌ

ԫՇԭԹՊՁՋԣՊԹՆԻԽՈՈ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

Բ԰ ԢԭԞ   Ԡԣԯ ԭԹՊՌ  ԣԽԼԽՊԹՄ ԦՆՋԽԻՌՁԻՁԼԽ ԣՍՆԿՁԻՁԼԽ ԹՆԼ ԯՇԼԽՆՌՁԻՁԼԽ ԞԻՌ ԤՇՇԼ

ԩԹԺՇՊԹՌՇՊՑ ԭՊԹԻՌՁԻԽՋ ԰ՌԹՆԼԹՊԼՋ ԣՁՆԹՄ ԯՍՄԽ ԬԾԾՁԻԽ ՇԾ ՌՀԽ ԣԽԼԽՊԹՄ ԯԽԿՁՋՌԽՊ ԫԹՌՁՇՆԹՄ ԞՊԻՀՁՎԽՋ ԹՆԼ

ԯԽԻՇՊԼՋԞԼՅՁՆՁՋՌՊԹՌՁՇՆԲ԰ԤՇՎԽՊՆՅԽՆՌԭՊՁՆՌՁՆԿԬԾԾՁԻԽԴԹՋՀՁՆԿՌՇՆԡԠ

Բ԰ԢԭԞ԰ՀՇՊՌՌԽՊՅՅԽՌՀՇԼՋԾՇՊԽՋՌՁՅԹՌՁՆԿՌՀԽԻՀՊՇՆՁԻՌՇՐՁԻՁՌՑՇԾԽԾԾՄՍԽՆՌՋԹՆԼՊԽԻԽՁՎՁՆԿՏԹՌԽՊՋ

ՌՇ ՅԹՊՁՆԽ ԹՆԼ ԽՋՌՍԹՊՁՆԽ ՇՊԿԹՆՁՋՅՋ ԱՀՁՊԼ ԽԼՁՌՁՇՆ ԬԾԾՁԻԽ ՇԾ ԴԹՌԽՊ Բ ԰ ԢՆՎՁՊՇՆՅԽՆՌԹՄ ԭՊՇՌԽԻՌՁՇՆ

ԞԿԽՆԻՑԴԹՋՀՁՆԿՌՇՆԡԠԢԭԞԯ

Բ԰ԢԭԞԬԾԾՁԻԽՇԾԭՊԽՎԽՆՌՁՇՆԭԽՋՌՁԻՁԼԽՋԹՆԼԱՇՐՁԻ԰ՍԺՋՌԹՆԻԽՋԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌԽՊ԰ԻՊԽԽՆՁՆԿ

ԭՊՇԿՊԹՅԱԽՋՌԤՍՁԼԽՄՁՆԽԬԠ԰ԭԭԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑԢԭԞԠ

ԬԻՌՇԺԽՊԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑԴԹՋՀՁՆԿՌՇՆԡԠ

Page 163 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԞԭԭԢԫԡԦԵԦԬԲԱԭԲԱԬԣԯԢԳԦԢԴԢԯ0԰԰ԱԞԱԦ԰ԱԦԠԞԩԳԢԯԦԣԦԠԞԱԦԬԫ

 

 Fisher's Exact Test 

 ============================================================================ 

 NUMBER OF 

 ---------------------------------------- 

 IDENTIFICATION ALIVE DEAD TOTAL ANIMALS 

 -------------------------- ----- ----- --------------- 

 CONTROL 24 0 24 

 0.001 20 4 24 

 ---------------------------------------------------------------------------- 

 TOTAL 44 4 48 

 ============================================================================ 

 Critical Fisher's value (24,24,24) (alpha=0.05) is 19.0. b value is 20. 

 Since b is greater than 19.0 there is no significant difference 

 between CONTROL and TREATMENT at the 0.05 level. 

 

 

 

 Fisher's Exact Test 

 ============================================================================ 

 NUMBER OF 

 ---------------------------------------- 

 IDENTIFICATION ALIVE DEAD TOTAL ANIMALS 

 -------------------------- ----- ----- --------------- 

 CONTROL 24 0 24 

 0.0093 18 6 24 

 ---------------------------------------------------------------------------- 

 TOTAL 42 6 48 

 ============================================================================ 

 Critical Fisher's value (24,24,24) (alpha=0.05) is 19.0. b value is 18. 

 Since b is less than or equal to 19.0 there is a significant difference 

 between CONTROL and TREATMENT at the 0.05 level. 

 

 

 

 Summary of Fisher's Exact Tests 

 ---------------------------------------------------------------------------- 

 NUMBER NUMBER SIG 

 GROUP IDENTIFICATION EXPOSED DEAD 0.05 

 ----- ------------------------- ----------- ----------- ----- 

 CONTROL 24 0 

 1 0.001 24 4 

 2 0.0093 24 6 * 

 ---------------------------------------------------------------------------- 

 

 

 

Test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR01 ( F body weight (g) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Page 164 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.934 0.421 0.388 0.689 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 1.51 0.11 0.06 7.43 1.33, 1.69 

 Dose1 4 1.55 0.16 0.08 10.44 1.29, 1.81 

 Dose2 4 1.33 0.19 0.10 14.35 1.03, 1.63 

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

 Ctrl 1.52 1.40 1.61 . . 

 Dose1 1.54 1.39 1.75 102.58 -2.58 

 Dose2 1.29 1.15 1.59 87.85 12.15 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 2.26 0.160 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 1.51 . 1.53 . . . . . . 

 Dose1 1.55 0.916 1.53 0.654 . . . . . 

 Dose2 1.33 0.226 1.33 0.084 0.170 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 4.19 0.123 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 1.52 . . 

 Dose1 1.54 0.889 0.614 

 Dose2 1.29 0.156 0.054 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 165 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR02 ( M body weight (g) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.897 0.146 1.040 0.392 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 3.18 0.59 0.30 18.62 2.23, 4.12 

 Dose1 4 3.11 0.71 0.36 22.94 1.97, 4.24 

 Dose2 4 2.69 0.27 0.13 10.03 2.26, 3.12 

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

 Ctrl 2.94 2.77 4.05 . . 

 Dose1 2.96 2.41 4.10 97.80 2.20 

 Dose2 2.77 2.31 2.90 84.61 15.39 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 0.90 0.440 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 3.18 . 3.18 . . . . . . 

 Dose1 3.11 0.977 3.11 0.508 . . . . . 

 Dose2 2.69 0.393 2.69 0.156 0.559 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 2.92 0.232 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 2.94 . . 

 Dose1 2.96 0.889 0.614 

 Dose2 2.77 0.235 0.094 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 166 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR03 ( F body length (mm) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.958 0.749 0.033 0.968 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 51.25 1.26 0.63 2.46 49.25, 53.25 

 Dose1 4 52.00 1.41 0.71 2.72 49.75, 54.25 

 Dose2 4 51.00 1.41 0.71 2.77 48.75, 53.25 

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

 Ctrl 51.00 50.00 53.00 . . 

 Dose1 51.50 51.00 54.00 101.46 -1.46 

 Dose2 51.50 49.00 52.00 99.51 0.49 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 0.58 0.578 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 51.25 . 51.63 . . . . . . 

 Dose1 52.00 0.666 51.63 0.734 . . . . . 

 Dose2 51.00 0.952 51.00 0.504 0.574 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 0.80 0.671 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 51.00 . . 

 Dose1 51.50 0.467 0.822 

 Dose2 51.50 1.000 0.561 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 167 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR04 ( M body length (mm) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.905 0.184 1.641 0.247 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 62.25 2.22 1.11 3.56 58.72, 65.78 

 Dose1 4 62.75 5.12 2.56 8.16 54.60, 70.90 

 Dose2 4 62.25 1.89 0.95 3.04 59.24, 65.26 

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

 Ctrl 62.00 60.00 65.00 . . 

 Dose1 61.50 58.00 70.00 100.80 -0.80 

 Dose2 61.50 61.00 65.00 100.00 0.00 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 0.03 0.972 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 62.25 . 62.50 . . . . . . 

 Dose1 62.75 0.969 62.50 0.626 . . . . . 

 Dose2 62.25 1.000 62.25 0.618 0.977 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 0.04 0.980 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 62.00 . . 

 Dose1 61.50 1.000 0.442 

 Dose2 61.50 1.000 0.530 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 168 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR05 ( F vitellogenin (ng/mL) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.869 0.063 2.862 0.109 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 1440000 518716.4 259358.2 36.02 614606.5, 2265393 

 Dose1 4 950000.0 574224.1 287112.1 60.44 36281.29, 1863719 

 Dose2 4 1430000 1600458 800229.1 111.92 -1116686, 3976686 

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

 Ctrl 1350000 960000.0 2100000 . . 

 Dose1 1070000 160000.0 1500000 65.97 34.03 

 Dose2 740000.0 440000.0 3800000 99.31 0.69 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 0.30 0.749 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 1440000 . 1440000 . . . . . . 

 Dose1950000.0 0.732 1190000 0.438 . . . . . 

 Dose2 1430000 1.000 1190000 0.467 0.791 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 1.42 0.491 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 1350000 . . 

 Dose1 1070000 0.346 0.124 

 Dose2 740000.0 0.494 0.153 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 169 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR06 ( M vitellogenin (ng/mL) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.672 <.001 8.295 0.009 USE NON-PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 27478.00 44186.91 22093.45 160.81 -42833.2,97789.23 

 Dose1 4 8064.75 9220.67 4610.33 114.33 -6607.39,22736.89 

 Dose2 4 350353.0 699764.8 349882.4 199.73 -763129, 1463835 

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

 Ctrl 8450.00 12.00 93000.00 . . 

 Dose1 8046.50 66.00 16100.00 29.35 70.65 

 Dose2 665.00 82.00 1400000 1275.03 -1175.03 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 0.90 0.439 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 27478.00 . 128631.9 . . . . . . 

 Dose1 8064.75 0.997 128631.9 0.722 . . . . . 

 Dose2350353.0 0.453 128631.9 0.756 0.485 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 0.04 0.981 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 8450.00 . . 

 Dose1 8046.50 1.000 0.500 

 Dose2 665.00 0.889 0.500 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 170 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR07 ( F GSI ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.943 0.538 0.989 0.409 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 12.50 1.91 0.96 15.32 9.45, 15.55 

 Dose1 4 11.30 3.22 1.61 28.48 6.18, 16.42 

 Dose2 4 8.23 3.26 1.63 39.66 3.03, 13.42 

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

 Ctrl 12.00 11.00 15.00 . . 

 Dose1 11.50 7.20 15.00 90.40 9.60 

 Dose2 8.60 4.70 11.00 65.80 34.20 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 2.36 0.149 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 12.50 . 12.50 . . . . . . 

 Dose1 11.30 0.784 11.30 0.339 . . . . . 

 Dose2 8.23 0.112 8.23 0.039 0.329 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 3.93 0.140 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 12.00 . . 

 Dose1 11.50 0.775 0.328 

 Dose2 8.60 0.135 0.028 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere Dose2 

Page 171 of 260
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR08 ( M GSI ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.874 0.074 0.161 0.854 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 1.33 0.32 0.16 24.16 0.82, 1.83 

 Dose1 4 1.45 0.38 0.19 26.11 0.85, 2.05 

 Dose2 4 1.29 0.26 0.13 20.27 0.87, 1.71 

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

 Ctrl 1.20 1.10 1.80 . . 

 Dose1 1.30 1.20 2.00 109.43 -9.43 

 Dose2 1.35 0.96 1.50 97.36 2.64 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 0.27 0.769 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 1.33 . 1.39 . . . . . . 

 Dose1 1.45 0.811 1.39 0.692 . . . . . 

 Dose2 1.29 0.983 1.29 0.551 0.770 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 0.54 0.764 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing INCREASING trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl -1.20 . . 

 Dose1 -1.30 0.467 0.178 

 Dose2 -1.35 1.000 0.380 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 172 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR09 ( F tubercle score (median) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 . . . . NO DATA FOR TEST 

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

Page 173 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR10 ( M tubercle score (median) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.953 0.686 1.098 0.374 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 26.00 2.94 1.47 11.32 21.32, 30.68 

 Dose1 4 29.50 5.00 2.50 16.95 21.54, 37.46 

 Dose2 4 12.50 6.45 3.23 51.64 2.23, 22.77 

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

 Ctrl 25.50 23.00 30.00 . . 

 Dose1 27.00 27.00 37.00 113.46 -13.46 

 Dose2 15.00 3.00 17.00 48.08 51.92 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 12.84 0.002 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 26.00 . 27.75 . . . . . . 

 Dose1 29.50 0.534 27.75 0.769 . . . . . 

 Dose2 12.50 0.008 12.50 0.002 0.003 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 8.46 0.015 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 25.50 . . 

 Dose1 27.00 0.225 0.930 

 Dose2 15.00 0.067 0.052 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere >highest dose (no sign. differences) 

Page 174 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR11 ( fecundity ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.904 0.180 2.959 0.103 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 15.85 6.95 3.48 43.87 4.78, 26.92 

 Dose1 4 19.00 12.91 6.45 67.95 -1.54, 39.54 

 Dose2 4 3.01 2.35 1.17 78.05 -0.73, 6.74 

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

 Ctrl 17.50 6.40 22.00 . . 

 Dose1 14.00 10.00 38.00 119.87 -19.87 

 Dose2 2.55 0.83 6.10 18.97 81.03 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 3.91 0.060 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 15.85 . 17.43 . . . . . . 

 Dose1 19.00 0.827 17.43 0.687 . . . . . 

 Dose2 3.01 0.110 3.01 0.039 0.064 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 7.38 0.025 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 17.50 . . 

 Dose1 14.00 1.000 0.500 

 Dose2 2.55 0.067 0.010 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere Dose2 

Page 175 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for fish screen study - Phosmet 

ANALYSIS RESULTS FOR VARIABLE VAR12 ( fertility ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Shapiro-Wilks test for Normality of Residuals -- alpha-level=0.01 

Levenes test for homogeneity of variance(absolute residuals) -- alpha-level=0.05 

Use parametric analyses if neither test rejected, otherwise non-parametric analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.987 0.998 3.109 0.094 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

 Level N Mean StdDev StdErr Coef of Var 95% Conf.Interval 

 Ctrl 4 97.00 2.16 1.08 2.23 93.56, 100.44 

 Dose1 4 95.75 1.89 0.95 1.98 92.74, 98.76 

 Dose2 4 90.25 4.79 2.39 5.30 82.63, 97.87 

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

 Ctrl 96.50 95.00 100.00 . . 

 Dose1 96.50 93.00 97.00 98.71 1.29 

 Dose2 90.00 85.00 96.00 93.04 6.96 

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

PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Analysis of Variance (ANOVA) - overall F-test 

 Numerator df Denominator df F-stat P-value 

 2 9 4.97 0.035 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing negative trend 

Tukey - two-sided tests, all possible comparisons, not used for NOEC or LOEC 

Level Mean Dunnett Isotonic Williams Tukey p-values 

 p-value mean p-value Dose1 Dose2 Dose3 Dose4 Dose5 

 Ctrl 97.00 . 97.00 . . . . . . 

 Dose1 95.75 0.810 95.75 0.356 . . . . . 

 Dose2 90.25 0.029 90.25 0.009 0.090 . . . . 

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

NON-PARAMETRIC ANALYSES - use alpha-level=0.05 for all tests 

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 2 5.10 0.078 

MannWhit - testing each trt median signif. different from control 

Jonckheere - test assumes dose-response relationship, testing negative trend 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 96.50 . . 

 Dose1 96.50 0.775 0.328 

 Dose2 90.00 0.125 0.016 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere Dose2 

Male tubercle score (exact Mann-Whitney) 

Obs conc endpoint 

1 0 23 

2 0 30 

3 0 26 

Page 176 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

Obs conc endpoint 

4 0 25 

5 1 37 

6 1 27 

7 1 27 

8 1 27 

9 2 17 

10 2 16 

11 2 14 

12 2 3 

13 3 . 

14 3 . 

15 3 . 

16 3 . 

Page 177 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

The NPAR1WAY 

Procedure 

ԭԹԿԽՇԾ

Wilcoxon Scores (Rank Sums) for Variable end

point 

Classified by Variable conc 

conc N 

Sum 

of 

Scor

es 

Expected 

Under H0 

Std Dev 

Under H0 

Mean 

Score 

0 4 29.0 26.0 5.846522 7.250 

1 4 39.0 26.0 5.846522 9.750 

2 4 10.0 26.0 5.846522 2.500 

Average scores were used for ties. 

Kruskal-Wallis Test 

Chi-Square 8.4645 

DF 2 

Asymptotic Pr > Chi-Square 0.0145 

Exact Pr >= Chi-Square 0.0017 

Page 178 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

The NPAR1WAY 

Procedure 

ԭԹԿԽՇԾ

Page 179 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

The NPAR1WAY 

Procedure 

ԭԹԿԽՇԾ

Wilcoxon Scores (Rank Sums) for Variable endpoint 

Classified by Variable conc 

conc N 

Sum of 

Scores 

Expected 

Under H0 

Std Dev 

Under H0 

Mean 

Score 

0 4 13.0 18.0 3.380617 3.250 

1 4 23.0 18.0 3.380617 5.750 

Average scores were used for ties. 

Kruskal-Wallis Test 

Chi-Square 2.1875 

DF 1 

Pr > Chi-Square 0.1391 

Wilcoxon Two-Sample Test 

Statistic (S) 13.0000 

Normal Approximation 

Z -1.3311 

One-Sided Pr < Z 0.0916 

Two-Sided Pr > |Z| 0.1832 

t Approximation 

One-Sided Pr < Z 0.1124 

Two-Sided Pr > |Z| 0.2249 

Exact Test 

One-Sided Pr <= S 0.1000 

Two-Sided Pr >= |S - Mean| 0.2000 

Z includes a continuity correction of 0.5. 

Page 180 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

The NPAR1WAY 

Procedure 

ԭԹԿԽՇԾ

Page 181 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

The NPAR1WAY 

Procedure 

ԭԹԿԽՇԾ

Wilcoxon Scores (Rank Sums) for Variable endpoin

t 

Classified by Variable conc 

conc N 

Sum of 

Scores 

Expected 

Under H0 

Std Dev 

Under H0 

Mean 

Score 

0 4 26.0 18.0 3.464102 6.50 

2 4 10.0 18.0 3.464102 2.50 

Wilcoxon Two-Sample Test 

Statistic (S) 26.0000 

Normal Approximation 

Z 2.1651 

One-Sided Pr > Z 0.0152 

Two-Sided Pr > |Z| 0.0304 

t Approximation 

One-Sided Pr > Z 0.0336 

Two-Sided Pr > |Z| 0.0671 

Exact Test 

One-Sided Pr >= S 0.0143 

Two-Sided Pr >= |S - Mean| 0.0286 

Z includes a continuity correction of 0.5. 

Kruskal-Wallis Test 

Chi-Square 5.3333 

DF 1 

Pr > Chi-Square 0.0209 

Page 182 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

The NPAR1WAY 

Procedure 

ԭԹԿԽՇԾ

Page 183 of 260
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆ ՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՀՇՋՅԽՌ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

The NPAR1WAY 

Procedure 

ԭԹԿԽՇԾ

Page 184 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1400, In vivo Hershberger Assay

EPA Contract No. EP10H001452 

Task Assignment No. 2-4-2012 (MRID 48618706) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

Rebecca Bryan, B.S. Date: 12/20/2011

Secondary Reviewer Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 1/03/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 1/04/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 1/04/2012

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by Dynamac Corporation personnel. 

Page 185 of 260
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).

Page 186 of 260
PHOSMET/059201 

Primary Reviewer: Greg Akerman, Ph.D. 

Health Effects Division 

Secondary Reviewer: John Liccione. Ph.D. 

Health Effects Division 

/11 vivo Hershberger Assay (2011)/ Page I of 13 

OCSPP 890.1400/ OECD 441 

Signature: _e,;.......,..1£.9,,........:::.L...---

Da te: ,,.--....;~""-~~!...,.._­

Signature: ::::zS~~==~z:= 

Date: =-~'64~..+--!'-.;2---

DATA EVALUATION RECORD 

STUDY TYPE: In Vivo Hershberger Assay (Rat); OCSPP 890.1400; OECD 441 

PC CODE: 059201 DP BARCODE: D397165 

TXR#: 0056199 CAS#: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8% a.i.) 

SYNONYMS: 0 , 0-dimethyl S-phthalimidomethylphosphorodithioate 

CITATION: Zorrilla, L. (2011 ). The Hershberger assay with phosmet in castrated 

CRL:CD(SD) IGS Rats. Integrated Laboratory Systems, Inc., Durham, NC. 

Laboratory Project Study ID: C 194-200, October 26, 2011. MRID 48618706. 

Unpublished. 

SPONSOR: Gowan Company, P.O. Box 5569, Yuma, AZ 

TEST ORDER#: EDSP-059201 -54 

EXECUTIVE SUMMARY: The Hershberger Assay consists of androgenic and antiandrogenic components. To screen for potential androgenic activity, phosmet (96.8% a.i., Batch 

# 6QH9118000) in 0.5% aqueous carboxymethyl cellulose was administered daily via oral 

gavage to 59- to 60-day old, castrated male Sprague Dawley rats (8/dose group) at dose levels of 

0 (vehicle), 5 or 25 mg/kg/day. An androgenic positive control group consisted of 10 castrated 

rats dosed by subcutaneous injection with 0.4 mg/kg/day testosterone propionate (TP) prepared 

in com oil. 

To screen for potential anti-androgenic activity phosmet (96.8% a.i., Batch# 6QH91l8000) in 

0.5% aqueous carboxymethyl cellulose was administered daily via oral gavage to 59 to 60-day 

old, castrated male Sprague Dawley rats (8/dose group) at dose levels ofO (vehicle), 5, 15, or 25 

mg/kg/day in conjunction with a daily dose of reference androgen TP at 0.4 mg/kg/day by 

subcutaneous injection. An anti-androgenic positive control group consisted of 10 castrated rats 

exposed to 0.4 mg/kg/day TP and 3.0 mg/kg/day flutamide (FT). Flutamide and TP were 

prepared in com oil. 

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. 

Page 187 of 260
In vivo Hershberger Assay (2011)/ Page 2 of 13

PHOSMET/059201 OCSPP 890.1400/ OECD 441

All animals survived until scheduled termination. Cholinergic signs (tremors) and a 12% 

decrease in terminal bodyweight was seen at 25 mg/kg/day suggesting that the high dose may 

have been excessive.

In the androgen agonist assay, clinical signs in the 25 mg/kg/day group included tremors, 

uncoordinated movements and porphyrin staining around the eyes. No clinical signs were 

observed in the 5 mg/kg/day group. Body weights in the 5 and 25 mg/kg/day groups were 

comparable to controls throughout the duration of the assay. At 25 mg/kg/day, mean overall 

(Days 1-11) body weights gains were decreased (p≤0.05) by 69%. Animals dosed with 

0.4 mg/kg/day TP had increased (p≤0.05) mean body weights of 12% on Day 11, and increased 

mean overall body weight gains (p≤0.05) of 105%. There were no significant increases in the 

accessory sex organ weights in animals dosed with the test compound. Animals in the 0.4 

mg/kg/day TP group had accessory sex organ weight increases (p≤0.05) as follows: 1926% in 

seminal vesicles; 1264% in ventral prostate; 251% in levator ani-bulbocavernosus (LABC); 

794% in Cowper’s gland; and 72% in glans penis. All tissue weight CVs were below the 

maximum values recommended by the test guideline. The performance criteria indicated that 

this assay was performing as expected. 

In the anti-androgen assay, clinical signs in the 25 mg/kg/day group included tremors, and 

uncoordinated movements. No clinical signs were observed in the 5 or 15 mg/kg/day groups. At 

25 mg/kg/day, mean body weights were decreased (p≤0.05) by 12% on Day 11, and overall body 

weight gains were decreased (p≤0.05) by 60%. There were no effects on body weights or body 

weight gains in the 5 and 15 mg/kg/day group, or the positive control group. At 15 mg/kg/day, 

the weights of seminal vesicles were decreased 25% (p≤0.05). At 25 mg/kg/day, accessory sex 

organ weight decreases (p≤0.05) were noted as follows: 50% in seminal vesicles; 40% in ventral 

prostate; 27% in LABC; 34% in Cowper’s gland; and 10% in glans penis. Animals dosed with 

0.4 mg/kg/day TP + 3 mg/kg/day FT had decreased (p≤0.05) accessory sex organ weights as 

follows: 85% in seminal vesicles; 76% in ventral prostate; 50% in LABC; 66% in Cowper’s 

gland; and 21% in glans penis. All tissue weight CVs were below the maximum values 

recommended by the test guideline. The performance criteria indicated that this assay was 

performing as expected. 

Phosmet was negative for androgenic activity as no statistically significant increases in organ 

weights were seen in two or more of the five androgen sensitive tissues in the androgen agonist 

assay. However, phosmet was positive for anti-androgenicity in the Hershberger assay as 

statistically significant decreases in organ weights were seen in all five androgen sensitive tissues 

in the androgen antagonist assay. However, the decreases in androgen-sensitive tissue weights 

were seen at a dose (25 mg/kg/day) that resulted in overt toxicity (12% decrease in body weight 

and clinical signs), which confounds the interpretation of the results. . 

The assay satisfies the EDSP Tier 1 Test Order requirements for a Hershberger assay (OCSPP 

890.1400). 

COMPLIANCE: Signed and dated GLP Compliance and Quality Assurance statements were

provided. 

Page 188 of 260
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PHOSMET/059201 OCSPP 890.1400/ OECD 441

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Integrated Laboratory Systems, Inc.

Location: Durham, NC

Study Director: L. Zorrilla

Other Personnel: Not provided

Study Period: April 28, 2011-May 9, 2011

2. Test Substance: Phosmet

Description: Off white solid

Source: Gowan Company (commercial technical product)

Batch #: 6QH9118000, expires January 31, 2012

Purity: 96.8 %

Stability: Stable in the vehicle for up to 11 days at 2-8°C.

CAS #: 732-11-6

Structure:

3. Reference Androgen: Testosterone propionate (TP)

Supplier: Sigma-Aldrich Company (St. Louis, MO)

Lot #: 048K1328

Purity: 100.2%, expires March 17, 2012

CAS # : 57-85-2

4. Reference Anti-androgen: Flutamide (FT)

Supplier: Sigma-Aldrich Company (St. Louis, MO)

Lot #: 107K1293

Purity: >99%

CAS # : 13311-84-7

5. Solvent/Vehicle Control (Phosmet): Carboxymethyl cellulose

(in sodium phosphate buffer)

Supplier: Sigma-Aldrich Company (St. Louis, MO)

Lot #: 100M0113

Rationale (if other than water): CMC (0.5%) was the vehicle used in several sponsor studies where th 

test substance was administered by gavage.

Final concentration: 0.5%

6. Solvent/Vehicle Control 

(Testosterone propionate and Flutamide): Corn Oil

Supplier: MP Biomedicals, LLC (Solon, OH)

Lot/Batch #: 7862K

Rationale (if other than water): Not provided.

Final concentration: Not applicable

Page 189 of 260
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PHOSMET/059201 OCSPP 890.1400/ OECD 441

7. Test Animals:

Species: Rat (castrated males)

Strain: Sprague Dawley (Crl:CD[SD])

Age/weight at dose initiation: Post-natal day (PND) 59-60; 240.0-313.5 g 

Source: Charles River Laboratories International, Inc., Raleigh, NC

Housing: 2/cage in polycarbonate cages with absorbent heat-treated 

hardwood bedding (Northeastern Products Corp., Warrensburg, 

NY)

Diet: Teklad Global 16% Protein Rodent Diet (Teklad Diets, Madison, 

WI), ad libitum; low phytoestrogen with total geinstein equivalents 

= 6.2 μg/g diet.

Water: Reverse osmosis treated tap water, ad libitum

Environmental conditions: Temperature:

Humidity:

Air changes:

Photoperiod:

22-26oC

33-48% 

Not provided

12 hrs light/12 hrs dark

Acclimation period: 10 days at test facility

B. STUDY DESIGN

1. In life dates: Start: 4/28/11 End: 5/9/11 

2. Study Design: The present Hershberger Assay was conducted to screen for both potential 

anti-androgenic and androgenic activity. The test substance was administered daily via oral 

gavage to groups of castrated male rats both without TP (androgenic activity) and with a 

daily dose of TP (0.4 mg/kg/day) by subcutaneous injection (anti-androgenic activity). 

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. Positive androgenic activity is defined as a significant increase in two or 

more organ weights compared to the vehicle control. For both assays, the animals were 

dosed for 10 consecutive days and necropsied approximately 24 hours after the final dose 

administration for organ weight measurements. 

3. Study Schedule: Following a 10-day acclimation period at the test facility, castrated male 

rats (surgical manipulation performed by Supplier at PND 42) were administered the test 

substance from PND 59-60 to PND 68-69. Rats were euthanized on PND 69-70, 

approximately 24 hours after the last dose and necropsied for organ weight measurements.

4. Animal Assignment: Animals were randomly assigned, stratified by body weight, to the 

test groups noted in Table 1. Statistical analysis indicated that there were no significant 

differences in group means at study initiation.

Page 190 of 260
In vivo Hershberger Assay (2011)/ Page 5 of 13

PHOSMET/059201 OCSPP 890.1400/ OECD 441

Table 1. Study design a

Test group Dose (mg/kg/day) # of Males

Androgen Agonist Assay

Vehicle control (0.5% CMC) 0 8

Low 5 8

High 25 8

Positive control (0.5% CMC) +TP b 0.4 8

Anti-Androgen Assay

Vehicle control (0.5% CMC) +TP b 0 8

Low (+TP) 5 8

Mid (+TP) 15 8

High (+TP) 25 8

Flutamide (oral gavage) + TP (s.c.), positive control 3 8

a Data were obtained from Tables 1 and 2 on page 17 of the study report.

b Same animals dosed for both androgen agonist (serves as positive control) and anti-androgen (served as vehicle control) 

assays. This did not affect the outcome or conclusions of this study.

5. Dose Selection Rationale: The phosmet dose levels were selected based on the results 

from an acute oral gavage study (MRID 46593101), repeated-dose studies (MRIDs 

44811801, 41520001, and 41916401), and a non-GLP six week range-finding study (no 

MRID or study number). Mortality was observed in ≥75 mg/kg treatment groups for the 

acute study. No mortality was observed in the repeated-dose dietary studies conducted at 

doses of up to 98.3 mg/kg/day. Cholinergic clinical signs were observed in 36 mg/kg males 

in the acute oral gavage study; however, no effects were observed at 22.5 mg/kg. In the 

range finding study, no cholinergic effects were observed for dietary doses up to 49.2 

mg/kg/day and body weights were reduced 11.2% at 22.5 mg/kg/day. Based on these 

results, doses of 0, 5 and 25 mg/kg/day were used for both the androgen agonist and antiandrogen assays. 

6. (a) Dose Preparation: Dose formulations were prepared once prior to initiation of 

treatment and twice during treatment by initially suspending the appropriate amounts of test 

substance in 0.5% aqueous carboxymethyl cellulose. Flutamide and TP were prepared daily 

as solutions in corn oil. Homogeneity and concentration analyses were performed on all 

dose formulations. Stability analyses were performed on 1.00, 3.00, and 5.00 mg a.i./mL 

formulations prior to administration following storage at 2-8°C for up to 8 days.

In a previous storage stability study1, phosmet (lot number not reported) was determined to 

be stable in the 0.5% aqueous carboxymethyl cellulose for up to 11 days (temperature not 

reported). 

 

1 Reibach, R. 2011. Storage Stability of Phosmet in 0.5% Aqueous Carboxymethylcellulose. Unpublished study 

report prepared by Smithers Viscient Inc., Study No. 12791-6139.

Page 191 of 260
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PHOSMET/059201 OCSPP 890.1400/ OECD 441

(b) Dose Analysis 

Results

Homogeneity (%CV): 2.45-5.45% 

Stability (% of Day 0): 98-104% following storage for up 8 days at 2-8°C.

Concentration (% of nominal): 87-105%

The analytical data indicated that the mixing procedure was adequate and that the variation 

between nominal and actual dosage to the animals was acceptable. 

7. Dosage administration: Test formulations were administered to the animals daily via oral 

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 and accessory sex organ weights were 

analyzed using studentized residual plots for outliers and Levene’s test for homogeneity of 

variance. Heterogeneous data (glans penis weights) were transformed and re-analyzed using 

Kruskal-Wallis and Dunn’s test. Body weights, body weight gains, and accessory sex organ 

weights were analyzed using one-way ANOVA followed by Dunnett’s t-tests. The positive 

controls were compared to the vehicle controls using the t-test. Significance was denoted at 

p≤0.05. The statistical analyses were considered adequate.

C. METHODS

1. Clinical Examinations: Animals were checked for mortality or moribundity twice daily on 

weekdays and once daily on weekends. Rats were also checked for clinical signs of toxicity 

prior to dose administration and at termination. If adverse clinical signs were seen, 

additional observations were noted. 

2. Body Weight: Animals were weighed at randomization, daily prior to dosing throughout 

the dosing period, and at termination.

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 69-70 

(approximately 24 hours after the final administration of the test substance), all rats were 

weighed, anesthetized by CO2 inhalation followed by cervical dislocation and subjected to a 

gross necropsy. The five mandatory androgen-dependent organs (ventral prostate, seminal 

vesicles with coagulating glands and fluid, 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). 

Page 192 of 260
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PHOSMET/059201 OCSPP 890.1400/ OECD 441

II. RESULTS

A. OBSERVATIONS

1. Mortality: All animals survived until scheduled termination. 

2. Clinical signs of toxicity: In the androgen agonist assay, clinical signs at 1-4 hours after 

dosing included one 25 mg/kg/day rat with tremors on Days 3-9 and the same animal 

showed uncoordinated movement on Days 4 and 5. Six other 25 mg/kg/day rats also 

exhibited tremors 1-4 hours post-dose on Days 3-9 (7 total rats). At 24 hours after dosing, 

one 25 mg/kg/day rat exhibited porphyrin staining around the eyes on Day 9. No clinical 

signs were observed in the 5 mg/kg/day group. 

Table 2. Incidence of Clinical Observations in the Androgen Agonist Assay a,b

Observation

Dose (mg/kg/day)

Vehicle Control

Positive Control

Vehicle + TP 

(0.4) b 

5 25

# 

Obs.

# 

Exam

# 

Obs.

# 

Exam

# 

Obs.

# 

Exam

# 

Obs.

# 

Exam

Porphyrin 

staining 

around eyes

0 8 0 8 0 8 1 8 

a Data were obtained from page 83 of the study report.

b The observations of tremors were reported on page 21 of the study report but were not included in the clinical 

observation tables in the appendices.

# Obs. = number of observed incidences.

# Exam = number of animals examined.

In the anti-androgen assay, clinical signs at 1-4 hours after dosing included one 

25 mg/kg/day rat with tremors on Days 3 and 7 and uncoordinated movement on Day 3. 

Another 25 mg/kg rat exhibited tremors on days 3-9 and uncoordinated movement on day 5. 

Six other 25 mg/kg/day rats also exhibited tremors between Days 4 and 8. At 24 hours after 

dosing, no clinical signs were observed in any dose group. No clinical signs were observed 

in the 5 or 15 mg/kg/day groups. 

Table 3. Incidence of Clinical Observations in the Anti-Androgen Assay a

Observation

Dose (mg/kg/day)

Vehicle 

Control

+ TP (0.4) b 

TP + FT

Positive 

Control

5 15 25

# 

Obs.

# 

Exam

#

Obs.

# 

Exam

#

Obs.

# 

Exam

# 

Obs.

# 

Exam

# 

Obs. # Exam

None

a Data were obtained from page 84 of the study report.

b The observations of tremors were reported on page 22 of the study report but were not included in the clinical 

observation tables in the appendices.

# Obs. = number of observed incidences.

# Exam = number of animals examined.

Page 193 of 260
In vivo Hershberger Assay (2011)/ Page 8 of 13

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B. BODY WEIGHT AND WEIGHT GAIN: Selected body weight and body weight gain 

data are presented in Table 4 for the agonist assay. Body weights in the 5 and 25 mg/kg/day 

groups were comparable to controls throughout the duration of the assay. At 25 mg/kg/day, 

mean overall (Days 1-11) body weights gains were decreased (p≤0.05) by 69%. Animals 

dosed with 0.4 mg/kg/day TP had a mean body weight increase (p≤0.05) of 12% on Day 11, 

and increased (p≤0.05) mean overall body weight gains of 105%. 

Table 4. Selected Group Mean (±SE) Body Weights and Cumulative Body Weight Gains (g) in the 

Androgen Agonist Assay a

Study Day #

Dose (mg/kg/day)

Vehicle Control Positive Control

Vehicle + TP (0.4) b Phosmet 5 Phosmet 25

N Mean SD N Mean SD N Mean SD N Mean SD

1 8 274.0 19.2 8 276.6 17.2 8 276.7 19.0 8 275.4 19.5

4 8 282.2 21.5 8 298.8 18.3 8 284.9 22.0 8 278.8 21.6

7 8 290.3 23.0 8 314.9 23.5 8 295.9 23.5 8 280.3 19.8

11 8 305.1 28.0 8 340.5*

(↑12)

28.5 8 311.5 27.6 8 285.1 19.7

BWG

(days 1-11)

8 31.1 12.3 8 63.9*

(↑105)

11.9 8 34.8 11.3 8 9.7*

(↓69)

10.7

a Data were obtained from Tables 6 on page 23 and Appendix V on pages 92-93 of the study report. Percent differences from 

controls were calculated by the reviewers and included in parentheses.

b The positive control group for the androgen agonist assay is same as the vehicle control group for the anti-androgen assay. 

This did not affect the outcome or conclusions of this study.

N = Number of animals in the group

SE= Standard Deviation 

* Significantly different from vehicle controls at p<0.05. 

Body weight and body weight gain data for the anti-androgen assay are presented in Table 

5. At 25 mg/kg/day, mean body weights were decreased (p≤0.05) by 12% on Day 11, and 

mean overall body weight gains were decreased (p≤0.05) by 60%. There were no effects 

from phosmet on body weights or body weight gains in the 5 and 15 mg/kg/day group, or in 

the positive control group. 

Page 194 of 260
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PHOSMET/059201 OCSPP 890.1400/ OECD 441

Table 5. Selected Group Mean (±SD) Body Weights and Cumulative Body Weight Gains (g) in the AntiAndrogen Assay a

Study 

Day #

Dose (mg/kg/day)

Vehicle Control

+ TP (0.4) b 

TP + FT

Positive Control Phosmet 5 Phosmet 15 Phosmet 25

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 8 276.6 17.2 8 275.5 15.6 8 277.4 18.5 8 279.8 12.8 8 275.4 14.2

4 8 298.8 18.3 8 292.7 18.7 8 295.8 19.1 8 296.8 15.7 8 282.4 14.7

7 8 314.9 23.5 8 306.2 23.2 8 313.8 20.1 8 313.8 15.8 8 290.3 12.9

11 8 340.5 28.5 8 329.8 25.2 8 337.4 21.4 8 339.3 17.4 8 301.0*

(↓12)

17.1

BWG

(days 1-11)

8 63.9 11.9 8 54.3 26.2 8 60.0 8.8 8 59.5 10.8 8 25.6*

(↓60)

15.4

a Data were obtained from Table 7 on pages 24 and Appendix V on pages 93-94 of the study report. Percent differences from 

controls were calculated by the reviewers and included in parentheses.

b The vehicle control group for the anti-androgen assay is same as the positive control group for the androgen agonist assay. 

This did not affect the outcome or conclusions of this study.

N = Number of animals in the group

SD= Standard Deviation

* Significantly different from vehicle controls at p<0.05. 

C. FOOD CONSUMPTION (OPTIONAL): Food consumption was not determined 

(optional).

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 6 for the agonist assay. There were no treatment-related effects in any of 

the accessory sex organs of animals dosed with the phosmet. Animals in the 0.4 mg/kg/day 

TP group had accessory sex organ weight increases (p≤0.05) as follows: 1926% in seminal 

vesicles; 1264% in ventral prostate; 251% in LABC; 794% in Cowper’s gland; and 72% in 

glans penis. The CVs for all treatment groups were compared to the performance criteria 

values as stated in the Guidelines. All %CV values were less than the maximum 

recommended values.

Page 195 of 260
In vivo Hershberger Assay (2011)/ Page 10 of 13

PHOSMET/059201 OCSPP 890.1400/ OECD 441

Table 6. Accessory Sex Organ Weights (mg) from Androgen Agonist Assay in Sprague-Dawley Rats a

Organ

Dose (mg/kg/day)

Vehicle Control Phosmet 5 Phosmet 25 Positive Control

Vehicle + TP (0.4) b

N Mean SD CV N Mean SD CV N Mean SD CV N Mean SD CV

Seminal 

vesicles

8 33.7 3.6 11 8 39.1 9.2 24 8 30.4 3.8 12 8 682.9*

(↑1926)

135.7 20

Ventral 

prostate

8 15.5 3.1 20 8 16.1 2.7 17 8 13.2 2.0 15 8 211.4*

(↑1264)

37.6 18

LABC 8 143.8 14.1 10 8 158.3 21.1 13 8 120.5 19.1 16 8 505.4*

(↑251)

41.9 8

Cowper’s 

glands

8 5.1 1.1 21 8 5.6 1.5 27 8 4.8 1.0 22 8 45.6*

(↑794)

9.6 21

Glans penis 8 47.3 3.6 8 8 49.2 3.6 7 8 44.9 4.4 10 8 81.2*

(↑72) 

8.5 11

a Data were obtained from Table 8 on page 26 of the study report. Percent differences from controls were calculated by the 

reviewers and included in parentheses.

b The positive control group for the androgen agonist assay is same as the vehicle control group for the anti-androgen assay. 

This did not affect the outcome or conclusions of this study.

N = Number of animals in the group

SD= Standard Deviation

CV= Coefficient of Variation

* Significantly different from vehicle controls at p<0.05. 

Accessory sex organ weights for the anti-androgen assay are presented in Table 7. At 15

mg/kg/day, the weights of seminal vesicles were decreased by 25% (p≤0.05). At 25 

mg/kg/day, accessory sex organ weight decreases (p≤0.05) were noted as follows: 50% in 

seminal vesicles; 40% in ventral prostate; 27% in LABC; 34% in Cowper’s gland; and 10% 

in glans penis. Animals dosed with 0.4 mg/kg/day TP + 3 mg/kg/day FT had decreased 

(p≤0.05) accessory sex organ weights as follows: 85% in seminal vesicles; 76% in ventral 

prostate; 50% in LABC; 66% in Cowper’s gland; and 21% in glans penis. The CVs for all 

treatment groups were compared to the performance criteria values as stated in the 

Guidelines. All %CV values were less than the maximum recommended values.

Page 196 of 260
In vivo Hershberger Assay (2011)/ Page 11 of 13

PHOSMET/059201 OCSPP 890.1400/ OECD 441

Table 7. Accessory Sex Organ Weights (mg) from Anti-Androgen Agonist Assay in Sprague-Dawley Rats a

Organ

Dose (mg/kg/day)

Vehicle Control

+TP (0.4) b Phosmet 5 Phosmet 15 Phosmet 25 TP + FTPositive Control

N Mean SD CV N Mean SD CV N Mean SD CV N Mean SD CV N Mean SD CV

Seminal 

vesicles

8 682.9 135.7 20 8 612.7 123.6 20 8 510.5*

(↓25)

55.1 11 8 339.4*

(↓50)

60.8 18 8 103.3*

(↓85)

26.8 26

Ventral 

prostate

8 211.4 37.6 18 8 184.8 28.8 16 8 181.9 23.4 13 8 127.6*

(↓40)

16.0 13 8 50.2*

(↓76)

10.9 22

LABC

8 505.4 41.9 8 8 515.3 65.0 13 8 465.5 60.9 13 8 367.6*

(↓27) 

39.5 11 8 250.8*

(↓50) 

45.0 18

Cowper’s 

glands

8 45.6 9.6 21 8 41.5 9.2 22 8 40.0 5.8 15 8 30.2*

(↓34)

7.1 24 8 15.6*

(↓66)

1.5 10

Glans 

penis

8 81.2 8.5 11 8 79.9 3.3 4 8 78.0 5.5 7 8 73.0*

(↓10)

3.8 5 8 64.5*

(↓21)

7.4 12

a Data were obtained from Tables 9 on page 27 of the study report. Percent differences from controls were calculated by the reviewers and included in parentheses.

b The vehicle control group for the anti-androgen assay is same as the positive control group for the androgen agonist assay. This did not affect the outcome or conclusions of this study.

N = Number of animals in the group

SD= Standard Deviation

CV= Coefficient of Variation

* Significantly different from vehicle controls at p<0.05.

Page 197 of 260
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F. MACROSCOPIC PATHOLOGY: No gross observations were made at necropsy. 

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: In the agonist assay, final body weights of 

animals administered phosmet were not statistically different compared to the vehicle 

control (0.5% carboxymethylcellulose) animals. Mean body weight gain was significantly 

decreased in animals administered 25 mg/kg/day phosmet compared to vehicle control rats. 

In addition, cholinergic clinical signs (e.g. tremors) were observed following dose 

administration of 25 mg/kg/day phosmet on 7 of 10 days of the study. Phosmet 

administered at dose levels of 5 and 25 mg/kg/day to castrated SD male rats did not increase 

androgen dependent tissue weights.

In the androgen antagonist assay, final animal body weights and mean body weight gain 

were significantly decreased in rats co-administered 25 mg/kg/day phosmet and TP 

compared to control rats. Cholinergic clinical signs were observed following coadministration of 25 mg/kg/day phosmet and TP on 7 of 10 days of the study. Phosmet (25 

mg/kg) co-administered with TP was associated with significant decreases in LABC, glans 

penis, ventral prostate, Cowper's glands, and seminal vesicle weights, and a decrease in 

seminal vesicle weight with 15 mg/kg/day phosmet and TP compared to the control group 

(0.5% carboxymethylcellulose and TP). Using the castrated rat model Hershberger Assay, 

oral administration of phosmet up to 25 mg/kg/day resulted in cholinergic clinical signs and 

body weight effects, but did not show any androgen agonist activity. Co-administration of 

25 mg/kg/day phosmet and TP was also associated with cholinergic clinical signs, 

bodyweight effects, and a reduction in androgen-dependent tissue weights.

B. AGENCY COMMENTS: All animals survived until scheduled termination. 

In the androgen agonist assay, clinical signs in the 25 mg/kg/day group included tremors, 

uncoordinated movements and porphyrin staining around the eyes. No clinical signs were 

observed in the 5 mg/kg/day group. Body weights in the 5 and 25 mg/kg/day groups were 

comparable to controls throughout the duration of the assay. At 25 mg/kg/day, mean overall 

(Days 1-11) body weights gains were decreased (p≤0.05) by 69%. Animals dosed with 0.4 

mg/kg/day TP had increased (p≤0.05) mean body weights of 12% on Day 11, and increased 

(p≤0.05) mean overall (Days 1-11) body weight gains of 105%. There were no significant 

increases in the weights of the five target accessory sex organs of animals dosed with the 

test compound. Animals in the 0.4 mg/kg/day TP group had accessory sex organ weight 

increases (p≤0.05) as follows: 1926% in seminal vesicles; 1264% in ventral prostate; 251% 

in LABC; 794% in Cowper’s gland; and 72% in glans penis. The performance criteria 

indicated that this assay was performing as expected.

In the anti-androgen assay, clinical signs in the 25 mg/kg/day group included tremors, and 

uncoordinated movements. No clinical signs were observed in the 5 or 15 mg/kg/day 

groups. At 25 mg/kg/day, mean body weights were decreased (p≤0.05) by 12% on Day 11, 

and decreased (p≤0.05) overall body weight gains of 60%. There were no effects on body 

weights or body weight gains in the 5 and 15 mg/kg/day group, or the positive control 

group. At 15 mg/kg/day, the weights of seminal vesicles were decreased 25% (p≤0.05). At 

25 mg/kg/day, accessory sex organ weight decreases (p≤0.05) were noted as follows: 50% 

Page 198 of 260
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PHOSMET/059201 OCSPP 890.1400/ OECD 441

in seminal vesicles; 40% in ventral prostate; 27% in LABC; 34% in Cowper’s gland; and 

10% in glans penis. Animals dosed with 0.4 mg/kg/day TP + 3 mg/kg/day FT had 

decreased (p≤0.05) accessory sex organ weights as follows: 85% in seminal vesicles; 76% 

in ventral prostate; 50% in LABC; 66% in Cowper’s gland; and 21% in glans penis. The 

performance criteria indicated that this assay was performing as expected. All tissue weight 

CVs were below the maximum recommended values indicated in the test guideline. 

Administration of phosmet up to 25 mg/kg/day did not result in an increase in any of the 

five target organ weights indicating that the test substance is negative for androgenic 

activity. At 25 mg/kg/day, significant decreases were seen in all five of the target organ 

weights indicating that phosmet is positive for potential anti-androgenic activity in this 

bioassay. Cholinergic signs (tremors) and a 12% decrease in terminal bodyweight was seen 

at 25 mg/kg/day suggesting that the high dose may have been excessive (overt toxicity). 

No statistically significant increases in organ weights were seen in two or more of the five 

androgen responsive tissues in the androgen agonist assay. Phosmet was negative for 

androgenic activity. Statistically significant decreases in organ weights were seen in all five 

androgen responsive tissues only at the high dose in the androgen antagonist assay. Phosmet 

was positive for potential anti-androgenic activity in this Hershberger assay. However, the 

decreases in androgen-sensitive tissue weights were seen at a dose (25 mg/kg/day) that 

resulted in overt toxicity (12% decrease in body weight and clinical signs), which confounds 

the interpretation of the results.

C. STUDY DEFICIENCIES: None 

Page 199 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1450, Female Pubertal Assay

EPA Contract No. EP10H001452 

Task Assignment No. 2-61-2012 (MRID 48673003) 

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:

Ronnie J. Bever Jr., Ph.D., D.A.B.T. Date: 5/7/2012

Secondary Reviewer: Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 5/18/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 5/21/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 5/21/2012

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by CSS-Dynamac Corporation personnel.

Page 200 of 260
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).

Page 201 of 260
PHOSMET I 059201 

Primary Reviewer: Linda Taylor. Ph.D. 

Health Effects Division 

Secondary Reviewer: Elizabeth Mendez, Ph.D. 

Health Effects Division 

DATA EVALUATION RECORD 

STUDY TYPE: Female Pubertal Assay; OCSPP 890.1450; OECD None. 

PC CODE: 059201 DP BARCODE: D400672 

TXR#: 0056199 CAS No.: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8%) 

SYNONYMS: S-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)methyl] 0, 0-dimethyl 

phosphorodi thioate 

CITATION: Zorilla, L. (2012). Pubertal developmental and thyroid function with phosmet 

in juvenile/peripubertal CRL: CD (SD) IGS female and male rats. Integrated 

Laboratory Systems, Inc., Durham, NC, Laboratory Study No.: Cl 94-300, 

February 24, 2012. MRID 48673003. Unpublished. 

SPONSOR: Gowan Company, P.O. Box 5569, Yuma, AZ 

TEST ORDER#: EDSP-059201-54 

EXECUTIVE SUMMARY: In a female pubertal assay (MRID 48673003), 16 SpragueDawley (Crl:CD®(SD) IGS) rats/dose group were treated daily by oral gavage with phosmet 

(96.8% a.i., Batch #: GQH9118000) in aqueous 0.5% carboxymethylcelJulose (CMC) at doses of 

0, 10, or 20 mg/kg/day (5 mL/kg dosing volume) from post-natal day (PND) 22 to 42 or 43. The 

animals were examined for vaginal opening (VO) daily beginning on PND 22, and age and body 

weight at day of attainment was recorded. After sacrifice on PND 42/43, serum thyroxine (T 4) 

and thyroid stimulating hormone (TSH) concentrations were analyzed using radioimmunoassays. 

Various clinical chemistry parameters were measured in the serum. Liver, kidney, pituitary, 

adrenals, thyroid, ovaries, and uterus were weighed and examined macroscopically; microscopic 

examination was also conducted on the thyroid, ovaries, uterus, and kidneys. 

No treatment-related effects were observed on mortality, organ weights, serum TSH 

concentrations, clinical chemistry, or gross pathology. Changes (NS) in ovary, uterus, thyroid, 

and pituitary weights were noted in the low- and high-dose animals. There were no treatmentrelated histopathological findings noted in the ovaries, uterus, thyroid, or kidneys. In addition, 

no treatment-related effects were noted on cycle status, mean age at first estrus, mean cycle 

length, percent cycling, or percent regularly cycling. 

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Female Pubertal Assay (2012) / Page 2 of 17

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One 10-mg/kg/day rat exhibited localized head tremors on a single day, and tremors were 

observed at various times post-dose in up to 10/16 10-mg/kg/day rats on 10 days and up to 

sixteen 20-mg/kg/day rats at 18 days. No other treatment-related clinical signs were observed in 

animals from either dose group. Decreased body weights (p<0.05; ↓9% to 10%) were observed at 

20-mg/kg/day during PND 26 to 36. No significant change in mean final body weight or body 

weight gain was observed in either treatment group compared to the vehicle control group. 

The day of VO was comparable among the groups. Unadjusted and adjusted body weights at VO

were decreased (p<0.05) by 9% each in the 20 mg/kg/day group compared to control. No 

treatment-related effect was noted on cycle status, mean age at first estrus, mean cycle length, 

percent cycling, or percent regularly cycling. At 20 mg/kg/day, the number of ovarian antral 

follicles was increased (↑93%), and the number of atretic follicles was decreased (↓29%). All 

other values in the treated groups were similar to control. 

Serum T4 concentrations were increased (↑24 to 38%) in the treated groups. A marginal decrease 

in the thyroid colloid area and increase in the follicular cell height was observed in animals 

administered phosmet (10 and 20 mg/kg) compared to control. 

There were no effects on liver, kidney, pituitary, adrenal, uterus, or thyroid organ weights at 

either dose level compared to the control. 

Thyroid effects (increased serum T4 levels and thyroid histopathology) were seen at both doses. 

However, these doses (10 and 20 mg/kg/day) were determined to be excessive based on 

persistent tremors seen at both doses and severe body weight loss at the high dose. Additionally, 

data from the existing toxicity database show that lower doses should have been tested in this 

assay. Following the agency’s determination, the registrant submitted additional information

(MRID 49610501) in response to the agency’s review of this assay. The submitted data show 

that tremors were seen in 10/16 rats at the 10 mg/kg/day dose level (during 10 days) and all 

animals at the 20 mg/kg/day dose (during 18 days). The severity of the tremors ranged from “not 

characterized to moderate.” Upon review of these data, the agency reaffirms its previous 

conclusion that both doses tested in this assay were excessive. 

The assay does NOT satisfy the EDSP Tier 1 Test Order requirements for a Female Pubertal 

Assay (OCSPP 890.1450) since overt toxicity was seen at both doses tested. However, a new 

assay is not required at this time since the results from a repeat assay would have no impact on the 

risk assessment. The point of departure (PoD) for the phosmet risk assessment is based on 

cholinesterase inhibition at substantially lower doses than the ones tested in this assay. For 

additional information see the EDSP Tier 1 Weight of Evidence Analysis for Phosmet (TXR

0057145).

COMPLIANCE: Signed and dated GLP Compliance, Data Confidentiality, and Quality 

Assurance statements were provided. 

Page 203 of 260
Female Pubertal Assay (2012) / Page 3 of 17

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I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Integrated Laboratories Systems, Inc.

Location: Durham, NC

Study Directors: L. Zorilla.

Other Personnel: S. Borghoff, study toxicologist

M. Boyle, study pathologist

Study Period: May 25, 2011 through February 24, 2012

2. Test Substance: Phosmet

Description: Off white solid

Source: Gowan Company

Batch #: 6QH9118000 (expires January 31, 2013)

Purity: 96.8% a.i.

Stability: Report stated that the compound is stable in the vehicle at 1–10°C for up to 15 days

CAS #: 732-11-6

Structure: O

O

S

P

S

OCH3

N OCH3

3. Vehicle: 0.5% Carboxymethylcellulose in sodium phosphate buffer

4. Test Animals:

Species: Rat (females)

Strain: Sprague-Dawley (Crl:CD®(SD) IGS)

Age/Mean Weight 

at Study Initiation: PND 22 / 45.9–67.8 g 

Source: Charles River Laboratories International, Inc. (Raleigh, NC)

Housing: Parental dams were individually housed in polycarbonate cages with micro-isolator tops and 

absorbent, heat-treated, hardwood bedding; each dam was housed with her litter until weaning 

on PND 21. After weaning, up to 2 females were housed per cage.

Diet: Teklad Global 16% Protein Rodent Diet (Teklad Diets, Madison, WI), ad libitum. It was 

stated that the total genistein equivalents of genistein plus daidzein was determined to be 8.0

μg/g of feed.

Water: Reverse osmosis-purified tap water, ad libitum

Environmental 

Conditions:

Temperature:

Humidity:

Air changes:

Photoperiod:

19–24°C

43–78% 

Not reported

14 h light / 10 h dark

B. STUDY DESIGN

1. In-Life Dates: Start: July 1, 2011 End: December 12, 2011 

2. Mating: Time-mated pregnant nulliparous dams (age not reported) were received from the 

supplier on gestation day (GD) 8 and were allowed to deliver naturally and rear their pups to 

PND 21. Between postnatal days (PND) 3 and 5, litters with the same date of birth were 

standardized to 8 pups with equal numbers of males and females. 

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Female Pubertal Assay (2012) / Page 4 of 17

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3. Animal Assignment: Following weaning on PND 21, animals were assigned to study using 

a procedure that stratifies animals across groups by body weight such that mean body 

weight of each group was not statistically different from any other group using analysis of 

variance. Care was taken to avoid placing littermates in the same dose group. The test 

groups are provided in Table 1. 

TABLE 1. Study Design a

Test group Dose (mg/kg/day) # of Females

Control 0 16

Low 10 16

High 20 16

a Data were obtained from Table 1 on page 16 of the study report. 

4. Dose Selection Rationale: The doses were selected based on the results of several previous 

studies. A 7-day relative sensitivity study (MRID 44839301) compared the toxic responses 

of PND 11 rat pups versus adult rats following repeated gavage administration of phosmet. 

No treatment-related effects on body weight or cholinergic clinical signs were seen in either 

pups or adults at the highest tested dose (HTD) of 5 mg/kg/day, however significant 

cholinesterase inhibition was evident (e.g. responses were 57-62% of controls in adult RBC 

and 81-86% of controls in adult brain at the HTD). The U.S. EPA (ToxSAC memorandum, 

May 6, 2009) calculated a BMD10L of 0.60 mg/kg/day for adult rat RBC cholinesterase 

inhibition and a BMD10L of 2.84 mg/kg/day for brain cholinesterase inhibition from the 

study data.

Body weight effects were observed in a rat teratology study (MRID 41962902) that treated 

pregnant dams with 10 consecutive gavage doses of phosmet from GD 7–16. At the end of 

dosing, a statistically significant reduction in body weight gain was observed at 15 

mg/kg/day (the HTD). This was associated with a 7% reduction in body weight, compared 

to controls. Probable treatment-related cholinergic clinical effects (shaking and/or stains

around mouth) were seen in a few animals (4/24) after 6 days of dosing through the end of 

dosing in the 15 mg/kg/day group. There was no unambiguous evidence of treatmentrelated cholinergic clinical signs or body weight effects at 5 or 10 mg/kg/day.

In a recent Uterotrophic assay (MRID 48618707), there were no body weight effects after 3 

consecutive days of gavage dosing at 5 or 20 mg/kg/day. However, reduced activity was 

noted in a few of the 20 mg/kg/day animals on the third dosing day, within several hours of 

dosing. 

In a recent Hershberger assay (MRID 48618706), there were treatment-related cholinergic 

clinical signs in the agonist and antagonist cohorts at 25 mg/kg/day after ≥3 consecutive 

dosing days. These effects were typically noted within a few hours of dose administration 

but did not persist to the pre-dosing examination on the following treatment day. 

Treatment-related cholinergic clinical signs were not seen at ≤15 mg/kg/day. Statistically 

significant reductions in body weight gain were found for both agonist and antagonist 

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cohorts at the 25 mg/kg/day dose. Additionally, mean final body weight was significantly 

reduced at the 25 mg/kg/day treatment level as compared to controls in the antagonist 

portion of the study. No body weight effects were noted at ≤25 mg/kg/day in the agonist 

cohort. 

The highest doses tested in the relative sensitivity and Hershberger studies appear to bracket 

the appropriate range for the highest dose for the phosmet pubertal assays (>5 and <25 

mg/kg/day), based on the target of achieving significant body weight effects while avoiding 

severe clinical signs. Considering the longer exposure intervals employed in the pubertal 

assays, compared to those used in the other gavage studies, the available data suggest that 

20 mg/kg/day will elicit measurable body weight effects in the pubertal assays. It should be 

noted that it may not be possible to avoid the occurrence of some cholinergic clinical signs 

with an organophosphate such as phosmet, given the target to elicit body weight effects. 

However, such effects, if present, should be transient and would not be anticipated to be 

severe and persist, based on the 25 mg/kg/day data from the Hershberger assay. A robust 

existing database shows that substantial cholinesterase inhibition will occur at 10 and 20 

mg/kg/day. Both selected doses significantly exceed the regulatory benchmark of 0.6 

mg/kg/day, which is the EPA-calculated BMD10L, for RBC cholinesterase inhibition in the 

repeated-dose relative sensitivity study. Both doses also exceed the EPA-calculated 

BMD10 for brain cholinesterase inhibition (3.86 mg/kg/day) following repeated exposures. 

Accordingly, the selected doses ensure that an appropriately conservative experimental 

challenge is employed in the phosmet pubertal screening assays. 

5. Dose Preparation and Analysis: Phosmet dose formulations were prepared at ILS in 0.5% 

aqueous carboxymethylcellulose five times during the study at concentrations of 2 and 4 

mg/mL. Formulations were dispensed into vials to be used daily during the study. Dose 

concentrations were adjusted to correct for purity of phosmet. Samples of dose formulations 

prepared on June 28, 2011 and July 6, 13, 19, and 26, 2011 were collected from the top, 

middle, and bottom of the formulation and sent to Smithers Viscient (Wareham, MA) for 

analysis. Smithers Viscient analyzed, in duplicate, samples received for concentration and 

homogeneity. The report stated that dose formulations of phosmet in 0.5% aqueous 

carboxymethylcellulose held from 1 to 10°C for up to 15 days were considered stable (Dix, 

20121

); however, no data were submitted to allow independent verification. 

Results

Stability (% of time zero): Reported in Study No. 12791.6159.

Concentration (% of nominal): 96–106% 

Homogeneity (%CV): 2.3–11.8% 

The analytical data indicated that the mixing procedure was adequate and the variation 

between nominal and actual dosage to the animals was acceptable. Homogeneity as %CV 

only exceeded 10% for the 2 mg/mL formulation on July 13, 2011. 

 

1 Dix, M. (2012). Storage Stability of Phosmet in Aqueous, Buffered Carboxymethylcellulose. Unpublished study 

report prepared by Smithers Viscient Inc. Study No. 12791.6159.

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6. Dosage Administration: Dose formulations were administered by oral gavage at a dose 

volume of 5 mL/kg body weight. The dose formulations were administered for 21 or 22 

consecutive days on PND 22–42/43. Dosing occurred 24-hours (±2 hours) from the 

previous dose. Dose volume was adjusted daily based on individual animal body weight. 

The dosing sequence was stratified across all dose groups; one animal from each group and 

then repeated until all animals were dosed.

7. Statistics: Descriptive statistics (mean, standard deviation, coefficient of variance, and 

sample size) were calculated using Microsoft Excel 2003/2007 (Redmond, WA). Data sets 

listed below were analyzed using Statistical Analysis System version 9.2 (SAS Institute, 

Cary, NC). Studentized residual plots were used to detect possible outliers in the data and 

Levene’s test was used to assess homogeneity of variance. Heterogeneous data were 

transformed (logarithm, square root, and multiplicative inverse), and if still heterogeneous, 

analyzed using the non-parametric Kruskal-Wallis and Dunn’s test. If data sets were not 

homogenous, ANCOVA analyses were not performed. Trend tests were performed on body 

weight and tissue weight data sets and reported when significant (p<0.05) for endpoints that 

did not show any significant pairwise comparisons. 

Classification Procedure

Initial body weights

Final body weight (use last day all body weights collected)

Final body weight gain (use last day all body weights 

collected)

Age and body weight at VO

Age at first estrus

Cycle length

Ovarian counts (follicles, cysts, corpora lutea)

Homogeneous data sets:

One-way analysis of variance (ANOVA) followed by pairwise comparisons performed using Dunnett’s two-tailed 

t-tests

Tissue weights

Relative tissue weights (liver, kidneys, pituitary, and 

adrenals)

Hormone levels

Clinical chemistry levels

Two-way ANOVA with treatment and necropsy day (if >1 

day) as main effects. 

Pair-wise comparisons were performed using Dunnett’s 

two-tailed t-tests.

Initial body weights

Final body weight (use last day all body weights collected)

Final body weight gain (use last day all body weights 

collected)

Age and body weight at VO

Tissue weights

Two-way analysis of covariance (ANCOVA) with PND 21

body weight (weight on day of allocation) as the covariable. 

Pair-wise comparisons were performed using Dunnett’s 

two-tailed t-tests.

In the instances where VO had not occurred prior to 

necropsy, the last day of examination plus 1 was used as the 

age at VO and terminal body weight was used for body 

weight at VO. In instances when at least 1 animal in any

group exhibited incomplete VO, including partial threads 

for > 3 days, the day partial separation was first recorded 

was used in the analyses.

Cycling status

Percent of animals cycling regularly

Chi-square analysis

Thyroid scoring (colloid area and follicular cell height) Fisher’s Exact test

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Significance was reported as exact p-values. The statistical analyses were considered 

appropriate. 

C. METHODS

1. Mortality and Clinical Examinations: Animals were observed twice daily for mortality 

and moribundity on weekdays and once daily on weekends and holidays. Rats were 

observed prior to allocation of animals to study groups, daily prior to dose administration, 

and prior to euthanasia. 

2. Body Weight: Body weights were collected weekly following birth, prior to allocation of 

animals to study groups, daily prior to dose administration, and prior to euthanasia. 

3. Food Consumption: Food consumption was not measured. 

4. Vaginal Opening: Beginning on PND 22, all animals were examined daily for onset of 

VO. VO was recorded as: VO not initiated, appearance of a pin hole, vaginal thread, or 

complete VO. Age and weight on the day of completion of VO were recorded.

5. Estrous Cyclicity: Beginning on the day of complete VO through euthanasia, vaginal 

smears were prepared daily, evaluated and classified as diestrus, proestrus, or estrus; 

metestrus was classified as diestrus. The overall cycling pattern for each female was 

characterized as regular, irregular, or not cycling. Regular cycling was defined as having 

recurring 4 to 5 day cycles, while irregular cycling was defined as having cycles with 

diestrus for a period >3 days or estrus ≥3 days. Animals were not considered to be cycling 

if there was ≥3 consecutive days of estrus or ≥5 consecutive days of diestrus. Mean cycle 

length was defined as the number of days from one diestrus to the next diestrus. Incomplete 

cycles were not used in calculating mean cycle length.

In instances where the time between VO and humane euthanasia did not allow observation 

of more than 1 complete cycle, classification was based on data available and the 

assumption that animals were cycling regularly if the partial data fit the definition, and 

cycling irregularly if the study ends without being able to distinguish between irregular and 

not cycling.

6. Sacrifice and Pathology: At least 2 hours after the final dose administration, animals were 

humanely euthanized by decapitation, in the same order as they were dosed. After 

euthanasia and prior to tissue collection, trunk blood was collected, and serum was obtained. 

All serum samples were stored at or below −70°C. Serum samples were shipped on dry ice 

to AniLytics Inc. (Gaithersburg, MD) for analysis. 

a. Hormone Analysis: T4 and TSH were measured in serum using radioimmunoassays 

(RIAs). Samples were assayed in duplicate and in conjunction with multiple quality 

control samples. 

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Female Pubertal Assay (2012) / Page 8 of 17

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b. Clinical Chemistry: The following CHECKED (X) parameters were examined.

ELECTROLYTES OTHER

X Calcium X Albumin

X Chloride X Creatinine*

Magnesium X Urea nitrogen*

X Phosphorus Total cholesterol

X Potassium Globulins

X Sodium Glucose

ENZYMES X Total bilirubin

X Alkaline phosphatase (ALP) X Total protein

Cholinesterase (ChE) Triglycerides

Creatine phosphokinase Albumin/globulin ratio (calculated)

Lactic acid dehydrogenase (LDH) Bile acids

X Alanine aminotransferase (ALT/also SGPT)

X Aspartate aminotransferase (AST/also SGOT)

X Sorbitol dehydrogenase

X Gamma glutamyl transferase (GGT)

Glutamate dehydrogenase

* Recommended for the pubertal assay in female rats based on guideline 890.1450.

c. Organ Weights and Histopathology: The following CHECKED (X) tissues were 

collected and weighed and grossly observed from all study animals. 

UROGENITAL OTHER

X Ovaries (paired, without oviducts)*+ X Thyroid a*+

X Uterus*+ X Liver*

X Kidneys (paired)*+ X Adrenals (paired)*

X Pituitary*

a Thyroid was weighed post-fixation.

* Weights required based on guideline 890.1450. 

+ Histopathological examination required based on guideline 890.1450. 

Uterus (without fluid), left ovary, left kidney, and thyroid were fixed in 10% neutral 

buffered formalin for at least 24-hours. After fixation, tissues were transferred to 70% 

histology grade alcohol, histologically processed, embedded, sectioned, and stained with 

hematoxylin and eosin. Histologically-processed tissues (thyroid, kidneys, uterus, and 

ovary) from all animals were microscopically evaluated. Five random sections of the ovary 

were examined for follicular development (including presence/absence of tertiary/antral 

follicles, presence/absence of corpora lutea, changes in corpus luteum development, and 

changes in number of both primary and atretic follicles) in addition to any 

abnormalities/lesions, such as ovarian atrophy. Two sections of each of the 2 lobes of the 

thyroid were examined and evaluated for follicular cell height and colloid area. A 5-point 

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grading scale (1 = shortest/smallest; 5 = tallest/largest) was used, and the thyroids were 

evaluated relative to photomicrographs supplied by the U.S. EPA. 

II. RESULTS 

A. Mortality: All animals survived. 

B. Clinical Signs of Toxicity: No treatment-related clinical signs were observed in animals 

from any dose group 24 hours post-dose; i.e., at the subsequent time of dosing. One 10 

mg/kg/day rat exhibited localized head tremors on one day, and tremors were observed at 

various times post-dose in up to ten 10 mg/kg/day rats on 10 days and up to sixteen 20 

mg/kg/day rats on 18 days.

C. General Growth and Vaginal Opening: Body weights, body weight gains, age of 

attainment of VO, weight at VO, and proportion/incidence of unopened vagina are presented 

in Tables 2 and 3 below. 

Unadjusted and adjusted body weight at VO were decreased (p<0.05) by 9% each in the 20 

mg/kg/day group compared to controls. No significant change in mean final body weight or 

body weight gain was observed in females administered 10 or 20 mg/kg/day phosmet 

compared to the vehicle control group. The treated groups displayed body weight gain 

deficits that diminished with time on test; e.g., at 20 mg/kg/day, body weight gain was ↓ 

30% during Days 22-23; ↓20% during Days 26-29; and ↓6% during Days 29-36 (Table 2). 

At 20 mg/kg/day, body weights were decreased (p≤0.05) by 8–10% from PND 26–36. A 

water bottle malfunction is thought to have led to a body weight loss (compared to the 

previous day) in half the control group on PND 36–37. The report stated that it was likely 

that the terminal body weights of the 20 mg/kg/day phosmet group would have been ~90% 

of vehicle control body weights had the water bottle malfunction in the control not occurred. 

It is to be noted that all of the control females had attained VO by PND 36 so the 

malfunction had no impact on this parameter for this group. All but one of the 10 

mg/kg/day females and all but two of the 20 mg/kg/day females had attained VO by PND 36 

also. 

TABLE 2. Body Weight and Body Weight Gain (grams) a

Days Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

PND 22 57.0±4.9 56.8±4.2 56.6±5.0

PND 27 82.8±7.0 80.9±6.7 75.9±6.5 ↓8%* 

PND 29 95.8±8.2 92.5±7.3 86.3±7.7 ↓10%* 

PND 36 140.9±11.9 134.3±9.9 128.5±13.4 ↓9%* 

PND 37 139.6±12.1 139.7±9.4 131.6±14.9 ↓6%

PND 42 169.1±15.1 165.1±11.2 163.7±17.5 ↓4%

PND 22-23 4.0 3.4 ↓15% 2.8 ↓30%

PND 23-26 17.0 15.6 ↓8% 12.5 ↓26%

PND 26-29 17.8 16.7 ↓6% 14.4 ↓20%

PND 29-36 45.1 41.8 ↓8% 42.2 ↓6%

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TABLE 2. Body Weight and Body Weight Gain (grams) a

PND 26-36 62.9 58.5 ↓7% 56.6 ↓10%

PND 36-37 -1.3 5.4 3.1

PND 38-42 21.6 19.8 25.5 ↑18%

PND 22-36 83.9 77.5 ↓8% 71.9 ↓14%

PND 22-42 112.1 108.3 ↓4% 107.1 ↓4%

 a Data were obtained from Appendix IV, pages 101-103 of the study report. * p<0.05; body weight gains calculated by 

reviewer.

All performance criteria were met; however, weaning weight (PND 21) was not reported. 

TABLE 3. General Growth and Vaginal Opening (VO) a

Parameter Evaluated

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

Initial body weight

(PND 22; g)

U 16 57.0 4.9 8.5 16 56.8 4.2 7.4 16 56.6 5.0 8.8

A 16 57.0 --- --- 16 56.9 --- --- 16 56.5 --- --- 

Body weight at 

vaginal opening (g)

U 16 122.1 11.3 9.2 16 115.6 13.7 11.9 15 111.5*

(↓9) 9.8 8.8

A 16 122.1 --- --- 16 115.6 --- --- 15 111.6*

(↓9) --- --- 

Final body weight

(g)

U 16 169.1 15.1 8.9 16 165.1 11.2 6.8 16 163.7 17.5 10.7

A 16 169.1 --- --- 16 165.3 --- --- 16 163.4 --- --- 

Final body weight 

(% of control)

U 16 --- --- --- 16 97.6 --- --- 16 96.8 --- --- 

A 16 --- --- --- 16 97.8 --- --- 16 96.6 --- --- 

Body weight gain

(final – initial; g)

U 16 112.1 12.1 10.8 16 108.3 8.7 8.0 16 107.1 14.8 13.8

A 16 112.1 --- --- 16 108.4 --- --- 16 106.9 --- --- 

Age at vaginal 

opening (PND)

U 16 33.2 1.2 3.7 16 32.9 2.0 6.0 15 33.4 1.5 4.5

A 16 33.2 --- --- 16 32.9 --- --- 15 33.4 --- --- 

Proportion unopened 

(#/N) 0/16 0/16 1/16

a Data were obtained from Table 7 on page 27 of the study report. Percent difference from controls (calculated by reviewers) is 

presented parenthetically.

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

* Significantly different from controls at p<0.05.

D. Organ Weights: Organ weights at necropsy are presented in Table 4 below. No significant 

differences were observed in liver, kidney, adrenal, pituitary, thyroid, uterus (wet or 

blotted), or ovary weights of the treated groups compared to controls, but there was a doserelated significant trend (p≤0.05) in relative liver weights (↑3-5%). Although adrenal 

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weights in both groups were comparable to/ slightly lower than (↓2-3%) the control, the 

adrenal weight of the control was below the acceptable range of the performance criteria.

Compared to the low range value, the adrenal weights were ↓16-18%. Thyroid weight was 

slightly increased (↑6%) at 10 mg/kg/day and slightly decreased (↓8%) at 20 mg/kg/day. 

Pituitary weights were slightly lower than control (↓6% and ↓8%) at 10 mg/kg/day and 20 

mg/kg/day, respectively. 

The following performance criteria were not met: mean adrenal weight of 32.9 mg 

(acceptable range: 38.34–48.84); and %CV=11.4 for kidneys (top acceptable range: 10.76). 

TABLE 4. Organ Weights at Necropsya

Organ

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N Mean SD

CV 

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%)

Liver

(g)

U 16 7.52 0.67 9.0 16 7.60 0.66 8.7 16 7.74 1.15 14.8

A 16 --- --- --- 16 --- --- --- 16 --- --- ---

R* 16 4.45 0.2 4.6 16 4.57

(↑3) 0.25 5.5 16 4.66(↑5) 0.36 7.6

Kidneys

(g)

U 16 1.33 0.15 11.4 16 1.33 0.07 5.1 16 1.32 0.14 10.8

A 16 --- --- --- 16 --- --- --- 16 --- --- ---

R 16 0.78 0.06 7.3 16 0.8 0.05 6.4 16 0.8 0.04 5.6

Pituitary

(mg)

U 16 9.9 1.3 13.3 16 9.4 1.2 12.6 16 9.2 1.6 17.0

A 16 9.9 --- --- 16 9.4

(↓6) --- --- 16 9.2(↓8) --- --- 

R 16 5.8 0.7 11.8 16 5.7 0.7 13.1 16 5.6 1 16.9

Adrenals

(mg)

U 16 32.9 4.9 14.9 16 32.1 6.5 20.4 16 31.8 5.5 17.2

A 16 32.9 --- --- 16 32.1 --- --- 16 31.8

(↓4) --- --- 

R 16 19.7 3.7 18.9 16 19.4 4.3 22.3 16 19.5 4.3 22.2

Ovaries

(mg)

U 16 59.8 11.9 19.9 16 55.0

(↓8) 6.6 12 16 56.7(↓6) 10 17.7

A 16 59.8 --- --- 16 55.1 --- --- 16 56.6 --- ---

Uterus, wet

(mg)

U 16 418.6 206 49.2 16 383.4

(↓8) 194.8 50.8 16 373.5(↓11) 153.3 41.1

A 16 418.6 --- --- 16 384.4 --- --- 16 372.4

(↓12) --- --- 

Uterus, blotted

(mg)

U 16 330.3 74.9 22.7 16 301.1

(↓9) 90.8 30.1 16 321.3(↓3) 65.8 20.5

A 16 330.3 --- --- 16 301.8 --- --- 16 320.5 --- ---

Thyroid, fixed

(mg)

U 16 20.6 3.1 15.1 16 22.0

(↑6) 4.4 19.9 16 19.1(↓8) 3.7 19.5

A 16 20.6 --- --- 16 22 --- --- 16 19.1 --- ---

a Data were obtained from Table 8 on page 29 of the study report. No statistical differences were noted in pair-wise 

comparisons of treated groups with control.

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) 

* Significant trend (p<0.05) 

Page 212 of 260
Female Pubertal Assay (2012) / Page 12 of 17

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E. Estrus Cyclicity: Estrus cycle data are provided in Table 5. No treatment-related effect 

was noted on cycle status at necropsy, mean age at first estrus, mean cycle length, percent 

cycling, or percent regularly cycling. 

Page 213 of 260
Female Pubertal Assay (2012) / Page 13 of 17

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TABLE 5. Estrous Cyclicitya

Treatment 

Groups N

Mean Age at 

First Estrus 

(PND)

Mean Cycle 

Length 

(days)

Cycling 

(%)

Regularly 

Cycling 

(%)

Cycle Status at Necropsy (# Females)

Diestrus Proestrus Estrus

Not 

Cycling

Vehicle 16 35.1±2.2 4.1±1.4 93.75 87.5 5 2 9 1

10 mg/kg/day

Phosmet 16 35.6±3.2 3.5±0.9 100 87.5 10 3 3 0 

20 mg/kg/day

Phosmet 16 35.4±2.7 3.9±0.9 93.3 86.7 6 1 8 1 

a Data were obtained from Tables 8 and 9 on pages 29-30 of the study report. No statistical differences were noted in pairwise comparisons of treated groups with control.

N Number of animals

* Significantly different from controls at p<0.05.

F. Clinical Chemistry and Hormone Levels: Clinical chemistry and hormone levels are 

presented in Table 6 below. 

Serum T4 levels were increased (p<0.05) by 24–38% in the treated groups. The CV (28.7) 

was slightly greater than the performance criteria mean (21.38) but was less than the top of 

the acceptable range (29.39). Serum TSH levels in the treated groups were slightly greater 

than (↑2%-6%) the control. 

The following clinical chemistry parameters differed from control in one or both treatment 

groups, although statistical significance was not always attained (NS): (i) minor increases in 

sodium of 4–6% at 10 mg/kg/day and 20 mg/kg/day (p<0.05); (ii) increases in alanine 

aminotransferase of 11–17% (NS at 20 mg/kg/day); (iii) increases of alkaline phosphatase 

(↑14-24%, NS at 10 mg/kg/day); (iv ) increases in bilirubin at 10 mg/kg/day and 20 

mg/kg/day (↑23-38%; NS); (v) increases in blood urea nitrogen (↑8-23%, NS at 10 

mg/kg/day); and (vi) increases in sorbitol dehydrogenase (↑13-33%, NS at 10 mg/kg/day). 

 It is to be noted that several of the control values are outside the normal range. For example, 

the control ALP value is 246 U/L and the range provided in Table 12 of the study report is 

17-183 U/L; control ALT value is 94 U/L, whereas the range is 20-56 U/L. It is to be noted 

that Table 12 of the study report is labeled as female data, but the same hormone and clinical 

chemistry ranges are listed in Table 25 of the study report as male ranges. 

TABLE 6. Hormone Levels and Clinical Chemistry a

Parameter

Evaluated

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

Hormones

Serum T4, Total 

(μg/dL) 16 3.09 0.89 28.7 16 3.84*(↑24) 1.12 29.1 16 4.27*(↑38) 1.06 24.9

Serum TSH 

(ng/mL) 16 1.47 0.72 50.0 16 1.50

(↑2) 0.70 46.4 16 1.57(↑6) 1.02 65.0

Page 214 of 260
Female Pubertal Assay (2012) / Page 14 of 17

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TABLE 6. Hormone Levels and Clinical Chemistry a

Parameter

Evaluated

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

Clinical Chemistry

Sodium (mEq/L) 16 141 4 3 16 147*

(↑4) 2 2 16 150*(↑6) 2 2 

Potassium (mEq/L) 16 8.2 0.7 8.4 16 8.4 1 11.9 16 8.6 0.7 7.8

Chloride (mEq/L) 16 104 2 2 16 110

(↑6) 2 2 16 114(↑14) 2 2 

Calcium (mg/dL) 16 10.3 0.4 4.3 16 10.8*

(↑5) 0.4 3.5 16 10.5 0.7 6.4

Phosphorus 

(mg/dL) 16 9.7 0.5 5.4 16 10.0 1.0 9.7 16 10.0 1.0 9.9

AST (U/L) 16 281 48 17 16 284 87 31 16 294 74 25

ALT (U/L) 16 94 10 11 16 104*

(↑11) 21 20 16 110(↑17) 21 19

GGT (U/L) 16 0.1 0.5 400 16 0.2 0.5 290 16 0 0

ALP (U/L) 16 246 48 19 16 280

(↑14) 49 18 16 305*(↑24) 63 21

BUN (mg/dL) 16 13 2 16 16 14

(↑8) 2 14 16 16*(↑23) 2 15

Creatinine (mg/dL) 16 0.40 0.05 12.9 16 0.41 0.06 14.1 16 0.38 0.05 14.3

Total Bilirubin 

(mg/dL) 16 0.13 0.11 86.7 16 0.16

(↑23) 0.11 66.9 16 0.18(↑38) 0.18 97.1

SDH (U/L) 16 15 5 35 16 17

(↑13) 5 29 16 20*(↑33) 5 27

Total Protein 

(g/dL) 16 5.5 0.3 5.4 16 5.7 0.4 6.6 16 5.5 0.4 7.4

Albumin (g/dL) 16 4.3 0.3 6.3 16 4.5 0.3 6.9 16 4.3 0.4 8.7

a Data were obtained from Table 10 on page 30 and Table 11 on page 32 of the study report. Percent difference from 

controls (calculated by reviewers) is presented parenthetically.

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from controls at p<0.05.

F. Gross pathology: There was a focus on the median liver lobe proximal to the hilus 

observed in one animal administered 20 mg/kg/day phosmet. No other gross observations 

were noted in female rats surviving to the scheduled termination.

G. Histopathology: The incidences of histopathological findings of the thyroid gland are 

presented below in Table 7; follicular cell shape was not reported. A marginal decrease in 

the colloid area and increase in the follicular cell height was observed in animals 

administered phosmet (10 and 20 mg/kg) compared to controls. The number of rats with the 

largest follicular colloid area (Grades 4 or 5) included 14/16 in the control, 10/16 at 10 

mg/kg/day and 8/16 at 20 mg/kg/day. Likewise, the number of rats with the shortest 

follicular cell height (Grades 1 or 2) included 14/16 in the control, 10/16 at 10 mg/kg/day 

and 8/16 at 20 mg/kg/day. 

Page 215 of 260
Female Pubertal Assay (2012) / Page 15 of 17

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TABLE 7. Incidence of Histopathological Lesions of the Thyroid Gland a

Treatment Groups

Parameter Evaluated

Colloid Area Follicular Cell Height 

Grade b Incidence Grade Incidence

O E O E

Vehicle Control

1 0 16 1 1 16

2 0 16 2 13 16

3 2 16 3 2 16

4 13 16 4 0 16

5 1 16 5 0 16

10 mg/kg/day

Phosmet

1 0 16 1 0 16

2 0 16 2 10 16

3 6 16 3 6 16

4 10 16 4 0 16

5 0 16 5 0 16

20 mg/kg/day

Phosmet

1 0 16 1 1 16

2 1 16 2 7 16

3 7 16 3 7 16

4 7 16 4 1 16

5 1 16 5 0 16

a Data were obtained from Table 14 on page 35 of the study report.

b A 5-point grading scale (1 = shortest/smallest; 5 = tallest/largest) was used. 

O No. Observed

E No. Examined

The incidence of histopathological findings of the ovary, uterus, thyroid, and kidneys are 

presented in Table 8. In the ovary, the number of antral follicles was increased by 57% at 

10 mg/kg/day (NS) and by 93% (<0.05) at 20 mg/kg/day. The number of atretic follicles 

was decreased by 24% (NS) at 10 mg/kg/day and 29% (<0.05) at 20 mg/kg/day. All other 

ovarian values in the treated groups were similar to the control. There were no treatmentrelated histopathological findings noted in the uterus, thyroid (except as noted in Table 6), 

or kidneys at any dose. 

Page 216 of 260
Female Pubertal Assay (2012) / Page 16 of 17

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TABLE 8. Incidence of Histopathological Lesions of the Ovary, Thyroid, Uterus, and Kidneya

Findings

Dose Level (mg/kg bw/day)

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

#

Observed

# 

Examined

#

Observed

# 

Examined

#

Observed

# 

Examined

Ovary [Mean±SD (CV)]

Small follicles 27.7±9.6 (34.7)b 16 30.6±7.1 (23.2) 16 26.1±10.1 (38.7) 16

Medium follicles 13.7±4.0 (30.8) 16 14.4±3.1 (21.5) 16 14.6±5.0 (34.2) 16

Antral follicles

1.4±1.0 (69.9)b 16

2.2±0.7 (31.8)

[↑57]

16 2.7±2.2* (81.5)

[↑93] 16

Atretic follicles 7.9±2.5 (31.6)b 16 6.0±2.7 (45.0)

[↓24%] 16 5.6±1.5* (26.8)[↓29] 16

Follicular cysts 0.013±0.05 

(384.6)b 16

0.025±0.1

(400.0)b 

[↑92]

16 0.0±0.0 16

Corpora lutea 6.8±1.9 (27.9)b 16 7.5±1.7 (22.7) 16 6.6±2.2 (33.3) 16

Thyroid

Minimal C-cell 

hyperplasia 0 16 0 16 1 16

Uterus

Minimal dilatation 7 16 5 16 2 16

Minimal eosinophilic 

material 1 16 0 16 1 16

Minimal inflammatory 

cells/debris 3 16 0 16 6 16

Mild inflammatory 

cells/debris 0 16 0 16 1 16

Minimal endometrial 

folding 6 16 7 16 7 16

Minimal inflammatory 

cells in the endometrium 1 16 0 16 3 16

Kidneys

Minimal nephropathy 8 16 8 16 6 16

Minimal tubular dilatation 1 16 5 16 2 16

Minimal cysts 1 16 0 16 0 16

Minimal mineralization 0 16 1 16 0 16

a Data were obtained from Appendix X on pages 148, 150 and 152 of the study report. b

 (CV)

* Significantly different from controls at p<0.05.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Administration of phosmet to intact 

juvenile/peripubertal female rats at a dose that met, but did not exceed the MTD, did not 

cause any changes in the evaluated endpoints to suggest a disruption in pubertal 

development or thyroid function.

B. AGENCY COMMENTS: No treatment-related effects were observed on mortality, organ 

weights, serum TSH concentrations, clinical chemistry, or gross pathology. Changes (NS) in 

ovary, uterus, thyroid, and pituitary weights were noted in the low- and high-dose animals. 

There were no treatment-related histopathological findings noted in the ovaries, uterus, 

thyroid, or kidneys. In addition, no treatment-related effects were noted on cycle status, 

mean age at first estrus, mean cycle length, percent cycling, or percent regularly cycling

Page 217 of 260
Female Pubertal Assay (2012) / Page 17 of 17

PHOSMET / 059201 OCSPP 890.1450/ OECD None

One 10-mg/kg/day rat exhibited localized head tremors on a single day, and tremors were 

observed at various times post-dose in up to 10/16 10-mg/kg/day rats on 10 days and up to 

sixteen 20-mg/kg/day rats at 18 days. No other treatment-related clinical signs were 

observed in animals from either dose group. Decreased body weights (p<0.05; ↓9% to 10%) 

were observed at 20-mg/kg/day during PND 26 to 36. No significant change in mean final 

body weight or body weight gain was observed in either treatment group compared to the 

vehicle control group. 

The day of VO was comparable among the groups. Unadjusted and adjusted body weights at 

VO were decreased by 9% each in the 20 mg/kg/day group compared to controls. No 

treatment-related effect was noted on cycle status, mean age at first estrus, mean cycle 

length, percent cycling, or percent regularly cycling. At 20 mg/kg/day, the number of 

ovarian antral follicles was increased (↑93%), and the number of atretic follicles was 

decreased (↓29%). All other values in the treated groups were similar to control.

Serum T4 concentrations were increased by 24–38% in the treated groups compared to the 

control, and TSH was slightly increased (6%) at 20 mg/kg/day. A marginal decrease in the 

thyroid colloid area and increase in the follicular cell height was observed in animals 

administered phosmet (10 and 20 mg/kg) compared to control. 

There were no effects on liver, kidney, pituitary, adrenal, uterus, or thyroid organ weights at 

either dose compared to control 

 

The high dose tested (20 mg/kg/day) was determined to be an excessive dose due to the 

occurrence of tremors in up to 16 of 20 rats at 20 mg/kg/day rats on 18 days. In addition, 

tremors were observed at various times post-dose in up to 10/16 10 mg/kg/day rats on 10 

days. Also, decreased body weights (↓9%–10%) were observed at 20 mg/kg/day during 

PND 26–36. 

Following the agency’s determination, the registrant submitted additional information 

(MRID 49610501) in response to the agency’s review of this assay. The submitted data 

show that tremors were seen in 10/16 rats at the 10 mg/kg/day dose level (during 10 days) 

and all animals at the 20 mg/kg/day dose (during 18 days). The severity of the tremors 

ranged from “not characterized to moderate.” Upon review of these data, the agency 

reaffirms its previous conclusion that both doses tested in this assay were excessive. 

C. STUDY DEFICIENCIES: Dose levels tested were excessive. 

Page 218 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1500, Male Pubertal Assay

EPA Contract No. EP10H001452 

Task Assignment No. 2-61-2012 (MRID 48673003) 

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:

Ronnie J. Bever Jr., Ph.D., D.A.B.T. Date: 5/7/2012

Secondary Reviewer: Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 5/17/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 5/21/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 5/21/2012

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by CSS-Dynamac Corporation personnel.

Page 219 of 260
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).

Page 220 of 260
PHOSMET I 059201 

Primary Reviewer: Linda Tavlor. Ph.D. 

Health Effects Division 

Secondary Reviewer: John Liccione, Ph.D. 

Health Effects Division 

Male Pubertal Assay (2012) I Page I of 15 

OCSPP 890.1500/ OECD None 

DATA EVALUATION RECORD 

STUDY TYPE: Male Pubertal Assay; OCSPP 890.1500; OECD None. 

PC CODE: 059201 DP BARCODE: D400672 

TXR#: 0056199 CAS No.: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8% a.i.) 

SYNONYMS: S-[(1,3-dihydro-l ,3-dioxo-2H-isoindol-2-yl)methyl] 0, 0-dimethyl 

phosphorodithioate 

CITATION: Zorilla, L. (2012). Pubertal developmental and thyroid function with phosmet 

injuvenile/peripubertal CRL:CD(SD) IGS female and male rats. Integrated 

Laboratory Systems, Inc., Durham, NC, Laboratory Study No.: Cl94-300, 

February 24, 2012. MRID 48673003. Unpublished. 

SPONSOR: Gowan Company, P.O. Box 5569, Yuma, AZ 

TEST ORDER#: EDSP-059201-54 

EXECUTIVE SUMMARY: Jn a male pubertal assay (MRID 48673003), 16 Sprague-Dawley 

(Crl:CD®(SD) IGS) rats/dose group were treated daily via oral gavage with phosmet (96.8% a.i., 

Batch #: 6QH9118000) in aqueous 0.5% carboxymethylcellulose (5 mL/kg) at doses ofO, 10, or 

20 mg/kg/day from post-natal day (PND) 23 to 53 or 54. The animals were examined for 

preputial separation (PPS) daily beginning on PND 30, and age and body weight at day of 

attainment was recorded. Following sacrifice on PND 53154, total serum testosterone, thyroxine 

(T4), and thyroid stimulating hormone (TSH) levels were analyzed by radioimmunoassay. 

Various clinical chemistry parameters were measured in the serum. Liver, kidney, pituitary, 

adrenals, seminal vesicles with coagulating glands, and ventral and dorsolateral prostate were 

weighed and examined macroscopically; in addition, microscopic examinations were conducted 

on the epididyrnides, testis, thyroid, and kidneys. 

All rats survived until study termination. Tremors were observed periodically in the majority of 

the rats at 20 mg/kg/day. No other clinical signs of toxicity were observed in the study at either 

dose. 

The decreases in body weight gains and final body weights were minimal (<10%) and not 

biologically significant. The small variations in clinical chemistry parameters observed at 20 

mg/kg/day were not considered to be indicative of toxic effects on the kidney or liver. 

Page 221 of 260
Male Pubertal Assay (2012) / Page 2 of 15

PHOSMET / 059201 OCSPP 890.1500/ OECD None

There was no treatment-related effect on preputial separation at either dose level. 

The adjusted ventral prostate weights showed a linear trend of decreased weight with increasing 

dose; however, no statistically significant effect was detected between the treated groups and 

control. Both means were lower than historical control mean ventral weight for Sprague-Dawley 

male rats but were within the acceptable range. There were no effects on liver, kidney, pituitary, 

adrenal, testis, or other sex organ weights at either dose level compared to the control. 

Testosterone levels were lower in both dose groups compared to the control, but statistical 

significance was not attained and the means were within the expected range for Sprague-Dawley 

rats. It is to be noted that the standard deviation for testosterone in the 20 mg/kg/day dose group 

(1.62) was similar to the mean value (1.80). 

Serum T4 levels were increased in both treatment groups compared to the concurrent control and 

the mean value for Sprague-Dawley male rats, but they were within the acceptable range in the 

performance criteria. Additionally, these increases were within the range of control values 

observed at the analytical laboratory (3-7 μg/dL). TSH levels were slightly higher at both dose 

levels compared to the control, but the control value was below the acceptable range and the 

Guideline criteria for this parameter were not met. 

During the agency’s initial review, the doses (10 and 20 mg/kg/day) used in this study were 

considered excessive, based on the dose-selection rationale and the periodic occurrence of 

tremors in the majority of the males at 20 mg/kg/day. Subsequently, the registrant submitted 

additional data (MRID 4961502) in response to the agency’s review of this assay. The submitted 

data show at the 10 mg/kg/day dose level, mild tremors were seen during one day only in 6/16 

animals. In contrast, the severity of tremors at the 20 mg/kg/day dose level ranged from mild to 

moderate and were seen on multiple days in 11/16 animals. Based on this additional 

information, the low dose was determined to be adequate with only the high dose showing 

evidence of overt toxicity. 

The assay satisfies the EDSP Tier 1 Test Order requirements for a Male Pubertal Assay (OCSPP 

890.1500). 

COMPLIANCE: Signed and dated GLP Compliance, Data Confidentiality, and Quality 

Assurance statements were provided. 

Page 222 of 260
Male Pubertal Assay (2012) / Page 3 of 15

PHOSMET / 059201 OCSPP 890.1500/ OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Integrated Laboratories Systems, Inc.

Location: Durham, NC

Study Directors: L. Zorilla.

Other Personnel: S. Borghoff, study toxicologist

M. Boyle, study pathologist

Study Period: May 25, 2011 through February 24, 2012

2. Test Substance: Phosmet

Description: Off white solid

Source: Gowan Company

Batch #: 6QH9118000 (expires January 31, 2013)

Purity: 96.8% a.i.

Stability: Report stated that the compound is stable in the vehicle at 1–10°C for up to 15 days

CAS #: 732-11-6

Structure: O

O

S

P

S

OCH3

N OCH3

3. Vehicle: 0.5% Carboxymethylcellulose in sodium phosphate buffer

4. Test Animals:

Species: Rat (males)

Strain: Sprague-Dawley (Crl:CD®(SD) IGS)

Age/Mean Weight 

at Study Initiation: PND 23 / 51.5–72.1 g 

Source: Charles River Laboratories International, Inc. (Raleigh, NC)

Housing: Parental dams were individually housed in polycarbonate cages with micro-isolator tops and 

absorbent, heat-treated, hardwood bedding; each dam was housed with her litter until weaning 

on PND 21. After weaning, up to 2 males were housed per cage.

Diet: Teklad Global 16% Protein Rodent Diet (Teklad Diets, Madison, WI), ad libitum. It was 

stated that the total genistein equivalents of genistein plus daidzein was determined to be 8.0

μg/g of feed.

Water: Reverse osmosis-purified tap water, ad libitum

Environmental 

Conditions:

Temperature:

Humidity:

Air changes:

Photoperiod:

19–24°C

43–78% 

Not reported

14 h light / 10 h dark

B. STUDY DESIGN

1. In-Life Dates: Start: July 1, 2011 End: Approximately August 2, 2011 

2. Mating: Time-mated pregnant nulliparous dams (age not reported) were received from the 

supplier on gestation day (GD) 8 and were allowed to deliver naturally and rear their pups to 

PND 21. Between postnatal days (PND) 3 and 5, litters with the same date of birth were 

standardized to 8 pups with equal numbers of males and females.

Page 223 of 260
Male Pubertal Assay (2012) / Page 4 of 15

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3. Animal Assignment: Following weaning on PND 21, animals were assigned to study using 

a procedure that stratifies animals across groups by body weight such that mean body 

weight of each group was not statistically different from any other group using analysis of 

variance. Care was taken to avoid placing littermates in the same dose group. The test 

groups are provided in Table 1.

TABLE 1. Study Design a

Test group Dose (mg/kg/day) # of Males

Control 0 16

Low 10 16

High 20 16

a Data were obtained from Table 2 on page 16 of the study report. 

4. Dose Selection Rationale: The doses were selected based on the results of several previous 

studies. A 7-day relative sensitivity study (MRID 44839301) compared the toxic responses 

of PND 11 rat pups versus adult rats following repeated gavage administration of phosmet. 

No treatment-related effects on body weight or cholinergic clinical signs were seen in either 

pups or adults at the highest tested dose (HTD) of 5 mg/kg/day, however significant 

cholinesterase inhibition was evident (e.g. responses were 57-62% of controls in adult RBC 

and 81-86% of controls in adult brain at the HTD). The U.S. EPA (ToxSAC memorandum, 

May 6, 2009) calculated a BMD10L of 0.60 mg/kg/day for adult rat RBC cholinesterase 

inhibition and a BMD10L of 2.84 mg/kg/day for brain cholinesterase inhibition from the 

study data.

Body weight effects were observed in a rat teratology study (MRID 41962902) that treated 

pregnant dams with 10 consecutive gavage doses of phosmet from GD 7–16. At the end of 

dosing, a statistically significant reduction in body weight gain was observed at 15 

mg/kg/day (the HTD). This was associated with a 7% reduction in body weight, compared 

to controls. Probable treatment-related cholinergic clinical effects (shaking and/or stains 

around mouth) were seen in a few animals (4/24) after 6 days of dosing through the end of 

dosing in the 15 mg/kg/day group. There was no unambiguous evidence of treatmentrelated cholinergic clinical signs or body weight effects at 5 or 10 mg/kg/day.

In a recent Uterotrophic assay (MRID 48618707), there were no body weight effects after 3 

consecutive days of gavage dosing at 5 or 20 mg/kg/day. However, reduced activity was 

noted in a few of the 20 mg/kg/day animals on the third dosing day, within several hours of 

dosing. 

In a recent Hershberger assay (MRID 48618706), there were treatment-related cholinergic 

clinical signs in the agonist and antagonist cohorts at 25 mg/kg/day after ≥3 consecutive 

dosing days. These effects were typically noted within a few hours of dose administration 

but did not persist to the pre-dosing examination on the following treatment day. 

Treatment-related cholinergic clinical signs were not seen at ≤15 mg/kg/day. Statistically 

significant reductions in body weight gain were found for both agonist and antagonist 

cohorts at the 25 mg/kg/day dose. Additionally, mean final body weight was significantly 

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reduced at the 25 mg/kg/day treatment level as compared to controls in the antagonist 

portion of the study. No body weight effects were noted at ≤25 mg/kg/day in the agonist 

cohort. 

The highest doses tested in the relative sensitivity and Hershberger studies appear to bracket 

the appropriate range for the highest dose for the phosmet pubertal assays (> 5 and < 25 

mg/kg/day), based on the target of achieving significant body weight effects while avoiding 

severe clinical signs. Considering the longer exposure intervals employed in the pubertal 

assays, compared to those used in the other gavage studies, the available data clearly suggest 

that 20 mg/kg/day will elicit measurable body weight effects in the pubertal assays. It 

should be noted that it may not be possible to avoid the occurrence of some cholinergic 

clinical signs with an organophosphate such as phosmet, given the target to elicit body 

weight effects. However, such effects, if present, should be transient and would not be 

anticipated to be severe and persist, based on the 25 mg/kg/day data from the Hershberger 

assay. A robust existing database shows that substantial cholinesterase inhibition will occur 

at 10 and 20 mg/kg/day. Both selected doses significantly exceed the regulatory benchmark 

of 0.6 mg/kg/day, which is the EPA-calculated BMD10L, for RBC cholinesterase inhibition 

in the repeated-dose relative sensitivity study. Both doses also exceed the EPA-calculated 

BMD10 for brain cholinesterase inhibition (3.86 mg/kg/day) following repeated exposures. 

Accordingly, the selected doses ensure that an appropriately conservative experimental 

challenge is employed in the phosmet pubertal screening assays.

5. Dose Preparation and Analysis: Phosmet dose formulations were prepared at ILS in 0.5% 

aqueous carboxymethylcellulose five times during the study at concentrations of 2 and 4 

mg/mL. Formulations were dispensed into vials to be used daily during the study. Dose 

concentrations were adjusted to correct for purity of phosmet. Samples of dose formulations 

prepared on June 28, 2011 and July 6, 13, 19, and 26, 2011 were collected from the top, 

middle, and bottom of the formulation and sent to Smithers Viscient (Wareham, MA) for 

analysis. Smithers Viscient analyzed, in duplicate, samples received for concentration and 

homogeneity. The report stated that dose formulations of phosmet in 0.5% aqueous 

carboxymethylcellulose held from 1 to 10°C for up to 15 days were considered stable (Dix, 

20121

); however, no data were submitted to allow independent verification. 

Results

Stability (% of time zero): Not reported

Concentration (% of nominal): 96–106% 

Homogeneity (%CV): 2.3–11.8% 

The analytical data indicated that the mixing procedure was adequate and the variation 

between nominal and actual dosage to the animals was acceptable. Homogeneity as %CV 

only exceeded 10% for the 2 mg/mL formulation on July 13, 2011. Stability data should be 

submitted for review. 

 

1 Dix, M. (2012). Storage Stability of Phosmet in Aqueous, Buffered Carboxymethylcellulose. Unpublished study 

report prepared by Smithers Viscient Inc. Study No. 12791.6159.

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6. Dosage Administration: Dose formulations were administered by oral gavage at a dose 

volume of 5 mL/kg body weight. The dose formulations were administered for 31 or 32 

consecutive days on PND 23–53/54. Dosing occurred 24-hours (±2 hours) from the 

previous dose. Dose volume was adjusted daily based on individual animal body weight. 

The dosing sequence was stratified across all dose groups; one animal from each group and 

then repeated until all animals were dosed.

7. Statistics: Descriptive statistics (mean, standard deviation, coefficient of variance, and 

sample size) were calculated using Microsoft Excel 2003/2007 (Redmond, WA). Data sets 

listed below were analyzed using Statistical Analysis System version 9.2 (SAS Institute, 

Cary, NC). Studentized residual plots were used to detect possible outliers in the data and 

Levene’s test was used to assess homogeneity of variance. Heterogeneous data were 

transformed (logarithm, square root, and multiplicative inverse) and if still heterogeneous 

analyzed using the non-parametric Kruskal-Wallis and Dunn’s test. If data sets were not 

homogenous, ANCOVA analyses were not performed. Trend tests were performed on body 

weight and tissue weight data sets and reported when significant (p<0.05) for endpoints that 

did not show any significant pairwise comparisons. 

Classification Procedure

Initial body weights

Final body weight (use last day all body weights collected)

Final body weight gain (use last day all body weights 

collected)

Age and body weight at PPS

Homogeneous data sets:

One-way analysis of variance (ANOVA) followed by pairwise comparisons performed using Dunnett’s two-tailed 

t-tests

Tissue weights

Relative tissue weights (liver, kidneys, pituitary, and 

adrenals)

Hormone levels

Clinical chemistry levels

Two-way ANOVA with treatment and necropsy day (if >1 

day) as main effects. 

Pair-wise comparisons were performed using Dunnett’s 

two-tailed t-tests.

Initial body weights

Final body weight (use last day all body weights collected)

Final body weight gain (use last day all body weights 

collected)

Age and body weight at PPS

Tissue weights

Two-way analysis of covariance (ANCOVA) with PND 21

body weight (weight on day of allocation) as the covariable. 

Pair-wise comparisons were performed using Dunnett’s 

two-tailed t-tests.

In the instances where PPS had not occurred prior to 

necropsy, the last day of examination plus 1 was used as the 

age at PPS and terminal body weight was used for body 

weight at PPS. In instances when at least 1 animal in any

group exhibited incomplete PPS, including partial threads 

for >3 days, the day partial separation was first recorded 

was used in the analyses.

Thyroid scoring (colloid area and follicular cell height) Fisher’s Exact test

Significance was reported as exact p-values, except no p-value was reported for Dunn's Test 

(p<0.05). The statistical analyses were considered appropriate.

C. METHODS

1. Mortality and Clinical Examinations: Animals were observed twice daily for mortality 

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and moribundity on weekdays and once daily on weekends and holidays. Rats were 

observed prior to allocation of animals to study groups, daily prior to dose administration, 

and prior to euthanasia. 

2. Body Weight: Body weights were collected weekly following birth, prior to allocation of 

animals to study groups, daily prior to dose administration, and prior to euthanasia. 

3. Food Consumption: Food consumption was not measured. 

4. Preputial Separation (PPS): Beginning on PND 30, males were examined daily following 

dosing, and PPS was noted as: progression not initiated, partial separation, a persistent 

thread of tissue between the glans and prepuce, or complete PPS. 

5. Sacrifice and Pathology: At least 2 hours after the final dose administration, animals were 

humanely euthanized by decapitation, in the same order as they were dosed. After 

euthanasia and prior to tissue collection, trunk blood was collected, and serum was obtained. 

All serum samples were stored at or below −70°C. Serum samples were shipped on dry ice 

to AniLytics Inc. (Gaithersburg, MD) for analysis. 

a. Hormone Analysis: Testosterone, T4, and TSH were measured in serum using 

radioimmunoassays (RIAs). Samples were assayed in duplicate and in conjunction with 

multiple quality control samples. 

b. Clinical Chemistry: The following CHECKED (X) parameters were examined.

ELECTROLYTES OTHER

X Calcium X Albumin

X Chloride X Creatinine*

Magnesium X Urea nitrogen*

X Phosphorus Total cholesterol

X Potassium Globulins

X Sodium Glucose

ENZYMES X Total bilirubin

X Alkaline phosphatase (ALP) X Total protein

Cholinesterase (ChE) Triglycerides

Creatine phosphokinase Albumin/globulin ratio (calculated)

Lactic acid dehydrogenase (LDH) Bile acids

X Alanine aminotransferase (ALT/also SGPT)

X Aspartate aminotransferase (AST/also SGOT)

X Sorbitol dehydrogenase

X Gamma glutamyl transferase (GGT)

Glutamate dehydrogenase

* Recommended for the pubertal assay in male rats based on guideline 890.1500.

c. Organ Weights and Histopathology: The following CHECKED (X) tissues were 

collected and weighed and grossly observed from all study animals. 

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UROGENITAL OTHER

X Testes (left and right separately)*+ X Thyroid a*+

X Epididymides (left and right separately)*+ X 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*

X Kidneys (paired)*+

Gross lesions and masses

a Thyroid was weighed post-fixation.

* Weights required based on guideline 890.1500. 

+ Histopathological examination required based on guideline 890.1500. 

Left kidney and thyroid were fixed in 10% neutral buffered formalin for at least 24-hours. 

Left testis and left epididymis were each placed in Bouin’s fixative for 18- to 24-hours and 

then washed in 70% histology grade alcohol. After fixation, tissues were transferred to 70% 

histology grade alcohol, histologically processed, embedded, sectioned, and stained with 

hematoxylin and eosin. Histologically-processed tissues (thyroid, kidneys, epididymis, and 

testis) from all animals were microscopically evaluated. Two sections of each of the 2 lobes 

of the thyroid were examined and evaluated for follicular cell height and colloid area. A 

5-point grading scale (1 = shortest/smallest; 5 = tallest/largest) was used, and the thyroids 

were evaluated relative to photomicrographs supplied by the U.S. EPA. 

II. RESULTS 

A. Mortality: All animals survived.

B. Clinical Signs of Toxicity: No treatment-related clinical signs were observed in animals 

from any dose group 24 hours post-dose. However, it was noted in the report that tremors 

were observed in 6/16 animals receiving 10 mg/kg/day (during one day only) and in eleven 

20 mg/kg/day rats (on 16 days). 

C. General Growth and Preputial Separation: Body weights, body weight gains, age of 

attainment of preputial separation (PPS), weight at PPS, and proportion/incidence of 

unseparated preputia are presented in Table 2 below. 

Body weight gains (adjusted and unadjusted) were decreased (p≤0.05) by 6-7% in the 

treated groups. Final body weights (adjusted and unadjusted) were decreased by 6% 

(p≤0.05) at 10 mg/kg/day and by 4% (NS) at 20 mg/kg/day. 

There was no treatment-related effect on PPS at either dose level. Although adjusted age at 

PPS showed a statistically significant increase at 10 mg/kg/day (PND 45.4 treated vs. PND 

43.7 controls; 1.7 days), this difference is considered to be within biological variation. 

Body weight at PPS, age at partial PPS, and initial body weight were similar in the treated 

groups compared to the control. 

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The following performance criteria were outside of the specified values: %CV=11.7% for 

body weight at PPS (top of acceptable range: 7.57%); and %CV=7.7% for final body weight 

(top of acceptable range: 7.47%). Additionally, weaning weight (PND 21) was not reported. 

TABLE 2. General Growth and Preputial Separation (PPS) a

Parameter Evaluated

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

Age at PPS 

(PND)

U 15 43.6 2.1 4.8 16 45.3 2.4 5.3 15 44.7 1.5 3.3

A 15 43.7 --- --- 16 45.4* --- --- 15 44.6 --- ---

Body weight at 

PPS (g)

U 15 226.1 26.5 11.7 16 225.4 17.6 7.8 15 228.5 17.0 7.5

A 15 227.0 --- --- 16 226.4 --- --- 15 227.6 --- --- 

Age at partial 

PPS (PND)

U 12 41.7 0.9 2.1 14 41.1 1.4 3.4 9 41.4 1.1 2.7

A 12 41.7 --- --- 14 41.1 --- --- 9 41.4 --- --- 

Initial body 

weight 

(PND 23; g)

U 16 62.2 4.1 6.6 16 61.9 5.0 8.1 16 63.8 4.1 6.4

A 16 62.2 --- --- 16 62.1 --- --- 16 63.5 --- --- 

Final body 

weight (g)

U 16 313.2 24.0 7.7 16 294.5*

(↓6) 17.8 6.1 16 300.3(↓4) 18.6 6.2

A 16 313.3 --- --- 16 295.0*

(↓6) --- --- 16 299.8(↓4) --- --- 

Final body 

weight 

(% of control)

U 16 --- --- --- 16 94.0 --- --- 16 95.9 --- --- 

A 16 --- --- --- 16 94.2 --- --- 16 95.7 --- --- 

Body weight 

gain

(final – initial; g)

U 16 256.3 21.6 8.4 16 237.5*

(↓7) 18.1 7.6 16 239.9*(↓6) 19.0 7.9

A 16 256.3 --- --- 16 237.8*

(↓7) --- --- 16 239.6* (↓7) --- --- 

Proportion 

unseparated (#/N) 1/16 0/16 1/16

a Data were obtained from Table 21 on page 45 of the study report. Percent difference from controls (calculated by 

reviewers) is presented parenthetically.

U Unadjusted for body weight on PND 23

A Adjusted for body weight on PND 23

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from controls at p<0.05.

 

D. Organ Weights: Organ weights at necropsy are presented in Table 3 below. The adjusted 

ventral prostate weights showed a linear trend of decreased (p≤0.05) weight with increasing 

dose (↓9-15%); however, no statistically significant effect was detected between the treated 

groups and control using Dunnett’s test. It is noted that some of the criteria values CV(%) 

were greater than the specified range. No other trend or statistically significant effect was 

detected for the sex tissues or any other organ weighed.

The following performance criteria were outside of the specified ranges: (i) mean kidney 

weight of 2.07 g (acceptable range: 2.242–3.050 g); (ii) %CV=29.9% for seminal vesicles 

with coagulating gland and fluid (top acceptable range: 21.06%); (iii) %CV=23.3% for 

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ventral prostate (top acceptable range: 22.32%); (iv) %CV=27.4% for left epididymis (top 

acceptable range: 16.39%; right epididymis was within acceptable range); and (v) mean 

thyroid weight of 27.0 mg (acceptable range: 14–26 mg).

TABLE 3. Organ Weights at Necropsy a

Organ

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

Liver

(g)

U 16 14.39 1.59 11 16 13.84 1.43 10.4 16 13.79 1.36 9.9

A 16 14.39 - - 16 13.87 - - 16 13.76 - - 

R 16 4.51 0.25 5.5 16 4.62 0.31 6.8 16 4.54 0.26 5.7

Kidneys

(g)

U 16 2.07 0.17 8.1 16 2 0.18 9.1 16 2.06 0.21 10.4

A 16 2.07 - - 16 2 - - 16 2.06 - -

R 16 0.65 0.03 4.2 16 0.67 0.04 5.7 16 0.68 0.05 7.4

Pituitary

(mg)

U 16 10 1.5 14.9 16 9.2 1.7 18.5 16 9.8 1.2 12.5

A 16 10 - - 16 9.2 - - 16 9.8 - - 

R 16 3.1 0.5 16 16 3.1 0.6 18 16 3.2 0.4 13.4

Adrenals

(mg)

U 16 49.8 10.5 21 16 44.7 8.6 19.3 16 45.1 5.9 13

A 16 49.9 - - 16 44.9 - - 16 45 - -

R 16 15.6 2.7 17.1 16 14.9 2.6 17.4 16 14.9 1.9 12.9

Seminal vesicle 

+ coagulating 

gland, with 

fluid (mg)

U 16 558 167 29.9 16 497.9 112.7 22.6 16 476.5 96.8 20.3

A 16 558 - - 16 498.2 - - 16 476.2 - - 

Seminal vesicle 

+ coagulating 

gland, without 

fluid (mg)

U 16 354.7 83.8 23.6 16 316 54.1 17.1 16 320.5 57.3 17.9

A 16 354.7 - - 16 316.1 - - 16 320.3 - - 

Ventral 

prostate (mg)

U 16 238.8 55.7 23.3 16 216.6 43.9 20.3 16 205.3 36.8 17.9

A c 16 238.9 - - 16 217.7

(↓9) - - 16 204.1(↓15) - - 

Dorsolateral 

prostate (mg)

U 16 148.8 27.6 18.5 16 140.3 31.5 22.5 16 146.8 33.9 23.1

A 16 148.8 - - 16 140.1 - - 16 146.9 - - 

LABC 

(mg)

U 16 529.8 62.9 11.9 16 513.4 66.8 13 16 549.6 61.4 11.2

A 16 529.8 - - 16 513.5 - - 16 549.6 - - 

Epididymis, left 

(mg)

U 15 b 191.8 52.6 27.4 16 209.5 22 10.5 16 205.4 18.4 9

A 15 b 204.3 - - 16 209.9 - - 16 205.2 - -

Epididymis, 

right (mg)

U 16 212.9 14.6 6.9 16 211.9 25.2 11.9 16 208 16.2 7.8

A 16 - - - 16 - - - 16 - - - 

Testis, left (mg) U 15 b 1343.3 372.6 27.7 16 1406.1 111.1 7.9 16 1367.1 93.3 6.8

A 15 b 1432.6 - - 16 1406.8 - - 16 1366.6 - -

Testis, right 

(mg)

U 16 1481.1 154.9 10.5 16 1403.4 106 7.6 16 1396.2 107 7.7

A 16 1481.2 - - 16 1403.8 - - 16 1395.8 - -

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TABLE 3. Organ Weights at Necropsy a

Organ

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

Thyroid, fixed

(mg)

U 16 27 8.9 33.1 16 23.8 3.7 15.4 16 25.3 4 15.8

A 16 25 - - 16 23.8 - - 16 25.3 - -

a Data were obtained from Table 22 on pages 47–48 of the study report. No differences (p≤0.05) were noted between treated 

groups and controls.

b One animal removed due to potential recording error.

c Significant trend (p<0.05)

U Unadjusted for body weight on PND 23

A Adjusted for body weight on PND 23

R Organ-to-body weight ratio (relative to body weight) 

SD Standard Deviation

CV Coefficient of Variation

E. Clinical Chemistry and Hormone Levels: Clinical chemistry and hormone levels are 

presented in Table 4 below. 

Serum T4 levels were increased (p<0.0001) at both dose levels (↑48% at 10 mg/kg/day and 

↑43% at 20 mg/kg/day) compared to the control. Serum TSH was slightly increased (↑7%-

8%) to a similar extent at both dose levels compared to the control, although the control 

value was low (3.63 ng/mL) compared to the acceptable range (4.212-24.112 ng/mL) and 

the performance criteria were not met. Testosterone levels in the treated groups were lower 

than the control (↓18% at 10 mg/kg/day and ↓12% at 20 mg/kg/day), but statistical 

significance was not attained, and the means were within the background levels. 

The following performance criteria were outside of the specified ranges: mean serum TSH 

level of 3.63 ng/mL (acceptable range: 4.212–24.112 ng/mL); and %CV=61.2% for serum 

TSH (top acceptable range: 58.29%).

The following clinical chemistry parameters differed (p<0.05) in the 20 mg/kg/day group 

compared to controls: (i) sodium (↓2%); (ii) potassium (↓8%); (iii) phosphorus (↓9%); (iv) 

aspartate transferase (↓14%); and (v) creatinine (↓12%). The values for sodium and 

aspartate transferase were within the range of control values; all values for potassium and 

phosphorus were slightly above the range of control values; and all values for creatinine 

were slightly below the range of control values. These small variations were not considered 

to be indicative of toxic effects on the kidney or liver. All measured clinical chemistry 

parameters in the 10 mg/kg/day group were similar to controls. 

TABLE 4. Hormone Levels and Clinical Chemistry a

Parameter

Evaluated

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N b Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

Hormones

Serum T4, 

Total 15 4.13 0.72 17.3 16 6.10*

(↑48) 0.81 13.3 16 5.91*(↑43) 0.99 16.7

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TABLE 4. Hormone Levels and Clinical Chemistry a

Parameter

Evaluated

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

N b Mean SD

CV

(%) N Mean SD

CV

(%) N Mean SD

CV

(%)

(μg/dL)

Serum TSH 

(ng/mL) 15 3.63 2.22 61.2 16 3.92 2.24 57.0 16 3.89 2.53 65.0

Serum 

testosterone 

(ng/mL)

15 2.04 0.92 45.1 16 1.67 0.99 59.0 16 1.80 1.62 90.1

Clinical Chemistry

Sodium 

(mEq/L) 15 153 2 1 16 151 4 2 16 150* 

(↓2) 3 2 

Potassium 

(mEq/L) 15 9.1 0.6 6.8 16 8.7 0.6 7 16 8.4* 

(↓8) 0.8 9.2

Chloride 

(mEq/L) 15 114 2 2 16 112 2 2 16 113 2 2 

Calcium 

(mg/dL) 15 10.9 0.3 2.6 16 10.8 0.5 4.8 16 10.8 0.3 3.1

Phosphorus 

(mg/dL) 15 10.7 0.9 8.8 16 10.4 0.9 8.3 16 9.7* 

(↓9) 0.8 8 

AST (U/L) 15 217 42 19 16 213 43 20 16 186* 

(↓14) 26 14

ALT (U/L) 15 93 15 16 16 97 14 14 16 90 11 12

GGT (U/L) 15 0 --- --- 16 0.2 0.5 290 16 0.2 0.8 400

ALP (U/L) 15 318 72 23 16 325 62 19 16 320 58 18

BUN 

(mg/dL) 15 14 2 13 16 15 3 19 16 15 2 15

Creatinine 

(mg/dL) 15 0.43 0.06 14.2 16 0.39

(↓10) 0.07 17.3 16 0.38* (↓12) 0.06 15.4

Total 

Bilirubin 

(mg/dL)

15 0.1 0.15 146 16 0.08 0.1 133 16 0.18 0.16 92.1

SDH (U/L) 15 20 3 17 16 22 3 16 16 20 4 18

Total 

Protein 

(g/dL)

15 5.8 0.3 5.3 16 5.7 0.3 5 16 5.6 0.3 5.1

Albumin 

(g/dL) 15 4.2 0.3 6.3 16 4.2 0.3 6 16 4.1 0.3 6.7

a Data were obtained from Table 23 on page 50 and Table 24 on page 51 of the study report. Percent difference from controls 

(calculated by reviewers) is presented parenthetically. 

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from controls at p<0.05.

* Significantly different from controls at p<0.01.

* Significantly different from controls at p<0.001.

F. Gross pathology: There were no effects of treatment observed at necropsy. In one control 

rat, the right testis was noted as enlarged, the left testis and epididymis were noted as 

markedly small, and the seminal vesicle was also noted as being small. No other gross 

observations were noted in male rats surviving to the scheduled termination. 

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G. Histopathology: The incidences of histopathological findings of the thyroid gland are 

presented below in Table 5; follicular cell shape was not reported. A marginal increase in 

the colloid area and decrease in the follicular cell height was observed in animals 

administered phosmet (10 and 20 mg/kg) compared to controls. The number of rats with 

Grade 3 follicular colloid area decreased in a dose-related manner from 10/16 in the control 

(62%), to 6/16 at 10 mg/kg/day (38%), and 3/16 at 20 mg/kg/day (18%). Similarly, the 

number of animals having Grade 4 increased in a dose-related manner from 6/16 in the 

control (38%), to 10/16 at 10 mg/kg/day (62%), and 12/16 at 20 mg/kg/day (75%). There 

was a dose-related increase in the number of rats with Grade 2 follicular cell height (6/16 in 

the control (38%), 10/16 at 10 mg/kg/day (62%), and 12/16 at 20 mg/kg/day (75%), and a 

dose-related decrease in the number of the animals with Grade 3 follicular cell height (10/16 

in the control (38%), 6/16 at 10 mg/kg/day (62%), and 3/16 at 20 mg/kg/day (18%). 

TABLE 5. Incidence of Histopathological Lesions of the Thyroid Gland a

Treatment Groups

Parameter Evaluated

Colloid Area Follicular Cell Height 

Grade b Incidence Grade b Incidence

O E O E

Vehicle Control

1 0 16 1 0 16

2 0 16 2 6 16

3 10 16 3 10 16

4 6 16 4 0 16

5 0 16 5 0 16

10 mg/kg/day

Phosmet

1 0 16 1 0 16

2 0 16 2 10 16

3 6 16 3 6 16

4 10 16 4 0 16

5 0 16 5 0 16

20 mg/kg/day

Phosmet

1 0 16 1 0 16

2 1 16 2 12 16

3 3 16 3 3 16

4 12 16 4 1 16

5 0 16 5 0 16

a Data were obtained from Table 26 on page 53 of the study report.

b A 5-point grading scale (1 = smallest/ shortest; 5 = largest/tallest) was used.

O No. Observed

E No. Examined

The incidence of histopathological findings of the testes, epididymides, liver, thyroid, and 

kidneys are presented in Table 6. There were no treatment-related histopathological 

findings noted in the testes, epididymides, or kidneys at any dose. 

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TABLE 6. Incidence of Histopathological Lesions of the Epididymides, Testis, and Kidneya

Findings

Dose Level

Vehicle Control 10 mg/kg/day Phosmet 20 mg/kg/day Phosmet

# 

Observed

# 

Examined

# 

Observed

# 

Examined

# 

Observed

# 

Examined

Epididymides

Minimal interstitium inflammation 5 16 6 16 4 16

Minimal aberrant cells in tubule 

lumen 15 16 15 16 13 16

Mild aberrant cells in tubule lumen 0 16 0 16 1 16

Marked atrophy 1 16 0 16 0 16

Testis

Minimal cellular debris in the 

seminiferous tubules 0 16 4 16 2 16

Minimal atrophy/hypoplasia 2 16 1 16 0 16

Marked atrophy/hypoplasia 1 16 0 16 0 16

Kidneys

Minimal nephropathy 13 16 8 16 8 16

Minimal tubular dilatation 4 16 4 16 2 16

Minimal cysts 0 16 0 16 1 16

a Data were obtained from Appendix X on pages 160, 162, and 164 of the study report.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Administration of phosmet to intact 

juvenile/peripubertal male rats at a dose that met, but did not exceed the MTD, did not cause 

changes in any endpoints evaluated to suggest a disruption in pubertal development or 

thyroid function.

B. AGENCY COMMENTS: No treatment-related related effects were observed on survival, 

body weight at PPS, age at partial PPS, organ weights, serum TSH and testosterone levels, 

clinical chemistry, necropsy, or histology at dose up to 20 mg/kg/day. 

No clinical signs of toxicity were observed at either dose level at the time of dosing 

throughout the study. However, tremors were observed periodically in the majority of the 

rats at 20 mg/kg/day. 

The decreases in body weight gains and final body weights were minimal and not 

biologically significant. The small variations in clinical chemistry parameters observed at 

20 mg/kg/day were not considered to be indicative of toxic effects on the kidney or liver. 

There was no treatment-related effect on PPS at either dose level. 

Page 234 of 260
Male Pubertal Assay (2012) / Page 15 of 15

PHOSMET / 059201 OCSPP 890.1500/ OECD None

The adjusted ventral prostate weights showed a linear trend of decreased weight with 

increasing dose; however, no statistically significant effect was detected between the treated 

groups and control using Dunnett’s test. Both means were lower than historical control 

mean ventral weight for Sprague-Dawley male rats but were within the acceptable range. 

Serum T4 levels were increased in both treatment groups compared to the concurrent control 

and mean values for Sprague-Dawley male rats, but they were within the acceptable range in 

the performance criteria. Additionally, these increases were within the range of control 

values provided by the analytical laboratory (3-7 μg/dL). 

A marginal decrease in the follicular cell height and an increase in the colloid area were

observed in animals administered phosmet at both dose levels compared to controls. There 

were no treatment-related histopathological findings in the testes, epididymides, or kidneys 

at either dose level. 

During the agency’s initial review, the doses (10 and 20 mg/kg/day) used in this study were 

considered excessive, based on the dose-selection rationale and the periodic occurrence of 

tremors in the majority of the males at 20 mg/kg/day. Subsequently, the registrant submitted 

additional data (MRID 4961502) in response to the agency’s review of this assay. The 

submitted data show at the 10 mg/kg/day dose level, mild tremors were seen during one day 

only in 6/16 animals. In contrast, the severity of tremors at the 20 mg/kg/day dose level 

ranged from mild to moderate and were seen on multiple days in 11/16 animals. Based on 

this additional information, the low dose was determined to be adequate with only the high 

dose showing evidence of overt toxicity. 

 

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: 

• CV=11.7% for body weight at PPS (top of acceptable range: 7.57%) 

• CV=7.7% for final body weight (top of acceptable range: 7.47%) 

• weaning weight (PND 21) was not reported

• mean kidney weight of 2.07 g (acceptable range: 2.242–3.050 g) 

• CV=29.9% for seminal vesicles with coagulating gland and fluid (top acceptable range: 

21.06%) 

• CV=23.3% for ventral prostate (top acceptable range: 22.32%) 

• CV=27.4% for left epididymis (top acceptable range: 16.39%; right epididymis was 

within acceptable range)

• mean thyroid weight of 27.0 mg (acceptable range: 14–26 mg) 

• mean serum TSH level of 3.63 ng/mL (acceptable range: 4.212–24.112 ng/mL) 

• CV=61.2% for serum TSH (top acceptable range: 58.29%) 

Page 235 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1550, Steroidogenesis Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 2-4-2012 (MRID 48618701) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer: Signature:

Ronnie J. Bever Jr., Ph.D., D.A.B.T. Date: 12/19/2011

Secondary Reviewer Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 12/19/2011

Program Manager: Signature:

Jack D. Early, M.S. Date: 12/27/2011

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 12/27/2011

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by Dynamac Corporation personnel. 

Page 236 of 260
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).

Page 237 of 260
PHOSMET I 059201 

Primary Reviewer: Gregory Akerman 

Health Effects Division 

Secondary Reviewer: John Liccione, Ph.D. 

Health Effects Division 

Steroidogenesis Assay (2011) I Page 1 of 14 

OCSPP 890.1550/ OECD None 

Signature: ~,.If--:. 

Signature: Date~ 

Date. - - Template version 0812011 

DATA EVALUATION RECORD 

STUDY TYPE: Steroidogenesis Assay (H295R Cells); OCSPP 890.1550 

PC CODE: 059201 DP BARCODE: 0397165 

TXR#: 0056199 CAS No.: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8% a.i.) 

SYNONYMS: S-[( l ,3-dihydro-l ,3-dioxo-2H-isoindol-2-yl)methyl] 0 ,0-dimethyl 

phosphorodithioate 

CITATION: Wagner, H. (2011). Phosmet: H295R Steroidogenesis Assay. CeeTox, Inc., 

Kalamazoo, Ml. Laboratory Study No. 9142V-100348STER, November 3, 

201 I. MRID 48618701. Unpublished. 

SPONSOR: Gowan, 370 Main Street, Yuma, AZ 85364 

TEST ORDER#: EDSP-059201 -54 

EXECUTIVE SUMMARY: In a steroidogenesis assay (MRID 48618701), H295R cells 

cultured in vitro in 24-well plates were incubated with phosmet (96.8% purity, Batch# 

GQH9118000) at concentrations of 100, IO, 1, 0.1, 0.01, 0.001, and 0.0001 μM for 48 hours in 

triplicate for four independent experiments. Run 1 was not analyzed because one of the forskolin 

concentrations on the quality control plate was different than the proposed concentration outlined 

in the test guideline (3.33 μM was used instead of l μM). Dimethyl sulfoxide (DMSO) was used 

as a vehicle, at a final concentration of 0.05% v/v. 

Testosterone and estradiol levels were measured using HPLC-MS/MS. A Quality Control (QC) 

plate was run concurrently with each independent run of a test chemical plate to demonstrate that 

the assay responded properly to positive control agents at two concentration levels. Positive 

controls included the known inhibitor (prochloraz) and inducer (forskolin) of estradiol and 

testosterone production. 

All guideline acceptability recommendations and requirements were met, including lack of 

cytotoxicity, adequate production of testosterone and estradiol, acceptable reproducibility (low 

%CV), and appropriate induction and inhibition with positive controls. 

Neither testosterone nor estradiol concentrations were affected by phosmet. Decreases (p<0.05) 

of I 0-11 % in estradiol concentration were observed at 0.0001, 0.001, and 0.0 I μM of phosmet in 

Run 2, but not at higher concentrations nor at any concentration in the other runs. An increase 

Page 238 of 260
Steroidogenesis Assay (2011) / Page 2 of 14

PHOSMET / 059201 OCSPP 890.1550/ OECD None

(p≤0.05) of 10% in estradiol concentration was observed at 100 μM of phosmet in only one of 

the three runs. 

Based on hormone responses in each of three independent runs, phosmet treatment did not result 

in statistically significant and reproducible alterations in testosterone or estradiol production. 

The assay satisfies/ the EDSP Tier 1 Test Order requirements for a Steroidogenesis assay 

(OCSPP 890.1550). 

COMPLIANCE: Signed and dated GLP Compliance and Quality Assurance statements were 

provided. 

Page 239 of 260
Steroidogenesis Assay (2011) / Page 3 of 14

PHOSMET / 059201 OCSPP 890.1550/ OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: CeeTox

Location: Kalamazoo, MI

Study Director: Hilary Wagner, M.S.

Other Personnel: Colleen Toole, Ph.D., Director of Project Management

Karen Rutherford, B.S., Director of Laboratory Operations

David Blakeman, B.S., Senior Scientist/Endocrine Group Leader

Briana Wallace, B.S., Lead Cell Culture Scientist

Steven McColley, M.S., Scientist

Cameron Haines, B.S., Scientist

Francisca Wong, M.S., Scientist

Joey Burgam, B.S., Associate Scientist

Lisa Blakeman, B.S., Associate Scientist

Study Period: July 15, 2011 through November 2, 2011

2. Test Substance: Phosmet

Description: Off-white crystals

Batch # (expiration date): GQH9118000 (January 31, 2013)

Purity: 96.8% a.i.

Solubility (in solvent): Approximately 10−3.5 M

Vapor pressure at 25°C: 0.065 mPa

Stability: Not reported

Storage conditions: Room temperature

CAS #: 732-11-6

Molecular weight: 317.3

Structure:

3. Positive Control: Forskolin

Description (molecular weight): White powder (410.50)

Source: Sigma Aldrich (St. Louis, MO)

Lot # (expiration date): 109K50571V (July 2016)

Purity: 98%

Solubility (in solvent): DMSO

Storage conditions: Room temperature

CAS #: 66575-29-9

4. Negative Control: Prochloraz

Description (molecular weight): White powder (376.67)

Source: Sigma Aldrich (St. Louis, MO)

Lot # (expiration date): SZE6220X (August 8, 2012)

Purity: 99.1%

Solubility (in solvent): DMSO

Storage conditions: Room temperature

CAS #: 67747-09-5

Page 240 of 260
Steroidogenesis Assay (2011) / Page 4 of 14

PHOSMET / 059201 OCSPP 890.1550/ OECD None

5. Solvent/Vehicle Control: Dimethyl Sulfoxide (DMSO)

Description (molecular weight): Clear liquid (78.13)

Source: Sigma-Aldrich (St. Louis, MO)

Lot # (expiration date): RNBB7617 (Not provided)

Purity: Not provided

Storage conditions: Sigma-Aldrich (Cat. # D2650)

CAS #: 67-68-5

Justification for choice of 

solvent:

Not provided

Final concentration in assay: 0.05% v/v

6. Other Materials: 22R-Hydroxycholesterol

Description (molecular weight): White powder (402.65)

Source: Sigma-Aldrich (St. Louis, MO)

Lot # (expiration date): 089K4132, 060M4098 (not provided)

Purity: 99.0%

Storage conditions: Room temperature

Solvent used: Ethanol, final concentration in assay, 0.025% v/v

CAS #: 17954-98-2

7. Stock Medium: Dulbecco’s modified Eagle’s medium/nutrient mixture F12 

Ham

Source: Sigma-Aldrich (St. Louis, MO) 

Lot # (expiration date): 021M8304 (not provided)

HEPES: 15 mM; Sigma-Aldrich (St. Louis, MO); Lot # 021M8304

Sodium bicarbonate: Sigma-Aldrich (St. Louis, MO); Lot # 068K0105; purity not reported

Nu-Serum: 2.5%; Becton-Dickinson (Franklin Lakes, NJ); Catalog # 355500; Lot # 81515); 

tested for background hormone concentrations by performing laboratory

ITS+premix: Becton-Dickinson (Franklin Lakes, NJ); Catalog # 354352; Lot # 05245,

09233)

8. Test Cells: H295R human adrenocortical carcinoma cells (ATCC CLR-2128; lot # 

7635054). Cells were used in the assay at passage 7.5 – 8.5 and were incubated in the 

stock medium supplemented with 10 μM 22R-hydroxycholesterol in ethanol at the time of 

plating, dosing, and harvest. Incubation conditions were at 5% CO2 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 #: 7.5 – 8.5

X Cells frozen down at passage 5

x Frozen cells cultured for at least 4 additional passages

x Total number of passages does not exceed 10

B. METHODS

1. Pre-Test Information: 

a. Hormone Assay Interference Test: A hormone assay interference test was not performed. 

b. Hormone Extraction: See Section on “Hormone Measurement Section.”

c. Laboratory Proficiency Test: The laboratory proficiency test data were not provided. 

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2. Test Solutions: Phosmet was dissolved in DMSO to make a 200 mM stock solution and 

then serially diluted in DMSO. 22R-Hydroxycholesterol was dissolved in ethanol to make a 

40 mM stock and then diluted in supplemented medium to a final concentration of 10 μM. 

Phosmet was then diluted in supplemented medium containing 10 μM 22Rhydroxycholesterol to prepare mastermix solutions. Forskolin and prochloraz were 

dissolved in DMSO to make 100 mM solutions and then serially diluted in DMSO. 

Forskolin and prochloraz were then diluted in supplemented medium containing 10 μM 

22R-hydroxycholesterol. When added to the cell culture plates, these dilutions yielded final 

concentrations of 1 μM and 10 μM for forskolin, 0.1 μM and 1 μM for prochloraz and 

0.0001, 0.001, 0.01, 0.1, 1, 10, and 100 μM for phosmet, with the final concentration of 

DMSO in the medium being held constant at 0.05% (v/v). The final ethanol concentration 

in the supplemented medium was 0.025% (v/v). No precipitation was visible. 

3. Cell Plating and Preincubation: Cells were maintained in the Stock Medium described 

above. It was reported that hormone concentrations in undiluted Nu-Serum were 3754 

pg/mL testosterone and 3846 pg/mL estradiol. H295R cells were grown for five passages, 

frozen in liquid nitrogen, then thawed and cultured for seven or eight additional passages 

prior to use in the assay. The culture medium was supplemented with 10 uM 22Rhydroxycholesterol at the time of plating, dosing, and harvest. The concentration of 22Rhydroxycholesterol was chosen based on laboratory proficiency experiments previously 

conducted at the Performing Laboratory. The cells were plated into wells of a 24-well cell 

culture plate at a density of approximately 300,000 cells/mL. The cells were then placed 

into a 5% CO2 incubator at 37±2°C for approximately 24 hours prior to chemical exposure. 

Prior to dosing, the cells were checked microscopically for attachment and proper 

morphology. 

4. Exposure: The medium was removed from the cells and replaced with 1 mL of medium 

containing 10 μM 22R-hydroxycholesterol and concentrations of test chemical in triplicate, 

according to the schematic presented in Table 1. 

TABLE 1. Dosing Schematic for the Exposure of H295R Cells to Phosmet (Final Concentrations in μM).a

1 2 3 4 5 6

A DMSO DMSO DMSO 0.1 0.1 0.1

B 100 100 100 0.01 0.01 0.01

C 10 10 10 0.001 0.001 0.001

D 1 1 1 0.0001 0.0001 0.0001

a Data were obtained from page 13 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 2. 

Page 242 of 260
Steroidogenesis Assay (2011) / Page 6 of 14

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TABLE 2. Dosing Schematic for the QC Plate for Positive Controls (Final Concentrations in μM).a

1 2 3 4 5 6

A Blankb Blank Blank Backgroundc Background Background

B DMSO DMSO DMSO DMSO + MeOHd DMSO + MeOH DMSO + MeOH

C Forskolin 1μM Forskolin 1μM Forskolin 1μM Prochloraz 

0.1μM

Prochloraz 

0.1μM

Prochloraz 

0.1μM

D Forskolin 10μM Forskolin 10μM Forskolin 10μM Prochloraz 1μM Prochloraz 1μM Prochloraz 1μM

a Data were obtained from page 13 of the study report. 

b Blank wells received medium containing 22R-hydroxycholesterol. 

c Background wells received medium only.

d MeOH = methanol was added to these wells for 30 minutes at room temperature following medium removal.

Following dosing, the plates were incubated for 48±2 hours under the conditions previously 

described. After the 48±2 hour exposure, each well was examined under the microscope 

and images were taken of the vehicle control wells as well as the two greatest non-cytotoxic 

concentrations (based on observation under the microscope). The media was collected from 

all wells in two equal aliquots and stored at -80±10°C until shipment to the analytical 

laboratory for hormone measurement. 

5. Cell Viability/Cytotoxicity Assay: After media removal, cell viability was measured by 

MTT assay. On the QC plates, wells designated to receive methanol (control wells for cell 

death measurements) were rinsed twice with phosphate buffered saline (PBS), then 

incubated in methanol for 30 minutes at room temperature. After the methanol incubation, 

the methanol-treated wells were rinsed again with PBS three times. Following media 

removal and/or methanol treatment, 0.5 mL of 0.5 mg/mL MTT (Sigma, Cat#M5655, Lot# 

MKBG1611V) solution in supplemented medium containing 10 μM 22Rhydroxycholesterol was added to each well of the test chemical and QC plates. The plates 

were incubated at 37±2°C in a 5% CO2 incubator for 3 hours. Following the 3 hour 

incubation, the MTT solution was removed and 0.5 mL of isopropanol was added to each 

well. Plates were incubated at room temperature for 20 minutes with shaking. Following 

this incubation, absorbance at 570 nm and 650 nm were measured on a Packard Fusion plate 

reader. The absorbance at 650 nm was subtracted from the absorbance at 570 nm to 

calculate the MTT value for each well. The change in cell viability was determined by 

comparing treated wells to the solvent control (SC) wells. A greater than 20% reduction in 

cell viability was considered evidence of cytotoxicity.

6. Hormone Measurement System: Testosterone and estradiol levels were measured at 

OpAns, LLC (Durham, NC). Testosterone and estradiol were extracted from H295R 

supplemented medium by liquid-liquid extraction using methyl tert-butyl ether (MTBE) 

after the addition of [2H5]-testosterone and [2H5]-estradiol as internal standards. Extracts 

were analyzed by HPLC-MS/MS using positive ion multiple reaction monitoring. This 

method was validated over the range 100 to 100,000 pg/mL for testosterone and 10 to 

10,000 pg/mL for estradiol (OpAns Document Number OPR-OPP-0006). The lower limit 

of quantification (LLQ) was 100 pg/mL for testosterone and 10 pg/mL for estradiol using a 

300 μL aliquot of H295R supplemented medium. Freshly prepared calibration standards 

(n = 7) were prepared in supplemented medium for each run. QC samples spiked in 

supplemented medium at three concentrations (2 replicates per concentration), were 

included with each run. No study samples were re-analyzed during this study. 

Page 243 of 260
Steroidogenesis Assay (2011) / Page 7 of 14

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The following performance criteria were met (indicated by an “x”):

X Method detection limit (100 pg/mL testosterone; 10 pg/mL estradiol)

X Spiked sample recovery acceptable for two concentrations of testosterone and estradiol (mean measured amount 

from triplicate samples within 30% of nominal concentration)

NA Hormone cross-reactivity (antibody-based assays only; ≤30% of basal production of the respective hormone)

NR 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 (pg/mL) and standard deviations for testosterone and 

estradiol were calculated for each concentration of the test chemical, reference chemicals, 

and the solvent controls. Relative changes in testosterone and estradiol production were 

calculated using the equation below: 

Relative Change = [Hormone] in each well ÷ [Hormone] of mean solvent (vehicle) control 

For forskolin induction of testosterone, relative change was calculated both with and without 

subtracting the background hormone production from the forskolin-treated wells and blank 

and solvent control wells. This was done because of the high background production of 

testosterone and the small dynamic range for forskolin induction. Background hormone 

production was calculated from three wells with cells on the QC plate that received no 22Rhydroxycholesterol at the time of exposure. 

Normality of the data was evaluated using Shapiro-Wilk's test. Homogeneity of the 

variances between the treatment groups was evaluated using Levene's test. If the p-values 

were greater than 0.05 in both tests, statistical significance between each treatment group 

and the control group was evaluated using Dunnett's test. If the p-values were less than or 

equal to 0.05 in either the normality or the homogeneity test, a log transformation was 

performed on the data to attempt to approximate a normal distribution. If, following the 

transformation, p-values were greater than 0.05 in both the normality and homogeneity tests, 

Dunnett's test was performed on the transformed data to evaluate statistical significance 

between the each treatment group and the control group. If following the log 

transformation, p-values were less than or equal to 0.05 in either the normality or the 

homogeneity test, the non-transformed data set was analyzed using the nonparametric 

Kruskal-Wallis test followed by Dunn's test to evaluate statistical significance between each 

treatment group and the control group. Data analysis was conducted in Microsoft Excel. 

Statistics were calculated using Unistat 6.0 Light for Excel. Graphs were generated using 

Microsoft Excel. 

II. RESULTS

A. TEST COMPOUND: Compared to the minimum detection level (MDL), basal hormone 

production in the SC wells was 18 to 30-fold MDL for testosterone and 17 to 23-fold MDL 

for estrogen. The between plate %CV for the SC based on absolute hormone concentrations 

was 26% for testosterone and 14% for estradiol. The %CVs for the absolute concentration 

within replicate wells of a plate were 4.87-6.68% for testosterone and 2.25-5.32% for 

estradiol. These values were below the maximum guideline recommended level of 30%. 

The Sponsor stated: “Four independent runs of the steroidogenesis assay were conducted. 

Run 1 was not analyzed because one of the forskolin concentrations on the quality control 

Page 244 of 260
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plate was different than the proposed concentration outlined in the test guideline (3.33 uM 

was used instead of 1 uM). Data from Run 1 will not be presented in this report as the 

media was not analyzed for testosterone and estradiol.” The concentrations of estradiol and 

testosterone observed in the other three assay runs are summarized in Table 3 and 

graphically depicted in Figures 1 and 2. 

Neither testosterone or estradiol concentration was affected by phosmet. Decreases 

(p<0.05) of 10-11% in estradiol concentration were observed at 0.0001, 0.001, and 0.01 μM 

phosmet, but not at higher concentrations nor at any concentration in the other runs. An 

increase (p≤0.05) of 10% in estradiol concentration was observed at 100 μM phosmet in 

only 1 of the three runs. 

TABLE 3. Mean (±SD) Hormone Concentrations Following Treatment with Phosmet for 48 Hours.a

Nominal 

Concentration 

(μM)

Run 2 Run 3 Run 4 Run 2 Run 3 Run 4 Meanb ± SDb Statistical 

Significance

Testosterone (pg/mL) Fold Difference

DMSO 3044±203 1801±93 2292±112 NA NA NA NA --

0.0001 2778±108 1803±49 2351±19 0.91 1.00 1.03 0.98 0.06 —

0.001 2833±176 1858±75 2248±91 0.93 1.03 0.98 0.98 0.05 —

0.01 2781±40 1814±56 2303±134 0.91 1.01 1.00 0.97 0.06 —

0.1 2883±91 1904±56 2205±144 0.95 1.06 0.96 0.99 0.06 —

1 2981±113 1793±93 2422±14 0.98 1.00 1.06 1.01 0.04 —

10 2899±106 1892±108 2359±60 0.95 1.05 1.03 1.01 0.05 —

100 2813±84 1647±10 2223±41 0.92 0.91 0.97 0.93 0.03 —

Estradiol (pg/mL) Fold Difference

DMSO 227±12 171±4 206±8 NA NA NA NA --

0.0001 202±4 166±4 217±2 0.89* 0.97 1.06 0.97 0.09 Run 2

0.001 203±4 167±3 208±3 0.90* 0.97 1.01 0.96 0.06 Run 2

0.01 202±3 164±5 214±8 0.89* 0.96 1.04 0.96 0.08 Run 2

0.1 212±9 175±3 203±11 0.93 1.03 0.99 0.98 0.05 —

1 222±9 161±4 218±1 0.98 0.94 1.06 0.99 0.06 —

10 222±6 175±7 226±3 0.98 1.03 1.10 1.04 0.06 —

100 239±4 170±2 226±5 1.06 0.99 1.10* 1.05 0.06 Run 4

a Data were obtained from pages 25-26 and 32-34 of the study report. The lower limit of quantification (LLQ) was 100 

pg/mL for testosterone and 10 pg/mL for estradiol.

b Calculated by the reviewers.

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FIGURE 1. Change in Testosterone Production Relative to Phosmet Concentration.

Page 246 of 260
Steroidogenesis Assay (2011) / Page 10 of 14

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FIGURE 2. Change in Estradiol Production Relative to Phosmet Concentration. 

B. CYTOTOXICITY: It was stated that cytotoxicity was not assessed in Run 3 because the 

plate was dropped by the plate reader prior to data acquisition. Less than 5% cytotoxicity 

Page 247 of 260
Steroidogenesis Assay (2011) / Page 11 of 14

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was noted, except in the positive control (92-95% cytotoxicity). Data are summarized in 

Table 4 and depicted graphically in Figure 3. 

TABLE 4. Mean (±SD) MTT Cell Viability Results after Treatment with Forskolin, Prochloraz, or 

Phosmet for 48 Hours. a 

Compound Concen. 

(μM)

Cell Viability – Run 2 Cell Viability – Run 3 Cell Viability – Run 4

Mean SD Mean SD Mean SD

Blank NA 99.4 10.54 100.1 4.93 103.0 1.84

Background NA 102.5 5.95 98.7 0.69 104.0 1.76

SC + Methanol NA 4.9 0.99 5.7 0.64 8.3 1.79

Forskolin 1 103.9 3.88 97.2 2.2 107.3 0.91

Forskolin 10 105.1 4.9 97.5 2.67 106.7 4.11

Prochloraz 0.1 100.7 1.89 97.8 1.79 101.7 2.17

Prochloraz 1 101.1 2.01 96.1 2.79 105.0 4.29

Phosmet 0.0001 95.4 2.80 ND ND 95.6 2.97

Phosmet 0.001 98.3 1.60 ND ND 98.0 1.12

Phosmet 0.01 99.1 3.07 ND ND 97.7 0.92

Phosmet 0.1 97.8 2.59 ND ND 99.2 0.37

Phosmet 1 97.3 3.12 ND ND 101.6 3.54

Phosmet 10 97.6 3.51 ND ND 99.4 1.58

Phosmet 100 99.1 3.59 ND ND 99.4 4.51

a Data were obtained from pages 19-20 of the study report.

NA Not applicable

ND Not determined due to dropped plate

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FIGURE 3. MTT cell viability results for phosmet-treated cells. 

C. QC PLATE: The hormone concentrations after exposure to the reference chemicals, SC, 

and blank samples, as well as the fold difference change relative to SC (individual and mean 

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± SD) for the three assay runs are presented in Table 5. The minimum basal hormone 

production levels (500 pg/mL for testosterone, 40 pg/mL for estradiol) were met in both 

blank and SC wells. OCSPP 890.1550 guideline requirements for basal hormone production 

in SC wells, induction by 10 μM forskolin, and inhibition by 1 μM prochloraz were met for 

testosterone and estradiol. Basal hormone production in SC wells was ≥ 5-fold MDL for 

testosterone and ≥ 2.5-fold MDL for estrogen. Compared to SC, 10 μM forskolin on 

average induced testosterone 1.74-fold (instead of 2-fold as per the guideline) and estradiol 

by 9.55-fold. However, when the background is subtracted, 10 μM forskolin induced 

testosterone an average of 2.74-fold. Compared to SC, 1 μM prochloraz inhibited the 

synthesis of testosterone to 0.48-fold and estradiol to 0.35-fold. Thus, the guideline 

requirements were met indicating that the assay was sensitive to induction and inhibition of 

testosterone and estradiol. 

The variability (%CV) between the runs (calculated by the reviewer) based on the absolute 

hormone concentrations in the SC were 19% for testosterone and 14% for estradiol, which 

meets the guideline criteria of ≤30% for the assay. The %CVs within each run for the QC 

plates were 2.19 to 2.64% for testosterone and 1.89 to 4.01% for estradiol.

TABLE 5. Mean (±SD) Hormone Concentrations Following Treatment with Forskolin or Prochloraz for 48 Hours.a

Concentration (μM)

Trial 1 Trial 2 Trial 3 Trial 1 Trial 2 Trial 3 Meanb ± SDb

Testosterone (pg/mL) Fold Difference (Relative to DMSO)

Background 1493 1035 1359 0.57 0.58 0.59 0.58 0.01

Blank 2921 1799 2338 1.12 1.01 1.01 1.05 0.06

DMSO 2612 1782 2319 1.00 1.00 1.00 1.00 0.00

1 μM Forskolin 4325 2403 3108 1.66c 1.35c 1.34c 1.45c 0.18

10 μM Forskolin 5604 2561 3765 2.15d 1.44d 1.62d 1.74d 0.37

0.1 μM Prochloraz 2145 1505 1843 0.82 0.84 0.79 0.82 0.03

1 μM Prochloraz 1351 740 1168 0.52 0.42 0.50 0.48 0.05

Estradiol (pg/mL) Fold Difference (Relative to DMSO)

Background 66 57 76 0.29 0.33 0.34 0.32 0.03

Blank 244 179 242 1.07 1.02 1.08 1.06 0.03

DMSO 229 175 223 1.00 1.00 1.00 1.00 0.00

1 μM Forskolin 1550 1014 1559 6.76 5.79 6.99 6.51 0.64

10 μM Forskolin 2396 1363 2321 10.46 7.78 10.41 9.55 1.53

0.1 μM Prochloraz 168 151 176 0.73 0.86 0.79 0.79 0.07

1 μM Prochloraz 77 62 78 0.34 0.36 0.35 0.35 0.01

a Data were obtained from pages 21-22 of the study report. The lower limit of quantification (LLQ) was 100 pg/mL for

testosterone and 10 pg/mL for estradiol.

b Calculated by the reviewers. 

c When the background is subtracted, the values are 2.53-, 1.83-, and 1.82-fold difference for Runs 2, 3, and 4, respectively, 

with a mean of 2.06-fold change.

d When the background is subtracted, the values are 3.67-, 2.04-, and 2.51-fold difference for Runs 2, 3, and 4, respectively, 

with a mean of 2.74-fold change.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Phosmet did not induce or inhibit testosterone at 

any of the concentrations tested in the three independent runs of the assay. Based on the 

Page 250 of 260
Steroidogenesis Assay (2011) / Page 14 of 14

PHOSMET / 059201 OCSPP 890.1550/ OECD None

results of the three independent assays using H295R cells, phosmet was not considered to be 

an inducer or inhibitor of estradiol or testosterone in this steroidogenesis assay. 

B. AGENCY COMMENTS: All performance criteria were met, including lack of 

cytotoxicity, adequate production of testosterone and estradiol, acceptable reproducibility 

(low %CV), and appropriate induction and inhibition with positive controls. 

Neither testosterone nor estradiol concentrations were affected by phosmet. Decreases 

(p<0.05) of 10-11% in estradiol concentration were observed at 0.0001, 0.001, and 0.01 μM 

phosmet, but not at higher concentrations nor at any concentration in the other runs. An 

increase (p≤0.05) of 10% in estradiol concentration was observed at 100 μM phosmet in 

only 1 of the three runs. 

Based on hormone responses in each of three independent runs, phosmet treatment did not 

result in a statistically significant reproducible alteration in testosterone or estradiol 

production. 

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: 

• Total number of cell passages was 12-13, exceeding 10. 

• The laboratory proficiency test data were not provided. 

• Mean±SD and %CV for the fold-differences were not reported.

Page 251 of 260
DATA EVALUATION RECORD

PHOSMET

Study Type: OCSPP 890.1600, In vivo Uterotrophic Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 2-4-2012 (MRID 48618707) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

Rebecca Bryan, B.S. Date: 12/05/11

Secondary Reviewer Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 12/07/11

Program Manager: Signature:

Jack D. Early, M.S. Date: 12/15/2011

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 12/15/2011

This Data Evaluation Record may have been altered by the Health Effects Division subsequent to 

signing by Dynamac Corporation personnel. 

Page 252 of 260
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).

Page 253 of 260
PHOSMET/ 059201 

Primary Reviewer: Sheila Healy. Ph.D. 

In vivo Uterotrophic Assay (2011) I Page I of 7 

OCSPP 890.1600/ OECD 440 

Health Effects Division Date: --=-J.6..1....~::...L-_,.,__ 

Secondary Reviewer: _""'""Je=s=s""""R=o;...;.w'""l=an=d=---------Signature: d;? ~ - ~ 

Health Effects Division Date: <9.LSi t r 

Template version 0912011 

DATA EVALUATION RECORD 

STUDY TYPE: Uterotrophic Assay (Rat); OCSPP 890.1600; OECD 440 

PC CODE: 059201 DP BARCODE: D397165 

TXR#: 0056199 CAS#: 732-11-6 

TEST MATERIAL (PURITY): Phosmet (96.8% a.i.) 

SYNONYMS: S-[( 1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)methyl] 0 , 0-dimethyl 

phosphorodithioate; Imidan technical 

CITATION: Zorrilla, L., and Codrea, E. (20 11 ). The Uterotrophic Assay with Phosmet in 

Ovariectomized CRL:CD(SD) IGS Rats. Integrated Laboratory Systems, Inc., 

Durham, NC. Laboratory Project Study ID: C194-100, October 19, 2011. 

MRID 48618707. Unpublished. 

SPONSOR: Gowan Company, P.O. Box 5569, Yuma, AZ 

TEST ORDER#: EDSP-059201-54 

EXECUTIVE SUMMARY: In an uterotrophic assay (MRID 48618707) conducted to screen 

for potential estrogenic activity, phosmet (96.8% a.i., Batch# 6QH9118000) in 0.5% 

carboxymethyl cellulose was administered daily via oral gavage to groups of eight 

ovariectomized female Sprague-Dawley rats at dose levels ofO (vehicle), 5, or 20 mg/kg/day on 

post-natal days (PND) 63-65. A positive control group was treated with 17a-ethynyl estradiol 

(EE) by daily oral gavage at a dose level ofO.l mg/kg/day. All animals were terminated and 

necropsied on PND 66 approximately 24 hours after the final dose to determine wet and blotted 

uterine weights. 

All animals survived until scheduled termination. Two 20 mg/kg/day rats had decreased 

movements at 1-4 h post-dosing on Days 1 and 2. Body weights in the dose groups were 

comparable to the controls throughout the duration of the assay. Uterine weights in the dose 

groups were comparable to the controls. Absolute wet and blotted uterus weights for the 0.1 

mg/kg/day EE group were increased (p<0.05) by 407% and 231 %, respectively. 

The dose levels selected for this study are adequate based on previously conducted studies which 

showed no mortality at doses up to 27 mg/kg/day and significant cholinesterase inhibition at 10 

mg/kg/day. 

No statistically significant changes were seen in uterine weight in this assay. Phosmet was 

negative in the uterotrophic assay. 

Page 254 of 260
In vivo Uterotrophic Assay (2011) / Page 2 of 7 

PHOSMET/ 059201 OCSPP 890.1600/ OECD 440

The assay satisfies the EDSP Tier 1 Test Order requirements for a uterotrophic assay (OCSPP 

890.1600). 

COMPLIANCE: Signed and dated GLP Compliance and Quality Assurance statements were

provided. 

Page 255 of 260
In vivo Uterotrophic Assay (2011) / Page 3 of 7 

PHOSMET/ 059201 OCSPP 890.1600/ OECD 440

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Integrated Laboratory Systems, Inc.

Location: Durham, NC

Study Director: L. Zorrilla

Other Personnel:

Study Period: May 3-6, 2011

2. Test Substance: Phosmet

Description: Off white solid

Source: Gowan Company (commercial technical product)

Batch #: 6QH9118000, expires January 13, 2012

Purity: 96.8 % a.i.

Stability: Stable in the vehicle for up to 8 days at 1-10°C (Smithers 

Viscient Inc., Study No. 12791-6159)

CAS #: 732-11-6

Structure:

3. Reference Estrogen: 17α-ethynyl estradiol (EE)

Supplier Sigma Aldrich, St. Louis, MO

Lot/Batch #: 090M1241V, expires February 2012 

Purity: ≥98 %

CAS # : 57-63-6

4. Solvent/Vehicle Control (Phosmet): Carboxymethyl cellulose 

Supplier Spectrum Chemical Mfg. Corp.

Lot/Batch #: ZE0383, expires August 1, 2011

Rationale (if other than water) Not provided

Final concentration 0.5%

5. Solvent/Vehicle Control (EE): Corn Oil 

Supplier MP Biomedicals, LLC, Solon, OH

Lot #: 7862K, expires August 1, 2011

Rationale (if other than water) Not Provided

Final concentration Not Applicable

6. Test Animals:

Species: Rat (ovariectomized females)

Strain: Sprague-Dawley (Crl:CD[SD] IGS)

Age/weight at dose initiation: PND 63 days old / 236.6-298.7 g females

Source: Charles River Laboratories International, Inc., Raleigh, NC

Housing: 2/cage in polycarbonate cages with absorbent heat-treated 

hardwood bedding (Northeastern Products Corp., Warrensburg, 

NY)

Diet: Teklad Global 16% Protein Rodent Diet (Teklad Diets, Madison, 

WI), ad libitum; low phytoestrogen with total genistein 

equivalents = 6.2 μg/g diet.

Water: Reverse osmosis-treated tap water, ad libitum

Environmental conditions: Temperature:

Humidity:

Air changes:

Photoperiod:

22-26oC

33-48% 

Not provided

12 hrs light/12 hrs dark

Acclimation period: 8 days

Page 256 of 260
In vivo Uterotrophic Assay (2011) / Page 4 of 7 

PHOSMET/ 059201 OCSPP 890.1600/ OECD 440

B. METHODS

1. In Life Dates: Start: May 3, 2011 End: May 6, 2011 

2. Study Design: Following an 8-day acclimation period, ovariectomized female rats (surgery 

performed by Supplier) were administered the test substance from PND 63-65. Rats were 

euthanized approximately 24 hours after the last dose and necropsied for uterine weight 

measurements. 

3. 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 between group mean weights at study initiation. 

Table 1. Study Design of Estrogen Agonist Assaya

Test Group Dose (mg/kg/day) # of Females

Vehicle Control 0 8

Low 5 8

High 20 8

17α-ethynyl estradiol (EE), Reference Estrogen 0.1 8

a Data were obtained from Table 1 on page 16 of the study report.

4. Dose Selection Rationale: The phosmet dose levels were selected based on the results 

from an acute oral gavage study (MRID 46593101) and repeated-dose studies (MRIDs 

44811801, 41962902, 41520001, 41916401, and 44839301). Mortality was observed in ≥75 

mg/kg treatment groups for the acute oral study. No mortality was observed in the repeateddose dietary studies conducted at doses of up to 27 mg/kg/day, or in repeated-dose gavage 

studies with doses up to 15 mg/kg/day. An acute relative sensitivity study (MRID 

47087401) compared the toxic responses of PND 11 rat pups versus adult rats following 

single-dose gavage administration of phosmet. No cholinergic clinical signs were found in 

either pups or adults at 10 mg/kg; however, significant cholinesterase inhibition was 

observed at this dose, especially in RBC. The adult rat RBC cholinesterase response was 62-

63% of controls at 10 mg/kg. EPA has calculated a BMD10L of 5.122 mg/kg for brain 

cholinesterase inhibition from the data. In the 7-day relative sensitivity study (MRID 

44839301), no cholinergic clinical signs were observed for the 5 mg/kg/day dose group. 

Based on these results, doses selected for the main study were 0, 5 and 20 mg/kg/day. 

5. Dose Preparation and Analysis: Dose formulations were prepared once prior to initiation 

of treatment by initially dissolving the appropriate amounts of test substance in 0.5% 

carboxymethyl cellulose. The reference estrogen, EE, was mixed with corn oil for dosing. 

Doses were adjusted daily based on individual body weight measurements. Homogeneity 

and concentration analyses were measured prior to administration in the 5 and 20 mg/kg/day 

formulations. In a previous storage stability study1, phosmet (lot number not reported) was 

 

1 Reibach, R. (2011) Storage Stability of Phosmet in Aqueous, Buffered Carboxymethylcellulose. Unpublished 

study report prepared by Smithers Viscient Inc., Study No. 12791-6159.

Page 257 of 260
In vivo Uterotrophic Assay (2011) / Page 5 of 7 

PHOSMET/ 059201 OCSPP 890.1600/ OECD 440

determined to be stable in the 0.5% aqueous carboxymethyl cellulose for up to 8 days at 1-

10°C. 

Results of Dose Analysis 

Homogeneity (% CV): 2.45-14.1% 

Stability: Stable for up to 8 days following storage at 1-10°C (Smithers Viscient Inc., 

Study No. 12791-6159). 

Concentration (% of nominal): 81-109% (the 5 mg/kg dose measured at 4.06 mg/kg was 

only used on study day 1, and for days 2-3 the 5 mg/kg dose was 87% of nominal).

The analytical data indicated that the mixing procedure was marginally adequate and that 

the variation between nominal and actual dosage to the animals was marginally acceptable. 

6. Dosage Administration: Animals were administered the test formulations and/or EE or 

vehicle daily via oral gavage for three consecutive days in a dose volume of 5 mL/kg body 

weight. Dose volumes were adjusted daily based on the concurrent body weight 

measurement.

7. Statistics: Body weights, body weight gains, and uterine weights were analyzed using 

studentized residual plots for outliers and Levene’s test for homogeneity of variance. Body 

weights and body weight gains were analyzed using one-way ANOVA followed by 

Dunnett’s two tailed t-test. The wet and blotted uterine weights were analyzed by KruskalWallis and Dunn’s test. Significance was denoted at p≤0.05. The statistical analyses were 

considered adequate.

C. METHODS

1. Clinical Examinations: Animals were checked for mortality or moribundity twice daily on 

weekdays and once daily on weekends. Rats were also checked for clinical signs of toxicity 

prior to dose administration and three h (±30 min) post-dosing. 

2. Body Weight: Animals were weighed at randomization, daily prior to dosing throughout 

the dosing period, and at termination.

3. Food Consumption (Optional): Food consumption was not measured. 

4. Necropsy and Measurement of Uterine Weight: On PND 66 (approximately 24 hours 

after final administration of the test substance), all surviving animals were euthanized by 

CO2 inhalation followed by cervical dislocation and subjected to a gross necropsy. 

Dissection of the uterus was performed according to the U.S. EPA Guideline. Briefly, the 

vagina was removed just below the cervix in order to retain the luminal fluid in the uterus. 

The “wet” uterus (i.e., containing the luminal fluid) was weighed. Subsequently, the uterine 

horns were cut longitudinally and gently blotted with moist filter paper to remove the 

luminal fluid while preventing desiccation and the blotted uterus was weighed. 

Page 258 of 260
In vivo Uterotrophic Assay (2011) / Page 6 of 7 

PHOSMET/ 059201 OCSPP 890.1600/ OECD 440

5. Microscopic Examination (Optional): Microscopic examinations were not conducted. 

II. RESULTS

A. OBSERVATIONS

1. Mortality: All animals survived until scheduled termination. 

2. Clinical Signs of Toxicity: Two 20 mg/kg/day rats had decreased movements at 1-4 h postdosing on Days 1 and 2. No clinical signs of toxicity were observed in the 5 mg/kg/day 

animals.

B. BODY WEIGHT AND WEIGHT GAIN: Selected body weight and body weight gain 

data are presented in Table 2. Body weights in the 5 and 20 mg/kg/day dose groups were 

comparable to controls throughout the duration of the assay. 

Table 2. Selected Group Body Weights and Cumulative Body Weight Gains (g) In the Estrogen Agonist 

Assay a

Study Day

#

Dose (mg/kg/day)

Vehicle Control 5 20 EE (0.1) 

N Mean SD N Mean SD N Mean SD N Mean SD

1 8 264.3 18.4 8 265.3 19.8 8 262.1 12.2 8 265.7 16.4

2 8 266.5 19.9 8 268.2 19.4 8 266.2 17.1 8 266.8 21.0

3 8 268.7 19.6 8 270.3 21.6 8 266.5 16.1 8 264.1 19.8

4 8 270.6 20.4 8 271.2 20.4 8 265.3 17.0 8 258.7 20.8

Body Weight 

Gain (1-4)

8 6.4 3.0 8 5.9 5.8 8 3.2 5.9 8 -7.0 5.8

a Data were obtained from Table 3 on page 20 and Appendix V on page 66 of the study report.

N= No. of animals in the group

SD = Standard Deviation

* Significantly different from controls at p <0.05. 

C. FOOD CONSUMPTION (Optional): Food consumption was not measured.

D. PATHOLOGY

1. Uterine Weights: Selected uterine weight data are presented in Table 3. Uterine weights in 

the dose groups were comparable to the controls. Due to an outlier (666 mg wet; 601 mg 

blotted), the uterine weight means for the 20 mg/kg/day dose group were based on 7 

animals. The mean blotted vehicle control uterine weight was <0.04% of the mean vehicle 

control terminal body weight, which meets the guideline requirement.

Absolute wet and blotted uterus weights for the 0.1 mg/kg/day EE group were increased 

(p<0.05) by 407% and 231%, respectively. These increased uterine weights were in the 

expected range.

Page 259 of 260
In vivo Uterotrophic Assay (2011) / Page 7 of 7 

PHOSMET/ 059201 OCSPP 890.1600/ OECD 440

Table 3. Uterine Weights from Estrogen Agonist Assay in SD Ratsa

Parameter

Dose (mg/kg/day)

Vehicle Control 5 20 Reference Estrogen

EE (0.1) 

N Mean SD N Mean SD N Mean SD N Mean SD

Terminal BW (g) 8 270.6 20.4 8 271.2 20.4 8 265.3 17.0 8 258.7 20.8

Wet, absolute (mg) 8 70.9 12.0 8 74.1 6.5 7C 68.2 6.8 8 359.6*

(↑407)

94.8

Wet, relative (%) b 8 0.026 0.004 8 0.027 0.001 8 0.026 0.004 8 0.140 0.039

Blotted, absolute (mg) 8 63.9 10.1 8 66.5 4.8 8 61.0 5.3 8 211.3*

(↑231)

29.7

Blotted, relative (%) b 8 0.024 0.003 8 0.025 0.002 8 0.023 0.003 8 0.082 0.011

a Data were obtained from Table 4 on page 21 and Appendix VI on page 68 of the study report.

b Relative wet and blotted uterine weights were calculated by the reviewer from the individual data.

BW= body weight

C Outlier removed

N= No. of animals in the group

SD = Standard Deviation

* Significantly different from vehicle control at p < 0.05. 

2. Microscopic Examination (Optional): Microscopic examinations were not conducted. 

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Phosmet administered at dose levels of 5 and 20 

mg/kg/day to ovariectomized Sprague-Dawley rats did not induce a change in body weight, 

body weight gain or uterine weight, wet or blotted, as compared to the vehicle control. 

Using the ovariectomized rat model, Uterotrophic Assay (OPPTS 890.1600), oral 

administration of phosmet at dose levels up to 20 mg/kg/day is not estrogenic under these 

experimental conditions. 

B. AGENCY COMMENTS: All animals survived until scheduled termination. Two 20 

mg/kg/day rats had decreased movements at 1-4 h post-dosing on Days 1 and 2. No clinical 

signs of toxicity were observed in the 5 mg/kg/day animals. Body weights in the dose 

groups were comparable to the controls throughout the duration of the assay. Uterine 

weights in the treatment groups were comparable to the controls. The mean blotted vehicle 

control uterine weight was <0.04% of the mean vehicle control terminal body weight, which 

meets the guideline requirement. Absolute wet and blotted uterus weights for the 0.1 

mg/kg/day EE group were increased (p<0.05) by 407% and 231%, respectively. These 

increased uterine weights were in the expected range. No statistically significant changes 

were seen in uterine weight in this study. Phosmet was negative in the uterotrophic assay.

C. STUDY DEFICIENCIES: None 

Page 260 of 260