UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: 6/29/2015 

SUBJECT: Propyzamide (Pronamide): Data Evaluation Records (DERs) for EDSP Tier 1 

Assays 

PC Code: 101701 

Decision No.: 460658, 467265 

DP Barcode: D398506, D403721 

D403723, D405597 

Registration No.: NA 

467267,470123 

Petition No.: NA 

Risk Assessment Type: NA 

TXR No.: 0056255 

MRID No.: See Table 

Regulatory Action: NA 

Case No.: NA 

CAS No.: 23950-58-5 

40 CFR: NA 

FROM: Greg Akerman, Ph.D. L:J~ .IJc.-.___ 

Immediate Office 

Health Effects Division (7509P) 

THROUGH: Jess Rowland ~~ Deputy 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 propyzamide: Test Order# CON-101701-

37. 

Page I of2 

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II. RESPONSE

Attached are the EDSP Tier 1 assay DERs for propyzamide.

III. MRID Table

Chemical: Propyzamide (Pronamide) PC Code: 101701

Guideline Assay MRID 

890.1100 Amphibian Metamorphosis Assay (Frog) 48619101

890.1150 Androgen Receptor Binding (Rat Prostate) 48619102

890.1200 Aromatase Assay (Human Recombinant) 48619103

890.1250 Estrogen Receptor Binding 48619104

890.1300 Estrogen Receptor Transcriptional Activation 

(Human Cell Line HeLa-9903) 48619105 

890.1350 Fish Short-Term Reproduction 48619106

890.1400 Hershberger (Rat) 48673401

890.1450 Female Pubertal (Rat) 48673402

890.1500 Male Pubertal (Rat) 48688001

890.1550 Steroidogenesis (Human Cell Line – H295R) 48619107

890.1600 Uterotrophic (Rat) 48619108

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԡԹՌԹԯԽՉՍՁՊԽՅԽՆՌ    ԢԭԞԡԭԟԹՊԻՇԼԽ  

ԬԢԠԡԡԹՌԹԭՇՁՆՌ  

ԢԭԞԪԯԦԡ   

ԢԭԞԤՍՁԼԽՄՁՆԽ   

      ԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԣՊՇԿ

 

ԱԽՋՌԪԹՌԽՊՁԹՄ  ԭՊՇՆԹՅՁԼԽ  ԭՍՊՁՌՑ
    

ԠՇՅՅՇՆՆԹՅԽ ԭՊՇՈՑՒԹՅՁԼԽ

ԠՀԽՅՁԻԹՄՆԹՅԽ ԦԲԭԞԠԼՁԻՀՄՇՊՇԫ
ՅԽՌՀՑՄԺՍՌՑՆՑՄԺԽՆՒԹՅՁԼԽ

 ԠԞ԰ՆԹՅԽԼՁԻՀՄՇՊՇԫ
ԼՁՅԽՌՀՑՄՈՊՇՈՑՆՑՄԺԽՆՒԹՅՁԼԽ

 ԠԞ԰ԫՇ

 ԰ՑՆՇՆՑՅՋԭՊՇՈՑՒԹՅՁԼԽ

 ԢԭԞԭԠԠՇԼԽ

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊ ԧՇՀՆԪԹՊՌՇՆ ԡԹՌԽ

԰ՌԹԾԾ԰ԻՁԽՆՌՁՋՌԠԹՅԺՊՁԼԿԽԢՆՎՁՊՇՆՅԽՆՌԹՄԦՆԻ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊ
ՋԱԽՊՁ԰ԪՑԽՊՋ      ԡԹՌԽ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԠԹՅԺՊՁԼԿԽԢՆՎՁՊՇՆՅԽՆՌԹՄԦՆԻ

ԭՊՁՅԹՊՑԯԽՎՁԽՏԽՊԞՆԼՊԽՏ԰ԹՑԽՊԭՀԡ     ԡԹՌԽ

ԟՁՇՄՇԿՁՋՌԢԭԞԬԭԭԢԣԢԡԢԯԟ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊԢԼՏԹՊԼ԰ԻՇՄՄՇՆ
ՆՇՄՇՆԿԽՊՏՁՌՀԢԭԞ ԡԹՌԽ

ԱՇՐՁԻՇՄՇԿՁՋՌԢԭԞԬԭԭԢԣԢԡԢԯԟ 

ԞԼԼՁՌՁՇՆԹՄԯԽՎՁԽՏԽՊԠԹՌՀԽՊՁՆԽԞՍԺԽԽ      ԡԹՌԽ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԢԭԞԬԭԭԢԣԢԡԢԯԟ 

ԡԹՌԽԢՎԹՄՍԹՌՁՇՆԠՇՅՈՄԽՌԽԼ#ԼԼՅՅՑՑՑՑ%

Digitally signed by ANDREW 

SAYER 

DN: c=US, o=U.S. Government, 

ou=USEPA, ou=Staff, 

cn=ANDREW SAYER, 

dnQualifier=0000051409 

Date: 2015.06.09 13:43:25 

-04'00'

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԠԦԱԞԱԦԬԫԠՍՊՊՁԽԯԧԨԨԠՇԹԼՑԨԩԥՍՌԻՀՁՆՋՇՆԠԪԩԽՀՅԹՆԫԞԪԹՄՇՏՁՆՋՃՁԹՆԼԧԱՀՇՅԹՋ

ԭՊՇՆԹՅՁԼԽԱՀԽԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑՏՁՌՀՌՀԽԞԾՊՁԻԹՆԠՄԹՏԽԼԣՊՇԿԵԽՆՇՈՍՋՄԹԽՎՁՋ԰ՌՍԼՑ

ՈԽՊԾՇՊՅԽԼԺՑԱՇՐՁԻՇՄՇԿՑԹՆԼԢՆՎՁՊՇՆՅԽՆՌԹՄԯԽՋԽԹՊԻՀԹՆԼԠՇՆՋՍՄՌՁՆԿԱՀԽԡՇՏԠՀԽՅՁԻԹՄԠՇՅՈԹՆՑԪՁԼՄԹՆԼ

ԪՁԻՀՁԿԹՆ  ԩԹԺՇՊԹՌՇՊՑ ՊԽՈՇՊՌ ՆՍՅԺԽՊ  ԰ՌՍԼՑ ՋՈՇՆՋՇՊԽԼ ԺՑ ԡՇՏ ԞԿՊՇ԰ԻՁԽՆԻԽՋ ԩԩԠ

ԦՆԼՁԹՆԹՈՇՄՁՋԦՆԼՁԹՆԹ԰ՌՍԼՑԻՇՅՈՄԽՌԽԼ԰ԽՈՌԽՅԺԽՊ

ԫՇՌԽԱՀԽԲ԰ԢԭԞԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅ
Ԣԡ԰ԭԱՁԽՊՋԻՊԽԽՆՁՆԿԺԹՌՌԽՊՑՁՋԻՇՅՈՊՁՋԽԼՇԾԽՄԽՎԽՆ

ՋԻՊԽԽՆՁՆԿԹՋՋԹՑՋՁՆՌԽՆԼԽԼՌՇՁԼԽՆՌՁԾՑԹԻՀԽՅՁԻԹՄ0ՋՄՁՃԽՄՑԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՁԽՁՌՋՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀ

ՌՀԽԽՋՌՊՇԿԽՆԹՆԼՊՇԿԽՆՇՊՌՀՑՊՇՁԼ
ԢԞՇՊԱՈԹՌՀՏԹՑՋԱՀԽՊՇԺՍՋՌՆԽՋՋՇԾՌՀԽԱՁԽՊԺԹՌՌԽՊՑՁՋԺԹՋԽԼՇՆ

ՌՀԽՋՌՊԽՆԿՌՀՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՌՇՁԼԽՆՌՁԾՑՈՇՌԽՆՌՁԹՄԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՏՁՌՀԻՇՅՈՄԽՅԽՆՌԹՊՑԽՆԼՈՇՁՆՌՋ

ՏՁՌՀՁՆՌՀԽԹՋՋԹՑՏՀԽՊԽԹՎԹՁՄԹԺՄԽԹՆԼՊԽԼՍՆԼԹՆԻՑԹԻՊՇՋՋՌՀԽԺԹՌՌԽՊՑԱՀՍՋՌՀԽՊԽՋՍՄՌՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄ

ԹՋՋԹՑՋՀՇՍՄԼՆՇՌԺԽԻՇՆՋՁԼԽՊԽԼՁՆՁՋՇՄԹՌՁՇՆԺՍՌՊԹՌՀԽՊՋՀՇՍՄԼԺԽԻՇՆՋՁԼԽՊԽԼՁՆՌՀԽԻՇՆՌԽՐՌՇԾՇՌՀԽՊԹՋՋԹՑՋ

ՁՆՌՀԽԺԹՌՌԽՊՑԹՋՏԽՄՄԹՋԬՌՀԽՊ԰ԻՁԽՆՌՁԾՁԻԹՄՄՑԯԽՄԽՎԹՆՌԦՆԾՇՊՅԹՌՁՇՆ
Ԭ԰ԯԦԦՆՇՊԼԽՊՌՇԼԽՌԽՊՅՁՆԽՁԾԹԻՀԽՅՁԻԹՄ

ՀԹՋՌՀԽՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀՌՀԽԢԞՇՊԱՈԹՌՀՏԹՑՋԹԴԽՁԿՀՌՇԾԢՎՁԼԽՆԻԽ
ԴՇԢԽՎԹՄՍԹՌՁՇՆՇԾԱՁԽՊ

ԹՋՋԹՑՊԽՋՍՄՌՋՁՆԻՇՅԺՁՆԹՌՁՇՆՏՁՌՀՌՀԽԾՁՆԼՁՆԿՋՁՆՌՀԽԬ԰ԯԦՋՀՇՍՄԼԺԽՍՆԼԽՊՌԹՃԽՆ
ՊԽԾԽՊՌՇՌՀԽԴՇԢ

ԡՇԻՍՅԽՆՌ

ԢԵԢԠԲԱԦԳԢ԰ԲԪԪԞԯԶ

ԱՀԽԼԹՑԹՋՋԹՑՇԾՈՊՇՆԹՅՁԼԽ
ԹՄՋՇՃՆՇՏՆԹՋՈՊՇՈՑՒԹՅՁԼԽՈՍՊՁՌՑՇՆԹՅՈՀՁԺՁԹՆՅԽՌԹՅՇՊՈՀՇՋՁՋՇԾ

ԞԾՊՁԻԹՆ ԻՄԹՏԽԼ ԾՊՇԿՋ 
ԵԽՆՇՈՍՋ ՄԹԽՎՁՋ ՏԹՋ ԻՇՆԼՍԻՌԽԼ ՍՆԼԽՊ ԾՄՇՏՌՀՊՇՍԿՀ ԻՇՆԼՁՌՁՇՆՋ ԞՅՈՀՁԺՁԹՆ ՄԹՊՎԹԽ ԹՌ

ԫՁԽՍՏՃՇՇՈԣԹԺԽՊ
ԫԣՋՌԹԿԽ
ՁՆԽԹԻՀՇԾՊԽՈՄՁԻԹՌԽՋՏԽՊԽԽՐՈՇՋԽԼՌՇՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋ


ՅԩԩԼՁՅԽՌՀՑՄԾՇՊՅԹՅՁԼԽԡԪԣԹՆԼՆՇՅՁՆԹՄՈՊՇՆԹՅՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩ

ԱՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽ
ԱԴԞԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽ
ԩԬԮԻՇՆՌՊՇՄՋԹՆԼՅԿԹՁԩ

ԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋՅԹՁՆՌԹՁՆԽԼԹՌՌՇոԠԹՆԼԹՈԥՇԾՌՇ

ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԹՄՄԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ

ԫՇՅՇՊՌԹՄՁՌՁԽՋՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՀԽԻՇՆՌՊՇՄՋԱՀՊԽԽՌԹԼՈՇՄԽՋ
ԼՁԽԼՁՆՌՀԽՄՇՏԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼ

ՌԹԼՈՇՄԽՋ
ԼՁԽԼՁՆՌՀԽՅՁԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈԠՄՁՆՁԻԹՄՋՁԿՆ
ՌԹԼՈՇՄԽՋՊԽՋՌՁՆԿՇՆՌՀԽՋՍՊԾԹԻԽՏԽՊԽՇԺՋԽՊՎԽԼՁՆ

ՇՆԽՌՇՌՀՊԽԽՌԹԼՈՇՄԽՋՁՆԽԹԻՀՇԾՌՀԽԾՇՍՊՊԽՈՄՁԻԹՌԽՋՇԾՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆԿՊՇՍՈՇՆԡԹՑՋԹՆԼՁՆՌՏՇ

ՌԹԼՈՇՄԽՋԹՌՌՀԽՄՇՏԻՇՆԻԽՆՌՊԹՌՁՇՆԹՆԼՇՆԽԹՌՌՀԽՅԽԼՁՍՅԻՇՆԻԽՆՌՊԹՌՁՇՆՇՆԡԹՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭՊՇՆԹՅՁԼԽՋՁԿՆՁԾՁԻԹՆՌՄՑ
ՈԼԽԻՊԽԹՋԽԼՆՇՊՅԹՄՁՒԽԼՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩԹՌԡԹՑ
ԹՆԼԡԹՑ


ՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՌՌՀԽԱԴԞՅԿԹՁԩՄԽՎԽՄ԰ՁԿՆՁԾՁԻԹՆՌԼԽՄԹՑ
ՈՇԾՅԽԼՁԹՆ

ԫՁԽՍՏՃՇՇՈԣԹԺԽՊ
ԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽՏԹՋՇԺՋԽՊՎԽԼԹՌԡԹՑ
ՋՌԹԿԽԹՆԼԡԹՑ
ՋՌԹԿԽՋՁՆՌՀԽ

ԱԴԞՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԟԽՌՏԽԽՆՌԹԼՈՇՄԽՋՌՇՌԹՄՏԽՊԽԽՐԻՄՍԼԽԼԾՊՇՅՌՀԽ
ՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄՋԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԺԽԻԹՍՋԽՌՀԽՑԼԽՎԽՄՇՈԽԼՈԹՋՌՋՌԹԿԽՇՆՌՀԽԫԣՋԻԹՄԽ

ԱՀԽԽՐԻՄՍԼԽԼՌԹԼՈՇՄԽՋՏԽՊԽՋՈՊԽԹԼԹԻՊՇՋՋՊԽՈՄՁԻԹՌԽՌԹՆՃՋԹՆԼՌՀԽՊԽՏԹՋՆՇՈԹՌՌԽՊՆՇԾՌՀԽՁՊՇԻԻՍՊՊԽՆԻԽԹՋԹ

ԾՍՆԻՌՁՇՆՇԾՌՊԽԹՌՅԽՆՌԫՇՌԹԼՈՇՄԽՋԼԽՎԽՄՇՈԽԼԺԽՑՇՆԼԫԣՋՌԹԿԽՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԬՌՀԽՊ

ԹԾԾԽԻՌԽԼԡԹՑԽՆԼՈՇՁՆՌՋ
ԻՇՆՋՁԼԽՊՁՆԿԽՐԻՄՍՋՁՇՆՇԾԫԣՁՆԼՁՎՁԼՍԹՄՋՁՆԻՄՍԼԽԼՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻՌՁՇՆՋՁՆՏԽՌ

ՏԽՁԿՀՌ 
 ՇԾ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ Ո ԹՆԼ ԰Գԩ 
 ՇԾ ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ Ո ԹՌ ԹՄՄ

ՈՊՇՆԹՅՁԼԽՌՊԽԹՌԽԼՄԽՎԽՄՋԹՆԼԹՊԽԼՍԻՌՁՇՆ
ՈՁՆԥԩԩԹՌՌՀԽՅԿԹՁԩՄԽՎԽՄԻՇՅՈԹՊԽԼՌՇՌՀԽ

ՆԽԿԹՌՁՎԽ ԻՇՆՌՊՇՄ ԫՇ ԹՋՑՆԻՀՊՇՆՇՍՋ ԼԽՎԽՄՇՈՅԽՆՌ ՏԹՋ ՇԺՋԽՊՎԽԼ ՁՆ ԹՆՑ ՌՊԽԹՌՅԽՆՌ ԿՊՇՍՈ ԪՁՄԼ ԾՇՄՄՁԻՍՄԹՊ ԻԽՄՄ

ՀՑՈԽՊՌՊՇՈՀՑՏԹՋԾՇՍՆԼՁՆԺՇՌՀԻՇՆՌՊՇՄՋԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԹՄՄԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼ

ԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ

ԱՀԽՊԽՏԽՊԽՋԽՎԽՊԹՄԽՆԼՈՇՁՆՌՋԾՇՊՏՀՁԻՀՌՀԽՊԽՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌ
ՈԼՁԾԾԽՊԽՆԻԽՋԺԽՌՏԽԽՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈՋՁՆԻՄՍԼՁՆԿԡԹՑՏԽՌՏԽՁԿՀՌԹՆԼ԰ԳԩԹՋՏԽՄՄԹՋԡԹՑՏԽՌՏԽՁԿՀՌԥԩԩԹՆԼՆՇՊՅԹՄՁՒԽԼ

ԥԩԩԦՆՌՀԽՋԽՁՆՋՌԹՆԻԽՋՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈԽՐՀՁԺՁՌԽԼՀՁԿՀԽՊՎԹՄՍԽՋՌՀԹՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈԲՈՇՆ

ԹՆԹՄՑՌՁԻԹՄՎԽՊՁԾՁԻԹՌՁՇՆՌՀԽԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՈՊՇՆԹՅՁԼԽՊԹՆԿԽԼՁՆՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՌԽՋՌ

ՁՆՁՌՁԹՌՁՇՆ
ԡԹՑԼՍԽՌՇՁՆՁՌՁԹՄԻՄՇԿԿՁՆԿՇԾՌՀԽՅՁՐՁՆԿԻԽՄՄԞԼԼՁՌՁՇՆԹՄՄՑՌՀԽՅԽԼՁՍՅԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌԠԳՋ

ՋՄՁԿՀՌՄՑԽՐԻԽԽԼԽԼՊԽՈՇՊՌԽԼՄՑԼՍԽՌՇԼԽԻՊԽԹՋԽՋՁՆՎԽՋՋԽՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇՆԡԹՑԞՄՄՇՌՀԽՊՈԽՊԾՇՊՅԹՆԻԽ

ԹՆԼՎԹՄՁԼՁՌՑԻՊՁՌԽՊՁԹՏԽՊԽՋԹՌՁՋԾՁԽԼՁՆՌՀՁՋՋՌՍԼՑ

ԱՀԽԹՋՋԹՑՋԹՌՁՋԾՁԽՋՌՀԽԢԡ԰ԭԱՁԽՊԱԽՋՌԬՊԼԽՊՊԽՉՍՁՊԽՅԽՆՌՋԾՇՊԹՆԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԬԠ԰ԭԭ

ԤՍՁԼԽՄՁՆԽ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌՇՊԿԹՆՁՋՅԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԫԣ

ԱԽՋՌՇՊԿԹՆՁՋՅՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՇՈՌՁՇՆԹՄԫՇՌԯԽՈՇՊՌԽԼ

ԱԽՋՌՌՑՈԽԾՄՇՏՌՀՊՇՍԿՀ

Page 5 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

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

ԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ
ԞԪԞՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ%

ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ

԰ՌԹԿԽ

ԥՁՆԼԩՁՅԺ

ԩԽՆԿՌՀ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԡԽՎԽՄՇՈՅԽՆՌ

ԱՀՑՊՇՁԼԤՊՇՋՋ

ԹՆԼ

ԥՁՋՌՇՈԹՌՀՇՄՇԿՑ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

 ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ

 ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ

 ԶԽՋ ԶԽՋ ԶԽՋ ԶԽՋ ԫՇ ԫՇ ԫՇ



 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԰ 

 ԤՍՁԼԽՄՁՆԽԣՇՄՄՇՏԽԼ ԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼԾՇՄՄՇՏՁՆԿԿՍՁԼԽՄՁՆԽՋՇՍՌՄՁՆԽԼՁՆԲ԰ԢԭԞԬԠ԰ԭԭ

ԱՀԽԾՇՄՄՇՏՁՆԿԼԽՎՁԹՌՁՇՆՋԾՊՇՅԬԠ԰ԭԭԹՆԼԬԢԠԡ

ՏԽՊԽՆՇՌԽԼ

 ԱՀԽԠԳՊԹՆԿԽԼԾՊՇՅՌՇՁՆՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԱՀՁՋԽՐԻԽԽԼՋՌՀԽ

ՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁՇՆԠԳՇԾՆՇՅՇՊԽՌՀԹՆ

 ԫՇԼԽՌԹՁՄՋՈԽՊՌԹՁՆՁՆԿՌՇՈԹՊԽՆՌԹՄԹԻԻՄՁՅԹՌՁՇՆԽՅԺՊՑՇԻՍՄՌՍՊՁՆԿԾԽԽԼՁՆԿՇՊՈՊԽՌԽՋՌՀԽԹՄՌՀՏԽՊԽ

ՋՈԽԻՁԾՁԽԼ

 ԱՀԽԼՍՊԹՌՁՇՆՇԾՌՀԽԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԾՇՊՌՀԽՈԹՊԽՆՌԹՄԾՊՇԿՋԹՆԼԼԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄԾԽԽԼՁՆԿԹՆԼՀԽԹՄՌՀ

ՏԽՊԽՆՇՌՋՈԽԻՁԾՁԽԼ

 ԱՀԽԽՅԺՊՑՇՋԽՄԽԻՌՁՇՆՅԽՌՀՇԼ
ԽԿԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆՏԹՋՆՇՌՋՈԽԻՁԾՁԽԼ

 ԱՀԽՆՇՅՁՆԹՄԾՄՇՏՊԹՌԽ
ՅԩՅՁՆՏԹՋԿՊԽԹՌԽՊՌՀԹՆՊԽԻՇՅՅԽՆԼԽԼ
ՅԩՅՁՆԺՍՌՌՀԽՎՇՄՍՅԽ

ՌՍՊՆՇՎԽՊՏԹՋԹԻԻԽՈՌԹԺՄԽ
ԻՇՅՈՄԽՌԽՎՇՄՍՅԽՌՍՊՆՇՎԽՊԽՎԽՊՑՀՇՍՊՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 ԱՀԽՀԹՊԼՆԽՋՋՇԾՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊ
ՅԿԩԹՋԠԹԠԬԽՐԻԽԽԼԽԼՌՀԽՊԽԻՇՅՅԽՆԼԽԼՀԹՊԼՆԽՋՋ

ՇԾՅԿԩԹՋԠԹԠԬ

 ԱՀԽԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՈՊՇՆԹՅՁԼԽՊԹՆԿԽԼՁՆՌՀԽՅԿԹՁԩՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՌԽՋՌ

ՁՆՁՌՁԹՌՁՇՆ
ԡԹՑ

 ԱՀԽՊԽՎՁԽՏԽՊԹՆԼՋՌՍԼՑԹՍՌՀՇՊՋԼԽՌԽԻՌԽԼՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋ
ՈԺԽՌՏԽԽՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԾՇՊՌՀԽԾՇՄՄՇՏՁՆԿԽՆԼՈՇՁՆՌՋԡԹՑՋԹՆԼՏԽՌՏԽՁԿՀՌԡԹՑ԰ԳԩԡԹՑԥԩԩ

ԹՆԼԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩԱՀԽՋՌՍԼՑԹՍՌՀՇՊՋԼՁԼՆՇՌԹԼԼՊԽՋՋԹՆՑՁՅՈԹԻՌՇԾՌՀԽՋԽԼՁԾԾԽՊԽՆԻԽՋՇՆ

ՌՀԽՋՌՍԼՑՏՀՁՄԽՌՀԽՊԽՎՁԽՏԽՊՆՇՌԽՋՌՀԹՌԾՇՊԹՄՄԹԾԾԽԻՌԽԼԽՆԼՈՇՁՆՌՋՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈՏԹՋ

ՈՊՇՅՇՌԽԼՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԿՊՇՍՈ

ԱՀԽՋԽԼԽՎՁԹՌՁՇՆՋԼՇՆՇՌՁՅՈԹԻՌՌՀԽԹԻԻԽՈՌԹԺՁՄՁՌՑՇԾՌՀԽՋՌՍԼՑ

 ԠՇՅՈՄՁԹՆԻԽ   ԰ՁԿՆԽԼ ԹՆԼ ԼԹՌԽԼ ԫՇ ԡԹՌԹ ԠՇՆԾՁԼԽՆՌՁԹՄՁՌՑ Ԥԩԭ ԹՆԼ ԮՍԹՄՁՌՑ ԞՋՋՍՊԹՆԻԽ

ՋՌԹՌԽՅԽՆՌՋՏԽՊԽՈՊՇՎՁԼԽԼԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼՁՆԻՇՅՈՄՁԹՆԻԽՏՁՌՀԲՆՁՌԽԼ

԰ՌԹՌԽՋ ԢՆՎՁՊՇՆՅԽՆՌԹՄ ԭՊՇՌԽԻՌՁՇՆ ԞԿԽՆԻՑ  ԭԽՋՌՁԻՁԼԽ ԭՊՇԿՊԹՅՋ ԤՇՇԼ

ԩԹԺՇՊԹՌՇՊՑ ԭՊԹԻՌՁԻԽ ԰ՌԹՆԼԹՊԼՋ ԣՁՆԹՄ ԯՍՄԽ 
 Ԡԣԯ ԭԹՊՌ  ՏՁՌՀ ՌՀԽ

ԾՇՄՄՇՏՁՆԿԽՐԻԽՈՌՁՇՆՋՌՀԽՄԹՌԽՋՌՏԹՌԽՊԻՀԹՊԹԻՌԽՊՁՒԹՌՁՇՆՈԽՊԾՇՊՅԽԼՁՆԣԽԺՊՍԹՊՑ

ՏԹՋՆՇՌՈԽՊԾՇՊՅԽԼՁՆԹԻԻՇՊԼԹՆԻԽՌՇՌՀԽՋՌԹՌԽԼԤՇՇԼԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽՋ

ԹՆԼՌՀԽՌԽՋՌՋՍԺՋՌԹՆԻԽՏԹՋՆՇՌԻՀԹՊԹԻՌԽՊՁՒԽԼԹԻԻՇՊԼՁՆԿՌՇՌՀԽՋՌԹՌԽԼԤՇՇԼ

ԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽՋ

ԞԱԽՋՌԪԹՌԽՊՁԹՄ   ԭՊՇՆԹՅՁԼԽ

ԡԽՋԻՊՁՈՌՁՇՆ   ԴՀՁՌԽՈՇՏԼԽՊ

ԬԢԠԡՊԽԻՇՅՅԽՆԼՋԼԽՋԻՊՁԺՁՆԿՏԹՌԽՊՋՇՄՍԺՁՄՁՌՑՅԽՄՌՁՆԿԺՇՁՄՁՆԿՈՇՁՆՌՋՌԹԺՁՄՁՌՑՁՆՏԹՌԽՊԹՆԼՄՁԿՀՌՈԨԹԭՇՏ

ՇՊԨՇՏՎԹՈՇՊՈՊԽՋՋՍՊԽՇԾՌԽՋՌԻՇՅՈՇՍՆԼԽՐՈՁՊԹՌՁՇՆԼԹՌԽ

ԩՇՌԫՇԟԹՌԻՀԫՇ ԵԤԯԱ԰ԫ
ԩՇՌ

ԭՍՊՁՌՑ    

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԦՅՈՍՊՁՌՁԽՋ    ԦՅՈՍՊՁՌՁԽՋՄՁՋՌԽԼՇՆՈԹԿԽՇԾԡԢԯ

԰ՌԹԺՁՄՁՌՑՇԾԠՇՅՈՇՍՆԼԯԽՄԹՌՁՎԽՄՑ ՋՌԹԺՄԽ ԼՍՊՁՆԿ ՌՀԽ ԼԹՑ ԽՐՈՇՋՍՊԽ ՈԽՊՁՇԼ ԺԹՋԽԼ ՇՆ ԱԴԞ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏՀՁԻՀԹՎԽՊԹԿԽԼՌՇՇԾՆՇՅՁՆԹՄԥՇՏԽՎԽՊՌՀԽԠԳՁՆՌՀԽ

ՌՏՇՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԹՆԿԽԼԾՊՇՅՌՇ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾ

ԱԽՋՌԠՀԽՅՁԻԹՄՋ  ԫՇՌԯԽՈՇՊՌԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԟԱԽՋՌԬՊԿԹՆՁՋՅ

ԱԹԺՄԽԤԽՆԽՊԹՄԦՆԾՇՊՅԹՌՁՇՆԞԺՇՍՌՌՀԽԱԽՋՌ԰ՈԽԻՁԽՋԹՆԼԭԹՊԽՆՌԹՄԠԹՊԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

԰ՈԽԻՁԽՋԻՇՅՅՇՆՆԹՅԽ ԞԾՊՁԻԹՆԻՄԹՏԽԼԾՊՇԿ ԢԭԞՊԽԻՇՅՅԽՆԼՋԞԾՊՁԻԹՆԻՄԹՏԽԼԾՊՇԿ


ԵԽՆՇՈՍՋՄԹԽՎՁՋԴԽՋՌԽՊՆ#ԞԾՊՁԻԹ%ԻՄԹՏԽԼ

ԾՊՇԿ԰ՁՄՍՊԹՆԹ
ԵԽՆՇՈՍՋՌՊՇՈՁԻԹՄՁՋՅԹՑԺԽ

ՍՋԽԼԹՋԹՆԹՄՌԽՊՆԹՌԽՋՈԽԻՁԽՋՀՇՏԽՎԽՊԹՄՁՋՌ

ՇԾԹՄՄՇԾՌՀԽՆԽԻԽՋՋԹՊՑՈՊՇՌՇԻՇՄԼԽՎՁԹՌՁՇՆՋՌՇ

ԹԻԻՇՅՅՇԼԹՌԽՌՀՁՋՋՈԽԻՁԽՋՁՋՊԽԻՇՅՅԽՆԼԽԼ

ԾՇՊՁՆԻՄՍՋՁՇՆՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌԱՀԽԿՍՁԼԽՄՁՆԽ

ՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹ

ՍՋԽԼՌՇՋՍՈՈՇՊՌՌՀԽՊԽՄՁԹԺՁՄՁՌՑՇԾՌՀԽՌԽՋՌԺԽ

ՁԼԽՆՌՁԾՁԽԼ

԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԵԽՆՇՈՍՋՄԹԽՎՁՋ԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼ ԫՇՌՋՌԹՌԽԼԴԽՊԽՈԹՊԽՆՌՋՅԹՁՆՌԹՁՆԽԼԹՋՁՆՀՇՍՋԽՋՌՇԻՃ!

ԶԽՋ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՄԹՊՎԹԽ ՍՋԽԼ ՁՆ ՌՀԽ

ԹՋՋԹՑԺԽԼԽՊՁՎԽԼԾՊՇՅՁՆՀՇՍՋԽԹԼՍՄՌՋ

 Բ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ

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

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԽՊԽՈԹՊԽՆՌԹՄԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!

ԫՇՌԻՄԽԹՊՄՑՋՈԽԻՁԾՁԽԼ ԱՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌԹԼՈՇՄԽՋՏԽՊԽ

ՅԹՁՆՌԹՁՆԽԼՍՆԼԽՊԾՄՇՏՌՀՊՇՍԿՀԻՇՆԼՁՌՁՇՆՋԹՌԹԼԽՆՋՁՌՑՌՀԹՌՏՇՍՄԼԹԾԾԽԻՌԼԽՎԽՄՇՈՅԽՆՌ
ՌԹԼՈՇՄԽՋԩՍՆՌՁՄՌՀԽՑՊԽԹԻՀԽԼՌՀԽԹՈՈՊՇՈՊՁԹՌԽՌԽՋՌՋՁՒԽՋՌԹԿԽ

ԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԾՇՊՈԹՊԽՆՌԹՄԾՊՇԿՋ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԭԹՊԽՆՌՋ ՅԹՁՆՌԹՁՆԽԼ ԹՋԻՇՆՌՁՆՍՇՍՋ ՁՆՀՇՍՋԽԻՍՄՌՍՊԽՋ

ԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄԾԽԽԼՁՆԿ ԫՇՌՋՈԽԻՁԾՁԽԼԡԽՌԹՁՄՋՇՆՈԹՊԽՆՌԹՄՀԽԹՄՌՀ ԫՇՌՋՈԽԻՁԾՁԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԩԹՊՎԹՄ԰ԽՄԽԻՌՁՇՆԹՆԼԠԹՊԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԟԽՋՌՋՁՆԿՄԽՋՈԹՏՆ! ԫՇ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌՀԽԺԽՋՌ-

ՁՆԼՁՎՁԼՍԹՄՋՈԹՏՆՋՏՁՌՀԹՅՁՆՁՅՍՅՇԾ

ՄԹՊՎԹԽՋՈԹՏՆԺԽԽՎԹՄՍԹՌԽԼՌՇՁԼԽՆՌՁԾՑՌՀԽ

ԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆԹՆԼՌՀԹՌՌՀԽՄԹՊՎԹԽՋԽՄԽԻՌԽԼ

ԾՇՊՌԽՋՌՁՆԿՇՊՁԿՁՆԹՌԽԾՊՇՅՌՀԽԺԽՋՌՋՁՆԿՄԽՋՈԹՏՆ


ՁԽՌՀԽՋՈԹՏՆՋԹՊԽՆՇՌԻՇՅՁՐԽԼ

ԫՍՅԺԽՊՇԾՋՈԹՏՆՋԽՎԹՄՍԹՌԽԼ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ

ԫՍՅԺԽՊՇԾԽԿԿՋՋԹՅՈՄԽԼՈԽՊՋՈԹՏՆ

ԫԞ 

ԫԣՋՌԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԺԽ

ՁՆՁՌՁԹՌԽԼՏՁՌՀՄԹՊՎԹԽԹՌԫՁԽՍՏՃՇՇՈ-ԣԹԺԽՊ


ԫԣԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ
ԼԹՑՋ

ՈՇՋՌԾԽՊՌՁՄՁՒԹՌՁՇՆ

ԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ԱԹԼՈՇՄԽՋՏԽՊԽԼԹՑՋ

ՇՄԼ

ԪԽԹՆՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՊԽՈՇՊՌԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ

ԯԹՆԿԽՇԾՌՇՌԹՄՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾՊԽՈՇՊՌԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ

ԴԹՋՌՀԽՇՈՌՁՇՆԹՄՋՁՒԽՋԽՄԽԻՌՁՇՆՅԽՌՀՇԼՍՋԽԼ!

ԫՇՌՋՈԽԻՁԾՁԽԼ 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆՄԹՊՎԹՄՋԽՄԽԻՌՁՇՆ ԱԹԼՈՇՄԽՋՏԽՊԽՊԹՆԼՇՅՄՑ

ՋԽՄԽԻՌԽԼԹՆԼԻՀՇՋԽԾՇՊՌՀԽԹՋՋԹՑՁԾՌՀԽՑՏԽՊԽԫԣՋՌԹԿԽ

ԩՇԹԼՁՆԿՊԹՌԽ
ՊԽԹՊՁՆԿԼԽՆՋՁՌՑ ՄԹՊՎԹԽԩ ԱՏԽՆՌՑՌԹԼՈՇՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽՌԽՋՌ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՊԽԹՊՁՆԿ ԼԽՆՋՁՌՑ


ՄՇԹԼՁՆԿ ՊԹՌԽ ՆՇՌ ԽՐԻԽԽԼ ԹՈՈՊՇՐՁՅԹՌԽՄՑ 

ՄԹՊՎԹԽԩ ԻՍՄՌՍՊՁՆԿ ՋՑՋՌԽՅ ԾՇՊ ԾՄՇՏՌՀՊՇՍԿՀ

ՋՑՋՌԽՅՋ ՇՊ  ՌԹԼՈՇՄԽՋԩ ՁՆ ՋՌԹՌՁԻՊԽՆԽՏԹՄ

ԽՐՈՇՋՍՊԽՋՑՋՌԽՅՋ

ԱՑՈԽՇԾԾՇՇԼ ԰ԽՊԹԪՁԻՊՇՆն ԢԭԞՊԽԻՇՅՅԽՆԼՋ԰ԽՊԹԪՁԻՊՇՆն ՌՀՊՇՍԿՀՇՍՌ

ՈՊԽԽՐՈՇՋՍՊԽ
ԹԾՌԽՊԫԣՋՌԹԿԽԹՆԼ

ԼՍՊՁՆԿՌՀԽԽՆՌՁՊԽԼԼԽԾՁՆՁՌՁՎԽՋՌՍԼՑԦԾ

ԹՆՇՌՀԽՊԼՁԽՌՁՋՍՋԽԼՌՀԽՋՌՍԼՑՊԽՈՇՊՌՋՀՇՍՄԼ

ՈՊՇՎՁԼԽԹՆԹՄՑՋՁՋՇԾՁՇԼՁԼԽԻՇՆՌԽՆՌԹՆԼՈՇՌԽՆՌՁԹՄ

ԻՇՆՌԹՅՁՆԹՆՌՋԹՆԼՌՀԽԼՁԽՌՋՀՇՍՄԼ

ԼԽՅՇՆՋՌՊԹՌԽԽՉՍԹՄՈԽՊԾՇՊՅԹՆԻԽՌՇ԰ԽՊԹ

ԪՁԻՊՇՆն 

԰ՇՍՊԻԽՇԾԾՇՇԼ ԰ԽՊԹԪՁԻՊՇՆնԦՇԼՁԼԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆԼՁԽՌ
ՁԾՃՆՇՏՆ

ՅԿՃԿ 

ԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿ ՌՁՅԽՋԼԹՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾԽԽԼՁՆԿՇԻԻՍՊԹՌՄԽԹՋՌ

ՌՏՁԻԽՈԽՊԼԹՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿՊԽԿՁՅԽ ԣՇՄՄՇՏԽԼԢԭԞԹՆԼ

ԬԢԠԡՊԽԻՇՅՅԽՆԼԽԼՊԽԿՁՅԽ

ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋԼՍՊՁՆԿՌՀԽ

ՈՊԽԽՐՈՇՋՍՊԽՈԽՊՁՇԼԺԽՁՆԻՊԽԹՋԽԼԹՄՇՆԿՏՁՌՀ

ՄԹՊՎԹՄԿՊՇՏՌՀՌՇԹՈՈՊՇՐՁՅԹՌԽՄՑ

ՅԿՄԹՊՎԹԼԹՑԺՑՌԽՋՌՁՆՁՌՁԹՌՁՇՆԢԭԞԹՆԼ

ԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌԾՇՇԼՊԹՌՁՇՆՋՁՆԻՊԽԹՋԽ

ԾՊՇՅՅԿՄԹՊՎԹԼԹՑԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
԰ՌՍԼՑ

ԡԹՑՌՇՅԿՄԹՊՎԹԼԹՑՁՆՌՀԽՄԹՋՌՏԽԽՃ

ՇԾՌՀԽՌԽՋՌ
԰ՌՍԼՑԡԹՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԠԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱՑՈԽՇԾԽՐՈՇՋՍՊԽ ԣՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏՌՀՊՇՍԿՀ

ՋՑՋՌԽՅ

ԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԠՇՆՌՁՆՍՇՍՋԾՄՇՏ ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ

ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ

ՊԽԻՇՅՅԽՆԼԽԼ

ԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ

չՅԩՅՁՆ ԣՄՇՏՊԹՌԽՈՊՇՎՁԼԽԼԻՇՅՈՄԽՌԽՎՇՄՍՅԽՌՍՊՆՇՎԽՊ

ԹՈՈՊՇՐՁՅԹՌԽՄՑԽՎԽՊՑՀՇՍՊՋ

ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋ

ՅԩՅՁՆ
ԻՇՅՈՄԽՌԽՎՇՄՍՅԽՊԽՈՄԹԻԽՅԽՆՌԻԹ

ԽՎԽՊՑՀՊՋ

 ԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԞԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋՑՊՁՆԿԽ

ՈՍՅՈԼԽՄՁՎԽՊՑՋՑՋՌԽՅՍՋՁՆԿԿԹՋՌՁԿՀՌՋՑՊՁՆԿԽՋԼԽՄՁՎԽՊԽԼԹԻՇՆԻԽՆՌՊԹՌԽԼՌԽՋՌՋՍԺՋՌԹՆԻԽՋՌՇԻՃՋՇՄՍՌՁՇՆԹՌԹԼԽՋՁԿՆԹՌԽԼՊԹՌԽԾՊՇՅԹՋՌՇԻՃՎԽՋՋԽՄՌՇԹՋՌԹՁՆՄԽՋՋՋՌԽԽՄՅՁՐՁՆԿԻՀԹՅԺԽՊՏՀԽՊԽՁՌՏԹՋՅՁՐԽԼՏՁՌՀԼՁՄՍՌՁՇՆՏԹՌԽՊ

ԱՀԽՌԽՋՌՋՇՄՍՌՁՇՆՏԹՋԿՊԹՎՁՌՑԾԽԼԾՊՇՅՌՀԽՅՁՐՁՆԿԻՀԹՅԺԽՊԹՆԼՋՈՄՁՌԽՉՍԹՄՄՑՌՇՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄՋ
ԻՇՆՌԹՁՆԽԼՁՆԹՌԽՅՈԽՊԹՌՍՊԽԻՇՆՌՊՇՄՄԽԼՏԹՌԽՊՌՊՇՍԿՀՎՁԹԹԱԽԾՄՇՆՅԹՆՁԾՇՄԼՏՁՌՀԱԽԾՄՇՆԼԽՄՁՎԽՊՑՌՍԺՁՆԿԹՌԹԾՄՇՏՊԹՌԽՇԾչՅՄՅՁՆԱՀՁՋԾՄՇՏՊԹՌԽՈՊՇՎՁԼԽԼԹԻՇՅՈՄԽՌԽՎՇՄՍՅԽՌՍՊՆՇՎԽՊԹՈՈՊՇՐՁՅԹՌԽՄՑԽՎԽՊՑՀՇՍՊՋԾՇՊԽԹԻՀՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄ

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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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ ԡՁՄՍՌՁՇՆՏԹՌԽՊՏԹՋԩԹՃԽ

ԥՍՊՇՆՏԹՌԽՊՋՍՈՈՄՁԽԼՌՇԱՀԽԡՇՏԠՀԽՅՁԻԹՄԠՇՅՈԹՆՑԺՑՌՀԽԠՁՌՑՇԾԪՁԼՄԹՆԼԴԹՌԽՊԱՊԽԹՌՅԽՆՌԭՄԹՆՌԴԹՌԽՊՏԹՋՇԺՌԹՁՆԽԼԾՊՇՅՌՀԽՍՈՈԽՊ԰ԹԿՁՆԹՏԟԹՑՇԾԩԹՃԽԥՍՊՇՆՇԾԾԴՀՁՌԽՋՌՇՆԽԭՇՁՆՌԹՆԼՏԹՋՄՁՅԽԼԹՆԼԾՄՇԻԻՍՄԹՌԽԼՏՁՌՀԾԽՊՊՁԻԻՀՄՇՊՁԼԽ

ԴԹՌԽՊՏԹՋՈՍՅՈԽԼՌՇՌՀԽՄԹԺՇՊԹՌՇՊՑՈՊՁՇՊՌՇՅՍՆՁԻՁՈԹՄՌՊԽԹՌՅԽՆՌԾՇՊՀՍՅԹՆԻՇՆՋՍՅՈՌՁՇՆԭՊՁՇՊՌՇՍՋԽՁՆՌՀԽՄԹԺՇՊԹՌՇՊՑՏԹՌԽՊՏԹՋՋԹՆԼԾՁՄՌԽՊԽԼՈԥԹԼՂՍՋՌԽԼՏՁՌՀԠԬ

ԻԹՊԺՇՆԾՁՄՌԽՊԽԼԹՆԼԲԳՁՊՊԹԼՁԹՌԽԼ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼ

ՏԹՌԽՊՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄՏԹՌԽՊ

ԺԽՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊ

ՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊ

ՈՇՋՋՁԺՄԽԻՇՆՌԹՅՁՆԹՆՌՋՁՆԻՄՍԼՁՆԿՃՆՇՏՆ

ՋՍԺՋՌՊԹՌԽՋՇԾՌՀԽՁՇԼՁՆԽՌՊԹՆՋՈՇՊՌԽՊՇԾՌՀԽ

ՌՀՑՊՇՁԼԿՄԹՆԼ
ԽԿԾՄՍՇՊՁԼԽԻՀՄՇՊԹՌԽ

ՈԽՊԻՀՄՇՊԹՌԽԬԢԠԡԹԻԻԽՈՌՋԹՆՑՏԹՌԽՊՁՆ

ՏՀՁԻՀՌՀԽՌԽՋՌՋՈԽԻՁԽՋՋՀՇՏԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄ

ԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌ

ԿՍՁԼԽՄՁՆԽ

ԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!

ԶԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԦՇԼՁԼԽՋՍՈՈՄԽՅԽՆՌԹՌՁՇՆՁՆՏԹՌԽՊ!

ԫՇ  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 ՐՐԻՅՏՁՌՀԹ

ՌԽՋՌՋՇՄՍՌՁՇՆԼԽՈՌՀՇԾԻՅ

ԣՁՄՄՎՇՄՍՅԽ +ԩ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽՋՑՋՌԽՅ

ԫԞ 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ

ԪԽԹՋՍՊԽՅԽՆՌ

ԦՆՌԽՊՎԹՄ

ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԥԹՊԼՆԽՋՋ
ՅԿԩԹՋԠԹԠԬ   

ԴԽԽՃՄՑՁՆՌՀԽ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼ

ՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՀԹՊԼՆԽՋՋՌՇ

ՅԿԩԹՋԠԹԠԬ

Ոԥ   

ԴԽԽՃՄՑՁՆԽԹԻՀ

ՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥչ

ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ

ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼ

ԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ՅԿԩ   

ԴԽԽՃՄՑՁՆԽԹԻՀ

ՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄ

ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ԡԬ

 ՅԿԩ
 ԹՁՊՋԹՌՍՊԹՌՁՇՆԬԢԠԡ

ՊԽԻՇՅՅԽՆԼՋԡԬԻՇՆԻԽՆՌՊԹՌՁՇՆ ՅԿԩ


 ԹՁՊՋԹՌՍՊԹՌՁՇՆ

ԱԽՅՈԽՊԹՌՍՊԽ
ոԠ   

ԴԽԽՃՄՑՁՆԽԹԻՀ

ՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչՇԠ

ՁՆՌԽՊՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌ

ԼՁԾԾԽՊԽՆՌՁԹՄՋՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼՇԠ

ԦՇԼՁԼԽ ՅԿԩ

ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՉՍԹՌՁԻՁՇԼՁԼԽՊԹՆԿԽ

-սԿԩ
ՋՍՈՈՄԽՅԽՆՌԹՄՁՇԼՁԼԽՋՀՇՍՄԼՆՇՌ

ԽՐԻԽԽԼսԿԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ

ԪԽԹՋՍՊԽՅԽՆՌ

ԦՆՌԽՊՎԹՄ

ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞՅՅՇՆՁԹ ՅԿԩ ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑՇԾ

ՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ

ՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋԺԽՅԽԹՋՍՊԽԼՁՆԹ

ԻՇՆՌՊՇՄԹՆԼԹՌՇՆԽՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԹՌՄԽԹՋՌՏԽԽՃՄՑԦՆՋՌԹՌՁԻՊԽՆԽՏԹՄՋՑՋՌԽՅՋ

ՏԹՌԽՊՉՍԹՄՁՌՑՈԹՊԹՅԽՌԽՊՋՁՆԻՄՍԼՁՆԿ

ԹՅՅՇՆՁԹՋՀՇՍՄԼԺԽՅԽԹՋՍՊԽԼՂՍՋՌՈՊՁՇՊՌՇ

ՊԽՆԽՏԹՄԦՆԹԼԼՁՌՁՇՆԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ

ԡԬԺԽՅԽԹՋՍՊԽԼԹՌԽԹԻՀԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌ

ՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌՌԽՅՈԽՊԹՌՍՊԽԺԽ

ՅԽԹՋՍՊԽԼԻՇՆՌՁՆՍՇՍՋՄՑԬԢԠԡ

ՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԡԬԹՆԼՌԽՅՈԽՊԹՌՍՊԽԺԽ

ՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌՏԽԽՃՄՑԹՆԼՌՀԹՌՈԥԹՆԼ

ՀԹՊԼՆԽՋՋԺԽՅԽԹՋՍՊԽԼԹՌՄԽԹՋՌԹՌՌՀԽ

ԺԽԿՁՆՆՁՆԿԹՆԼԽՆԼՇԾՌՀԽՌԽՋՌ

ԣՄՍՇՊՁԼԽ ՅԿԩԭԽՊԻՀՄՇՊԹՌԽ ԫՇՌՊԽՈՇՊՌԽԼԠՀՄՇՊԹՌԽ ԫՇՌՊԽՈՇՊՌԽԼ

ԞՄՃԹՄՁՆՁՌՑ
ՅԿԩԹՋԠԹԠԬ   

ԴԽԽՃՄՑՁՆՌՀԽ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼ

ՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ ԠՇՆԼՍԻՌՁՎՁՌՑ
սՅՀՇՋԻՅ   

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 ԡ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋ

ԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ! ԶԽՋԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!

ԯԽԻՇՎԽՊՁԽՋԹՆԼՊԽՈՇՊՌԽԼՋՇՄՍԺՁՄՁՌՑ
ՅԿԩՇԾՌԽՋՌՅԹՌԽՊՁԹՄ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ

ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ

ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ

ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ

԰ՈԽԻՁԽՋ ԵԽՆՇՈՍՋՄԹԽՎՁՋԩՁԾԽՋՌԹԿԽ ԫԣԱԽՋՌԼՍՊԹՌՁՇՆ ՀՇՍՊՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋ ԞՀՊՊԹՆԿԽԾՁՆԼԽՊ

ՏԹՋԻՇՆԼՍԻՌԽԼՍՆԼԽՊՋՌԹՌՁԻԻՇՆԼՁՌՁՇՆՋԹՌՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾ
ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩ

ՌԹԼՈՇՄԽՋՏԽՊԽՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇԹՌԽՋՌՎԽՋՋԽՄՈԽՊՊԽՈՄՁԻԹՌԽԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԞԾՌԽՊՀՇՍՊՋՈՇՇՊՋՇՄՍԺՁՄՁՌՑՏԹՋ

ՇԺՋԽՊՎԽԼԹՆԼՇՆՄՑԹՋՁՆԿՄԽՌԹԼՈՇՄԽԼՁԽԼԹՌՁՆՌՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԱՀԽՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏԹՋԹՈՈՊՇՐՁՅԹՌԽՄՑՅԿԹՁԩ

ԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԱԽՋՌԼՍՊԹՌՁՇՆ ԼԹՑՋ ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ԼՍՊԹՌՁՇՆ ՇԾ ՌՀԽ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԼԹՑՋ

ԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԯԹՆԿԽԾՁՆԼՁՆԿՋՌՍԼՁԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ

ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ

ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿ

ՅՇՊՌԹՄՁՌՑՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ

԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌՀԽ ՅԹՐՁՅՍՅ

ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՋԽՈԹՊԹՌՁՇՆ ԺԽ  ԹՆԼ ՌՀԽ

ՅՁՆՁՅՍՅԺԽ

ԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄՁԾԹՈՈՊՇՈՊՁԹՌԽ

ԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!

ԶԽՋ 

ԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

԰ՌՍԼՑԹՍՌՀՇՊՈՊԽՋԽՆՌԽԼՅԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԡՍԽՌՇՀՁԿՀՎԹՊՁԹԺՁՄՁՌՑՊԽՎՁԽՏԽՊԻԹՄԻՍՄԹՌԽԼՌՁՅԽՏԽՁԿՀՌԽԼԹՎԽՊԹԿԽ
ԱԴԞԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿԹՁԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ

ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋ

ԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡ ԫՇՌՊԽՈՇՊՌԽԼ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԡԹՑՋԹՆԼ  ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԺԽՅԽԹՋՍՊԽԼՁՆՇՆԽՌԹՆՃԹՌԽԹԻՀՌՊԽԹՌՅԽՆՌ

ՄԽՎԽՄԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԹՆԼԽՎԽՊՑՏԽԽՃ

ՌՀԽՊԽԹԾՌԽՊ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ

  ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԽՍՋԽՇԾԹ

ԻՇՆԻՍՊՊԽՆՌՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿ

ԹԿԽՆՌՁՋՍՋԽԼԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՄԹՊՎԹԽՈԽՊՌՊԽԹՌՅԽՆՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ


ՊԽՈ 

ԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ! ԶԽՋ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԡԪԣ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

Յԩԩ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌԽՐԻԽԽԼ

ՅՄԩԬԢԠԡՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՇՄՎԽՆՌ

ՀԹՎԽՆՇԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊՈՊՇԼՍԻԽԹՆՑ

ՇՌՀԽՊԹԼՎԽՊՋԽԽԾԾԽԻՌՋԹՆԼՌՀԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆ

ՆՇՌԺԽԿՊԽԹՌԽՊՌՀԹՆՅՄԩ

ԴԹՋԹՈՇՋՁՌՁՎԽԻՇՆՌՊՇՄՍՋԽԼ! ԫՇԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԫԞԭՇՋՁՌՁՎԽԻՇՆՌՊՇՄԻՇՆԻԽՆՌՊԹՌՁՇՆ
Ջ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ 

ԭՀՇՌՇՈԽՊՁՇԼ ՀՊՋՄՁԿՀՌ

ՀՊՋԼԹՊՃ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ


ՄՁԿՀՌԼԹՊՃ

ԩՁԿՀՌՁՆՌԽՆՋՁՌՑԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ ՄՍՐ ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑ-ԨՄՍՐ


ԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋ ԫԞ

 ԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏ

ԞՉՍԹՌՁԻԱՇՐՁԻՇՄՇԿՑՈՈ-

 ԬԢԠԡ
ԤՍՁԼԹՆԻԽԡՇԻՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋ

ՇՆԱԽՋՌՁՆԿԹՆԼԞՋՋԽՋՋՅԽՆՌԫՇԭԹՊՁՋԣՊԹՆԻԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱՊԽԹՌՅԽՆՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԞՅՈՀՁԺՁԹՆԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌԦԡ

ԫՇՅՁՆԹՄ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԱԴԞ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԪԽԹՆԠԳ
 ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ   ԫԞ

԰ԽԽԯԽՎՁԽՏԽՊ0Ջ

ԠՇՅՅԽՆՌՋ

ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՌԽՋՌՁՌԽՅ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՅԹՁՆՌԹՁՆԽԼԹՌԹԻՇԽԾԾՁԻՁԽՆՌՇԾ

ՎԹՊՁԹՌՁՇՆ
ԠԳ

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ   ԫԞ

ԱՊԽԹՌՅԽՆՌ   ԱՊԽԹՌՅԽՆՌ   

ԱՊԽԹՌՅԽՆՌ   

ԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ

 ԢԬԺՋԽՊՎԹՌՁՇՆՋ

ԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋ ԡԹՑԫԣՋՌԹԿԽՏԽՌՏԽՁԿՀՌՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩՆՇՊՅԹՄՁՒԽԼԥԩԩ

        ԡԹՑԫԣՋՌԹԿԽՏԽՌՏԽՁԿՀՌՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԥԩԩՆՇՊՅԹՄՁՒԽԼԥԩԩՀՁՋՌՇՈԹՌՀՇՄՇԿՑ

        ԡԹՁՄՑՅՇՊՌԹՄՁՌՑՋՍԺՄԽՌՀԹՄԽԾԾԽԻՌՋ

ԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ!ԶԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՅՇՊՌԹՄՁՌՑԹՆԼԻՄՁՆՁԻԹՄՋՁԿՆՋՇԻԻՍՊԼԹՁՄՑԹՌԹՅՁՆՁՅՍՅՇՌՀԽՊՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽՊԽԻՇՅՅԽՆԼԽԼԹՋԾՇՄՄՇՏՋԫԣ

ԼԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽ
ԡԹՑՋԹՆԼԹՆՑԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՁՆԼՁԻԹՌԽԼԺՑՌԹԼՈՇՄԽՋՌՀԹՌԻԹՆՆՇՌԺԽԹՋՋՁԿՆԽԼԹՆԫԣՋՌԹԿԽ
ԡԹՑՋԹՆԼ

ՀՁՆԼՄՁՅԺՄԽՆԿՌՀ
ԡԹՑՋԹՆԼՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
ԡԹՑՋԹՆԼԺՇԼՑՏԽՁԿՀՌ
ՌԽՋՌՁՆՁՌՁԹՌՁՇՆԾՇՊՇՈՌՁՇՆԹՄՋՁՒԽԺԹՋԽԼՄԹՊՎԹՄՋԽՄԽԻՌՁՇՆԹՆԼՌՀՑՊՇՁԼ

ԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑ
ԡԹՑԫՇՌԽՌՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՑՋԽԻՌՁՇՆՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԹՄՋՇՁՆԻՄՍԼԽՋՌՀՑՊՇՁԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑՇԺՋԽՊՎԹՌՁՇՆՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԦԦ ԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫ

Ԟ ԯԽՋՍՄՌՋ

ԫՇՅՇՊՌԹՄՁՌՁԽՋՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՀԽԻՇՆՌՊՇՄՋՇՊՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՇՆԡԹՑ
ԱԹԺՄԽԞՌՇՌԹՄՇԾՌԹԼՈՇՄԽՋ

ԼՁԽԼԺԽՌՏԽԽՆԡԹՑՋԹՆԼԱՀՊԽԽ
ԼՁԽԼՁՆՌՀԽՄՇՏԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼԾՁՎԽ
ԼՁԽԼՁՆՌՀԽ

ՁՆՌԽՊՅԽԼՁԹՌԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ԱԹԺՄԽԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ%

ԩԹՊՎԹՄԪՇՊՌԹՄՁՌՑ

ԡԹՑ ԡԹՑ

Ն ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ Ն ԪՇՊՌԹՄՁՌՑ ԪՇՊՌԹՄՁՌՑ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ      

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ      

      

      

      



 ԰ԹՅՈՄԽՋՁՒԽԹՆԼԻՍՅՍՄԹՌՁՎԽՅՇՊՌԹՄՁՌՑՎԹՄՍԽՋԹՌԡԹՑՈՊՁՇՊՌՇՁՆՌԽՊՁՅՋԹԻՊՁԾՁԻԽ



 ԠՍՅՍՄԹՌՁՎԽՅՇՊՌԹՄՁՌՑՇՆԡԹՑՁՋԺԹՋԽԼՇՆՌՀԽՆՍՅԺԽՊՇԾՌԹԼՈՇՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
Ն

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԪԽԼՁԹՆԡԹՑԫԣՋՌԹԿԽՊԹՆԿԽԼԾՊՇՅՁՆՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈՌՇՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ԦՆԼՁՎՁԼՍԹՄՌԹԼՈՇՄԽՋՌԹԿԽՊԹՆԿԽԼԾՊՇՅՌՇ
ԱԹԺՄԽԡԹՑՅԽԼՁԹՆԫԣՋՌԹԿԽՊԹՆԿԽԼԾՊՇՅ

ՁՆՌՀԽՀՁԿՀԽՋՌԿՊՇՍՈՌՇՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ-ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽԹՆԼԞՋՑՆԻՀՊՇՆՇՍՋԡԽՎԽՄՇՈՅԽՆՌ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ%

ԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽ

ԡԹՑ ԡԹՑ

Ն

ԪԽԼՁԹՆ

԰ՌԹԿԽ

ԞՋՑՆԻՀՊՇՆՇՍՋ Ն

ԪԽԼՁԹՆ

԰ՌԹԿԽ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ      

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ      

      

      

      

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԪԽԹՆԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩՊԹՆԿԽԼԾՊՇՅՁՆԻՇՆՌՊՇՄՋՌՇՁՆՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄ
ԱԹԺՄԽ

ԬՆԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩՎԹՄՍԽՋՊԹՆԿԽԼԾՊՇՅՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌՇՁՆՌՀԽՀՁԿՀԽՋՌ

ՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ԱԹԺՄԽԩԹՊՎԹՄԡԽՎԽՄՇՈՅԽՆՌՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ-ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ%

ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ
ԥԩԩ

ԡԹՑ ԡԹՑ

Ն

ԪԽԹՆ


ՅՅ

չ԰ԡ

ԥԩԩ

԰Գԩ Ն

ԪԽԹՆ


ՅՅ

չ԰ԡ

ԥԩԩ

԰Գԩ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ        

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ        

        

        

        

ԞԺԺՊԽՎՁԹՌՁՇՆՋ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ



԰ՍՅՅԹՊՑՊԽՋՍՄՌՋԾՇՊՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰ԳԩԹՊԽՈՊԽՋԽՆՌԽԼՁՆՌՀԽՆԽՐՌՌԹԺՄԽ
ԱԹԺՄԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԪԽԹՆ԰ԳԩՇՆԡԹՑՊԹՆԿԽԼԾՊՇՅՅՅՁՆՌՀԽՅԿԹՁԩԿՊՇՍՈՌՇՅՅՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ


ԱԹԺՄԽԡԹՑՏԽՌՏԽՁԿՀՌՊԹՆԿԽԼԾՊՇՅԿՁՆՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄՌՇԿՁՆՌՀԽՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄ
ԱԹԺՄԽԟՑԡԹՑ԰Գԩ
ՅՅԹՆԼՅԽԹՆՏԽՌՏԽՁԿՀՌ
ԿՏԽՊԽՀՁԿՀԽՋՌՁՆՌՀԽՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄԹՆԼՄՇՏԽՋՌՁՆՌՀԽՅԿԹՁԩԿՊՇՍՈԹՌՅՅԹՆԼԿՊԽՋՈԽԻՌՁՎԽՄՑ

ԱԹԺՄԽԩԹՊՎԹՄԤՊՇՏՌՀՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ԱԴԞ

ՅԽԹՋՍՊԽԼ%

԰ՆՇՍՌԳԽՆՌԩԽՆԿՌՀ
԰Գԩ ԟՇԼՑԴԽՁԿՀՌ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

Ն

ԪԽԹՆ


ՅՅ

չ԰ԡ Ն

ԪԽԹՆ


ՅՅ

չ԰ԡ Ն

ԪԽԹՆ


Կ

չ԰ԡ Ն

ԪԽԹՆ


Կ

չ԰ԡ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ            

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ            

            

            

            

ԞԺԺՊԽՎՁԹՌՁՇՆՋ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ



 ԞՄՋՇՊԽԾԽՊՊԽԼՌՇԹՋ՟ՏԽՌՏԽՁԿՀՌՠՁՆՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽ

ԫՇԿՄԹՆԼՍՄԹՊԹՌՊՇՈՀՑՇՊՀՑՈԽՊՌՊՇՈՀՑՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՀԽԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌՅԽՆՌՌԹԼՈՇՄԽՋ
ԱԹԺՄԽ

ԪՁՄԼ
ԿՊԹԼԽՌԹՄՄԻՇՄՍՅՆԹՊԻԽՄՄՋՄՁՆՁՆԿՌՀԽԾՇՄՄՁԻՄԽՋ
ԾՇՄՄՁԻՍՄԹՊԻԽՄՄՀՑՈԽՊՌՊՇՈՀՑՏԽՊԽՇԺՋԽՊՎԽԼՁՆԺՇՌՀ

ԻՇՆՌՊՇՄՋԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՏՁՌՀՌՀԽՆՍՅԺԽՊՇԾԹԾԾԽԻՌԽԼՁՆԼՁՎՁԼՍԹՄՋՊԹՆԿՁՆԿԾՊՇՅՁՆՌՀԽՄՇՏԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՌՇՁՆՌՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՊՇՋՋԭԹՌՀՇՄՇԿՑԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑՇԾՌՀԽԱՀՑՊՇՁԼԤՄԹՆԼՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ԱԴԞ

ՅԽԹՋՍՊԽԼ%

ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԱՀՑՊՇՁԼԤՄԹՆԼ

ԥՑՈԽՊՌՊՇՈՀՑ

ԱՀՑՊՇՁԼԤՄԹՆԼ

ԞՌՊՇՈՀՑ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՌՊՇՈՀՑ

ԣՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ         

        

        

        

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ         

        

        

        

         

        

        

        

         

        

        

        

         

        

        

        



 ԱՀՑՊՇՁԼԿՄԹՆԼԿՊՇՋՋՈԹՌՀՇՄՇԿՑԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽ

ԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԬԢԠԡԫՇԾՇՊՊԽԾԽՊԽՆԻԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԱՀՑՊՇՁԼԤՄԹՆԼԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋԫԞ

ԱՀՁՋՌԹԺՄԽՁՋՇՅՁՌՌԽԼԺԽԻԹՍՋԽԹԼԼՁՌՁՇՆԹՄՌՀՑՊՇՁԼԿՄԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՇԺՋԽՊՎԹՌՁՇՆՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ

ԬՆԡԹՑՇՆԽՌՇՌՀՊԽԽՌԹԼՈՇՄԽՋՁՆԹՄՄԾՇՍՊՊԽՈՄՁԻԹՌԽՋՇԾՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄՏԽՊԽՇԺՋԽՊՎԽԼՊԽՋՌՁՆԿՌՀԽՋՍՊԾԹԻԽԹՆԼՌՀՁՋԺԽՀԹՎՁՇՊՏԹՋՇԺՋԽՊՎԽԼ

ՌՀՊՇՍԿՀԡԹՑ
ԱԹԺՄԽԬՆԡԹՑՌՀԽՋԹՅԽՇԺՋԽՊՎԹՌՁՇՆՏԹՋՅԹԼԽԾՇՊՌՏՇՌԹԼՈՇՄԽՋՁՆՌՀԽՄՇՏԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼՇՆԽՁՆՌՀԽՅՁԼԼՄԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈԦՌՁՋՆՇՌՊԽՈՇՊՌԽԼՁԾՌՀԽՋԽՇԺՋԽՊՎԹՌՁՇՆՋԻՇՆՌՁՆՍԽԼՌՀՊՇՍԿՀՌՇՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ

ԱԹԺՄԽԠՄՁՆՁԻԹՄ԰ՁԿՆՋՁՆԵԽՆՇՈՍՋՄԹԽՎՁՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ%

ԠՄՁՆՁԻԹՄ԰ՁԿՆՋ

ԱՑՈԽ Ն ԦՆԻՁԼԽՆԻԽ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ ԞՄՄԹՈՈԽԹՊԽԼՆՇՊՅԹՄԹՆԼՀԽԹՄՌՀՑ  

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ ԞՄՄԹՈՈԽԹՊԽԼՆՇՊՅԹՄԹՆԼՀԽԹՄՌՀՑ  

ՅԿԹՁԩ ԰ԽԽԻՇՅՅԽՆՌՋԹԺՇՎԽ  

ՅԿԹՁԩ ԰ԽԽԻՇՅՅԽՆՌՋԹԺՇՎԽ  

ՅԿԹՁԩ ԰ԽԽԻՇՅՅԽՆՌՋԹԺՇՎԽ  

 ԟԹՋԽԼՇՆՌՀԽՆՍՅԺԽՊՇԾՇԺՋԽՊՎԽԼՁՆԼՁՎՁԼՍԹՄՋՇՆԡԹՑՇՆՄՑԠՄՁՆՁԻԹՄՋՁԿՆՋՇԺՋԽՊՎԽԼՈՊՁՇՊՌՇԡԹՑԹՊԽՊԽՈՇՊՌԽԼՁՆՌՀԽՌԽՐՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԟ ԰ՌՍԼՑԞՍՌՀՇՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋԽՋՇԾՌՀԽԻՇՆՌՁՆՍՇՍՋԼԹՌԹՋԽՌՁՆԻՄՍԼՁՆԿՅԽԹՋՍՊԽՅԽՆՌՋՇԾԥԩԩՏԽՌՏԽՁԿՀՌԹՆԼ԰Գԩ

ՏԽՊԽԻՇՆԼՍԻՌԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌՁՆԹՋՌԽՈԼՇՏՆՅԹՆՆԽՊՁԾՌՀԽԼԹՌԹՏԽՊԽԻՇՆՋՁՋՌԽՆՌ

ՏՁՌՀ Թ ՅՇՆՇՌՇՆԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ ԦԾ ՌՀԽՋԽ ԽՆԼՈՇՁՆՌՋ ՏԽՊԽ ԻՇՆՋՁՋՌԽՆՌ ՏՁՌՀ Թ ՅՇՆՇՌՇՆԽ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽ ՌՀԽ ԼԹՌԹ ՏԽՊԽ ԹՋՋԽՋՋԽԼ ԾՇՊ ՆՇՊՅԹՄՁՌՑ ՍՋՁՆԿ ԰ՀԹՈՁՊՇԴՁՄՃ0Ջ ՌԽՋՌ ԹՆԼ ԾՇՊ

ՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՍՋՁՆԿԩԽՎԽՆԽ0ՋՌԽՋՌԴՀԽՆՆԽԻԽՋՋԹՊՑՌՊԹՆՋԾՇՊՅԹՌՁՇՆՋՏԽՊԽԹՈՈՄՁԽԼՌՇԹՌՌԽՅՈՌ

ՌՇՅԽԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՈԹՊԹՅԽՌՊՁԻՋՌԹՌՁՋՌՁԻՋԦԾԼԹՌԹՅԽՌՌՀԽՋԽԹՋՋՍՅՈՌՁՇՆՋԼԹՌԹՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿ

ԞԫԬԳԞԾՇՄՄՇՏԽԼՍՈԡՍՆՆԽՌՌ0ՋՌԽՋՌԦԾՌՀԽԼԹՌԹՏԽՊԽՆՇՊՅԹՄՄՑԼՁՋՌՊՁԺՍՌԽԼՏՁՌՀՀԽՌԽՊՇԿԽՆԽՇՍՋՎԹՊՁԹՆԻԽ

ՌՀԽ ԪԹՆՆԴՀՁՌՆԽՑԴՁՄԻՇՐՇՆ Բ ՌԽՋՌ ՏԹՋ ՍՋԽԼ ԦԾ ՆՇ ՆՇՊՅԹՄՁՒՁՆԿ ՌՊԹՆՋԾՇՊՅԹՌՁՇՆ ՏԹՋ ԾՇՍՆԼ ՌՀԽ

ԪԹՆՆԴՀՁՌՆԽՑԴՁՄԻՇՐՇՆԲՌԽՋՌՍՋՁՆԿԹԟՇՆԾԽՊՊՇՆՁԥՇՄՅԹԼՂՍՋՌՅԽՆՌՏԹՋՍՋԽԼ

ԡԹՑԴԽՌՏԽՁԿՀՌԹՆԼ԰ԳԩԺՇՌՀԽՐՀՁԺՁՌԽԼԹՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽԺՍՌԼՁԼՆՇՌՅԽԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾ

ՈԹՊԹՅԽՌՊՁԻ ՋՌԹՌՁՋՌՁԻՋ ԽՎԽՆԾՇՄՄՇՏՁՆԿ Թ ՊԹՆՃՌՊԹՆՋԾՇՊՅԹՌՁՇՆ ԹՆԼ ԹՆԹՄՑՋԽՋՏԽՊԽ ԻՇՆԼՍԻՌԽԼ ՍՋՁՆԿՌՀԽ

ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԱԹԼՈՇՄԽՋՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՀԹԼՋՁԿՆՁԾՁԻԹՆՌՄՑԿՊԽԹՌԽՊՏԽՌՏԽՁԿՀՌ
Ո

ԹՆԼ԰Գԩ
ՈԹՆԼԹՄՄՌՊԽԹՌՅԽՆՌԼԹՌԹՏԽՊԽԻՇՅՈԹՊԽԼՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՇՆՄՑ

ԟՇՌՀԿՊՇՏՌՀՈԹՊԹՅԽՌԽՊՋՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌԹՄՄՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՄԹՌՁՎԽՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ԫՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋՆՇՌՅՇՆՇՌՇՆՁԻԹՆԼՌՀԽՍՆՌՊԹՆՋԾՇՊՅԽԼԼԹՌԹՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՆՇՊՅԹՄՁՌՑԹՆԼ

ՀՇՅՇՋԻԽԼԹՋՌՁԻՁՌՑ ԫՇ ԼՁԾԾԽՊԽՆԻԽՋ ՏԽՊԽ ԼԽՌԽԻՌԽԼ ԺԽՌՏԽԽՆ ՌՀԽ ՆԽԿԹՌՁՎԽ ԹՆԼ ՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄՋ ԹՆԼ

ՆՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋԻՇՅՈԹՊԽԼՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄՍՋՁՆԿԡՍՆՆԽՌՌ0ՋՌԽՋՌՆՇԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽԼԽՌԽԻՌԽԼ

ԾՇՊԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩԟԹՋԽԼՇՆՌՀԽՅՍՄՌՁՉՍԹՆՌԹՄԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԫԣՋՌԹԿԽՇՆԡԹՑՏԹՋ

ԻՇՅՈԹՊԹԺՄԽԺԽՌՏԽԽՆՌՀԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԹՆԼՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ

ԟՇՌՀՏԽՌՏԽՁԿՀՌԹՆԼ԰ԳԩՇՆԡԹՑՀԹԼՆՇՆՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽՋԺՍՌՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՈԹՊԹՅԽՌՊՁԻ

ՋՌԹՌՁՋՌՁԻՋՏՁՌՀՇՍՌՌՀԽՆԽԽԼԾՇՊՌՊԹՆՋԾՇՊՅԹՌՁՇՆՋԟՇՌՀԽՆԼՈՇՁՆՌՋՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿԡՍՆՆԽՌՌ0ՋՌԽՋՌԞ

ՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՏԹՋԼԽՌԽԻՌԽԼԺԽՌՏԽԽՆՌՏՇԻՇՆՌՊՇՄՋԾՇՊՏԽՌՏԽՁԿՀՌ
ԿՊԽԹՌԽՊՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ՈԹՆԼՌՊԽԹՌՅԽՆՌԼԹՌԹՏԽՊԽԻՇՅՈԹՊԽԼՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԠՇՆՎԽՊՋԽՄՑՆՇԼՁԾԾԽՊԽՆԻԽՋՏԽՊԽ

ԾՇՍՆԼԺԽՌՏԽԽՆՌՀԽԻՇՆՌՊՇՄՋԾՇՊ԰ԳԩԼԹՌԹԹՆԼՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՏԽՊԽԻՇՅՈԹՊԽԼՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ

ԠՇՅՈԹՊԹԺՄԽՌՇԡԹՑԺՇՌՀԿՊՇՏՌՀՈԹՊԹՅԽՌԽՊՋՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑՁՆՀՁԺՁՌԽԼԹՌԹՄՄՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՄԹՌՁՎԽ

ՌՇՌՀԽՁՊՊԽՋՈԽԻՌՁՎԽԻՇՆՌՊՇՄԫՇՊՅԹՄՁՒԽԼԥԩԩՇՆԡԹՑՏԹՋՅՇՆՇՌՇՆՁԻԹՆԼՏԹՋՌՀԽՊԽԾՇՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿ

ՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԱՊԽԹՌՅԽՆՌԼԹՌԹՏԽՊԽԻՇՅՈԹՊԽԼՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՋՌՀԽՊԽՏԹՋԹ

ՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽԺԽՌՏԽԽՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋ
ԿՊԽԹՌԽՊՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄՈ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԫՇՊՅԹՄՁՒԽԼԥԩԩՏԹՋՇՆՄՑՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈ԰ՁՅՁՄԹՊՄՑԡԹՑ

ԫԣՋՌԹԿԽՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՊԽԼՍԻԽԼԹՌՌՀԽՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌՄԽՎԽՄՊԽՄԹՌՁՎԽՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ

 ԠԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋԪՇՊՌԹՄՁՌՑՏԹՋՁՆՌՀԽԻՇՆՌՊՇՄՋԹՆԼՀՁԿՀԽՋՌՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼԼՁԼՆՇՌԽՐԻԽԽԼ

ՁՆՌՀԽՊԽՅԹՁՆՁՆԿՌՏՇՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԱՀԽՊԽԾՇՊԽՌՀԽՊԽՎՁԽՏԽՊՎՁՋՍԹՄՄՑԼԽՌԽՊՅՁՆԽԼՆՇՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌ

ՇՆՋՍՊՎՁՎԹՄԡԽՎԽՄՇՈՅԽՆՌԹՄՋՌԹԿԽԼԹՌԹՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՇՆԽՋՁԼԽԼԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼ

ՌԽՋՌՇՊՌՀԽՌՏՇՋՁԼԽԼԪԹՆՆԴՀՁՌՆԽՑԲԺԹՋԽԼՇՆԹՎՁՋՍԹՄԼԽՌԽՊՅՁՆԹՌՁՇՆՇԾՏՀԽՌՀԽՊՌՀԽԼԹՌԹՋՀՇՏԽԼԹ

ՅՇՆՇՌՇՆՁԻԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԡԹՑՏԽՌՏԽՁԿՀՌԼԹՌԹԼՁԼՆՇՌԽՐՀՁԺՁՌԹՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽԹՆԼԼՁԼ

ՆՇՌՅԽԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՆՇՊՅԹՄՁՌՑԹՆԼՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՌՀԽՊԽԾՇՊԽՌՀԽՑՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿ

ՌՀԽԪԹՆՆԴՀՁՌՆԽՑԲՌԽՋՌԡԹՑ԰ԳԩԼԹՌԹՏԽՊԽԹՆԹՄՑՒԽԼՏՁՌՀԡՍՆՆԽՌՌ0ՋՌԽՋՌԡԹՑԥԩԩԹՆԼՆՇՊՅԹՄՁՒԽԼ

ԥԩԩՋՀՇՏԽԼԹՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽԹՆԼՏԽՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌ



ԱԹԼՈՇՄԽՋՅԹՌՍՊՁՆԿԺԽՑՇՆԼԫԣՋՌԹԿԽԺՑԡԹՑՏԽՊԽԽՐԻՄՍԼԽԼԾՊՇՅԾՍՊՌՀԽՊԹՆԹՄՑՋՁՋՇԾԡԹՑ

ԽՆԼՈՇՁՆՌՋԱՀԽՊԽՏԹՋՆՇԹՈՈԹՊԽՆՌՈԹՌՌԽՊՆՌՇՌՀԽՇԻԻՍՊՊԽՆԻԽՇԾԫԣՋՌԹԿԽՁՆԼՁՎՁԼՍԹՄՋԹԻՊՇՋՋՊԽՈՄՁԻԹՌԽՋ

ՇՊԹՅՇՆԿՌՊԽԹՌՅԽՆՌՋԺԽՌՏԽԽՆՌԹԼՈՇՄԽՋՌՇՌԹՄՏԽՊԽԽՐԻՄՍԼԽԼԾՊՇՅԽԹԻՀՇԾՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄՋԹՆԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԡԹՑՏԽՌՏԽՁԿՀՌ԰ԳԩԥԩԩԹՆԼՆՇՊՅԹՄՁՒԽԼ

ԥԩԩԼԹՌԹՏԽՊԽՆՇՌՅՇՆՇՌՇՆՁԻԺՍՌՌՀԽՑՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՈԹՊԹՅԽՌՊՁԻՋՌԹՌՁՋՌՁԻՋԹՆԼՏԽՊԽԹՆԹՄՑՒԽԼ

ՍՋՁՆԿԡՍՆՆԽՌՌ0ՋՌԽՋՌԫՇԹՋՑՆԻՀՊՇՆՇՍՋԼԽՎԽՄՇՈՅԽՆՌՏԹՋՇԺՋԽՊՎԽԼԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋ

ՏԽՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈԞՄՄԹՆԹՄՑՋԽՋՏԽՊԽԻՇՆԼՍԻՌԽԼՍՋՁՆԿ԰Ԟ԰ԳԽՊՋՁՇՆ

ԣՇՊԹՄՄԿՊՇՏՌՀԽՆԼՈՇՁՆՌՋԹՆԼՆՇՊՅԹՄՁՒԽԼԥԩԩՌՀԽՊԽՎՁԽՏԽՊԻՇՅՈԹՊԽԼՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄԼԹՌԹ

ՍՋՁՆԿԹՌՌԽՋՌԹՋՋՍՅՁՆԿՍՆԽՉՍԹՄՎԹՊՁԹՆԻԽՎՁԹԪՁԻՊՇՋՇԾՌԢՐԻԽՄ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 ԠՇՆԻՄՍՋՁՇՆՋ

ԭՊՇՆԹՅՁԼԽԽՐՈՇՋՍՊԽԹՌՅԿԹՁԩՏԹՋԹՋՋՇԻՁԹՌԽԼՏՁՌՀՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋՇՆԡԹՑԹՆԼ

ԡԹՑԫԣՋՌԹԿԽ
ԹՆԼՋՌԹԿԽՋՊԽՋՈԽԻՌՁՎԽՄՑԹՆԼՇՆԡԹՑԹՆԼԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩ


ԹՆԼՊԽՋՈԽԻՌՁՎԽՄՑ
ՈՏՀԽՆԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԡԹՑԹՆԼԡԹՑ԰ԳԩԹՆԼ

ԡԹՑԺՇԼՑՏԽՁԿՀՌՏԽՊԽԹՄՋՇՋՁԿՆՁԾՁԻԹՆՌՄՑՄՇՏԽՊՁՆՌԹԼՈՇՄԽՋԽՐՈՇՋԽԼԹՌՅԿԹՁԩԞՌՄՇՏԽՊՌՊԽԹՌՅԽՆՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾԹՆԼՅԿԹՁԩՇՆՄՑԡԹՑ԰ԳԩԹՆԼԡԹՑԺՇԼՑՏԽՁԿՀՌՏԽՊԽԹԾԾԽԻՌԽԼԹՆԼ

ՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑՄՇՏԽՊՌՀԹՆՁՆՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՋ
Ո

ԠՇՆՎԽՊՋԽՄՑԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩԡԹՑ԰ԳԩԹՆԼԡԹՑԹՆԼԡԹՑԺՇԼՑՏԽՁԿՀՌՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑ

ԿՊԽԹՌԽՊՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋՌՀԹՆՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ԰ՁՆԻԽՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋՏԽՊԽԿԽՆԽՊԹՄՄՑ

ՇԺՋԽՊՎԽԼՁՆՈՊՇՆԹՅՁԼԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՁՆՌՀԽՇՈՈՇՋՁՌԽԼՁՊԽԻՌՁՇՆ
ԽԿՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼՁՆԻՊԽԹՋԽՁՆՋՌԽԹԼ

ՇԾԼԽԻՊԽԹՋԽՌՀԽՋՇՄՎԽՆՌԽԾԾԽԻՌՋԼՇՆՇՌԹՈՈԽԹՊՌՇՀԹՎԽՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌԽԼՌՀԽՇՎԽՊԹՄՄՊԽՋՍՄՌՋՇՊ

ՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽՋՌՍԼՑԥՇՏԽՎԽՊՁՌՁՋՈՇՋՋՁԺՄԽՌՀԹՌՌՀԽՅԹԿՆՁՌՍԼԽՇԾԽԾԾԽԻՌՋՅԹՑՀԹՎԽԺԽԽՆԿՊԽԹՌԽՊ

ԹՌՌՀԽՀՁԿՀՌՊԽԹՌՅԽՆՌՄԽՎԽՄՁՆՌՀԽԹԺՋԽՆԻԽՇԾՌՀԽՋՇՄՎԽՆՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԡԽՎԽՄՇՈՅԽՆՌԹՄԹՆԼԱՀՑՊՇՁԼԤՊՇՋՋԭԹՌՀՇՄՇԿՑԥՁՋՌՇՈԹՌՀՇՄՇԿՑ ԢՆԼՈՇՁՆՌՋՁՆՌՀԽԞԪԞՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ%

ԫԣԡԽՎԽՄՇՈՅԽՆՌԹՄ԰ՌԹԿԽ ԥՁՆԼԩՁՅԺԩԽՆԿՌՀ ԞՋՑՆԻՀՊՇՆՇՍՋԡԽՎԽՄՇՈՅԽՆՌ ԱՀՑՊՇՁԼԤՊՇՋՋԹՆԼ

ԥՁՋՌՇՈԹՌՀՇՄՇԿՑ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

ԪԽԼՁԹՆ Ո

ԪԽԼՁԹ

Ն

Ո



ԡՁԾԾ

Ո



ԡՁԾԾ

Ո



ԡՁԾԾ

Ո



ԡՁԾԾ

Ո

ԱՊԽԹՌՅԽՆՌԯԽՄԹՌԽԼ

ԢԾԾԽԻՌՋ!
ԶԽՋԫՇ

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ  ԫԞ  ԫԞ  ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ  ԫԞ  ԫԞ     ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ         ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ         ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ         ԫԞ ԫԞ ԫԞ ԫԞ ԫՇ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԧՇՆԻՃՀԽԽՊԽ ԧՇՆԻՃՀԽԽՊԽ ԧՇՆԻՃՀԽԽՊԽ ԡՍՆՆԽՌՌ0Ջ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼ

ԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԥՁՆԼՄՁՅԺՄԽՆԿՌՀՁՋՆՇՊՅԹՄՁՒԽԼՌՇՋՆՇՍՌՎԽՆՌՄԽՆԿՌՀ
԰Գԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋՁՆՌՀԽԞԪԞՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ԱԴԞՅԽԹՋՍՊԽԼ%

԰ՆՇՍՌԳԽՆՌԩԽՆԿՌՀ ԟՇԼՑԴԽՁԿՀՌ

ԡԹՑ ԡԹՑ ԡԹՑ ԡԹՑ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԫԽԿԹՌՁՎԽԠՇՆՌՊՇՄ  ԫԞ  ԫԞ  ԫԞ  ԫԞ

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ        

        

        

        

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԪԹՆՆԴՀՁՌՆԽՑ ԡՍՆՆԽՌՌ0Ջ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ

 ԰ՁԿՆՁԾՁԻԹՆՌՄՑԼՁԾԾԽՊԽՆՌ
ՈԻՇՅՈԹՊԽԼՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՈՍՋՁՆԿԹՌՌԽՋՌԹՋՋՍՅՁՆԿՍՆԽՉՍԹՄ

ՎԹՊՁԹՆԻԽՎՁԹԪՁԻՊՇՋՇԾՌԢՐԻԽՄ

Ԣ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

ԱՀԽՊԽՏԽՊԽՌՏՇՅԹՂՇՊԼԽՎՁԹՌՁՇՆՋՁՆՌՀՁՋՋՌՍԼՑ

ԱՀԽԠԳՇԾՌՀԽՅՁԼԼՄԽԹՆԼՀՁԿՀԼՇՋԽՋԽՐԻԽԽԼԽԼՌՀԽՅԹՐՁՅՍՅԹԻԻԽՈՌԹԺՄԽ
ԹԻԻՇՊԼՁՆԿՌՇՌՀԽ

ԬԠ԰ԭԭԞԪԞՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹ

 ԱՀԽՊԽՏԽՊԽ ՋԽՎԽՊԹՄ ԽՆԼՈՇՁՆՌՋ ԾՇՊՏՀՁԻՀ ՌՀԽ ՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄ ՈԽՊԾՇՊՅԹՆԻԽ ՋՁԿՆՁԾՁԻԹՆՌՄՑ 
Ո

ԽՐԻԽԽԼԽԼՌՀԹՌՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ
ՁԽԡԹՑՋԹՆԼՏԽՌՏԽՁԿՀՌԡԹՑ԰ԳԩԡԹՑԥԩԩԹՆԼԡԹՑ

ՆՇՊՅԹՄՁՒԽԼԥԩԩԣՇՊՅՇՋՌՇԾՌՀԽՋԽԽՆԼՈՇՁՆՌՋԹՌՊԽՆԼՌՇՏԹՊԼԹՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌ
Ո

ՏԹՋԼԽՌԽԻՌԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋՁՋԹՆԼՌՀԽՊԽՎՁԽՏԽՊՁՋՆՇՌԻԽՊՌԹՁՆՁԾՌՀԽՋՇՄՎԽՆՌՁՆՌԽՊԾԽՊԽԼՏՁՌՀ

ԼԽՌԽԻՌՁՇՆՇԾՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋԼՍԽՌՇՌՀԽՌԽՋՌՅԹՌԽՊՁԹՄԹՄՇՆԽ

ԱՀԽՋԽԼԽՎՁԹՌՁՇՆՋԼՁԼՆՇՌՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌՌՀԽՊԽՋՍՄՌՋՇՊՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽՋՌՍԼՑԞՄՄՇՌՀԽՊՎԹՄՁԼՁՌՑ

ԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹՏԽՊԽՅԽՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԣԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋ

ԱՀԽՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋԽՋՏԽՊԽԻՇՆԼՍԻՌԽԼԺՑԻՇՅՈԹՊՁՆԿՌՊԽԹՌՅԽՆՌԼԹՌԹՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՏՀԽՊԽԹՋ

ՌՀԽՋՌՍԼՑԹՍՌՀՇՊՋԻՇՅՈԹՊԽԼՌՊԽԹՌՅԽՆՌԼԹՌԹՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԼՍԽՌՇՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋԺԽՌՏԽԽՆ

ՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՇՊՈՇՇՄԽԼԻՇՆՌՊՇՄԱՀԽՊԽՎՁԽՏԽՊԼԽՌԽԻՌԽԼՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋԺԽՌՏԽԽՆ

ՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋԾՇՊՌՀԽԾՇՄՄՇՏՁՆԿԽՆԼՈՇՁՆՌՋԡԹՑՋԹՆԼՏԽՌՏԽՁԿՀՌԡԹՑ԰ԳԩԡԹՑ

ԥԩԩԹՆԼԡԹՑՆՇՊՅԹՄՁՒԽԼԥԩԩ

ԬՎԽՊՌՀԽԻՇՍՊՋԽՇԾՌՀԽԼԹՑՌԽՋՌՌՀԽԠԳՇԾՌՀԽՅԽԹՋՍՊԽԼՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԾՇՊԹՄՄՇԾՌՀԽՊԽՈՄՁԻԹՌԽ

ՌԹՆՃՋՊԹՆԿԽԼԾՊՇՅՌՇԱՀԽՄՇՏԻՇՆԻԽՆՌՊԹՌՁՇՆՏԹՋՌՀԽՇՆՄՑԻՇՆԻԽՆՌՊԹՌՁՇՆՄԽՎԽՄՌՀԹՌՀԹԼԠԳ

ՎԹՄՍԽՋՇԾՌՀԽՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՌՀԹՌՏԽՊԽԱՀԽՅՁԼԻՇՆԻԽՆՌՊԹՌՁՇՆՄԽՎԽՄՀԹԼԠԳՎԹՄՍԽՋՌՀԹՌ

ՊԹՆԿԽԼԾՊՇՅՌՇՏՀՁՄԽՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՀԹԼՌՀԽՀՁԿՀԽՋՌԠԳՎԹՄՍԽՋՇԾՌՇ

ԱՀԽՅՁԼԻՇՆԻԽՆՌՊԹՌՁՇՆՇՆՄՑՅՁՆՁՅԹՄՄՑԽՐԻԽԽԼԽԼԼՍԽՌՇՌՀԽԼԽԻՊԽԹՋԽՁՆՎԽՋՋԽՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇՆ

ՌԽՋՌԼԹՑԱՀԽԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՈՊՇՆԹՅՁԼԽՊԹՆԿԽԼՁՆՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՌԽՋՌ

ՁՆՁՌՁԹՌՁՇՆ
ԡԹՑԞՋԹՊԽՋՍՄՌԹՅՍԻՀՀՁԿՀԽՊԠԳՎԹՄՍԽՏԹՋԼԽՌԽՊՅՁՆԽԼԾՇՊՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՏՀՁԻՀ

ՏԹՋՊԽՈՇՊՌԽԼՌՇԺԽԾՊՇՅՁՆՁՌՁԹՄԻՄՇԿԿՁՆԿՇԾՌՀԽՅՁՐՁՆԿԻԽՄՄԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԬՆԻԽՌՀԽՅՁՐՁՆԿԻԽՄՄՏԹՋԻՄԽԹՊԽԼ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՁՆ ՌՀԽ ՀՁԿՀ ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՄԽՎԽՄՋ ՊԽՌՍՊՆԽԼ ՌՇ ԹՆԼ ՊԽՅԹՁՆԽԼ ԹՌ չ ՇԾ ՆՇՅՁՆԹՄ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԱՀԽԾՇՄՄՇՏՁՆԿԹՆԹՄՑՌԽՋՏԽՊԽԼԽՌԽԻՌԽԼԼՍՊՁՆԿՌՀԽՈԽՊՁՇԼՁԻՋԻՊԽԽՆՁՆԿԹՆԹՄՑՋՁՋՇԾՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊԻՀՄՇՊՁԼԽ


ՅԿԩՆՁՌՊԹՌԽ
ՅԿԫԩԺՇՊՇՆ
ՅԿԩԻԹՄԻՁՍՅ
ՅԿԩՈՇՌԹՋՋՁՍՅ


ՅԿԩՅԹԿՆԽՋՁՍՅ
ՅԿԩՋՇԼՁՍՅ
ՅԿԩՋՍՄԾԹՌԽ
ՅԿ԰ԩԹՆԼՒՁՆԻ
ՅԿԩ

ԫՇՈԽՋՌՁԻՁԼԽՋՇՊԭԠԟՋՏԽՊԽԼԽՌԽԻՌԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԦԦԦ ԯԢԣԢԯԢԫԠԢ԰

ԟԹՆՌՄԽԧԞԡՍՅՇՆՌԧԫԣՁՆԻՀԯԞԹՆԼԩՁՆԼԽՊԤ
ԞՌՄԹՋՇԾԞԺՆՇՊՅԹՄՁՌՁԽՋԞԿՍՁԼԽԾՇՊՌՀԽ

ՈԽՊԾՇՊՅԹՆԻԽՇԾԣԢԱԞԵ

ԠՊՇՍՋԽԠ
ԡԽՌԽՊՅՁՆԹՌՁՇՆՇԾՈՍՊՁՌՑԹՆԼՇՊԦԼԽՆՌՁՌՑՇԾԭՊՇՆԹՅՁԼԽ
ԨԽՊԺԱԽԻՀՆՁԻԹՄԩՇՌԵԤԯ

Ա԰ԫ ԾՇՊ ՍՋԽ ՁՆ Թ ԰ՌՍԼՑ ԣԞԭԠ ԫՍՅԺԽՊ  ԡՇՏ ԞԿՊՇ԰ԻՁԽՆԻԽՋ ԩԩԠ

ԦՆԼՁԹՆԹՈՇՄՁՋԦՆԼՁԹՆԹ

ԥՇՄՄԹՆԼԽՊԪԹՆԼԴՇՄԾԽԡԞ
ԫՇՆՈԹՊԹՅԽՌՊՁԻ԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋԧՇՀՆԴՁՄԽՑԫԽՏԶՇՊՃ

ԫՁԽՍՏՃՇՇՈԭԡԹՆԼԣԹԺԽՊԧ
ԫՇՊՅԹՄԱԹԺՄԽՇԾԵԽՆՇՈՍՋՄԹԽՎՁՋ
ԡԹՍԼՁՆԤԹՊՄԹՆԼԭՍԺՄՁՋՀՁՆԿԫԽՏ

ԶՇՊՃ

ԭԹՊՊՁՋՀԠԣ
԰ՇՄՎԽՆՌՋՁՆԼՍՋՌՊՁԹՄԦՆԤՊԹՑՋՇՆԪԢԻՃՊՇՌՀԡԪԹՊՃԥԣԬՌՀՅԽՊԡԣԬՎԽՊԺԽՊԿԽՊ

ԠԤԹՆԼ԰ԽԹԺՇՊԿԤԱԽԼՁՌՇՊՋԨՁՊՃԬՌՀՅԽՊԽՆԻՑԻՄՇՈԽԼՁԹՇԾԻՀԽՅՁԻԹՄՌԽԻՀՆՇՄՇԿՑԫԽՏԶՇՊՃԧՇՀՆ

ԴՁՄԽՑ԰ՇՆՋԦՆԻՈ

Page 39 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ԞԭԭԢԫԡԦԵԦԬԲԱԭԲԱԬԣԯԢԳԦԢԴԢԯ0԰԰ԱԞԱԦ԰ԱԦԠԞԩԳԢԯԦԣԦԠԞԱԦԬԫ

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.970 0.844 3.873 0.038 USE NON-PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 0.37 0.05 0.03 14.06 0.29, 0.46 

 Dose1 4 0.36 0.01 0.01 3.62 0.34, 0.38 

 Dose2 4 0.40 0.05 0.03 13.66 0.31, 0.49 

 Dose3 4 0.28 0.02 0.01 8.35 0.25, 0.32 

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

 Ctrl 0.36 0.33 0.44 . . 

 Dose1 0.36 0.35 0.38 96.78 3.22 

 Dose2 0.40 0.34 0.46 107.31 -7.31 

 Dose3 0.28 0.26 0.31 75.86 24.14 

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

*** 

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 6.27 0.008 

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 0.37 . 0.38 . . . . . . 

 Dose1 0.36 0.951 0.38 0.657 . . . . . 

 Dose2 0.40 0.664 0.38 0.692 0.533 . . . . 

 Dose3 0.28 0.021 0.28 0.005 0.073 0.007 . . . 

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

*** 

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

Page 40 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 9.07 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 0.36 . . 

 Dose1 0.36 1.000 0.500 

 Dose2 0.40 0.494 0.810 

 Dose3 0.28 0.067 0.046 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose3 

 Jonckheere Dose3 

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

*** 

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 6.27 0.008 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -0.37 . -0.35 . . . . . . 

 Dose1 -0.36 0.951 -0.35 0.820 . . . . . 

 Dose2 -0.40 0.664 -0.35 0.849 0.533 . . . . 

 Dose3 -0.28 0.021 -0.35 0.864 0.073 0.007 . . . 

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

*** 

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 9.07 0.028 

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 -0.36 . . 

 Dose1 -0.36 1.000 0.500 

 Dose2 -0.40 0.494 0.190 

 Dose3 -0.28 0.067 0.954 

Page 41 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.652 <.001 3.000 0.073 USE NON-PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 53.75 0.50 0.25 0.93 52.95, 54.55 

 Dose1 4 53.75 0.50 0.25 0.93 52.95, 54.55 

 Dose2 4 53.75 0.50 0.25 0.93 52.95, 54.55 

 Dose3 4 53.00 0.00 0.00 0.00 . , . 

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

 Ctrl 54.00 53.00 54.00 . . 

 Dose1 54.00 53.00 54.00 100.00 0.00 

 Dose2 54.00 53.00 54.00 100.00 0.00 

 Dose3 53.00 53.00 53.00 98.60 1.40 

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

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 6.43 0.093 

MannWhit - testing each trt median signif. different from control 

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

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 54.00 . . 

 Dose1 54.00 1.000 0.500 

 Dose2 54.00 1.000 0.500 

 Dose3 53.00 0.102 0.025 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose3 

 Jonckheere Dose3 

Page 42 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.903 0.090 0.855 0.491 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 15.55 1.07 0.53 6.86 13.85, 17.25 

 Dose1 4 15.89 0.47 0.24 2.98 15.13, 16.64 

 Dose2 4 15.79 0.93 0.46 5.86 14.32, 17.26 

 Dose3 4 14.00 0.71 0.35 5.04 12.87, 15.12 

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

 Ctrl 15.25 14.70 17.00 . . 

 Dose1 15.78 15.50 16.49 102.17 -2.17 

 Dose2 15.50 15.08 17.08 101.54 -1.54 

 Dose3 14.02 13.28 14.66 90.00 10.00 

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

*** 

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 

 3 12 4.62 0.023 

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 15.55 . 15.74 . . . . . . 

 Dose1 15.89 0.889 15.74 0.714 . . . . . 

 Dose2 15.79 0.954 15.74 0.749 0.998 . . . . 

 Dose3 14.00 0.051 14.00 0.012 0.031 0.041 . . . 

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

*** 

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

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

Page 43 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 3 8.93 0.030 

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 15.25 . . 

 Dose1 15.78 0.678 0.718 

 Dose2 15.50 0.494 0.670 

 Dose3 14.02 0.067 0.025 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose3 

 Jonckheere Dose3 

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

*** 

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 4.62 0.023 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -15.55 . -15.31 . . . . . . 

 Dose1 -15.89 0.889 -15.31 0.746 . . . . . 

 Dose2 -15.79 0.954 -15.31 0.779 0.998 . . . . 

 Dose3 -14.00 0.051 -15.31 0.797 0.031 0.041 . . . 

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

*** 

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 8.93 0.030 

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 -15.25 . . 

 Dose1 -15.78 0.678 0.282 

 Dose2 -15.50 0.494 0.330 

 Dose3 -14.02 0.067 0.975 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

Page 44 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.844 0.011 0.843 0.496 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 2.02 0.21 0.11 10.63 1.68, 2.36 

 Dose1 4 2.02 0.12 0.06 5.72 1.84, 2.20 

 Dose2 4 2.00 0.22 0.11 11.05 1.64, 2.35 

 Dose3 4 1.72 0.13 0.06 7.46 1.51, 1.92 

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

 Ctrl 1.93 1.88 2.34 . . 

 Dose1 2.02 1.88 2.16 100.00 0.00 

 Dose2 1.91 1.84 2.32 98.76 1.24 

 Dose3 1.71 1.58 1.86 84.90 15.10 

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

*** 

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 2.85 0.082 

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 2.02 . 2.02 . . . . . . 

 Dose1 2.02 1.000 2.02 0.583 . . . . . 

 Dose2 2.00 0.994 2.00 0.530 0.997 . . . . 

 Dose3 1.72 0.076 1.72 0.019 0.121 0.166 . . . 

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

*** 

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

Page 45 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 8.35 0.039 

MannWhit - testing each trt median signif. different from control 

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

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 1.93 . . 

 Dose1 2.02 0.780 0.668 

 Dose2 1.91 0.674 0.329 

 Dose3 1.71 0.067 0.007 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose3 

 Jonckheere Dose3 

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

*** 

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 2.85 0.082 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -2.02 . -1.94 . . . . . . 

 Dose1 -2.02 1.000 -1.94 0.821 . . . . . 

 Dose2 -2.00 0.994 -1.94 0.850 0.997 . . . . 

 Dose3 -1.72 0.076 -1.94 0.865 0.121 0.166 . . . 

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

*** 

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 8.35 0.039 

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 -1.93 . . 

 Dose1 -2.02 0.780 0.332 

 Dose2 -1.91 0.674 0.671 

 Dose3 -1.71 0.067 0.993 

Page 46 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.929 0.232 0.666 0.589 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 0.13 0.01 0.00 4.65 0.12, 0.14 

 Dose1 4 0.13 0.00 0.00 3.44 0.12, 0.13 

 Dose2 4 0.13 0.01 0.00 5.30 0.12, 0.14 

 Dose3 4 0.12 0.00 0.00 2.65 0.12, 0.13 

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

 Ctrl 0.13 0.12 0.14 . . 

 Dose1 0.13 0.12 0.13 98.47 1.53 

 Dose2 0.12 0.12 0.14 97.79 2.21 

 Dose3 0.12 0.12 0.13 95.34 4.66 

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

*** 

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 0.91 0.466 

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 0.13 . 0.13 . . . . . . 

 Dose1 0.13 0.910 0.13 0.360 . . . . . 

 Dose2 0.13 0.786 0.13 0.292 0.995 . . . . 

 Dose3 0.12 0.292 0.12 0.085 0.705 0.830 . . . 

Page 47 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

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

*** 

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 3.51 0.320 

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 0.13 . . 

 Dose1 0.13 0.780 0.332 

 Dose2 0.12 0.346 0.170 

 Dose3 0.12 0.156 0.034 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere Dose3 

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

*** 

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 0.91 0.466 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -0.13 . -0.13 . . . . . . 

 Dose1 -0.13 0.910 -0.13 0.839 . . . . . 

 Dose2 -0.13 0.786 -0.13 0.867 0.995 . . . . 

 Dose3 -0.12 0.292 -0.13 0.881 0.705 0.830 . . . 

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

*** 

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 3.51 0.320 

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 -0.13 . . 

 Dose1 -0.13 0.780 0.668 

Page 48 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Dose2 -0.12 0.346 0.830 

 Dose3 -0.12 0.156 0.966 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.842 0.010 1.636 0.233 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 59.00 0.00 0.00 0.00 . , . 

 Dose1 4 59.25 0.50 0.25 0.84 58.45, 60.05 

 Dose2 4 59.00 0.82 0.41 1.38 57.70, 60.30 

 Dose3 4 57.25 0.50 0.25 0.87 56.45, 58.05 

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

 Ctrl 59.00 59.00 59.00 . . 

 Dose1 59.00 59.00 60.00 100.42 -0.42 

 Dose2 59.00 58.00 60.00 100.00 0.00 

 Dose3 57.00 57.00 58.00 97.03 2.97 

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

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

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 10.24 0.017 

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 59.00 . . 

 Dose1 59.00 0.478 0.841 

 Dose2 59.00 1.000 0.539 

 Dose3 57.00 0.049 0.008 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose3 

Page 49 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Jonckheere Dose3 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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 

 0.962 0.696 0.848 0.494 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 1.59 0.09 0.04 5.43 1.46, 1.73 

 Dose1 4 1.07 0.12 0.06 11.21 0.88, 1.26 

 Dose2 4 1.14 0.06 0.03 5.35 1.04, 1.23 

 Dose3 4 1.23 0.07 0.03 5.28 1.13, 1.34 

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

 Ctrl 1.63 1.47 1.66 . . 

 Dose1 1.02 1.00 1.25 67.13 32.87 

 Dose2 1.12 1.09 1.22 71.22 28.78 

 Dose3 1.22 1.17 1.32 77.22 22.78 

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

*** 

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 29.36 <.001 

Dunnett - testing each trt mean signif. different than control 

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

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

Level Mean Dunnett Isotonic Williams Tukey p-values 

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

 Ctrl 1.59 . 1.59 . . . . . . 

 Dose1 1.07 <.001 1.15 <.001 . . . . . 

 Dose2 1.14 <.001 1.15 <.001 0.714 . . . . 

 Dose3 1.23 <.001 1.15 <.001 0.088 0.431 . . . 

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

*** 

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

Page 50 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 10.62 0.014 

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 1.63 . . 

 Dose1 1.02 0.067 0.010 

 Dose2 1.12 0.067 0.039 

 Dose3 1.22 0.067 0.187 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose1 

 Jonckheere >highest dose (no sign. differences) 

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

*** 

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 29.36 <.001 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -1.59 . -1.26 . . . . . . 

 Dose1 -1.07 <.001 -1.26 1.000 . . . . . 

 Dose2 -1.14 <.001 -1.26 1.000 0.714 . . . . 

 Dose3 -1.23 <.001 -1.26 1.000 0.088 0.431 . . . 

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

*** 

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

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

 3 10.62 0.014 

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 -1.63 . . 

 Dose1 -1.02 0.067 0.990 

 Dose2 -1.12 0.067 0.961 

 Dose3 -1.22 0.067 0.813 

Page 51 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.966 0.771 0.919 0.461 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 26.83 0.53 0.26 1.96 25.99, 27.66 

 Dose1 4 23.25 0.53 0.26 2.26 22.41, 24.09 

 Dose2 4 23.90 0.18 0.09 0.76 23.61, 24.19 

 Dose3 4 24.33 0.67 0.34 2.76 23.26, 25.39 

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

 Ctrl 26.95 26.10 27.30 . . 

 Dose1 23.10 22.80 24.00 86.67 13.33 

 Dose2 23.90 23.70 24.10 89.10 10.90 

 Dose3 24.25 23.60 25.20 90.68 9.32 

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

*** 

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 37.80 <.001 

Dunnett - testing each trt mean signif. different than control 

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

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

Level Mean Dunnett Isotonic Williams Tukey p-values 

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

 Ctrl 26.83 . 26.83 . . . . . . 

 Dose1 23.25 <.001 23.83 <.001 . . . . . 

 Dose2 23.90 <.001 23.83 <.001 0.317 . . . . 

 Dose3 24.33 <.001 23.83 <.001 0.048 0.649 . . . 

Page 52 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

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

*** 

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 11.49 0.009 

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 26.95 . . 

 Dose1 23.10 0.067 0.010 

 Dose2 23.90 0.067 0.062 

 Dose3 24.25 0.067 0.227 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose1 

 Jonckheere >highest dose (no sign. differences) 

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

*** 

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 37.80 <.001 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -26.83 . -24.58 . . . . . . 

 Dose1 -23.25 <.001 -24.58 1.000 . . . . . 

 Dose2 -23.90 <.001 -24.58 1.000 0.317 . . . . 

 Dose3 -24.33 <.001 -24.58 1.000 0.048 0.649 . . . 

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

*** 

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 11.49 0.009 

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 -26.95 . . 

 Dose1 -23.10 0.067 0.990 

Page 53 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Dose2 -23.90 0.067 0.938 

 Dose3 -24.25 0.067 0.773 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.949 0.467 2.616 0.099 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 16.73 0.69 0.34 4.12 15.63, 17.82 

 Dose1 4 17.30 2.66 1.33 15.39 13.06, 21.54 

 Dose2 4 15.98 2.25 1.13 14.11 12.39, 19.56 

 Dose3 4 12.15 1.00 0.50 8.22 10.56, 13.74 

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

 Ctrl 16.90 15.80 17.30 . . 

 Dose1 17.40 14.10 20.30 103.44 -3.44 

 Dose2 15.10 14.40 19.30 95.52 4.48 

 Dose3 11.80 11.40 13.60 72.65 27.35 

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

*** 

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 6.33 0.008 

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 16.73 . 17.01 . . . . . . 

 Dose1 17.30 0.945 17.01 0.673 . . . . . 

 Dose2 15.98 0.891 15.98 0.367 0.744 . . . . 

Page 54 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Dose3 12.15 0.011 12.15 0.003 0.009 0.054 . . . 

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

*** 

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 9.07 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 16.90 . . 

 Dose1 17.40 0.889 0.614 

 Dose2 15.10 0.346 0.232 

 Dose3 11.80 0.067 0.003 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose3 

 Jonckheere Dose3 

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

*** 

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 6.33 0.008 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -16.73 . -15.54 . . . . . . 

 Dose1 -17.30 0.945 -15.54 0.880 . . . . . 

 Dose2 -15.98 0.891 -15.54 0.904 0.744 . . . . 

 Dose3 -12.15 0.011 -15.54 0.916 0.009 0.054 . . . 

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

*** 

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 9.07 0.028 

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 

Page 55 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Ctrl -16.90 . . 

 Dose1 -17.40 0.889 0.386 

 Dose2 -15.10 0.346 0.768 

 Dose3 -11.80 0.067 0.997 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

test for amphib metamorph screen study - Propyzamide 

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

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

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

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

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

analyses. 

 Shapiro-Wilks Shapiro-Wilks Levenes Levenes Conclusion 

 Test Stat P-value Test Stat P-value 

 0.957 0.603 2.345 0.124 USE PARAMETRIC TESTS 

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

*** 

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 0.63 0.02 0.01 3.43 0.60, 0.66 

 Dose1 4 0.75 0.11 0.05 14.11 0.58, 0.92 

 Dose2 4 0.67 0.10 0.05 14.26 0.52, 0.82 

 Dose3 4 0.49 0.05 0.02 10.24 0.41, 0.57 

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

 Ctrl 0.63 0.61 0.66 . . 

 Dose1 0.77 0.61 0.85 119.05 -19.05 

 Dose2 0.64 0.60 0.81 106.35 -6.35 

 Dose3 0.47 0.45 0.56 77.38 22.62 

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

*** 

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 8.30 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 0.63 . 0.69 . . . . . . 

Page 56 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Dose1 0.75 0.111 0.69 0.916 . . . . . 

 Dose2 0.67 0.802 0.67 0.870 0.477 . . . . 

 Dose3 0.49 0.054 0.49 0.013 0.002 0.024 . . . 

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

*** 

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 9.59 0.022 

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 0.63 . . 

 Dose1 0.77 0.283 0.904 

 Dose2 0.64 1.000 0.587 

 Dose3 0.47 0.067 0.018 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose3 

 Jonckheere Dose3 

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

*** 

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 8.30 0.003 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -0.63 . -0.63 . . . . . . 

 Dose1 -0.75 0.111 -0.64 0.537 . . . . . 

 Dose2 -0.67 0.802 -0.64 0.571 0.477 . . . . 

 Dose3 -0.49 0.054 -0.64 0.589 0.002 0.024 . . . 

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

*** 

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 9.59 0.022 

MannWhit - testing each trt median signif. different from control 

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

Page 57 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl -0.63 . . 

 Dose1 -0.77 0.283 0.096 

 Dose2 -0.64 1.000 0.413 

 Dose3 -0.47 0.067 0.982 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN 

CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

 

Page 58 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϳtĞƚtĞŝŐŚƚ EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ Ϭ͘ϯϳϮΘϬρ Ϭ͘κεϯϳςρ

sĂƌŝĂŶĐĞ Ϭ͘ϬϬϮϳκϳΘκϳ Ϭ͘ϬϬϮϯΘεϳεκ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ ς 

ƚ^ƚĂƚ Ͳϯ͘ϯϳρϭϮρϭΘκ 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϬϬϳκϳϯϳρ 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů ϭ͘εκϯϭΘϬϮϳκ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘Ϭϭκεκϳκεε

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘κκςεϭϭΘκς 

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϳ^s> EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ ϭρ͘ρς ϭϳ͘ρϭϭϯϳρ

sĂƌŝĂŶĐĞ ϭ͘ϭϭϬςςςςςϳ Ϭ͘ϯϬϮϯρϳρςϮ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ ρ 

ƚ^ƚĂƚ Ͳϯ͘ϮΘϯϭΘεϯϯϮ 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϬϭϬεϯΘςςϳ 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů Ϯ͘ϬϭρϬκΘϯϳϮ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘ϬϮϭΘϳϳϯϯκ

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘ρϳϬρΘϭΘϯρ 

 

Page 59 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϳ,>> EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ Ϯ͘ϬϮ Ϯ͘Ϯϯ

sĂƌŝĂŶĐĞ Ϭ͘Ϭκςϭϯϯϯϯϯ Ϭ͘Ϭϯϳκςςςςϳ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ ς 

ƚ^ƚĂƚ Ͳϭ͘κρϮςϬϬϯϳκ 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϬεΘϮϳϯεϭε 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů ϭ͘εκϯϭΘϬϮϳκ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘ϭεςρκϳΘϯϳ

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘κκςεϭϭΘκς 

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϳEŽƌŵĂůŝnjĞĚ,>> EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ Ϭ͘ϭϮΘϳκϭκϬϭ Ϭ͘ϭϮςςρεϭεϮ

sĂƌŝĂŶĐĞ ϯ͘ρρϳϬϭͲϬρ Θ͘ςϭϭρϳͲϬρ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ ρ 

ƚ^ƚĂƚ Ϭ͘ϯϳϳρϭρϯκΘ 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϯςϬςκϮϮεϭ 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů Ϯ͘ϬϭρϬκΘϯϳϮ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘ϳϮϭϮΘκρΘϭ

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘ρϳϬρΘϭΘϯρ 

 

Page 60 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϮϭtĞƚtĞŝŐŚƚ EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ ϭ͘ρεκϳκκεϭΘ ϭ͘εΘϬϯΘϮςϳϯ

sĂƌŝĂŶĐĞ Ϭ͘ϬϬϳρϭϯΘρκ Ϭ͘ϬϮϮϯϳεϳϭϭ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ ρ 

ƚ^ƚĂƚ Ͳκ͘κςϬΘΘϭρ 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϬϬϯϯϭϳρϮϭ 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů Ϯ͘ϬϭρϬκΘϯϳϮ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘ϬϬςςϯρϬκϯ

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘ρϳϬρΘϭΘϯρ 

 

 

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϮϭ^s> EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ Ϯς͘ΘϯρϬϯκϯκ Ϯϳ͘ςΘϬεκρϯρ

sĂƌŝĂŶĐĞ Ϭ͘ϮϳϭϯςρΘΘρ Ϭ͘ΘςεΘϬϳϳϯϮ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ ρ 

ƚ^ƚĂƚ Ͳϭ͘ρΘϯϳϮϭκΘε 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϬΘϳϬρϯΘεϯ 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů Ϯ͘ϬϭρϬκΘϯϳϮ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘ϭϳκϭϬϳϳΘϳ

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘ρϳϬρΘϭΘϯρ 

 

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϮϭ,>> EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ ϭς͘ϳϭϳρκΘϬΘ ϮϬ͘ϬΘΘϯϭεΘϭ

sĂƌŝĂŶĐĞ Ϭ͘κΘεϬϮϮϭςκ Ϭ͘ϳκεϬϬϯςϳϳ

Page 61 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ ς 

ƚ^ƚĂƚ Ͳς͘ϬρΘεϬεϳρ 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϬϬϬκρΘϭϯε 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů ϭ͘εκϯϭΘϬϮϳκ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘ϬϬϬεϭςϮϳϳ

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘κκςεϭϭΘκς 

 

ƚͲdĞƐƚ͗dǁŽͲ^ĂŵƉůĞƐƐƵŵŝŶŐhŶĞƋƵĂůsĂƌŝĂŶĐĞƐ 

 

ĂLJϮϭEŽƌŵĂůŝnjĞĚ,>> EĞŐŽŶƚƌŽů ^ŽůŽŶƚƌŽů

DĞĂŶ Ϭ͘ςϯϭκϭΘϳϯϭ Ϭ͘ϳϯϳϳςεϮϮΘ

sĂƌŝĂŶĐĞ Ϭ͘ϬϬϬρϳΘςϯς Ϭ͘ϬϬϮΘςϬρρ

KďƐĞƌǀĂƚŝŽŶƐ κ κ

,LJƉŽƚŚĞƐŝnjĞĚDĞĂŶŝĨĨĞƌĞŶĐĞ Ϭ 

ĚĨ κ 

ƚ^ƚĂƚ Ͳϯ͘ςϮςερϬΘΘρ 

W;dфсƚͿŽŶĞͲƚĂŝů Ϭ͘ϬϭϭϭϬεεϭρ 

ƚƌŝƚŝĐĂůŽŶĞͲƚĂŝů Ϯ͘ϭϯϭΘκςϳΘϮ 

W;dфсƚͿƚǁŽͲƚĂŝů Ϭ͘ϬϮϮϮϭεΘϯϭ

ƚƌŝƚŝĐĂůƚǁŽͲƚĂŝů Ϯ͘ϳϳςκκρϭϬρ 

Page 62 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԱՇՐՁԻՁՌՑՇԾԭՊՇՆԹՅՁԼԽՌՇԞՅՈՀՁԺՁԹՆՋԪԽՌԹՅՇՊՈՀՇՋՁՋԞՋՋԹՑ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽՇԾ

Page 63 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE)

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

EPA Contract No. EP10H001452 

Task Assignment No. 2-19-2012 (MRID 48619102) 

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:

Sandra Hastings Date: 2/14/2012

Secondary Reviewer Signature:

Michelle Sharpe-Kass, M.S. Date: 2/20/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 2/27/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 2/27/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 64 of 285
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 65 of 285
PRONAMIDE/ 101701 

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

OCSPP 890.1150/ OECD None 

Primary Reviewer: Patience Browne, Ph.D. 

Health Effects Division,. Office of Pesticide Progr~ms 

Secondary Reviewer: Greg Akerman, Ph.D. 

Health Effects Division, Office of Pesticide Programs 

Signatu~ .e__. 

Signature: Date:~~ e 

Date: ~20ii2 Template version 08/2011 

DATA EVALUATION RECORD 

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

PCCODE: 101701 DP BARCODE: D398506 

TXR#: 0056255 CAS No.: 23950-58-5 

TEST MATERIAL (PURITY): Pronamide (96.2% a.i.) 

SYNONYMS: Propyzamide; 3,5-dichloro-N-(1 , 1-dimethyl-2-propynyl)benzamide 

CITATION: LeBaron, M.J., Schisler, M.R. , and Visconti, N.R. (2012). Evaluation of 

Pronamide In An In Vitro Androgen Receptor Binding Assay. The Dow 

Chemical Company, Toxicology & Environmental Research and Consulting, 

Midland, MI. Laboratory Project Study ID 111096, January 3, 2012. MRID 

48619102. Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Rd., Indianapolis, IN 

TEST ORDER#: CON-101701-37 

EXECUTIVE SUMMARY: In an androgen receptor (AR) binding assay (MRID 48619102), 

ventral prostate cytosol from Sprague Dawley rats was used as the source of AR to conduct a 

competitive binding experiment, which was conducted to measure the binding of a single 

concentration of [

3H]-R1881 (1 nM) in the presence of increasing concentrations ofpronamide 

(96.2% purity; logarithmic increase from 10- 10 to 10-3 M). Ethanol was used as a solvent at a 

final concentration of <3 %. No precipitation of pronamide was noted. The assay included 

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

A saturation binding experiment was conducted to demonstrate that the AR in the rat prostate 

cytosol was present in reasonable numbers and was functioning with appropriate affinity for the 

radio-labeled reference androgen (Rl 881) prior to conducting AR competitive binding 

experiments. The saturation binding experiment was conducted in duplicate and summarized in a 

submitted study profile (MRID 48619102). In the saturation binding experiments, the maximum 

binding capacity (Bmax) was 3.245 fmol/l 00 μg protein and the dissociation constant (Kd) was 

0.4641 nM; both values were below the acceptable ranges determined in the validation studies. 

The Scatchard plot showed a linear response across the concentrations of ligand added. 

Nonspecific binding as a percent of total binding was less than 20% across the entire 

concentration range in the saturation binding assays (range 6.2-19.8%), with the exception of the 

high concentration (10 nM) in one assay, which was 24.6%. 

Page 66 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 2 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

In the competitive binding experiment, the mean log IC50s for R1881 and the weak positive 

control (dexamethasone) were −9.0 and −4.5 M, respectively. The mean relative binding affinity 

(RBA) for the weak positive control was 0.0034%. The solvent control responses indicated no 

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

binding) of R1881 in Assay #3, which was low (−3.6 versus −2.0). Specific [

3

H]-R1881 binding 

in the presence of pronamide was >75% at all concentrations tested, therefore, an IC50 and RBA 

could not be calculated for pronamide. 

Based on the results from the three runs, pronamide is classified as a Non-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 GLP and Quality Assurance statements were provided. 

Page 67 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 3 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: The Dow Chemical Company, Toxicology & Environmental 

Research and Consulting

Location: Midland, MI 48674

Study Director: Schisler, M.R.

Other Personnel: LeBaron, M.J. (Lead Scientist), Visconti, N.R.(Research Biologist), Gollapudi, B.B. 

(Technical reviewer)

Study Period: June 16, 2011 – June 24, 2011 

2. Test substance: Pronamide

Description: Technical; powder white to off-white

Source: DowAgroSciences LLC, Indianapolis, IN

Lot #: XG188R301, TSN003588-0004 (expiry date: not reported)

Purity: 96.2%

Solubility: Soluble up to 30 mM in ethanol; insoluble in water

Volatility: Not reported

Stability: 2 years shelf life

Storage conditions: 5°C to ambient

CAS #: 23950-58-5

Molecular weight: 256.1

Structure:

3. Non-labeled ligand: R1881

Supplier: Perkin-Elmer, Boston, MA

Lot #: 614156

Purity: >97%

CAS #: 965-93-5

4. Radioactive ligand: [

3

H]-R1881

Supplier: Perkin-Elmer, Boston, MA

Catalog and Lot #: NET590250UC, Lot# 614814

Date of production: July 1, 2010

Date of use: June 6, 2011 to June 23, 2011

Radiochemical purity: >97%

Specific activity: 85.1 Ci/mmol

Concentration of stock: 1.0 mCi/mL

5. Positive control: Dexamethasone

Supplier: Sigma, St. Louis, MO

Lot #: BCBC9269

Purity: 98.9%

CAS # : 50-02-2

6. Solvent/vehicle control: Ethanol

Justification for choice of 

solvent:

Not soluble in water

Final Concentration: <3%

Page 68 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 4 of 13

PRONAMIDE/ 101701 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 (Wilmington, MA). Male Sprague Dawley rats 

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

approximately 24 hours later. 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 [0.01 M Tris, 1 mM sodium 

molybdate, 1.5 mM EDTA, 10% glycerol and 1 mM phenylmethylsulfonyl fluoride (PMSF) 

with dithiothreitol (DTT)] at pH 7.4 to the ventral prostate tissues at 10 mL/g of tissue. The 

tissues were minced, homogenized on ice, and centrifuged for 30 min at 30,000 × g at 4°C. 

The supernatant was collected, pooled from all tissues, aliquoted (amounts not reported) and 

stored at −80°C until used. Protein concentration of the cytosol prepared for this study was 

determined to be 6.566 mg/mL using the Pierce BCA method (Thermo Scientific Pierce 

Research Lab, Rockford, IL).

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. 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 prostate cytosol

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

Concentration of non-labeled ligand (100X [radioligand]) 25-1000 nM

Optimization of receptor concentration Sufficient to bind 8.6-9.0%b of radioligand 

at 0.25 nM

Temperature ~2-8 oC

Incubation time ~16 hours

Composition of assay buffer 

(TEDG)

Tris 10 mM (pH 7.4)

EDTA 1.5 mM

Glycerol 10%

Phenylmethylsulfonyl fluoride 1.0 mM

DTT 1.0 mM

a Data were not included in the study report, but are reported in the study profile (registrant’s DER for MRID 

48619102).

b As indicated in the guideline for acceptable assay performance the receptor concentration bound less than 25 to 

35% of the radiolabeled R1881.

On the day of the assay, the specific activity of the stock solution [3H]-R1881 was not 

adjusted for decay over time, and serial dilutions in TEDG buffer were prepared to achieve 

the final concentrations in cytosol of 0.25, 0.5, 0.7, 1.0, 1.5, 2.5, 5.0, and 10.0 nM to 

determine total binding. To determine non-specific 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 

Page 69 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 5 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

7.5, 15, 21, 30, or 45 μL of 10 nM [3H]-R1881 and 7.5, 15, or 30 μL of 100 nM [3H]-R1881 

was measured. For each batch of cytosol, the optimal protein concentration was determined 

by calculating specific binding to differing amounts of protein per tube, using 0.25 nM 

radiolabeled R1881. The optimal protein concentration was determined to be 1.97 mg 

protein/assay tube, which resulted in the binding of 8.6-9.0% of the total radioactivity 

added. As indicated in the guideline for acceptable assay performance the receptor 

concentration bound less than 25 to 35% of the radiolabeled R1881. 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 run contained three concurrent replicates at each concentration, 

resulting in the 72 samples depicted in Table 2. 

TABLE 2. Saturation Binding Experiment Run a, b

Total Binding Non-Specific Binding Radioligand alone

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

[

3

H]-R1881

Final conc. (nM)

[

3

H]-R1881

Final conc. (nM)

R1881

Final conc. (nM)

[

3

H]-R1881

Initial conc. (nM)

[3H]-R1881

(μL)

0.25 0.25 25 10 7.5

0.50 0.50 50 10 15

0.70 0.70 70 10 21

1.00 1.00 100 10 30

1.50 1.50 150 10 45

2.50 2.50 250 100 7.5

5.00 5.00 500 100 15

10.00 10.00 1000 100 30

a Data were not included in the study report, but are reported in the study profile (registrant’s DER for MRID 

48619102). 

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 for approximately 16 

hours at 2-8°C. Samples were maintained at temperatures of ~4°C except during whole rack 

vortexing. To separate bound from free R1881, hydroxyapatite (HAP) slurry was added to 

each tube and vortexed once every 5 minutes for 20 minutes. The samples were then 

centrifuged, and the supernatant was aspirated and discarded. The samples were washed 3 

times in 50 mM TRIS buffer. Following the last wash and decanting of the Tris buffer, 

pellets were then extracted by addition of 2 mL ethanol. The samples were vortexed 3 times 

at 5 minute intervals. Samples were maintained on ice at all times between vortexing. Each 

ethanol supernatant was then decanted into a scintillation vial, and the radiation was 

quantified by liquid scintillation counting. A total of 4 runs were performed on 2 batches of 

cytosol with similar results. For the batch of cytosol used for the competitive assay, 2 runs 

were performed rather than three runs as recommended in the test guideline; however, both 

runs had highly similar binding profiles. 

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3. Competitive Binding Experiment: A summary of the assay 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 ventral prostate cytosol

Concentration of radioligand 1 nM

Optimization of receptor concentration Sufficient to bind 5.3-5.8% of 1.0 nM 

radioligand b 

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

Incubation Temperature 4-8 oC 

Incubation time Overnight 

Composition of assay buffer Tris 0.01 M (pH 7.4)

EDTA 1.5 mM 

Glycerol 10% (v/v)

Phenylmethylsulfonyl fluoride 

with DTT 

1 mM 

Sodium molybdate 1 mM

Protease inhibitor 60 μM

a Data were obtained from pages 16, 20, and 21 of the study report.

b Data obtained from pages 39, 41 and 43 of the study report. Protein concentrations (μg/tube) were not 

reported. 

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 (specific activity of 85.1 Ci/mmol) to 

the AR in the presence of increasing concentrations of a test substance.

Ethanol was used as the solvent vehicle, and the solubility of the test material in the vehicle 

and assay buffer was evaluated visually. No precipitation was noted. 

It was reported that the results from the saturation binding experiment demonstrated that 

6.566 mg/ml or 1.97 mg/assay tube of cytosolic protein contained enough receptor to bind 

no more than 10-15% of the [3

H]-R1881, and that non-specific binding met the guideline 

recommended value of <20%. In the competitive binding experiment, the amount of 

cytosolic protein used in the assay contains enough receptor to bind 5.3-5.8% of the [3

H]-

R1881. 

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

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

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

and each run contained duplicate blanks, and three replicates at each concentration of the 

solvent blank, NSB, reference standard, weak positive control, and test chemical resulting in 

a total of 77 samples per run. In addition, duplicate blanks followed by six replicates [3

H]-

R1881 only (for total binding calculations) were run the day before each analysis run (the 

day of preparation of sample tubes). 

Page 71 of 285
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TABLE 4. Competitor Final Molar (M) Concentrations in Competitive Binding Assay a b

Solvent Control Reference standard Weak positive control Test Chemical None Ethanol R1881 Dexamethasone Pronamide

Tubes 3-5 and 72-74 Tubes 6-23 and 75-77 c Tubes 24-47 Tubes 48-71 Tubes 1-2

1×10−6 1×10−3 1×10−3

1×10−7 1×10−4 1×10−4

1×10−8 1×10−5 1×10−5

1×10−9 1×10−6 1×10−6

1×10−10 1×10−7 1×10−7

1×10−11 1×10−8 1×10−8

-- 1×10−9 1×10−9

-- 1×10−10 1×10−10

a Data were obtained from pages 39-44 of the study report.

b Each concentration of each chemical was run in triplicate, plus duplicate blanks for a total of 77 tubes per run. 

Tubes 3-77 contained 50 μL of triamcinolone acetonide and 30 μL [3

H]-R1881. Samples were dried, and 300 

μL of prostate cytosol were added. Tubes 3-77 also contained 10 μL of the solvent control, reference standard 

(non-radiolabeled R1881), weak positive control, or test substance, with the exception of Tubes 6-8 and 75-77 

that contained 30 μL of non-radiolabeled R1881 (used to evaluate non-specific binding). Six tubes analyzed the 

day prior to each run analysis contained only 30 μL of [3

H]-R1881 to determine ligand activity.

c Tubes 6-8 and 75-77 were used to evaluate non-specific binding by adding 100x of cold (non-radiolabeled) 

R1881. 

Sample tubes were stored overnight at 4-8°C in the dark to allow the reaction to reach 

equilibrium, bound R1881 was separated from free R1881 by washing with buffer and 

extraction with ethanol, followed by scintillation counting of bound [3H]-R1881. 

4. Data Analysis: The top and bottom of the curve, Hill slope, inhibition concentration (IC50), 

and standard deviations were assessed using GraphPad Prism v. 5, and the data were 

graphed using a “one site binding” non-linear regression. 

5. Definitions 

a. Classification of test material 

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

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

bound. 

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

radioligand binding (i.e. radioligand displacement is at least 25% but less than 50%), or the 

curve falls outside the range for the weak positive control (−0.6 to −1.4). 

Non-Binder: The average lowest portion of curves across runs is greater than 75% activity 

(i.e. less than 25% displacement of radioligand), or the data do not fit the model. 

Untestable: If the test compound is not soluble above 1×10−6

 M and the binding curve does 

not cross 50%, the chemical is judged to be untestable.

b. Descriptors for receptor binding

Page 72 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 8 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

Bmax: maximal binding capacity

Kd: dissociation constants

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

SATURATION BINDING EXPERIMENT: Saturation binding experiment parameters 

are presented in Table 5. The dissociation constant (Kd) for [3H]-R1881 was 0.4641, and 

the estimated Bmax (nM) was 0.06392 for the batch of prostate cytosol that was used for this 

study. The Kd and the Bmax were below the ranges reported in the EPA validation program 

(0.685-1.57 nM for Kd and 7-16 fmol/μg protein for Bmax). Both runs provided similar 

results and had goodness of fit (R2) values of 0.9871 and 0.9937. 

TABLE 5. Saturation Binding Experiment of R-1881 with Androgen Receptor from Rat Prostate Cytosola

Parameter Run 1b Run 2 b Run 3 b Mean Runs 1-2 c

R2 (unweighted) 0.9937 0.9871 ND 0.9871-0.9937

Bmax (nM) 0.06194 0.06590 ND 0.06392

Bmax (fmol/100 μg protein) 3.146 3.343 ND 3.245

Kd (nM) 0.4359 0.4922 ND 0.4641

a Data were not included in the study report, but are reported as a separate validation report.

b Two saturation runs were performed for this batch of cytosol.

c The range of R2 is reported and the mean is reported for the other parameters. 

R2 Goodness of fit for curve calculated for specific binding,

ND Not determined

Non-specific, specific, and total binding curves for [3H]-R1881 to the androgen receptor are 

presented in Figure 1. The specific binding reached a plateau and the non-specific binding 

was generally less than 20% of total binding at all concentrations (range 6.2%-19.8%) 

except at the highest concentration (10 nM) in Run 1 (24.6%). Figure 2 is a Scatchard plot 

that illustrates the binding of [3H]-R1881 to the androgen receptor. The data fit results in a 

linear plot.

Page 73 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 9 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

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

Binding Experiment.

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

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

binding experiments are summarized in Table 6 and shown graphically in Figures 3 and 4. 

The estimated mean log IC50 for pronamide could not be determined as it did not result in 

50% inhibition at any concentration. The estimated log IC50s for R1881 and the weak 

positive control (dexamethasone) were −9.0 and −4.5 M, respectively. The mean RBA for 

the positive control was 0.0034%. Confidence in these numbers is high due to the small 

variation. No precipitation of the test compound was visually observed at any concentration 

tested (≤10−3

 M). The solvent control responses indicated no drift in the study assay. 

Page 74 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 10 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

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

Parameter Run 1 Run 2 Run 3 Mean b

r

2 (unweighted) R1881 1.0000 1.0000 0.9981 0.9981-1.0000

Positive control 0.9996 0.9997 0.9956 0.9956-0.9997

Pronamide 0.8854 0.8600 0.1286 0.1286-0.8854

Log IC50 (M) R1881 −9.009 −8.949 −9.051 −8.996

Positive control −4.576 −4.525 −4.467 −4.522

Pronamide NA NA NA NA

IC50 (M) R1881 9.803 × 10−10 1.124 × 10−9 8.902 × 10−10 1.008 × 10−9

Positive control 2.655 × 10−5 2.988 × 10−5 3.410 × 10−5 3.004 × 10−5

Pronamide NA NA NA NA

Log RBA c Positive control −4.4 −4.4 −4.6 −4.5

Pronamide NA NA NA NA

RBA (%) Positive control 0.0037 0.0038 0.0026 0.0034

Pronamide NA NA NA NA

a Data were obtained from pages 32-33 of the study report.

b The range is reported for r2

; the mean is reported for the remaining parameters.

c Calculated by the study reviewer.

NA Not applicable 

r

2

 Goodness of fit

RBA Relative binding affinity

Page 75 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 11 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

FIGURE 3. Percentage R1881 Bound to the Androgen Receptor in the Presence of 

Radioinert R1881, Dexamethasone, and Pronamide (Assays 1 – 3). 

Assay #1 

Assay #2 

Assay #3 

Page 76 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 12 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

FIGURE 4. Mean of Percentage R1881 Bound to the Androgen Receptor in the Presence 

of Pronamide from Three Assays.

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

functioning properly, each run was evaluated using the following criteria (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.

≤15% 5.3-5.8% X 

Pronamide Top (% binding) 80 to 115 95.2 to 98.8 X

R1881 fitted curve parameters

Top (% binding) 82 to 114 96.7 to 100.9 X

Bottom (% binding) −2.0 to 2.0 −3.6 to −0.6 c X

Hill Slope −1.2 to −0.8 −1.1 to −0.8 X

Weak positive control (dexamethasone) fitted curve parameters

Top (% binding) 87 to 106 99.3 to 105.0 X

Bottom (% binding) −12 to 12 −1.8 to −1.1 X

Hill Slope −1.4 to −0.6 −1.0 to −0.9 X

Saturation Binding Experiment Kd (nM) 0.685-1.57 0.4641 X

Non-specific binding (%) ≤10.0 6.65 to 6.88 d X

a Data were obtained from pages 32-33, 39, 41 and 43 of the study report.

b These values represent ranges from the validation study. 

c In one run the calculated bottom of the curve was low (−3.6%); values were acceptable in the other two runs.

d Values reported for the three NSB tubes at the beginning of each run; does not include the three NSB tubes at 

the end of the run.

NR Not reported

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

unlabeled R1881 displaced [3H]-R1881 in a manner consistent with one-site binding, as 

indicated by a Hill slope of −1.1 to −0.8. Examination across the runs indicated consistency 

of the Hill slope, placement along the X-axis, and top and bottom plateaus, except for one 

run which had a low bottom % binding for the reference material (R1881). 

Page 77 of 285
Androgen Receptor Binding (Rat Prostate Cytosol) (2012) / Page 13 of 13

PRONAMIDE/ 101701 OCSPP 890.1150/ OECD None

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Based on the combined responses in each of three 

independent androgen receptor binding assays, it was determined that pronamide treatment 

did not result in significant alterations in the binding of the reference androgen (R1881) up 

to the assay limit concentration (1 mM, 10−3 M). The results of the in vitro androgen 

receptor binding assay using rat prostate cytosol indicate that, under the conditions of this 

study, pronamide was negative (non-binding) for androgen receptor binding.

B. AGENCY COMMENTS: The results of the saturation binding experiment were not 

reported in the study report; however, summary saturation data including graphs showing 

specific, non-binding curves for [3

H]-R1881 to the androgen receptor were reported in a 

study profile (registrant’s DER for MRID 48619102). The maximum binding capacity 

(Bmax) was 3.2 fmol/μg protein and the dissociation constant (Kd) was 0.4641 nM. Both the 

Bmax and the Kd fell outside of the expected range of 7 to 16 fmol/μg protein (Bmax) or 0.685 

to 1.57 nM (Kd). Only two saturation binding runs were performed instead of the 

recommended three runs. 

In the competitive binding experiment, the mean log IC50s for R1881 and the weak positive 

control (dexamethasone) were −9.0 and −4.5 M, respectively. The mean RBA for the weak 

positive control was 0.0034%. The solvent control responses indicated no drift in the study 

assay. All performance criteria were met, with the exception of the bottom (% binding) of 

R1881 in Assay #3 which was low (−3.6 versus −2.0). Pronamide is classified as “nonbinding” as specific radioligand binding was >75% at all concentrations tested. An IC50 and 

RBA could not be calculated for pronamide. 

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 protein concentration (μg/tube) used in the assay was not reported and radioligand

binding (5.3-5.8%) was lower than recommended in the test guidelines (10-15%). 

• The maximum binding capacity (Bmax) and the dissociation constant (Kd) in the 

saturation binding experiment fell outside of the expected ranges for these parameters. 

• Two runs of the saturation binding experiment were performed on the cytosol 

preparation used for the competitive binding experiment instead of the recommended 

three runs/cytosol preparation. 

Page 78 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE ) 

Study Type: OCSPP 890.1200, Aromatase Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 2-19-2012 (MRID 48619103) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

CSS-Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer: Signature:

Rebecca L. Bryan, B.S. Date: 2/28/2012

Secondary Reviewer: Signature:

David A. McEwen, B.S. Date: 3/01/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 3/02/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 3/02/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 79 of 285
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 80 of 285
Aromatase (Human Recombinant) Assay (2012) I Page I of 12 

PRONAMIDE I 101701 OCSPP 890.1200 I OECD None 

Primary Reviewer: Vincent Chen M.S. Signature:~ Health Effects Division (7509P) Date: e._y :rvA.J7-.VJ-5 

Secondary Reviewer: Greg Akerman Ph.D. Signature: 7-?c-.4 

Risk Assessment Branch III, Health Effects Division (7509P) Date: G /..J.r-/p--

Template version 08/2011 

DATA EVALUATION RECORD 

STUDY TYPE: Aromatase (Human Recombinant); OCSPP 890.1200 

PC CODE: 101701 DP BARCODE: 0398506 

TXR: 0056255 CAS: 23950-58-5 

TEST MATERIAL (PURITY): Pronamide (96.2% a.i.) 

SYNONYMS: RH-23315, Propyzamide 

IUPAC: 3,5-dichloro-N-(1, 1-dimethylprop-2-ynyl)benzamide 

CAS: 3,5-dichloro-N-(1 , l-dimethyl-2-propynyl)benzamide 

CITATION: Coady, K.K. and Kan, H.L. (2012) Evaluation of Pronamide in the Human 

Recombinant Aromatase Assay. Toxicology & Environmental Research and 

Consulting (The Dow Chemical Company [Midland, MI 48674, USA]). 

Laboratory Study ID: 101012. 04 Jan 2012. MRID 48619103. Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 

TEST ORDER: CON-101701-37 

EXECUTIVE SUMMARY: In an in vitro aromatase (CYP 19) assay (MRID 48619103), 

pronamide (96.2% a.i., batch/lot# XG 1088R301) was incubated with human recombinant 

aromatase and tritiated androstenedione (1-~ [

3H(N)]-androst-4-ene-3, 17-dione ([3H]ASDN)) in 

dimethyl sulfoxide (DMSO) at serial log concentrations of 10- 10 to 10-3 M (or 10-33 M) for 15 

minutes at 37 °C to assess the potential of pronamide to inhibit aromatase activity. After 

completion of the first run, the data were reviewed and precipitation of pronamide was observed 

at the highest concentration tested (10-3 M). The highest concentration for the second and third 

runs was set at the highest concentration that appeared to be soluble with mid-log concentrations 

(10-33 M), to define the lower portion of the curve. 

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

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

using liquid scintillation counting (LSC). Three runs were conducted and each run included a 

full activity control, a background activity control, a positive control series (10- 10 to 10-5 M) 

using a known inhibitor ( 4-hydroxyandrostenedione; 4-0H ASDN), and the pronamide series 

(10- 10 10 10-33 M) with 3 repetitions per concentration. 

Aromatase activity in the full activity controls ranged from 0.244 to 0.493 nmol·mgprotein- 1 ·min- 1 for the three test runs, with a mean and standard deviation of 0.342±0.108 

Page 81 of 285
Aromatase (Human Recombinant) Assay (2012) / Page 2 of 12

PRONAMIDE / 101701 OCSPP 890.1200 / OECD None

nmol∙mg-protein−1∙min−1. Activity in the background controls ranged from 0.23 to 0.65% of the 

full activity controls. The response of the full activity controls and background controls was 

acceptable.

Results for the positive control were generally within the recommended ranges for the top of the 

curve, bottom curve, Hill slope, log IC50, and coefficient of variation (CV) for replicates of each 

concentration within runs. For 4-OH ASDN, the estimated log IC50 averaged −7.30 M, and the 

Hill slope was −1.11. 

For pronamide, aromatase activity averaged 0.343±0.112 nmol∙mg-protein−1

∙min−1 at the lowest 

tested concentration (10−10 M) and 0.222±0.029 nmol∙mg-protein−1∙min−1 at the highest 

successfully tested concentration (10−3.3 M). The data for pronamide were modeled, and the 

goodness of fit (R2) values were 0.74-0.97. The average dose-response curve indicated that the 

aromatase activity of the test material at concentrations ranging from 10−10 M to 10−6 M was 

essentially equivalent to the activity observed in the full activity controls. However, pronamide 

reduced aromatase activity, on average, to approximately 74% at 10−4 M and 62% at 10−3.3 M. 

The average lowest portion of the response curve was between 50 and 75% activity (62% at 

10–3.3 M pronamide), indicating that pronamide is an equivocal inhibitor of aromatase. 

Based on the data from the average response curve, pronamide is classified as Equivocal for 

aromatase inhibition in this assay. 

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

890.1200). 

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

Assurance statements were provided. 

Page 82 of 285
Aromatase (Human Recombinant) Assay (2012) / Page 3 of 12

PRONAMIDE / 101701 OCSPP 890.1200 / OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Substance: Pronamide Technical

Description: White to Off-white powder 

Source: Dow AgroSciences LLC

Lot/Batch #: XG1088R301, TSN003588-0004

Purity: 96.2% a.i.

Volatility: Not reported

Storage Conditions: Ambient

Stability: Not reported

Solvent: Dimethyl sulfoxide (DMSO)

Solubility (in Test Solvent): Soluble in DMSO up to 0.05 M

Highest Concentration Tested: 10−3 M for first run; 10−3.3 M for Runs 2 and 3

Stock Solution Preparation Methodology: Dissolved the test material in DMSO.

Molecular Weight: 256.1 g/mol

CAS #: 23950-58-5

Structure:

Cl

Cl

O

N

H

CH3

C CH3 CH

2. Non-Labeled Substrate: Androstenedione (ASDN)

CAS # : 63-05-8

Source: Steraloids, Inc. (Cat. # A6030100)

Lot/Batch #: L1627 

Purity: 95.36%

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

Source: Perkin Elmer Life and Analytical Sciences (Cat. # not reported)

Lot/Batch #: 3615304 

Radiochemical Purity (Supplier): >97%

Specific Activity: 20.7 Ci/mmol

Radiochemical Purity (In-Lab 

Determination): Not reported

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

CAS # : 566-48-3

Source: Sigma-Aldrich (Cat. # F2552)

Lot/Batch #: 081K2133 

Purity: 99.6%

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

Source: Sigma Aldrich (Cat. # D5879)

Lot/Batch #: 037K0766

Justification for Choice of Solvent: DMSO is a Guideline recommended solvent

Concentration (% of Total Volume in 

Assays): 0.1% v/v

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

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

Lot/Batch #: 54390 

Protein Concentration: Not reported, but determined each day of use

Cytochrome C reductase activity: Not reported

Aromatase Activity: 2.8 pmol/min/pmol P450

Page 83 of 285
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PRONAMIDE / 101701 OCSPP 890.1200 / OECD None

B. METHODS

1. Assay Components and Preparations: A mixture of non-labeled and radiolabeled 

[

3

H]-ASDN was prepared to result in a 2 μM ASDN solution with a predicted radioactive 

content of 1.5 μCi/mL.

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

chemical formulation used per assay was no more than 1% v/v of the total assay volume. 

The report specified that DMSO was chosen because it was mentioned in the guideline as a 

preferred solvent and the test material was adequately soluble in this solvent at the specified 

concentration. 

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

Fresh serial dilutions of the stock solution were prepared each time the aromatase inhibition 

assay was conducted. Dilutions were prepared such that the target concentrations of the 

positive control substance (10−5

 to 10−10 M; 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 Gentest, and aliquoted into 

individual vials based on protein content. Microsomes were stored at approximately −80oC 

until use. 

Other assay components 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 6 mM

[3H]ASDN 2 μM

Propylene Glycol 100 μL 

Temperature 37°C

Incubation Time 15 min

2. Suitability Assessments: The protein concentration in an aliquot of the microsomes was 

determined each day of use, and microsomes were diluted with phosphate buffer such that 

approximately 0.004 mg/mL protein was present in the final reaction solution. Aromatase 

activity of the microsomes was provided by the vendor as 2.8 pmol/min/pmol P450 for Lot 

No. 54390. The minimum aromatase activity in the full activity control samples was 

determined to be 0.257 nmol/mg-protein/min, which was greater than the minimum 

acceptable aromatase activity of 0.10 nmol/mg-protein/min.

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

four tubes for the 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 test substance were established. The aromatase assay was conducted 

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

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 The amount of 3

H2O 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: No information was provided concerning proficiency 

testing. 

a. Positive Control: Data were not provided. 

(1) Initial Demonstration of Laboratory Proficiency: The positive control data 

(new/historical data for laboratory) were not reported in regards to 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 were reported for the test runs only (Table 2), and served as guidance 

in identifying runs that provided parameters in the preferred ranges. 

(2) Demonstration of Proficiency of New Technician for Conducting Assay (when 

applicable): Demonstration of proficiency by a new technician, if applicable, was not 

reported. The positive control data for slope, top and bottom percent, and log IC50 met the 

criteria as listed in section (i) of OCSPP 890.1200, with the following exceptions: (i) Hill 

slope for Run 1 (–1.5) was below the lower limit (–1.2); and (ii) log IC50 for Run 2 (–7.5) 

and Run 3 (–7.4) was below the lower limit (–7.3). 

TABLE 2. Performance Criteria for the Positive Controla

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

Slope −1.2 −0.8 –1.5 –0.84

Top (%) 90 110 99 110

Bottom (%) −5 +6 –0.56 4.2

Log IC50 (M) −7.3 −7.0 –7.5 –7.2 a Data were obtained from page 29 of the study report.

b. Proficiency Chemicals: Data were not provided. 

TABLE 3. Proficiency Chemicals

Compound CAS# Class Concentrations

Econazole 24169-02-6 Inhibitor Not reported

Fenarimol 60168-88-9 Inhibitor Not reported

Nitrofen 1836-75-5 Inhibitor Not reported

Atrazine 1912-24-9 Non-inhibitor Not reported

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

activity to the presence of eight concentrations of pronamide per run, in triplicate, was tested 

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

insolubility of pronamide was observed at the highest concentration tested (10−3 M). The 

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highest concentration for the second and third runs was set at the highest concentration that 

appeared to be soluble with mid-log concentrations (10−3.3 M), to define the lower portion of 

the curve. The lowest concentration tested was 10−10 M. The response of each full activity 

control within a run was between 96 to 106% of the average full activity, with the exception 

of two full activity control responses (86 and 112%) from the beginning of Run 3 that were 

outside of the guideline recommended range of 90 to 110%. 

 

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

Pronamide Conc 1b 3 All test components plus test chemical 1×10–3 (or 1×10–3.3) b

Pronamide Conc 2b 3 All test components plus pronamide 1×10–4

Pronamide Conc 3b 3 All test components plus pronamide 1×10–5

Pronamide Conc 4b 3 All test components plus pronamide 1×10–6

Pronamide Conc 5b 3 All test components plus pronamide 1×10–7

Pronamide Conc 6b 3 All test components plus pronamide 1×10–8

Pronamide Conc 7b 3 All test components plus pronamide 1×10–9

Pronamide Conc 8b 3 All test components plus pronamide 1×10–10

a The complete assay contained buffer, propylene glycol, microsomal protein, [3

H]ASDN, and NADPH. b

 The highest concentrations tested were 1×10–3 for Run 1, and 1×10–3.3 for Runs 2 and 3.

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 

Graph Pad Prism (Version 4.0, La Jolla, CA). Basic statistical analyses were performed on 

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

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standard deviation, and coefficient of variation. The Hill slope and log IC50 values across 

three independent runs were compared based on a one-way random effects analysis of 

variance, treating runs as random effects.

The response curve was fitted by nonlinear regression analysis. Model fits were carried out 

using a 4-parameter regression model. For each run, percent of full activity control were 

plotted versus logarithm (base 10) of the test chemical concentration or 4-OH ASDN 

concentration. Each run was plotted with the data’s best fit curve. Additionally, the average 

inhibition response curve across all runs was also plotted. 

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%a 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% activityb Non-inhibitor

Data do not fit model --- a Ordinarily, an inhibition curve will fall from 90% to 10% over 2 log units with a slope near −1. Unusually steep curves 

may indicate protein denaturing or solubility issues. If the slope of the curve is steeper than −2.0, the result is classified as 

equivocal. b

 If the test compound was not soluble above 10−6 M and the inhibition curve does not cross 50%, the chemical is typically 

determined to be untestable in the aromatase assay. 

II. RESULTS

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

0.244 to 0.493 nmol∙mg-protein−1∙min−1 for the three test runs, with a mean and standard 

deviation of 0.342±0.108 nmol∙mg-protein−1

∙min−1. Activity in the background controls 

ranged from 0.23 to 0.65% of the full activity controls. The response of each full activity 

control was generally between 90 to 110% of the average full activity. The response of the 

full activity controls and background controls were acceptable. 

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

activity averaged 0.351±0.125 nmol∙mg-protein−1∙min−1 at the lowest tested concentration 

(10−10 M) and 0.003±0.002 nmol∙mg-protein-1∙min−1 at the highest tested concentration 

(10−5 M). The mean aromatase activity of the positive control (expressed as % full control 

activity) for each concentration tested across all three runs is presented in Table 7, along 

with the overall standard deviation and %CV. Inhibition response curves for the positive 

control from each run and the average of all runs 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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TABLE 7. Effect of Pronamide on Aromatase Activity (as percent of control) from Independent Runs a

Chemical

Concen. 

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

4-OH ASDN

(positive control)

−5 3 1.01 0.74 0.30 73.5

−6 3 5.27 1.48 0.60 28.1

−6.5 3 12.25 2.77 1.13 22.6

−7 3 28.56 5.53 2.26 19.4

−7.5 3 59.32 9.99 4.08 16.9

−8 3 84.75 11.26 4.60 13.3

−9 3 103.67 6.51 2.66 6.3

−10 3 102.04 9.91 4.05 9.7

Pronamide −3b 1 79.17 2.43 0.99 3.1

−3.3b 2 62.01 13.94 5.69 22.5

−4 3 73.74 7.47 3.05 10.1

−5 3 94.41 7.54 3.08 8.0

−6 3 100.61 4.56 1.86 4.5

−7 3 97.63 6.25 2.55 6.4

−8 3 103.01 6.62 2.70 6.4

−9 3 99.17 4.84 1.97 4.9

−10 3 100.25 5.10 2.08 5.1 a Values were calculated by the reviewers based on data provided on pages 52-54. b

 The highest concentrations tested were 1×10–3 for Run 1, and 1×10–3.3 for Runs 2 and 3.

SD Standard Deviation

SEM Standard Error of the Mean

CV Coefficient of Variance

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

C. TEST SUBSTANCE: For pronamide, aromatase activity averaged 0.343±0.112 nmol∙mgprotein−1

∙min−1 at the lowest tested concentration (10−10 M) and 0.222±0.029 nmol∙mgprotein−1

∙min−1 at the highest successfully tested concentration (10−3.3). The mean 

aromatase activity of pronamide (expressed as %full control activity) for each concentration 

tested across all three runs is presented in Table 7 (above), along with the overall standard 

deviation and %CV. Inhibition response curves for pronamide from each run are shown in 

Figure 2, and the average inhibition response curve across all runs is shown in Figure 3. 

The overall %CV for the highest concentration (23%) exceeded the acceptable limit of 15%. 

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PRONAMIDE / 101701 OCSPP 890.1200 / OECD None

FIGURE 2. Inhibition Response Curves for Pronamide From Each Test Run. 

FIGURE 3. Mean Inhibition Response Curve for Pronamide. 

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The data for pronamide were modeled, and the goodness of fit (R2) values were 0.74-0.97. 

For test material curves, the best fit Hill slope and log IC50 values across three independent 

runs did not differ significantly. The average dose-response curve indicated that the 

aromatase activity of the test material at concentrations ranging from 10−10 M to 10−6 M was 

essentially equivalent to the activity observed in the full activity controls. However, 

pronamide reduced aromatase activity, on average, to approximately 74% at 10−4 M and 

62% at 10−3.3 M. 

For positive control curves, the best fit Hill slope and log IC50 values across three 

independent runs were significantly different. 

The effect of the positive control on inhibition of aromatase activity is presented in Table 8. 

For 4-OH ASDN, the estimated log IC50 averaged −7.37 M and the slope was −1.11. 

Confidence in the mean log IC50 for the positive control is high due to the small variation 

(<3% CV). Confidence in the mean slope is low due to the large variation (<32% CV). 

TABLE 8. Effect of Pronamide on Aromatase Activity (as Percent of Control) From Independent Runs a

Chemical Run 1 Run 2 Run 3 Mean SD %CV

Log IC50 (M)

Pronamide NA NA NA NA NA NA

4-OH ASDN −7.20 −7.50 −7.40 −7.37 0.15 −2.07

Slope

Pronamide NA NA NA NA NA NA

4-OH ASDN −1.50 −0.99 −0.84 −1.11 0.35 −31.17

a Data were provided on pages 27-28 of the study report. Mean, SD, and %CV were calculated by the reviewers based on 

these data. 

SD Standard Deviation

CV Coefficient of Variance

NA Not applicable. Values for pronamide were not suitable for modeling.

Based on the data from the average response curve and the criteria listed above in Table 7, 

the results support the conclusion that pronamide is equivocal in the aromatase assay. 

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS CONCLUSIONS: Based on the average of the three runs of the 

assay, the percent inhibition of aromatase at the highest concentration tested (1 x 10−3.3 M), 

was between 25% and 50% activity. Thus, pronamide is classified as having an “equivocal” 

ability to inhibit aromatase activity.

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

0.244 to 0.493 nmol∙mg-protein−1∙min−1 for the three test runs, with a mean and standard 

deviation of 0.342±0.108 nmol∙mg-protein−1

∙min−1. Activity in the background controls 

ranged from 0.23 to 0.65% of the full activity controls. The response of each full activity 

control was generally between 90 to 110% of the average full activity. 

For the positive control substance (4-OH ASDN), aromatase activity averaged 0.351±0.125 

nmol∙mg-protein−1

∙min−1 at the lowest tested concentration (10−10 M) and 0.003±0.002 

nmol∙mg-protein−1

∙min−1 at the highest tested concentration (10−5 M). These results were 

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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. The overall %CV 

for the highest concentration (21%) exceeded the acceptable limit of 15%. 

For pronamide, aromatase activity averaged 0.343±0.112 nmol∙mg-protein−1

∙min−1 at the 

lowest tested concentration (10−10 M) and 0.222±0.029 nmol∙mg-protein−1∙min−1 at the 

highest successfully tested concentration (10−3.3 M). The data for pronamide were modeled, 

and the goodness of fit (R2) values were 0.74-0.97. The average dose-response curve 

indicated that the aromatase activity of the test material at concentrations ranging from 10−10

M to 10−6 M was essentially equivalent to the activity observed in the full activity controls. 

However, pronamide reduced aromatase activity, on average, to approximately 74% at 10−4

M and 62% at 10−3.3 M. 

For 4-OH ASDN, the estimated log IC50 averaged −7.37 M and the slope was −1.11. 

The average lowest portion of the response curve was between 50 and 75% activity (62% at 

10–3.3 M pronamide), indicating that pronamide is an equivocal inhibitor of aromatase. 

In general, CVs often exceeded the acceptable limit of 15% (Table 7) and limit confidence 

in assay results.

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: 

• Coefficients of variation often exceeded 15% (e.g. CVs of positive control 

concentrations exceeded 15% for 5 of 8 chemical concentrations and were reported up to 

73.5%). 

Page 92 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE) 

Study Type: OCSPP 890.1250, Estrogen Receptor Binding Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 2-19-2012 (MRID 48619104) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

CSS-Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

Rebecca L. Bryan, B.S. Date: 2/16/2012

Secondary Reviewer Signature:

David A. McEwen, B.S. Date: 2/27/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 3/02/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 3/02/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 93 of 285
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 94 of 285
PRONAMIDE/101701 

Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) I Page 1 of 13 

OCSPP 890.1250/ OECD None 

Primary Reviewer: -=K=h=in"'--=0-=o-'--"-M-=·=D:....:.. __________ Signature: __ \£.;:::;' ~!\.~==·=;'!·'----- Health Effects Division Date: ----=LJ~_,,,'l.=--ct1 }_...... z.-=-cc.:..::1~,.___ 

Secondary Reviewer: Greg Akerman, Ph.D. Signature: ,/} /-2= 

Health Effects Division Date: __ , <o"'--''Z-- =-.:.. "f_,_I .:..... ' ,-__ 

Template version 08/2011 

DATA EVALUATION RECORD 

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

OCSPP 890.1250 

PC CODE: 101701 DP BARCODE: D398506 

TXR#: 0056255 CAS No.: 23950-58-5 

TEST MATERIAL (PURITY): Pronamide (96.2% a.i.) 

SYNONYMS: Propyzamide; KERBTM Technical; 3,5-Dichloro-N-(1 , 1-dimethyl-2-

propyny 1) benzamide 

CITATION: LeBaron, M.J. , Schisler, M.R., and Visconti, N.R. (2012). Evaluation of 

pronamide in an in vitro estrogen receptor binding assay. Toxicology & 

Environmental Research and Consulting, The Dow Chemical Company, Midland, 

MI. Laboratory Study No. : 111125, January 3, 2012. MRID 48619104. 

Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 

TEST ORDER#: CON-101701-37 

EXECUTIVE SUMMARY: In an estrogen receptor (ER) binding assay (MRID 48619104), 

uterine cytosol from Sprague Dawley rats was used as the source of ER for a competitive binding 

experiment, which was conducted to measure the binding of a single concentration of [3H]-17Pestradiol (1 nM) in the presence of increasing concentrations (10- 10 to 10-3 M) of pronamide 

(96.2% purity). Ethanol was used as a vehicle at a final concentration of <3%. The assay 

included 19-norethindrone as a weak positive control, octyltriethoxysilane as a negative control, 

and l 7P-estradiol as the natural ligand reference material. 

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. In the saturation binding experiments, the maximum binding capacity (B max) was 

59.28 fmol/100 μg protein and the dissociation constant (Kd) was 0.1032 nM; both within the 

recommended range from the validation studies. The Scatchard plot showed a linear response 

across the concentrations of ligand added. Nonspecific binding was I. 7% - 8.6% of the total 

binding. 

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In the competitive binding experiment, pronamide did not inhibit specific binding of the natural 

ligand at concentrations up to 10−3 M, but there was an apparent increase in specific binding of 

the [3H]-17β-estradiol in each run at the highest pronamide concentration tested (10−3 M). 

Across all three runs, specific radioligand binding averaged 95.7 – 98.2% at pronamide 

concentration of 10−10 to 10−4 M, but average binding was 121.4% at 10−3 M of pronamide. An 

IC50 and relative binding affinity (RBA) were not calculated for pronamide because radioligand 

binding was not reduced to ≤50%. 

The performance criteria were generally met for pronamide, and the reference compounds 

performed as expected in the assay. The negative control, octyltriethoxysilane, had no effect on 

binding, and the binding curves for 17β-estradiol and 19-norethindrone showed that increasing 

concentrations of each compound displaced [3H]-17β-estradiol in a manner consistent with onesite binding. The mean log IC50 was −5.5 M for 19-norethindrone and −8.9 M for 17β estradiol, 

and the mean RBA was 0.033% for 19-noirethindrone compared to the natural ligand. 

Based on the results from the three runs, pronamide is classified as Not Interactive in the 

Estrogen Receptor Binding Assay. 

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

assay (OCSPP 890.1250). 

COMPLIANCE: Signed and dated Confidentiality. GLP and Quality Assurance statements

were provided. 

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PRONAMIDE/101701 OCSPP 890.1250/ OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Toxicology & Environmental Research and Consulting

Location: Dow Chemical Company, Midland, MI

Study Director: M.R. Schisler

Other Personnel: M.J. LeBaron, Lead Scientist

N.R. Visconti, Research Biologist

B.B. Gollapudi, Technical Reviewer

Study Period: September 6, 2011 to January 3, 2012

2. Test substance: Pronamide

Description: White to off-white powder

Source: Dow AgroSciences LLC, Indianapolis, IN

Lot/Batch #: XG1088R301, TSN003588-0004

Purity: 96.2%

Solubility: Soluble in ethanol up to 50 mM; insoluble in water

Volatility: NR

Stability: 2 years shelf life

Storage conditions: 5°C to Ambient

CAS #: 23950-58-5

Molecular weight: 256.1

Structure:

Cl

Cl

O

N

H

CH3

C

CH3 CH

3. Non-labeled ligand: 17β-estradiol

Supplier: Sigma, St. Louis, MO

Catalog #: E8875

Batch #: 098K1372

Purity: 100%

CAS #: 50-28-2

4. Radioactive ligand: [

3

H]-17β-estradiol

Supplier: Perkin-Elmer, Boston, Massachusetts

Catalog #: NET517001MC

Batch #: 639068

Radiochemical purity: >97%

Specific activity: 162.9 Ci/mmol

Concentration of stock: 1.0 mCi/mL 

5. Positive control: 19-norethindrone

Supplier: Sigma, St. Louis, MO

Catalog #: N4128

Batch #: 030M1359

Purity: 99%

CAS #: 68-22-4

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6. Negative control: Octyltriethoxysilane

Supplier: Sigma, St. Louis, MO

Catalog # 440213

Batch #: 72596AMV

Purity: 98.58%

CAS #: 2943-75-1

7. Solvent/vehicle control: Ethanol

Justification for choice of 

solvent:

None reported.

Final Concentration: <3%

B. METHODS 

1. Preparation of Rat Uterine Cytosol (RUC): Trimmed uterine tissue from 85- to 100-day 

old female Crl:CD(SD) rats, which were ovariectomized approximately 7-10 days prior to 

being euthanized, was purchased from Charles River (Wilmington, MA). The uteri were 

weighed, minced and homogenized in ice-cold TEDG (Tris, EDTA, DTT, glycerol) + PMSF 

(phenylmethylsulfonyl fluoride) buffer, then 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 3.573 mg/mL 

using a protein kit compatible with DTT in the TEDG buffer (e.g., BioRad Protein Assay 

Kit). Cytosol was divided into aliquots (volume not reported) that were stored at −80 oC for 

up to 90 days until use.

2. Saturation (radioligand) Binding Experiment: A saturation binding experiment

measuring total and non-specific binding of [3H]-17β-estradiol was reportedly performed to 

demonstrate that the ER was present in reasonable concentrations and had the appropriate 

affinity for the native ligand. The conditions for the saturation binding experiment are

summarized in Table 1. Each run included three replicates of each test substance at each 

concentration, resulting in the 72 samples depicted in Table 2. 

TABLE 1. Summary of Conditions for Saturation Binding Experiment a

Source of receptor Rat uterine cytosol 

Concentration of radioligand (as serial dilutions) 0.03 – 3.0 nM

Concentration of non-labeled ligand (100X [radioligand]) 3.0 – 300 nM

Concentration of receptor Not ReportedSufficient to bind 40.77% of 

radioligand at 0.03nMb 

Temperature Not Reported 2 – 8 oC

Incubation time Not Reported16 hours

Composition of assay buffer Tris Not Reported 10 mM (pH 7.4)

EDTA Not Reported 1.5 mM

Glycerol Not Reported 10%

Phenylmethylsulfonyl fluoride Not Reported 1mM

DTT Not Reported 1mM

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

competitive binding experiment is presented in Table 3. 

Tubes were incubated with gentle vortexing for 16 to 20 hours at 4-8 °C. To separate bound 

from free estradiol, hydroxyapatite (HAP) slurry was added to each tube and vortexed (4 

times at 5 minute intervals). 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 bound [3H]-17β-estradiol, followed by vortexing, and 

centrifugation for 10 min at 1000 × g. An aliquot of supernatant was radioassayed by liquid

scintillation counting. The temperature was maintained at 4-8 oC throughout the assay prior 

to extraction with ethanol.

TABLE 3. Summary of Conditions for Competitive Binding Experiment a

Source of receptor Rat Uterine Cytosol 

Concentration of radioligand 1.0 nM 

Concentration of receptor Sufficient to bind 6.89-7.57% of 

radioligand

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

Temperature 4-8 °C 

Incubation time 16-20 hours 

Composition of assay buffer Tris 10 mM 

EDTA 1.5 mM 

Glycerol 10%

Phenylmethylsulfonyl fluoride 1 mM 

DTT 1 mM 

a Data were obtained from pages 17, 21, 41, 43, and 45 of the study report.

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Solubility of pronamide in ethanol and assay buffer was evaluated visually and no 

precipitation was noted. On the day of the assay, the specific activity of the stock solution 

[

3

H]-17β-estradiol was not adjusted for decay over time, and diluted in TEDG + PMSF 

buffer to achieve a final concentration of 1.0 nM. For each batch of cytosol, the optimal 

protein concentration was determined by testing serial amounts of protein per tube, using 1.0 

nM radiolabeled estradiol, until a concentration was reached that bound 6.89-7.57% of the 

total radioactivity added. Serial dilutions of the test substance, 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 run contained three replicates of each test substance at each 

concentration, resulting in a total of 112 samples.

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

Pronamide

Positive control Negative control Reference Chemical

19-norethindrone Octyltriethoxysilane Non-labeled

17β-estradiol

Tubes 83-106 c Tubes 35-58 c Tubes 59-82 c Tubes 1-34 and 107-112 c

10−10 10−8.5 10−10 Solvent control or blank 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 41-42 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 + PMSF 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 112 tubes per run. 

d Solvent is ethanol in Tubes 11-13 and 107-109.

C. DATA ANALYSIS: For the competitive binding assay, GraphPad Prism was used to 

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

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

estimated. For parameters reported from the competitive binding experiment (log IC50 and 

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

were calculated for the composite three runs.

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:

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). 

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

on the fitted response curve within the range of the data is above 75% (i.e., 

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

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

concentration groups in the data is above 75%. 

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 

Page 101 of 285
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II. RESULTS

A. SATURATION BINDING EXPERIMENT: Data pertaining to the saturation binding 

experiment are in Table 5.

 

TABLE 5. Saturation Binding Experiment of 17β-Estradiol with Estrogen Receptor from Rat Uterine 

Cytosola

Parameter Run 1b Run 2 Run 3 Runs 1-3

R2 (unweighted) 0.9617 N/A N/A N/A 

Bmax (nM) 0.07097 N/A N/A N/A 

Bmax (fmol/100 μg protein) 59.28 N/A N/A N/A 

Kd (nM) 0.1032 N/A N/A N/A 

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

binding experiments are summarized in Table 6 and presented graphically in Figures 1-3. 

Pronamide did not inhibit specific binding at concentrations up to 10−3 M in all three runs; 

however, there was an apparent increase in specific binding of the natural ligand at the 

highest concentration of pronamide tested (10−3 M). At pronamide concentrations of 10−10

to 10−4 M, the percent of total binding was 85.8 – 91.7% in Run 1, 97.9 – 101.3% in Run 2, 

and 96.8 – 103.2% in Run 3. However, at the highest concentration tested (10−3 M), 

pronamide increased specific binding to 101.4, 141.9, and 120.8% in Runs 1, 2, and 3, 

respectively. Across all three runs, specific binding averaged 95.7 – 98.2% at 10−10 to 10−4

M of pronamide, and 121.4% at 10−3 M. No explanation was provided regarding this 

apparent increase in specific binding. An IC50 and RBA were not calculated for pronamide 

as the minimum percent binding inhibition was ≥50%. 

The reference compounds performed as expected in the assay. Octyltriethoxysilane had no 

effect on binding of the radiolabeled ligand, and 17β-estradiol and 19-norethindrone 

inhibited binding at the expected concentrations. The mean log IC50 was −5.5 M for 

19-norethindrone and −8.9 M for 17β-estradiol. The mean RBA was 0.033% for 

19-noirethindrone. 

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

responses indicated no drift in the study assay, and additional runs were unnecessary. As 

pronamide had <25% inhibition of binding at concentrations up to 10−3

 M in all three runs, 

it is classified as not interactive (0) in this assay (Table 7).

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

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

r

2 (unweighted), 17β-estradiol 0.9974 0.9990 0.9997 0.9974-0.9997

19-norethindrone 0.9995 0.9999 0.9997 0.9995-0.9999

Pronamide 0.8091 0.9943 0.9360 0.8091-0.9943

Log IC50 (M), 17β-estradiol −8.917 −8.948 −8.942 −8.936

19-norethindrone −5.459 −5.462 −5.435 −5.451

Pronamide NA NA NA NA

IC50 (M), 17β-estradiol 1.209 x 10−9 1.127 x 10−9 1.142 x 10−9 1.159 x 10−9

19-norethindrone 3.477 x 10−6 3.448 x 10−6 3.637 x 10−6 3.544 x 10−6

Pronamide NA NA NA NA

Log RBA, 19-norethindrone −3.459 −3.486 −3.503 −3.485

Pronamide NA NA NA NA

RBA (%), 19-norethindrone 0.035 0.033 0.031 0.033

Pronamide NA NA NA NA

a Data were obtained from pages 34-35 of the study report.

b The mean is reported for the concurrent replicates within each run.

c The range is reported for r2

; the mean is reported for all other parameters.

NA Not applicable

r

2 Goodness of fit

RBA Relative binding affinity

TABLE 7. Binding Classification of Pronamide with Estrogen Receptor a

Run 1 2 3 Mean c Binding Classification d

Classification category value b 0 0 0 0 Not interactive

a Data were obtained from page 35 of the study report.

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 Mean of three runs expressed to the tenths place

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

FIGURE 3: Mean and Standard Error of the Mean for 3 Independent Assays- Relative 

ER Binding Activity for Pronamide. 

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FIGURE 4. Percentage E2 Bound to the Estrogen Receptor in the Presence of Unlabeled 

E2, 19-Norethindrone or Octyltriethoxysilane, Run 1.

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

E2, 19-Norethindrone or Octyltriethoxysilane, Run 2.

FIGURE 6. Percentage E2 Bound to the Estrogen Receptor in the Presence of Unlabeled 

E2, 19-Norethindrone or Octyltriethoxysilane, Run 3. 

Page 105 of 285
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PRONAMIDE/101701 OCSPP 890.1250/ OECD None

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

properly, each run was evaluated using the following criteria (Table 8): 

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

17β-estradiol fitted curve parameters

Loge residual SD ≤2.35 −0.11 to 1.06 X

Top (% binding) 94 to 111 99-101 X

Bottom (% binding) −4 to 1 −1.0 to −0.1 X

Hill Slope (log10(M)−1) −1.1 to −0.7 −1.0 to −0.98 X

Weak Positive control (19-norethindrone) fitted curve parameters b

Loge residual SD NA −1.1 to 0.21 X

Top (% binding) NA 99-100 X

Bottom (% binding) NA −1.2 to 0.6 X

Hill Slope (log10(M)−1) NA −1.1 to −0.98 X

Solvent concentration

Ethanol ≤3% <3% X

Negative control (octyltriethoxysilane) does not displace 

more than 25% of [

3

H]-17β-estradiol from the ER on 

average across all concentrations

≤25% ≤17% X 

a Data were obtained from page 34 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 to −0.98. 

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

However, due to the apparent increase (>100%) in specific binding observed at the highest 

concentration of pronamide tested (10−3 M), the percent binding at the top plateau in Runs 1 

and 2 (133.4 and 174.2%, respectively) was not within 25 percentage points of the lowest 

concentration of the estradiol standard (97.5 and 96.7%, respectively). In Run 3, the percent 

binding at the top plateau for pronamide (120.9%) was within 25 percentage points of the 

lowest concentration of the estradiol standard (98.1%). Examination across the runs 

indicated consistency of the Hill slope, placement along the X-axis, and top and bottom 

plateaus.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Based on the combined responses in each of three 

independent estrogen receptor binding assays, it was determined that pronamide had no 

appreciable effect in the binding of the reference estrogen (radiolabeled 17β-estradiol) at 

any concentration tested (up to 10−3 M). The results of the in vitro estrogen receptor binding 

Page 106 of 285
Estrogen Receptor Binding (Rat Uterine Cytosol) (2012) / Page 13 of 13

PRONAMIDE/101701 OCSPP 890.1250/ OECD None

assay using rat uterine cytosol indicate that, under the conditions of this study, pronamide 

was determined to be negative (not interactive) for estrogen receptor binding. 

B. AGENCY COMMENTS: For the competitive binding experiment, pronamide did not 

inhibit specific binding at concentrations up to 10−3 M, but there was an apparent increase in 

specific binding of the [3H]-17β-estradiol in each run at the highest pronamide concentration 

tested, 10−3 M. Across all three runs, specific binding averaged 95.7 – 98.2% at 10−10 to 

10−4 M of pronamide, and 121.4% at 10−3 M. No explanation was provided regarding this 

apparent increase in specific binding. An IC50 and RBA were not calculated for pronamide 

because the minimum percent binding inhibition was ≥50%. As the minimum binding 

observed with pronamide was >75% at concentrations up to 10−3 M across all runs, 

pronamide is classified as “not interactive” under conditions of this assay. 

The performance criteria were generally met for pronamide, and the reference compounds 

performed as expected in the assay. The negative control, octyltriethoxysilane, had no 

effect on binding, and the binding curves for 17β-estradiol and 19-norethindrone showed 

that increasing concentrations of each compound displaced [3

H]-17β-estradiol in a manner 

consistent with one-site binding. The mean log IC50 was −5.5 M for 19-norethindrone and 

−8.9 M for 17β-estradiol, and the mean RBA was 0.033% for 19-noirethindrone compared 

to the natural ligand. 

C. STUDY DEFICIENCIES: None. 

Page 107 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE) 

Study Type: OCSPP 890.1300, Estrogen Receptor Transcriptional Activation 

EPA Contract No. EP10H001452 

Task Assignment No. 2-19-2012 (MRID 48619105) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

CSS-Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

Michelle Sharpe-Kass, M.S. Date: 2/15/2012

Secondary Reviewer Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 2/29/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 3/02/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 3/02/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 108 of 285
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 109 of 285
PRONAMIDE/101701 

Estrogen Receptor Transcriptional Activation (2012) I Page I of 10 

OCSPP 890.1300/ OECD 455 

Primary Reviewer: _K==h=in"""--=-0_..;:;o.i...=.;.M=.=D-'-.---------

Health Effects Division 

Secondary Reviewer: Minerva Mercado, Ph.D. 

Health Effects Division 

DATA EVALUATION RECORD 

STUDY TYPE: Estrogen Receptor Transcriptional Activation (Human cell Line, HeLa-9903); 

OCSPP 890.1300; OECD 455. 

PCCODE: 101701 DP BARCODE: D398506 

TXR#: 0056255 CAS No.: 23950-58-5 

TEST MATERIAL (PURITY): Propyzamide (96.2% a.i.) 

SYNONYMS: Pronamide; 3,5-dichloro-N-(l, l-dimethyl-2-propynyl)benzamide 

CITATION: LeBaron, M.J.; Kan, H.L. (2012) Evaluation of pronamide in an in vitro 

estrogen receptor transcriptional activation assay in human cell line 

hERa-HeLa-9903. Toxicology & Environmental Research and Consulting, The 

Dow Chemical Company, Midland, MI. Laboratory Report No.: 101182, 

January 4, 2012. MRID 48619105 . Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 

TEST ORDER#: CON-101701-37 

EXECUTIVE SUMMARY: In an estrogen receptor transcriptional activation assay (MRID 

48619105), HeLa-9903 cells cultured in vitro were exposed to pronamide (96.2% a.i.; Lot # 

XG1088R301) at concentrations of 10- 10 M to 10-35 M in DMSO (final concentration 0.1%). The 

experiments were performed using 96-well plates and each pronamide concentration was tested in 

triplicate (3 wells/plate). Cells were exposed to the test agent for approximately 24 hours to induce 

reporter (luciferase) gene products. Luciferase expression in response to activation of the estrogen 

receptor was measured upon addition of a luciferase substrate and detection with a luminometer 

with acceptable sensitivity. 

Pronamide was tested up to the limit of solubility, 10-4 M. The mean RPCMax for pronamide was 

1.4% for run 1, 3.5% for run 2 and 7.6% for run 3, and the associated PCMax values were 10-

4

, 

10-s, and 1 o-s M, respectively. Performance criteria for the reference chemicals were met, with 

the following exceptions: the Hill slope for l 7a-estradiol was slightly lower than expected in run 

2, and the log PCso and log PC10 for l 7a-methyltestosterone were slightly lower than expected in 

run 4. These results indicate an increased sensitivity of the assay to weak agonists. Because the 

RPCMax < PC1 0 in three assay runs, pronamide was considered negative for estrogen receptor 

transcriptional activation in this test system. 

Page 110 of 285
Estrogen Receptor Transcriptional Activation (2012) / Page 2 of 10

PRONAMIDE/101701 OCSPP 890.1300/ OECD 455 

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 111 of 285
Estrogen Receptor Transcriptional Activation (2012) / Page 3 of 10

PRONAMIDE/101701 OCSPP 890.1300/ OECD 455 

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Substance: Pronamide

Description: Technical, white to off-white powder, MW 256.1

Source: Dow AgroSciences, LLC

Lot/Batch #: Lot # XG1088R301

Purity: 96.2%

Solubility: 0.1M in DMSO, insoluble in water

Volatility: NR

Stability: 2 years

Storage conditions: Ambient

Vapor pressure: 4.97 Pa

CAS #: 23950-58-5

Structure:

2. Reference substances

17β-estradiol (strong estrogen; positive control)

Supplier: Sigma, St Louis, MO

Catalogue and Batch #: Cat# E-8875 Lot # 079K0131

Purity: 100%

CAS # : 50-28-2

17α-estradiol (weak estrogen)

Supplier: Sigma, St Louis, MO

Catalogue and Batch #: Cat # E8750 Lot # 029K4116

Purity: ≥99.5%

CAS # : 57-91-0

Corticosterone (negative compound)

Supplier: Sigma, St Louis, MO

Catalogue and Batch #: Cat# C-2505, Lot # 010M2010

Purity: 100%

CAS # : 50-22-6

17α-methyltestosterone (very weak agonist)

Supplier: Sigma, St Louis, MO

Catalogue and Batch #: Cat # M-7252, Lot # 060M1543V

Purity: 99%

CAS # : 58-18-4

3. Vehicle(s)

Solvent: Dimethyl Sulfoxide; Sigma-Aldrich, Cat # 276855, Lot # 68996LMV & 

36296DM, Purity ≥ 99.9%

Solvent control 

(final concentration):

0.1%

Page 112 of 285
Estrogen Receptor Transcriptional Activation (2012) / Page 4 of 10

PRONAMIDE/101701 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 RT PCR. 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 (DCC-FBS; in-house prep: Lot # DCC-FBS 062410), in 

an incubator under 5% CO2 at 37oC. Upon reaching 75-90% confluence, cells were 

subcultured prior to exposure to the test material. Passages 6, 8 and 11 were used in the 

assays reported in this study. DCC-FBS was prepared at the performing laboratory using a 

protocol identical to that provided in the guideline. 

2. Transcriptional Activation Assays: For each test, cells were plated at a density of 

1-1.5 × 104 cells/100 μL medium/well in a 96 well plate and allowed to attach for 3 hours. 

The growth media was replaced with media containing serial log dilutions of pronamide in 

DMSO (0.1% total final concentration). Cells were incubated for approximately 24 hours at

approximately 37°C. Cytotoxicity was determined by the CellTiter96 Aqueous One 

Solution Cell Proliferation Assay Kit (Promega, Madison, WI). Transcriptional activation 

of the estrogen receptor was determined using Steady-Glo® Luciferase Assay System 

(Promega, Madison, WI). The luminometer was able to detect linear responses down to 100 

counts per second, and can detect ~5 cells in 100 μL of medium.

a. Preliminary Test: A preliminary test evaluating concentrations ranging from 10−3.5 M to 

10−9 M was conducted to determine the appropriate concentration range and to determine 

concentrations resulting in insolubility and/or cytotoxicity. 

b. Proficiency Chemicals: Laboratory validation assays with the 10 proficiency chemicals 

was performed. These non-GLP unpublished experimental results were reported to have 

demonstrated laboratory proficiency, and are included in a separate report.

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 100μM. PCMax approx. 50% of 

PC. Binds to 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.

Page 113 of 285
Estrogen Receptor Transcriptional Activation (2012) / Page 5 of 10

PRONAMIDE/101701 OCSPP 890.1300/ OECD 455 

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 relative transcriptional activity to the 1 nM E2 positive control 

(PC), the luminescence signals from the concurrent plate were analyzed by subtracting the 

mean value of the vehicle control from each well value to normalize the data; each 

normalized value was then divided by the mean value of the normalized PC. The resulting 

value was multiplied by 100 in order to express relative transcriptional activity as a 

percentage of the PC. Graph Pad Prism v. 5.0 (GraphPad Software, Inc., La Jolla, CA) was 

used to calculate the EC50, PC10, PC50, RPCMax, and PCMax for pronamide when applicable. 

The test material was defined as negative for inducing estrogen receptor transcriptional 

activation if the RPCMax < PC10 in at least 2 of 2 (or 2 of 3) runs. Log EC50 and Hill slope 

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 

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: In order to identify a suitable top concentration for use in the 

transcriptional activation assays, preliminary cytotoxicity and precipitation assays were 

conducted. No cytotoxicity was observed at any concentration. Precipitation was observed 

after 24 hours of treatment with 10−3.5 M pronamide. Based on these results, logarithmically 

increasing concentrations from 10−10 to 10−4 M were selected for the assay.

Page 114 of 285
Estrogen Receptor Transcriptional Activation (2012) / Page 6 of 10

PRONAMIDE/101701 OCSPP 890.1300/ OECD 455 

TABLE 1. Preliminary Test for Solubility, Cytotoxicity, and Concentration-Selection for Pronamidea

Concentration (M) % Viability Comments

10−3.5 121.0 Precipitation observed after 24 hours treatment

10−4 138.7

10−5 130.2

10−6 139.1

10−7 160.2

10−8 133.9

10−9 120.2

E2 1nM 137.7

VC b 100.0

a Data were obtained from page 47 of the study report. b VC = Vehicle control

B. Positive and Negative Reference Chemicals

1. Proficiency Chemicals: The results of the proficiency test were not reported

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 Positive if PC10 used as cutoff; negative if 

PC50 used as cut off b

Atrazine Negative Negative

Corticosterone Negative Negative

 a Proficiency testing data were not included in the study report; instead, they were compiled in a separate

proficiency/validation report. b

 Dibutyl Phthalate induced a weakly positive response consistent with prior studies and the validation report forthis

assay system. Classification based on PC50 would be clearly negative for DBP; however, using the PC10 calculation 

results in a positive response. Consistent assay performance for all the other proficiency chemicals, as well as QC 

parameters for each assay, indicated acceptable assay responsiveness.

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 log PC50, log PC 10, log EC50 and Hill Slope for the reference 

chemicals 17β-estradiol, 17α-estradiol, corticosterone and 17α-methyltestosterone all 

performed within the acceptable range with the following exceptions: the Hill Slope for 

17α-estradiol was slightly lower than the acceptable range in Run 2, and the log PC50 and 

log PC10 for 17α-methyltestosterone were slightly lower than the acceptable range in Run 4. 

For 17α-methyltestosterone, the mean RPCMax was 60.0% for the first run, 80.0% for the 

second run, and 109.4% for the fourth run. These results indicate an increased sensitivity to 

weak agonists. 

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Estrogen Receptor Transcriptional Activation (2012) / Page 7 of 10

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TABLE 3. Performance Criteria for Reference Chemicalsa

Reference Chemical 

Parameter

Acceptable 

Range

Values Acceptable

Run 1 Run 2 Run 4 Yes No

17β-estradiol

Log PC50 −11.4 to −10.1 −10.6 −10.6 −11.0 X

Log PC10 <−11 −11.9 −12.4 −12.9 X

Log EC50 −11.3 to −10.1 −10.5 −10.7 −11.2 X

Hill Slope 0.7 to 1.5 1.0 1.4 0.7 X

Test range 10−14 to 10−8 M 10−14 to 10−8 M 10−14 to 10−8 M 10−14 to 10−8 M

17α-estradiol

Log PC50 −9.6 to −8.1 −8.7 −9.0 −9.4 X

Log PC10 −10.7 to −9.3 −10.0 −10.0 −10.6 X

Log EC50 −9.6 to −8.4 −8.7 −8.9 −9.0 X

Hill Slope 0.9 to 2.0 1.0 0.7 1.0 X

Test range 10−12 to 10−6 M 10−12 to 10−6 M 10−12 to 10−6 M 10−12 to 10−6 M

Corticosterone

Test range 10−10 to 10−4 M 10−10 to 10−4 M 10−10 to 10−4 M 10−10 to 10−4 M X

17α-methyltestosterone

Log PC50 −6.0 to −5.1 −5.4 −6.1 −8.0 Xb

Log PC10 −8.0 to −6.2 −8.2 −8.8 −8.9 Xb

Test range 10−11 to 10−5 M 10−11 to 10−5 M 10−11 to 10−5 M 10−11 to 10−5 M X a Data were obtained from page 48 of the study report. b Indicated these parameters were slightly out of the suggested range but the values indicated increased sensitivity of the 

assay system (i.e. decreased log PC50 and logPC10 for 17α-methyltestosterone).

C. DEFINITIVE ASSAY

1. Vehicle and Positive Controls: Data for the vehicle and positive controls are included in 

Table 4. The overall mean TA value, expressed as arbitrary light units, for the vehicle 

control was 1539.6 for the first assay, 3395.4 for the second assay and 2323.4 for the fourth

assay. The mean normalized value for the positive control was 11729.0 for the first assay, 

19724.6 for the second assay and 14443.2 for the fourth assay. The PC50 (50% of the 

maximum response) for E2 in this assay is 5864.5 for the first assay, 9862.3 for the second 

assay and 7221.6 for the fourth assay and the PC10 (10% of the maximum response) is

1172.9 for the first assay, 1972.5 for the second assay and 1444.3 for the fourth assay. 

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 1539.6 244.4 11729.0 1251.0 7.6

2 3395.4 598.3 19724.6 3250.5 5.8

4 2323.4 261.9 14443.2 1361.8 6.2

a Data were obtained from page 49 of the study report. 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 

pronamide during the three assay runs is presented in Table 5. The concentration-response 

curves depicting fold induction of relative transcriptional activation is presented in Figures 

1-3. The mean RPCMax for pronamide was 1.4% for the first assay, 3.5% for the second 

assay, and 7.6% for the fourth assay, and the associated PCMax values were 10−4

, 10−5, and 

10−5 M, respectively. Because the RPCMax < PC10 in all three valid runs, pronamide was

considered negative for estrogen receptor transcriptional activation in this test system. 

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Estrogen Receptor Transcriptional Activation (2012) / Page 8 of 10

PRONAMIDE/101701 OCSPP 890.1300/ OECD 455 

TABLE 5. Relative Transcriptional Activation (RTA) of Pronamidea

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

Run 1 Run 2 Run 4

Conc. (M) Mean SD Mean SD Mean SD

10−3.5 −0.1 3.2 -- -- -- --

10−4 1.4 0.7 1.0 2.1 5.6 4.5

10−5 0.9 1.5 3.5 3.0 7.6 4.9

10−6 −0.9 0.3 1.2 2.5 3.7 4.0

10−7 −4.1 1.7 1.8 0.3 4.2 1.9

10−8 −1.0 2.1 −1.8 3.6 5.2 0.9

10−9 0.0 2.1 −0.6 4.1 1.7 0.3

10−10 -- -- 2.2 3.8 3.1 2.4

Log EC50 NA NA NA

Hill Slope NA NA NA

RPCMax 1.4% 3.5% 7.6%

PCMax 10−4 10−5 10−5

PC50 NA NA NA

PC10 NA NA NA

a Data were obtained from page 50 of the study report. 

NA = Not Applicable

FIGURE 1. Fold Induction of Relative Transcription Activation (RTA) of Pronamide

Compared to the Positive Control, Run 1. 

Page 117 of 285
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PRONAMIDE/101701 OCSPP 890.1300/ OECD 455 

FIGURE 2. Fold Induction of Relative Transcription Activation (RTA) of Pronamide 

Compared to the Positive Control, Run 2. 

FIGURE 3. Fold Induction of Relative Transcription Activation (RTA) of Pronamide 

Compared to the Positive Control, Run 3. 

3. Performance Criteria: The laboratory proficiency assays using the required reference 

compounds were not included in the study report and were not available to the reviewer. 

The log PC50, log PC10, log EC50 and Hill Slope for the reference chemicals 17β-estradiol, 

17α-estradiol, corticosterone and 17α-methyltestosterone all performed within the 

Page 118 of 285
Estrogen Receptor Transcriptional Activation (2012) / Page 10 of 10

PRONAMIDE/101701 OCSPP 890.1300/ OECD 455 

acceptable range with the following exceptions: the Hill Slope for 17α-estradiol was 

slightly lower than the acceptable range in Run 2, and the log PC50 and log PC10 for 17αmethyltestosterone were slightly lower than the acceptable range in Run 4. These results 

indicate an increased sensitivity to weak agonists, and therefore do not negatively impact the 

validity of the study. Triplicate samples of the PC and the VC were included in each plate, 

and the mean luciferase activity of the PC was greater than 4-fold that of the mean vehicle 

control on each plate. The variability among raw data triplicates (i.e., luminescence 

intensity data) was minimal (CV less than 20%), indicating a reliable PC10, and the results 

were reproducible among runs. 

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS’ CONCLUSIONS: Pronamide did not increase cytotoxicity at the 

concentrations tested. Based on the combined responses in each of three independent 

estrogen receptor transactivation assays, it was determined that pronamide treatment did not 

result in ER-mediated transcriptional activation up to the highest acceptable concentration 

tested (10−4 M).

B. AGENCY COMMENTS: Pronamide was tested up to the limit of solubility, 10−4

 M. The 

mean RPCMax was 1.4% for the first assay, 3.5% for the second assay and 7.6% for the 

fourth assay, and the associated PCMax values were 10−4, 10−5, and 10−5 M, respectively. 

Performance criteria were met; the Log PC50, Log PC 10, Log EC50 and Hill Slope for the 

reference chemicals 17β-estradiol, 17α-estradiol, corticosterone and 17α-methyltestosterone 

all performed within the acceptable range with the following exceptions: the Hill Slope for 

17α-estradiol was slightly lower than the acceptable range in Run 2, and the log PC50 and 

log PC10 for 17α-methyltestosterone were slightly lower than the acceptable range in Run 4. 

These results indicate an increased sensitivity to weak agonists. Based on the results of this 

assay, pronamide did not interact with the human estrogen receptor to cause transcriptional 

activation under the conditions of this assay. 

C. STUDY DEFICIENCIES: The following deficiency was noted: 

• The proficiency chemicals were slightly outside of the acceptable range, but indicate 

increased sensitivity to weak agonists. 

Page 119 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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ԢԭԞԪԯԦԡ  

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ԭՊՇՈՑՒԹՅՁԼԽ     ԭՍՊՁՌՑ 

ԠՇՅՅՇՆՆԹՅԽ  ԭՊՇՆԹՅՁԼԽ

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԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԠԹՅԺՊՁԼԿԽԢՆՎՁՊՇՆՅԽՆՌԹՄԦՆԻ    ԡԹՌԽ

԰ԽԻՇՆԼԹՊՑԯԽՎՁԽՏԽՊԱԽՊՁ԰ԪՑԽՊՋ      ԰ՁԿՆԹՌՍՊԽ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԠԹՅԺՊՁԼԿԽԢՆՎՁՊՇՆՅԽՆՌԹՄԦՆԻ    ԡԹՌԽ

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ԯՁՋՃԞՋՋԽՋՋՅԽՆՌԭՊՇԻԽՋՋԩԽԹԼԽՊԢԭԞԬԭԭԢԣԢԡԢԯԟ ԡԹՌԽ

ԞԼԼՁՌՁՇՆԹՄԯԽՎՁԽՏԽՊԠԹՌՀԽՊՁՆԽԞՍԺԽԽ ԰ՁԿՆԹՌՍՊԽ

԰ԽՆՁՇՊ԰ԻՁԽՆՌՁՋՌԢԭԞԬԭԭԢԣԢԡԢԯԟ     ԡԹՌԽ

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ԠԦԱԞԱԦԬԫ ԶՇՊՃ ԡԬ  ԭՊՇՆԹՅՁԼԽ  ԰ՀՇՊՌՌԽՊՅ ԯԽՈՊՇԼՍԻՌՁՇՆ ԞՋՋԹՑ ՏՁՌՀ ՌՀԽ ԣԹՌՀԽԹԼ ԪՁՆՆՇՏ


ԭՁՅԽՈՀԹՄԽՋ ՈՊՇՅԽՄԹՋ ԭԽՊԾՇՊՅԽԼ ԺՑ ԰ՅՁՌՀԽՊՋ ԳՁՋԻՁԽՆՌ 
ԾՇՊՅԽՊՄՑ ԰ՈՊՁՆԿԺՇՊՆ ԰ՅՁՌՀԽՊՋ ԩԹԺՇՊԹՌՇՊՁԽՋ

Digitally signed by ANDREW 

SAYER 

DN: c=US, o=U.S. 

Government, ou=USEPA, 

ou=Staff, cn=ANDREW SAYER, 

dnQualifier=0000051409 

Date: 2015.06.09 13:53:51 

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԴԹՊԽՀԹՅԪԹՋՋԹԻՀՍՋԽՌՌՋ԰ՍԺՅՁՌՌԽԼ ԺՑԡՇՏԠՀԽՅՁԻԹՄԠՇՅՈԹՆՑ԰ՌՍԼՑԫՇ ԧԹՆՍԹՊՑ



ԫՇՌԽԱՀԽԲ԰ԢԭԞԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿԭՊՇԿՊԹՅ
Ԣԡ԰ԭԱՁԽՊՋԻՊԽԽՆՁՆԿԺԹՌՌԽՊՑՁՋԻՇՅՈՊՁՋԽԼՇԾ

ԽՄԽՎԽՆՋԻՊԽԽՆՁՆԿԹՋՋԹՑՋՁՆՌԽՆԼԽԼՌՇՁԼԽՆՌՁԾՑԹԻՀԽՅՁԻԹՄ0ՋՄՁՃԽՄՑԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՁԽՁՌՋՈՇՌԽՆՌՁԹՄՌՇ

ՁՆՌԽՊԹԻՌՏՁՌՀՌՀԽԽՋՌՊՇԿԽՆԹՆԼՊՇԿԽՆՇՊՌՀՑՊՇՁԼ
ԢԞՇՊԱՈԹՌՀՏԹՑՋԱՀԽՊՇԺՍՋՌՆԽՋՋՇԾՌՀԽԱՁԽՊ

ԺԹՌՌԽՊՑՁՋԺԹՋԽԼՇՆՌՀԽՋՌՊԽՆԿՌՀՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՌՇՁԼԽՆՌՁԾՑՈՇՌԽՆՌՁԹՄԽՆԼՇԻՊՁՆԽԺՁՇԹԻՌՁՎՁՌՑՏՁՌՀ

ԻՇՅՈՄԽՅԽՆՌԹՊՑԽՆԼՈՇՁՆՌՋՏՁՌՀՁՆՌՀԽԹՋՋԹՑՏՀԽՊԽԹՎԹՁՄԹԺՄԽԹՆԼՊԽԼՍՆԼԹՆԻՑԹԻՊՇՋՋՌՀԽԺԹՌՌԽՊՑԱՀՍՋ

ՌՀԽՊԽՋՍՄՌՋՇԾԽԹԻՀՁՆԼՁՎՁԼՍԹՄԹՋՋԹՑՋՀՇՍՄԼՆՇՌԺԽԻՇՆՋՁԼԽՊԽԼՁՆՁՋՇՄԹՌՁՇՆԺՍՌՊԹՌՀԽՊՋՀՇՍՄԼԺԽԻՇՆՋՁԼԽՊԽԼ

ՁՆՌՀԽԻՇՆՌԽՐՌՇԾՇՌՀԽՊԹՋՋԹՑՋՁՆՌՀԽԺԹՌՌԽՊՑԹՋՏԽՄՄԹՋԬՌՀԽՊ԰ԻՁԽՆՌՁԾՁԻԹՄՄՑԯԽՄԽՎԹՆՌԦՆԾՇՊՅԹՌՁՇՆ
Ԭ԰ԯԦ

ԦՆՇՊԼԽՊՌՇԼԽՌԽՊՅՁՆԽՁԾԹԻՀԽՅՁԻԹՄՀԹՋՌՀԽՈՇՌԽՆՌՁԹՄՌՇՁՆՌԽՊԹԻՌՏՁՌՀՌՀԽԢԞՇՊԱՈԹՌՀՏԹՑՋԹԴԽՁԿՀՌՇԾ

ԢՎՁԼԽՆԻԽ
ԴՇԢԽՎԹՄՍԹՌՁՇՆՇԾԱՁԽՊԹՋՋԹՑՊԽՋՍՄՌՋՁՆԻՇՅԺՁՆԹՌՁՇՆՏՁՌՀՌՀԽԾՁՆԼՁՆԿՋՁՆՌՀԽԬ԰ԯԦՋՀՇՍՄԼ

ԺԽՍՆԼԽՊՌԹՃԽՆ
ՊԽԾԽՊՌՇՌՀԽԴՇԢԡՇԻՍՅԽՆՌ

ԢԵԢԠԲԱԦԳԢ԰ԲԪԪԞԯԶ

ԱՀԽ ԼԹՑ ՋՀՇՊՌՌԽՊՅ ՊԽՈՊՇԼՍԻՌՁՇՆ ԹՋՋԹՑ ՇԾ ՈՊՇՆԹՅՁԼԽ 
ԹՄՋՇ ՃՆՇՏՆ ԹՋ ՈՊՇՈՑՒԹՅՁԼԽ  ՈՍՊՁՌՑ ՏՁՌՀ

ԾԹՌՀԽԹԼ ՅՁՆՆՇՏՋ 
ԭՁՅԽՈՀԹՄԽՋ ՈՊՇՅԽՄԹՋ ՏԹՋ ԻՇՆԼՍԻՌԽԼ ՍՆԼԽՊ ԾՄՇՏՌՀՊՇՍԿՀ ԻՇՆԼՁՌՁՇՆՋ ԞԼՍՄՌ ԾՁՋՀ ՁՆ 

ՋՈԹՏՆՁՆԿ ԿՊՇՍՈՋ 
 ՅԹՄԽՋ ԹՆԼ  ԾԽՅԹՄԽՋ ՁՆ ԽԹԻՀ ԿՊՇՍՈ  ԿՊՇՍՈՋՌՊԽԹՌՅԽՆՌ ԻԹ  ՅՇՆՌՀՋ ՇՄԼ ՏԽՊԽ

ԽՐՈՇՋԽԼՌՇՈՊՇՆԹՅՁԼԽԹՌՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋՇԾ
ԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩ

ՅԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽԩԬԮ
ԻՇՆՌՊՇՄՋԹՆԼՅԿԹՁԩԱՀԽՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄԻՇՆՋՁՋՌԽԼՇԾԼՁՅԽՌՀՑՄԾՇՊՅԹՅՁԼԽ
ԡԪԣԹՌԹԾՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՅԩԩԱՀԽՌԽՋՌՋՑՋՌԽՅՏԹՋ

ՅԹՁՆՌԹՁՆԽԼ ԹՌ  ՌՇ Շ

Ԡ ԹՆԼ Թ Ոԥ ՇԾ  ՌՇ   ԲՆՄԽՋՋ ՇՌՀԽՊՏՁՋԽ ՋՈԽԻՁԾՁԽԼ ԹՄՄ ՊԽՋՍՄՌՋ ԹՊԽ ՊԽՈՇՊՌԽԼ

ԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

԰ՍՊՎՁՎԹՄ ՏԹՋ ՆՇՌ ԹԼՎԽՊՋԽՄՑ ԹԾԾԽԻՌԽԼ ԺՑ ՌՊԽԹՌՅԽՆՌ ԹՌ ՌՀԽ  ԹՆԼ  ՅԿ ԹՁԩ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԱՀԽ ՀՁԿՀ

ԻՇՆԻԽՆՌՊԹՌՁՇՆ ՌՊԽԹՌՅԽՆՌ 
 ՅԿ ԹՁԩ ՏԹՋ ՌԽՊՅՁՆԹՌԽԼ ՇՆ ԡԹՑ  ԼՍԽ ՌՇ ՅՇՊԺՁԼՁՌՑ 
ՊԽՈՇՊՌԽԼ ԹՋ ՄՇՋՋ ՇԾ

ԽՉՍՁՄՁԺՊՁՍՅԹՆԼՄԽՌՀԹՊԿՑՊԽՋՍՄՌՁՆԿՁՆՌՀԽԹՋՋԽՋՋՅԽՆՌՇԾՇՆՄՑՌՏՇՌՊԽԹՌՅԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԱՀԽՊԹՌՁՇՆԹՄԽԾՇՊ

ՋԽՄԽԻՌՁՇՆՇԾՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՏԹՋՆՇՌՈՊՇՎՁԼԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԦՆ ՌՀԽ ՊԽՅԹՁՆՁՆԿ ՌՏՇ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄՋ ՈՊՇՆԹՅՁԼԽ ԽՐՈՇՋՍՊԽ ՏԹՋ ՆՇՌ ԹՋՋՇԻՁԹՌԽԼ ՏՁՌՀ Թ ԼՁԾԾԽՊԽՆԻԽ ՁՆ ԺՇԼՑ

ՄԽՆԿՌՀՇՊԺՇԼՑՏԽՁԿՀՌԾՇՊԽՁՌՀԽՊՋԽՐԫՇԽԾԾԽԻՌՋՇՆՋԽԻՇՆԼԹՊՑՋԽՐԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋՇՊԻՄՁՆՁԻԹՄՋՁԿՆՋՇԾՌՇՐՁԻՁՌՑ


ՁԽԺԽՀԹՎՁՇՊԹՄԹՆԼՇՌՀԽՊՋՍԺՄԽՌՀԹՄԽԾԾԽԻՌՋՏԽՊԽՇԺՋԽՊՎԽԼԣԽԻՍՆԼՁՌՑՏԹՋՄՇՏԽՊԹՌՌՀԽՅԿԹՁԩ

ԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՈԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՊԽՄԹՌՁՎԽՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԣԽՊՌՁՄՁՌՑՏԹՋՋՁԿՆՁԾՁԻԹՆՌՄՑՄՇՏԽՊ


ՈԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԹՌՌՀԽՅԿԹՁԩԻՇՆԻԽՆՌՊԹՌՁՇՆԪԽԼՁԹՆՌՍԺԽՊԻՄԽՋԻՇՊԽՋՁՆՅԹՄԽԾՁՋՀ

ՏԽՊԽ  ԹՆԼ  ՁՆ ՌՀԽ  ԹՆԼ  ՅԿ ԹՁԩ ՌՊԽԹՌՅԽՆՌՋ ՊԽՋՈԽԻՌՁՎԽՄՑ ԻՇՅՈԹՊԽԼ ՌՇ  ՁՆ ՌՀԽ ՆԽԿԹՌՁՎԽ

ԻՇՆՌՊՇՄ
ՈԫՇՌՍԺԽՊԻՄԽՋՏԽՊԽՇԺՋԽՊՎԽԼՇՆԾԽՅԹՄԽԾՁՋՀԱՀԽՊԽՏԽՊԽՆՇԽԾԾԽԻՌՋՇՆՈՄԹՋՅԹՎՁՌԽՄՄՇԿԽՆՁՆ


ԳԱԤՇՊԿՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
Ԥ԰ԦԭՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋՏԽՊԽՊԽՈՇՊՌԽԼՄՑՅԽԹՋՍՊԽԼԺՍՌՆՇՊԽՋՍՄՌՋՏԽՊԽ

ՈՊՇՎՁԼԽԼ

ԱՀԽՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋԽՋՁՆՅԹՄԽՋԹՋՋՇԻՁԹՌԽԼԽՐՈՇՋԽԼՌՇՈՊՇՆԹՅՁԼԽԹՌՅԿԹՁԩՁՆԻՄՍԼԽԼԼԽԻՊԽԹՋԽԼ

ՈՊՇՈՇՊՌՁՇՆՋ ՇԾ ՋՈԽՊՅԹՌՇՒՇԹ ՁՆԻՊԽԹՋԽԼ ՁՆՌԽՊՋՌՁՌՁԹՄ ԻԽՄՄ ՀՑՈԽՊՈՄԹՋՁԹ ԹՆԼ ՈՊՇՌԽՁՆԹԻԽՇՍՋ ԾՄՍՁԼ ԹՆԼ ՁՆԻՊԽԹՋԽԼ

ՌԽՋՌՁԻՍՄԹՊԼԽԿԽՆԽՊԹՌՁՇՆԹՌՌՀԽՅԿԹՁԩՄԽՎԽՄՌՀԽՊԽՏԽՊԽՆՇՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋՁՆԾԽՅԹՄԽՋԱՏՇՇԾ

ՌՀԽՌԹՆՃՋՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՇՆԽՌԹՆՃՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԻՇՆՌԹՁՆԽԼՌՀՊԽԽՅԹՄԽՋԹՆԼՌՀՊԽԽԾԽՅԹՄԽՋ

ԼՍԽՌՇՅՁՋՋԽՐԽԼԾՁՋՀ

ԠՇՅՈԹՊՁՋՇՆՋԺԽՌՏԽԽՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈՋՊԽՎԽԹՄԽԼՆՇՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋ


Ո ԾՇՊԹՆՑԽՆԼՈՇՁՆՌԳԹՄՁԼՁՌՑԻՊՁՌԽՊՁԹԾՇՊՋՍՊՎՁՎԹՄ
ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՇՆՄՑԹՆԼԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆԻՇՆՌԽՆՌ

ՁՆ ՌՀԽ ԬԠ԰ԭԭ  ԿՍՁԼԹՆԻԽ ՏԽՊԽ ՆՇՌ ՅԽՌ ԺՍՌ ՌՀԽՋԽ ԼԽՎՁԹՌՁՇՆՋ ԼՁԼ ՆՇՌ ՋՍԺՋՌԹՆՌՁՎԽՄՑ ՁՅՈԹԻՌ ՌՀԽ

ՊԽՋՍՄՌՋՇՊՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀՁՋՋՌՍԼՑ

ԱՀՁՋ ԹՋՋԹՑ ՋԹՌՁՋԾՁԽՋ ՌՀԽ Ԣԡ԰ԭ ԱՁԽՊ  ԱԽՋՌ ԬՊԼԽՊ ԾՇՊ Թ ԣՁՋՀ ԰ՀՇՊՌԱԽՊՅ ԯԽՈՊՇԼՍԻՌՁՇՆ ԞՋՋԹՑ 
ԬԠ԰ԭԭ

ԤՍՁԼԽՄՁՆԽ

ԯԽՋՍՄՌՋ԰ՑՆՇՈՋՁՋ

ԱԽՋՌՇՊԿԹՆՁՋՅԹԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԻԹՅՇՆՌՀ
ՏԽԽՃՋ

ԪԽԹՆԺՇԼՑՏԽՁԿՀՌԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆՅԹՄԽԿ
ԿչՇԾՅԽԹՆԾԽՅԹՄԽԿ


ԿչՇԾՅԽԹՆ

ԪԽԹՆՄԽՆԿՌՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԫՇՌՅԽԹՋՍՊԽԼ

ԱԽՋՌՌՑՈԽԾՄՇՏՌՀՊՇՍԿՀ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢԾԾԽԻՌՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԣ԰ԱԯԞՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԣԽԻՍՆԼՁՌՑ

ԣԽՊՌ

԰ՍԻԻԽՋՋ

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ Ԥ԰Ԧ ԤՇՆԹԼԹՄԥՁՋՌՇ ԭՄԹՋՅԹԳԱԤ ԭՄԹՋՅԹԱ ԭՄԹՋՅԹԢ

Ԫ ԣ Ԫ ԣ Ԫ ԣ Ԫ ԣ Ԫ ԣ Ԫ ԣ

 ԫՇ ԫՇ ԶԽՋ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫՇ ԫԞ ԫԞ ԫԞ ԫԞ ԶԽՋ ԶԽՋ ԶԽՋ ԫՇ ԫՇ ԫՇ ԶԽՋ ԫՇ ԫՇ ԫՇ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԢȕԽՋՌՊԹԼՁՇՄԣԣԽՅԹՄԽԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԪԪԹՄԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ

 Ԟ՟ՑԽՋՠՁՆԼՁԻԹՌԽՋԹՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽ
ՈԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄՍՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼ

  ԱՀԽԻՊՁՌԽՊՁԹԾՇՊՋՁԿՆՁԾՁԻԹՆԻԽԹՊԽԼԽՋԻՊՁԺԽԼՁՆՌՀԽԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼ԰ՌԹՌՁՋՌՁԻԹՄԳԽՊՁԾՁԻԹՌՁՇՆՋԽԻՌՁՇՆՋՇԾՌՀԽԡԢԯԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽ

ՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

 ԱՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌՏԹՋՌԽՊՅՁՆԹՌԽԼՇՆԡԹՑԼՍԽՌՇՀՁԿՀՅՇՊԺՁԼՁՌՑ  ԱՀԽՈՎԹՄՍԽՏԹՋՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌԺՍՌՌՀԽԼԽԻՊԽԹՋԽՏԹՋԻՇՆՋՁԼԽՊԽԼՋՁԿՆՁԾՁԻԹՆՌԼՍԽՌՇՌՀԽՅԹԿՆՁՌՍԼԽԹՆԼԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋՁՎԽ

ՈԹՌՌԽՊՆ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

Ԧ ԪԞԱԢԯԦԞԩ԰ԞԫԡԪԢԱԥԬԡ԰ 

ԤՍՁԼԽՄՁՆԽԣՇՄՄՇՏԽԼ ԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼԹԻԻՇՊԼՁՆԿՌՇՌՀԽԲ԰ԢԭԞԬԠ԰ԭԭ՟ԣՁՋՀ

԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՎԽԞՋՋԹՑՠԤՍՁԼԽՄՁՆԽԼԽՎՁԹՌՁՇՆՋԹՊԽՆՇՌԽԼԺԽՄՇՏ

 ԡՍԽՌՇՇՎԽՊՌՅՇՊԺՁԼՁՌՑՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՅԿԹՁԩՌՊԽԹՌՅԽՆՌՏԹՋՌԽՊՅՁՆԹՌԽԼՇՆ

ԡԹՑ  ԱՀԽՊԽԾՇՊԽ ՇՆՄՑ ՌՏՇ ԽՐՈՇՋՍՊԽ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՏԽՊԽ ՋՌՍԼՁԽԼ ԱՀԽ ՇՆՄՑ ՊԹՌՁՇՆԹՄԽ ԾՇՊ

ՋԽՄԽԻՌՁՇՆ ՇԾ ՌՀԽ ՀՁԿՀԽՋՌ ՌԽՋՌ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ՏԹՋ ՄՁՋՌԽԼ ԹՋ ԻՇՆՋՍՄՌԹՌՁՇՆ ՏՁՌՀ ՌՀԽ ՋՌՍԼՑ

ՋՈՇՆՋՇՊԬԠ԰ԭԭ ՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՈԽՊՅՁՌՋՍՊՎՁՎԹՄ

ՍՈՌՇՌՀԽՄՁՅՁՌՇԾՋՇՄՍԺՁՄՁՌՑ

 ԱՀԽՋՍՊՎՁՎԹՄՎԹՄՁԼՁՌՑԻՊՁՌԽՊՁՇՆՇԾՏԹՋՆՇՌՅԽՌՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

 ԱՀԽԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆԼՊՇՈՈԽԼԺԽՄՇՏՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼԹՄՄՈՊՇՆԹՅՁԼԽՌՊԽԹՌԽԼ

ԿՊՇՍՈՋ ՏՁՌՀ ՅՁՆՁՅԹ ՊԹՆԿՁՆԿ ԾՊՇՅ  ԬՆՄՑ ՊԹՆԿԽՋ ՏԽՊԽ ՊԽՈՇՊՌԽԼ ՋՇ ՌՀԽ ՊԽՎՁԽՏԽՊ

ԻՇՍՄԼՆՇՌԼԽՌԽՊՅՁՆԽՀՇՏՅԹՆՑՇՊԾՇՊՏՀՁԻՀԼԹՑՋԡԬԼՊՇՈՈԽԼԺԽՄՇՏՌՀԽՅՁՆՁՅՍՅԬԠ԰ԭԭ

ՊԽՉՍՁՊԽՅԽՆՌ

 ԱՏՇՇԾՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌԹՆՃՋԹՆԼՇՆԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌԹՆՃՀԹԼՅԹՄԽՋԹՆԼԾԽՅԹՄԽՋ

ԼՍԽՌՇՅՁՋՋԽՐԽԼԾՁՋՀԬԠ԰ԭԭՊԽԻՇՅՅԽՆԼՋՌՏՇՅԹՄԽՋԹՆԼԾՇՍՊԾԽՅԹՄԽՋՁՆԽԹԻՀ

ՌԹՆՃ

 ԦՆՁՌՁԹՄՅԹՄԽԹՆԼԾԽՅԹՄԽԾՁՋՀՏԽՁԿՀՌՋԽՐԻԽԽԼԽԼՌՀԽՊԽԻՇՅՅԽՆԼԽԼՅԹՐՁՅՍՅՎԹՊՁԹՌՁՇՆԹՊՇՍՆԼ

ՌՀԽ ՋԹՅՈՄԽ ՅԽԹՆ 
ՁԽ չ ՁՆՁՌՁԹՄ ՅԹՄԽ ԾՁՋՀ ՏԽՁԿՀՌՋ ՎԹՊՁԽԼ չ ԹՆԼ ՁՆՁՌՁԹՄ ԾԽՅԹՄԽ

ՏԽՁԿՀՌՋՎԹՊՁԽԼչՇԾՌՀԽՋԹՅՈՄԽՅԽԹՆ

 ԱՀԽ ՍՆՁՇՆՁՒԽԼ ԹՅՅՇՆՁԹ ԹՆԼ ՊԽՋՁԼՍԹՄ ԻՀՄՇՊՁՆԽ ՁՆ ՌՀԽ ՌԽՋՌ ՏԹՌԽՊ ՏԽՊԽ ՆՇՌ ՊԽՈՇՊՌԽԼ ԱՀԽ

ԬԠ԰ԭԭՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԽՋՌԹԺՄՁՋՀՅԹՐՁՅՍՅՄԽՎԽՄՋԾՇՊՌՀԽՋԽՎԹՄՍԽՋԹՆԼՁՌՁՋ

ՍՆԻՄԽԹՊՁԾՌՀԽՅԹՐՁՅՍՅՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋՏԽՊԽԽՐԻԽԽԼԽԼ

 ԬՆՌԽՋՌԡԹՑ ՌՀԽՅԹՐՁՅՍՅՌԽՅՈԽՊԹՌՍՊԽՏԹՋ ՊԽԻՇՊԼԽԼՌՇ ԺԽ ոԠԾԹՄՄՁՆԿ ՇՍՌՋՁԼԽՌՀԽ

ՊԽՉՍՁՊԽԼՊԹՆԿԽՇԾչոԠ

ԱՀԽԼԽՎՁԹՌՁՇՆՋԼՇՆՇՌՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌՌՀԽՊԽՋՍՄՌՋՇՊՁՆՌԽՈՊԽՌԹՌՁՇՆՇԾՌՀՁՋՋՌՍԼՑ

ԠՇՅՈՄՁԹՆԻԽ  ԰ՁԿՆԽԼԹՆԼԼԹՌԽԼԫՇԡԹՌԹԠՇՆԾՁԼԽՆՌՁԹՄՁՌՑԤԩԭԹՆԼԮՍԹՄՁՌՑԞՋՋՍՊԹՆԻԽՋՌԹՌԽՅԽՆՌՋ

ՏԽՊԽՈՊՇՎՁԼԽԼԱՀՁՋՋՌՍԼՑՏԹՋԻՇՆԼՍԻՌԽԼՁՆԻՇՅՈՄՁԹՆԻԽՏՁՌՀԹՄՄՈԽՊՌՁՆԽՆՌԲ԰ԢԭԞ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԤՇՇԼ ԩԹԺՇՊԹՌՇՊՑԭՊԹԻՌՁԻԽ ՊԽԿՍՄԹՌՁՇՆՋՏՁՌՀՌՀԽԾՇՄՄՇՏՁՆԿ ԽՐԻԽՈՌՁՇՆՋ ՊՇՍՌՁՆԽ ԼՁՄՍՌՁՇՆ

ՏԹՌԽՊ ԹՆԼ ԾՇՇԼ ԻՇՆՌԹՅՁՆԹՆՌ ՋԻՊԽԽՆՁՆԿ ԹՆԹՄՑՋԽՋ ԾՇՊ ՈԽՋՌՁԻՁԼԽՋ ԭԠԟՋ ԹՆԼ ՌՇՐՁԻ

ՅԽՌԹՄՋ ԰ՁՆԻԽ ՌՀԽ ԹՆԹՄՑՋԽՋ ՏԽՊԽ ԻՇՆԼՍԻՌԽԼ ԾՇՄՄՇՏՁՆԿ ՋՌԹՆԼԹՊԼ ՎԹՄՁԼԹՌԽԼ ՅԽՌՀՇԼՋ

ՌՀԽՋԽԽՐԻԽՈՌՁՇՆՋՀԹԼՆՇՁՅՈԹԻՌՇՆՌՀԽՋՌՍԼՑՊԽՋՍՄՌՋ

Ԟ ԱԽՋՌԪԹՌԽՊՁԹՄ  ԭՊՇՆԹՅՁԼԽ

ԡԽՋԻՊՁՈՌՁՇՆ  ԞՈՀՑՋՁԻԹՄԼԽՋԻՊՁՈՌՁՇՆՏԹՋՆՇՌՈՊՇՎՁԼԽԼ

ԬԢԠԡՊԽԻՇՅՅԽՆԼՋԼԽՋԻՊՁԺՁՆԿՏԹՌԽՊՋՇՄՍԺՁՄՁՌՑՅԽՄՌՁՆԿԺՇՁՄՁՆԿՈՇՁՆՌՋՌԹԺՁՄՁՌՑՁՆՏԹՌԽՊԹՆԼՄՁԿՀՌՈԨԹ

ԭՇՏՇՊԨՇՏՎԹՈՇՊՈՊԽՋՋՍՊԽՇԾՌԽՋՌԻՇՅՈՇՍՆԼԽՐՈՁՊԹՌՁՇՆԼԹՌԽ

ԩՇՌԫՇԟԹՌԻՀԫՇ ԵԤԯ

ԭՍՊՁՌՑ   

ԦՅՈՍՊՁՌՁԽՋ   ԫՇՌՊԽՈՇՊՌԽԼ

԰ՌԹԺՁՄՁՌՑՇԾ

ԠՇՅՈՇՍՆԼ  ԱՀԽՌԽՋՌՅԹՌԽՊՁԹՄՏԹՋՋՀՇՏՆՌՇԺԽԻՇՆՋՁՋՌԽՆՌ ՁՆՋՇՄՍՌՁՇՆՇՎԽՊՌՀԽՌԽՋՌՈԽՊՁՇԼ

ՏՁՌՀՅԽԹՆՅԽԹՋՍՊԽԼՊԽԻՇՎԽՊՁԽՋՊԹՆԿՁՆԿԾՊՇՅՇԾՆՇՅՁՆԹՄ

԰ՌՇՊԹԿԽԠՇՆԼՁՌՁՇՆՋՇԾ

ԱԽՋՌԠՀԽՅՁԻԹՄՋ ԰ՌՇՊԽԼՁՆՌՀԽԼԹՊՃԹՌՊՇՇՅՌԽՅՈԽՊԹՌՍՊԽ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԟ ԱԽՋՌԬՊԿԹՆՁՋՅ

ԱԹԺՄԽԤԽՆԽՊԹՄԦՆԾՇՊՅԹՌՁՇՆԞԺՇՍՌՌՀԽԱԽՋՌ԰ՈԽԻՁԽՋԹՆԼԞԻԻՄՁՅԹՌՁՇՆ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՈԽԻՁԽՋԻՇՅՅՇՆՆԹՅԽ ԣԹՌՀԽԹԼԪՁՆՆՇՏ ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԹՌՀԽԹԼՅՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋ

ՈՊՇՅԽՄԹՋ ԰ՈԽԻՁԽՋՋԻՁԽՆՌՁԾՁԻՆԹՅԽ ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

԰ՈԽԻՁԽՋՋՌՊԹՁՆ
ՁԾՋՌԹՌԽԼ ԫՇՌՊԽՈՇՊՌԽԼԴԽՊԽԾՁՋՀՇԺՌԹՁՆԽԼԾՊՇՅԹՋՁՆԿՄԽՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃ!

ԶԽՋ ԦՆՀՇՍՋԽՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԾՊՇՅԹՋՁՆԿՄԽ

ՄԹԺՇՊԹՌՇՊՑՋՌՇԻՃ

ԴԽՊԽԹԻԻՄՁՅԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՋԹՅԽԹՋԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!

ԶԽՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԹԻԻՄՁՅԹՌԽԼՍՆԼԽՊ

ՏԹՌԽՊՉՍԹՄՁՌՑԹՆԼՁՄՄՍՅՁՆԹՌՁՇՆԻՇՆԼՁՌՁՇՆՋՌՀԹՌԹՊԽ

ՋՁՅՁՄԹՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԞԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼ ԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՌՏՇՏԽԽՃ

ԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԫՇՌԽՌՀԹՌՌՀԽԹԻԻՄՁՅԹՌՁՇՆ

ՈԽՊՁՇԼՁՋԼՁԾԾԽՊԽՆՌԾՊՇՅՌՀԽՋՍԺՋԽՉՍԽՆՌՁՆՋՁՌՍ

ՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՀԽԹՄՌՀ ԫՇՌՊԽԹՌՅԽՆՌՋԾՇՊԼՁՋԽԹՋԽ

ՋՌԹՊՌՁՆԿՌՏՇՏԽԽՃՋՈՊՁՇՊՌՇՌՀԽՋՈԹՏՆՁՆԿՉՍԹՄՁԾՁԻԹՌՁՇՆ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՅՇՊՌԹՄՁՌՑԼՍՊՁՆԿՌՀԽ

ԼԹՑՋՈՊՁՇՊՌՇՌՀԽՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽԺԽՄԽՋՋ

ՌՀԹՆՇԾՌՀԽԻՍՄՌՍՊԽՈՇՈՍՄԹՌՁՇՆԦԾՅՇՊՌԹՄՁՌՑ

ԼՍՊՁՆԿՌՀԽՋԽԼԹՑՋՁՋԿՊԽԹՌԽՊՌՀԹՆԢԭԞ

ՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԾՁՋՀԺԽՊԽՂԽԻՌԽԼԦԾ

ՅՇՊՌԹՄՁՌՑՁՋԺԽՌՏԽԽՆԢԭԞՊԽԻՇՅՅԽՆԼՋ

ՌՀԹՌԾՁՋՀԺԽՀԽՄԼԹՆՇՌՀԽՊԼԹՑՋԦԾՅՇՊՌԹՄՁՌՁԽՋ

ԿՊԽԹՌԽՊՌՀԹՆՇԻԻՍՊԼՍՊՁՆԿՌՀՁՋԽՐՌԽՆԼԽԼ

ԹԻԻՄՁՅԹՌՁՇՆՈԽՊՁՇԼԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽ

ԾՁՋՀՆՇՌԺԽՍՋԽԼ

ԱՑՈԽՇԾԾՇՇԼ ԩՁՎԽԺՊՁՆԽՋՀՊՁՅՈՆԹՍՈՄՁՁ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՁՋՀԺԽԾԽԼԾՊՇՒԽՆԺՊՁՆԽ

ՋՀՊՁՅՈՌՏՁԻԽՈԽՊԼԹՑՌՇՈՊՇՅՇՌԽԹԻՌՁՎԽ

ՊԽՈՊՇԼՍԻՌՁՇՆԹՆԼՅԹՁՆՌԹՁՆԺՇԼՑԻՇՆԼՁՌՁՇՆ

԰ՇՍՊԻԽՇԾԾՇՇԼ ԫՇՌՊԽՈՇՊՌԽԼ ԯԽՈՊԽՋԽՆՌԹՌՁՎԽՋԹՅՈՄԽՋՇԾՌՀԽԾՇՇԼՋՇՍՊԻԽ

ՏԽՊԽՈԽՊՁՇԼՁԻԹՄՄՑԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋԭԠԟՋԹՆԼՌՇՐՁԻՅԽՌԹՄՋԺՑԤԽՇԩԹԺՋԦՆԻԹՆԼԹՆԹՄՑՌԽՄԽՎԽՄՋՏԽՊԽԺԽՄՇՏԩԬԠՋՈԽԻՁԾՁԽԼԺՑԞ԰ԱԪ


ԣՊԽՉՍԽՆԻՑՇԾԾԽԽԼՁՆԿ ԱՏՇՌՁՅԽՋԼԹՑԡԽՌԹՁՄՋՇՆԾԽԽԼՁՆԿ ԫՇԼԽՌԹՁՄՋՇՆԹՅՇՍՆՌ

ՏԽՊԽՈՊՇՎՁԼԽԼ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԣՁՋՀ԰ԽՄԽԻՌՁՇՆԹՆԼԭՊԽԢՐՈՇՋՍՊԽԭԽՊԾՇՊՅԹՆԻԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞԿԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ ԻԹՅՇՆՌՀՋ
ՏԽԽՃՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՊՇԼՍԻՌՁՎԽՄՑՅԹՌՍՊԽ


ՋԽՐՍԹՄՄՑԼՁՅՇՊՈՀՁԻԾՁՋՀՅՇՆՌՀՋՇՄԼ

ԪԽԹՆՏԽՁԿՀՌՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

Կ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ ԹՋՍԺՋԹՅՈՄԽՇԾԾՁՋՀԺԽ

ՏԽՁԿՀԽԼԺԽԾՇՊԽՌՀԽՌԽՋՌՌՇԽՋՌՁՅԹՌԽՌՀԽՅԽԹՆ

ՏԽՁԿՀՌԾՇՊԽԹԻՀՋԽՐԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌՀԽ

ՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՇԾԽԹԻՀԾՁՋՀՋԽՄԽԻՌԽԼԾՇՊՌՀԽ

ՌԽՋՌԺԽՏՁՌՀՁՆչՇԾՌՀԽԽՋՌՁՅԹՌԽԼՅԽԹՆԾՇՊ

ԽԹԻՀՋԽՐ

ԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋ
ՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

Կ ԱՀԽՎԹՊՁԹՌՁՇՆՇԾՋԹՅՈՄԽՅԹՄԽԾՁՋՀՏԽՁԿՀՌՋ

ՏԹՋչՇԾՌՀԽՅԽԹՆԽՐԻԽԽԼՁՆԿՌՀԽչՅԹՐՁՅՍՅՎԹՊՁԹՌՁՇՆՁՆՌՀԽԬԠ԰ԭԭԿՍՁԼԽՄՁՆԽ

ԪԽԹՆՏԽՁԿՀՌՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

 

ԯԹՆԿԽՇԾՁՆԼՁՎՁԼՍԹՄՏԽՁԿՀՌՋ
ԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

Կ ԱՀԽՊԹՆԿԽՇԾՋԹՅՈՄԽԾԽՅԹՄԽԾՁՋՀՏԽՁԿՀՌՋ

ՏԹՋչՇԾՌՀԽՅԽԹՆԽՐԻԽԽԼՁՆԿՌՀԽչՅԹՐՁՅՍՅՎԹՊՁԹՌՁՇՆՁՆՌՀԽԬԠ԰ԭԭԿՍՁԼԽՄՁՆԽ

ԪԽԹՆՄԽՆԿՌՀՇԾՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ

ԪԽԹՆՄԽՆԿՌՀՇԾԾԽՅԹՄԽՋԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ
ՁԾԼԽՌԽՊՅՁՆԽԼ

ԫՇՌՊԽՈՇՊՌԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡՍՊԹՌՁՇՆՇԾՈՊԽԽՐՈՇՋՍՊԽՈՀԹՋԽ ԼԹՑՋ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾԼԹՑՋԴԽՊԽՈՊԽԽՐՈՇՋՍՊԽԻՇՆԼՁՌՁՇՆՋՁԼԽՆՌՁԻԹՄՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ!

ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽԻՇՆԼՁՌՁՇՆՋ

ՁՆԻՄՍԼՁՆԿՌԽՅՈԽՊԹՌՍՊԽՈՀՇՌՇՈԽՊՁՇԼԾԽԽԼՁՆԿԽՌԻ

ԺԽՁԼԽՆՌՁԻԹՄՌՇԼԽԾՁՆՁՌՁՎԽՌԽՋՌԻՇՆԼՁՌՁՇՆՋ

ԫՍՅԺԽՊՇԾՈՊԽԽՐՈՇՋՍՊԽՌԹՆՃՋ  ԢՐՌՊԹՊԽՈՄՁԻԹՌԽՋՏԽՊԽԽՋՌԹԺՄՁՋՀԽԼ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹԼԼՁՌՁՇՆԹՄՌԹՆՃՋՋԽՌՍՈԹՌ

ՌՀԽԺԽԿՁՆՆՁՆԿՇԾՈՊԽԽՐՈՇՋՍՊԽՏՁՄՄԽՆՋՍՊԽՌՀԹՌ

ՋՍԾԾՁԻՁԽՆՌՊԽՈՄՁԻԹՌԽՋՏՁՌՀՌՀԽԻՇՊՊԽԻՌՋԽՐՊԹՌՁՇԹՊԽ

ԹՎԹՁՄԹԺՄԽԾՇՊՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԫՍՅԺԽՊՇԾՅԹՄԽՋՈԽՊՌԹՆՃ  ԱՀՊԽԽՅԹՄԽԾՁՋՀՏԽՊԽՁՆԹԼՎԽՊՌԽՆՌՄՑԹԼԼԽԼՌՇ

ՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՊԽՈՄՁԻԹՌԽՋԞԹՆԼԟԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՊԽՈՄՁԻԹՌԽԠ

ԫՍՅԺԽՊՇԾԾԽՅԹՄԽՋՈԽՊՌԹՆՃ ԭՊԽԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑ

 ԽԿԿՋԾԽՅԹՄԽ

ՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՊԽՈՄՁԻԹՌԽ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՈՊԽԽՐՈՇՋՍՊԽԾԽԻՍՆԼՁՌՑՁՆ

ԽԹԻՀՊԽՈՄՁԻԹՌԽ
ՌԹՆՃՋԽՄԽԻՌԽԼԾՇՊՍՋԽՁՆՌՀԽ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԹՌՄԽԹՋՌ

ԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՊԽՈՄՁԻԹՌԽԼՍՊՁՆԿ

ՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԫՍՅԺԽՊՇԾՋՈԹՏՆՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽ

 ՌՏՇՌՁՅԽՋՁՆԼԹՑՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՈԹՏՆՁՆԿՇԻԻՍՊԹՌՄԽԹՋՌ

ՌՏՁԻԽՁՆՌՀԽԼԹՑՋՈՊՁՇՊՌՇՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԡԽՌԹՁՄՋՇՆՈՊԽԽՐՈՇՋՍՊԽ ԣՁՋՀՏԽՊԽԾԽԼԹՅԽԹՋՍՊԽԼԹՅՇՍՆՌՇԾՄՁՎԽ

ԺՊՁՆԽՋՀՊՁՅՈ
ԞՊՌԽՅՁԹ

Ԡ ԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԦՆԾՇՊՅԹՌՁՇՆՇՆՌՀԽԢՐՈՇՋՍՊԽ԰ՑՋՌԽՅԹՆԼԱԽՋՌԳԽՋՋԽՄԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱՑՈԽՇԾԽՐՈՇՋՍՊԽ ԾՄՇՏՌՀՊՇՍԿՀ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԾՄՇՏՌՀՊՇՍԿՀ

ՋՑՋՌԽՅԞՋՆՇՌԽԼՁՆՌՀԽԠՇՊՊԽԻՌՁՇՆՋԹՆԼ

ԠՄԹՊՁԾՁԻԹՌՁՇՆՋԼՇԻՍՅԽՆՌ ՌՀԽՍՋԽՇԾԹՋՌԹՌՁԻ

ՊԽՆԽՏԹՄՋՑՋՌԽՅՁՋՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՌՀՁՋ

ԹՋՋԹՑ

ԱՑՈԽՇԾԾՄՇՏՌՀՊՇՍԿՀԼՁՄՍՌՁՇՆՋՑՋՌԽՅ

ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋ

ԦՆՌԽՊՅՁՌՌԽՆՌԾՄՇՏՈՊՇՈՇՊՌՁՇՆԹՄԼՁՄՍՌԽՊՋՇՊ

ԻՇՆՌՁՆՍՇՍՋԾՄՇՏՋԽՊՁԹՄԼՁՄՍՌԽՊՋԹՊԽ

ՊԽԻՇՅՅԽՆԼԽԼ

Բ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ
ԢԭԞ
ԠՇՊՊԽԻՌՁՇՆՋԹՆԼԠՄԹՊՁԾՁԻԹՌՁՇՆՋՇՆԱԽԻՀՆՁԻԹՄԞՋՈԽԻՌՋՇԾՌՀԽԱԽՋՌԤՍՁԼԽՄՁՆԽՋԾՇՊՌՀԽԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿ

ԭՊՇԿՊԹՅԱՁԽՊԞՋՋԹՑՋ
ԬԠ԰ԭԭԱԽՋՌԤՍՁԼԽՄՁՆԽ԰ԽՊՁԽՋԪԹՊԻՀԬԾԾՁԻԽՇԾԠՀԽՅՁԻԹՄ԰ԹԾԽՌՑԹՆԼԭՇՄՄՍՌՁՇՆԭՊԽՎԽՆՌՁՇՆ
ԬԠ԰ԭԭԴԹՋՀՁՆԿՌՇՆԡԠ


ՀՌՌՈՏՏՏԽՈԹԿՇՎԽՆԼՇՈՍԺՋԹՋՋԹՑՎԹՄՁԼԹՌՁՇՆԻՄԹՊՁԾՁԻԹՌՁՇՆԼՇԻՈԼԾ

ԞԼԼՁՌՁՇՆԹՄԿՍՁԼԹՆԻԽԾՇՊԹՉՍԹՌՁԻՌԽՋՌԼԽՋՁԿՆՁՋՄՇԻԹՌԽԼՁՆԬԠ԰ԭԭԤՍՁԼԽՄՁՆԽ԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆՋԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԣՄՇՏՌՀՊՇՍԿՀՊԹՌԽ ՎՇՄՍՅԽ

ՊԽՈՄԹԻԽՅԽՆՌՋԼԹՑ

ԯԽԻՇՅՅԽՆԼԽԼԾՄՇՏՌՀՊՇՍԿՀՊԹՌԽՁՋ

ՅԩՅՁՆ
ԩՀՊՇՊԹՌՄԽԹՋՌՌՇՌԹՄ

ՎՇՄՍՅԽԽՐԻՀԹՆԿԽՋՈԽՊԼԹՑ

ԡԽՌԹՁՄՋՇՆՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏՌՀՊՇՍԿՀՋՑՋՌԽՅՋ

ԣՄՇՏՋՈՄՁՌՌՁՆԿԻՀԹՅԺԽՊՋՏԽՊԽՍՋԽԼԺԽՌՏԽԽՆՊԽՈՄՁԻԹՌԽՌԽՋՌՎԽՋՋԽՄՋ

ԢԹԻՀՅՁՐՁՆԿԾՄՇՏՋՈՄՁՌՌՁՆԿԻԽՄՄԼՁՎՁԼԽԼԽԹԻՀԩՎՇՄՍՅԽԾՇՍՊՏԹՑՋՊԽՋՍՄՌՁՆԿՁՆԻԹՅԩԼԽՄՁՎԽՊԽԼԽԹԻՀԻՑԻՄԽՌՇԽԹԻՀՇԾՌՀԽԿՄԹՋՋԹՉՍԹՊՁԹ

ԯԽԻՇՅՅԽՆԼԽԼՌՇՐՁԻԹՆՌՅՁՐՁՆԿԾՇՊԾՄՇՏ

ՌՀՊՇՍԿՀՋՑՋՌԽՅՋԪՁՐՁՆԿԻՀԹՅԺԽՊՁՋ

ՊԽԻՇՅՅԽՆԼԽԼԺՍՌՆՇՌՊԽՉՍՁՊԽԼԞԽՊԹՌՁՇՆՁՋ

ՆՇՌՊԽԻՇՅՅԽՆԼԽԼԾՇՊՅՁՐՁՆԿԞ

ԼԽՅՇՆՋՌՊԹՌՁՇՆՌՀԹՌՌՀԽՌԽՋՌՋՇՄՍՌՁՇՆՁՋ

ԻՇՅՈՄԽՌԽՄՑՅՁՐԽԼԺԽԾՇՊԽՁՆՌՊՇԼՍԻԽԼՁՆՌՇՌՀԽ

ՌԽՋՌՋՑՋՌԽՅՁՋՊԽԻՇՅՅԽՆԼԽԼԱՀԽ

ՊԽԻՇՅՅԽՆԼԽԼԾՄՇՏՋՈՄՁՌՌՁՆԿԹԻԻՍՊԹԻՑՁՋՏՁՌՀՁՆ



ԞԽՊԹՌՁՇՆ! ԶԽՋ ԰ՌԹՊՌԽԼՇՆԼԹՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹԽՊԹՌՁՇՆՁԾԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ

ՊԽԹԻՀԽՋՅԿԩ
ՋԹՌՍՊԹՌՁՇՆ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՇՍՊԻԽՇԾԼՁՄՍՌՁՇՆՏԹՌԽՊ ԴԽՄՄՏԹՌԽՊ ԢԭԞՊԽԻՇՅՅԽՆԼՋՆԹՌՍՊԹՄՇՊՊԽԻՇՆՋՌՁՌՍՌԽԼ

ՏԹՌԽՊՁՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՆԹՌՍՊԹՄՏԹՌԽՊ

ԺԽՋՌԽՊՁՄՁՒԽԼՏՁՌՀԲԳԹՆԼՌԽՋՌԽԼԾՇՊ

ՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊՈՇՋՋՁԺՄԽ

ԻՇՆՌԹՅՁՆԹՆՌՋԬԢԠԡԹԻԻԽՈՌՋԹՆՑՏԹՌԽՊՁՆ

ՏՀՁԻՀՌՀԽՌԽՋՌՋՈԽԻՁԽՋՋՀՇՏԻՇՆՌՊՇՄՋՍՊՎՁՎԹՄ

ԹՌՄԽԹՋՌԹՋԿՇՇԼԹՋՁՆԼՁԻԹՌԽԼՁՆՌՀԽՌԽՋՌ

ԿՍՁԼԽՄՁՆԽ

ԴԹՋԼՁՄՍՌՁՇՆՏԹՌԽՊԹՆԹՄՑՒԽԼԾՇՊՈԽՋՌՁԻՁԼԽՋՀԽԹՎՑՅԽՌԹՄՋԹՆԼՇՌՀԽՊԻՇՆՌԹՅՁՆԹՆՌՋ!

ԶԽՋ ԱՀԽՊԽՋՍՄՌՋՇԾՌՀԽԹՆԹՄՑՌՁԻԹՄՊԽՈՇՊՌՏԽՊԽՆՇՌ

ՈՊՇՎՁԼԽԼԦՌՏԹՋՇՆՄՑՋՌԹՌԽԼՌՀԹՌՆՇՆԽՇԾՌՀԽՋԽԻՇՅՈՇՍՆԼՋՏԽՊԽԼԽՌԽԻՌԽԼԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԻՇՆՋՁԼԽՊԽԼՌՇԺԽՌՇՐՁԻ

ԱԽՋՌՎԽՋՋԽՄՌՑՈԽՅԹՌԽՊՁԹՄՋ ԤՄԹՋՋԹՉՍԹՊՁԹ ԢԭԞԹՆԼԬԢԠԡՊԽԻՇՅՅԽՆԼՌՀԹՌՏԹՌԽՊ

ԻՇՆՌԹԻՌՈՇՊՌՁՇՆՋՇԾՌՀԽՋՑՋՌԽՅՆՇՌ

ԻՇՅՈՊՇՅՁՋԽՌՀԽՋՌՍԼՑ
ԽԿԹՄՄԿՄԹՋՋՎԽՋՋԽՄՋ

ՇՊԿՄԹՋՋՎԽՋՋԽՄՋՏՁՌՀՋՌԹՁՆՄԽՋՋՋՌԽԽՄԾՊԹՅԽՋ

ԹՊԽԹԻԻԽՈՌԹԺՄԽԽՐԹՅՈՄԽՋ

ԱԽՋՌՎԽՋՋԽՄՋՁՒԽ ԩՐՐԻՅ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԩՌԽՋՌ

ԻՀԹՅԺԽՊՋ
ԽԿՐՐԻՅ

ԣՁՄՄՎՇՄՍՅԽ ԩ ԢԭԞՊԽԻՇՅՅԽՆԼՋԩՋՇՄՍՌՁՇՆՈԽՊՌԹՆՃ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՅԹՌԽՊՁԹՄ ԞԿԽԼԭԳԠՈՁՈԽ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԽԹԻՀՌԹՆՃԻՇՆՌԹՁՆ

ՌՀՊԽԽՋԽՅՁԻՁՊԻՍՄԹՊՋՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋԽԿ

ԹԿԽԼԭԳԠՈՁՈԽԻՅՁՆՄԽՆԿՌՀՋՈՄՁՌ

ՄԽՆԿՌՀՏՁՋԽ

԰ՈԹՏՆՁՆԿՋՍԺՋՌՊԹՌԽՋՁՒԽ ԠՍՌ ՄԽՆԿՌՀՏՁՋԽ ՌՇ ՈՊՇԼՍԻԽ

ԹՊԻՀԽՋ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋՇՆԽՐՈՇՋՍՊԽ

ՋՑՋՌԽՅ

 ԫՇԾՍՊՌՀԽՊԼԽՌԹՁՄՋՈՊՇՎՁԼԽԼ

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԴԹՌԽՊԮՍԹՄՁՌՑԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋՁՆՌՀԽԱԽՋՌ԰ՑՋՌԽՅ

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ ԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՅՈԽՊԹՌՍՊԽ
ոԠ    ԠՇՆՌՁՆՍՇՍՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌԽՅՈԽՊԹՌՍՊԽչՇԠՁՆՌԽՊ

ՊԽՈՄՁԻԹՌԽԹՆԼՁՆՌԽՊՌՊԽԹՌՅԽՆՌԼՁԾԾԽՊԽՆՌՁԹՄՋ

ՋՀՇՍՄԼՆՇՌԽՐԻԽԽԼՇԠ

Ոԥ    ԡԹՁՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՈԥՌՇԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ՅԿԩ 
 
  ԡԹՁՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆ
ԡԬ

 ՅԿԩ
 ԹՁՊՋԹՌՍՊԹՌՁՇՆ

ԱՇՌԹՄԹՄՃԹՄՁՆՁՌՑ
ՅԿԩԹՋԠԹԠԬ    ԴԽԽՃՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՇՌԹՄԹՄՃԹՄՁՆՁՌՑ ՅԿԩ ԹՋԠԹԠԬԥԹՊԼՆԽՋՋ#ՅԿԩԹՋԠԹԠԬ%    ԴԽԽՃՄՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԪՁՆՁՅՍՅ ԪԹՐՁՅՍՅ ԪԽԹՆ ԪԽԹՋՍՊԽՅԽՆՌԦՆՌԽՊՎԹՄ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱՇՌԹՄՇՊԿԹՆՁԻԻԹՊԺՇՆ
ՅԿԩ    ԪՇՆՌՀՄՑ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՇՌԹՄՇՊԿԹՆՁԻԻԹՊԺՇՆՁՆ

ԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽՅԿԩ

ԲՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹ


μԿԩ ԫԯ ԫԯ ԫԯ 

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՍՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹՁՆ

ՌՀԽԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ

μԿԩ

ԯԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽ


μԿԩ ԫԯ ԫԯ ԫԯ 

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽՁՆ

ԼՁՄՍՌՁՇՆՏԹՌԽՊԺԽ

μԿԩ

ԠՇՆԼՍԻՌԹՆԻԽ
սՅՀՇՋԻՅ    ԴԽԽՃՄՑ

ԤԽՆԽՊԹՄՊԽԻՇՅՅԽՆԼԹՌՁՇՆՋԾՇՊԾՊԽՉՍԽՆԻՑՇԾ

ՅԽԹՋՍՊԽՅԽՆՌՋԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌ

ՌԽՅՈԽՊԹՌՍՊԽՈԥԹՆԼԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆԺԽ

ՅԽԹՋՍՊԽԼՁՆԹՄՄՌԽՋՌՌԹՆՃՋԹՌՄԽԹՋՌՏԽԽՃՄՑԹՆԼ

ՌՀԹՌՀԹՊԼՆԽՋՋԹՆԼԹՄՃԹՄՁՆՁՌՑԺԽՅԽԹՋՍՊԽԼՁՆ

ԻՇՆՌՊՇՄՋԹՆԼՁՆՇՆԽՌԹՆՃԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆԹՌՄԽԹՋՌՏԽԽՃՄՑԦՆԹԼԼՁՌՁՇՆ

ԻՇՆՌՁՆՍՇՍՋՌԽՅՈԽՊԹՌՍՊԽՅՇՆՁՌՇՊՁՆԿՇԾԹՌՄԽԹՋՌ

ՇՆԽՌԹՆՃՁՋԽՆԻՇՍՊԹԿԽԼ

ԫԯԫՇՌՊԽՈՇՊՌԽԼԪԽԹՆՋՏԽՊԽԻԹՄԻՍՄԹՌԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊԹՋՌՀԽԹՎԽՊԹԿԽՇԾՌՀԽՅՁՆՁՅԹԹՆԼՅԹՐՁՅԹԾՇՊՌՀԽՊԹՆԿԽՋՈՊՇՎՁԼԽԼԹԻՊՇՋՋԻՇՆՌՊՇՄԹՆԼՌՊԽԹՌԽԼՄԽՎԽՄՋ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԡ ԰ՌՍԼՑԡԽՋՁԿՆԹՆԼԞԼԼՁՌՁՇՆԹՄԢՐՈԽՊՁՅԽՆՌԹՄԠՇՆԼՁՌՁՇՆՋ

ԱԹԺՄԽԯԹՆԿԽԣՁՆԼՁՆԿ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ
ՁԾԞՈՈՄՁԻԹԺՄԽ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԴԹՋԹՊԹՆԿԽԾՁՆԼԽՊԻՇՆԼՍԻՌԽԼ! ԫՇ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊՁԾ

ՀՇՍՊԩԠԼԹՌԹԾՇՊՌՀԽԾԹՌՀԽԹԼՅՁՆՆՇՏԹՊԽ

ՍՆԹՎԹՁՄԹԺՄԽ

ԦԾՑԽՋՏՀԹՌՏԹՋՌՀԽՅԽՌՀՇԼԾՇՊԼԽՌԽՊՅՁՆՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽՊԹՆԿԽԾՁՆԼԽՊ!

ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽՋԽՄԽԻՌԽԼԺԹՋԽԼՇՆՌՇՐՁԻՁՌՑԼԹՌԹ

ԾՇՊՇՌՀԽՊԾՁՋՀՋՌՍԼՁԽՋՇՊՋՈԽԻՁԽՋՁԾԹՎԹՁՄԹԺՄԽ

ԬՌՀԽՊՏՁՋԽԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽՌԽՋՌ

ԻՇՅՈՇՍՆԼՇՊՅԿԩ
ՏՀՁԻՀԽՎԽՊՁՋՄՇՏԽՊՁՋ

ԹՈՈՊՇՈՊՁԹՌԽ

԰ՈԽԻՁԽՋ ԫԞԩՁԾԽՋՌԹԿԽ ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՊԹՆԿԽԾՁՆԼՁՆԿՌԽՋՌՋԺԽ

ՈԽՊԾՇՊՅԽԼՏՁՌՀԾՁՋՀՇԾՋՁՅՁՄԹՊԹԿԽԹՆԼՋՁՒԽՌՇ

ՌՀՇՋԽՌՀԹՌՏՇՍՄԼԺԽՍՌՁՄՁՒԽԼՁՆՌՀԽՌԽՋՌ

ԱԽՋՌԼՍՊԹՌՁՇՆ ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՀՇՍՊԽՐՈՇՋՍՊԽ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԞԼԼՁՌՁՇՆԹՄԼԽՌԹՁՄՋ ԫԞ ԢԭԞՊԽԻՇՅՅԽՆԼՋԻՇՆԼՍԻՌՁՆԿԹՊԹՆԿԽԾՁՆԼԽՊՏՁՌՀ

ԾՁՎԽՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋՈՄՍՋԹԻՇՆՌՊՇՄ
ՋՁՐՌՇՌԹՄ

ՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՏՁՌՀԾՇՍՊԾԽՅԹՄԽՋԹՆԼՌՏՇ

ՅԹՄԽՋՈԽՊԽՐՈՇՋՍՊԽՌԹՆՃ
ԾՁՋՀՌՇՌԹՄԱՀԽ

ՆՍՅԺԽՊՇԾՅՇՊՌԹՄՁՌՁԽՋՌՀԹՌՇԻԻՍՊՅԹՑԺԽՍՋԽԼՌՇ

ԼԽՎԽՄՇՈԹԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԻՍՊՎԽ

ԟԹՋԽԼՍՈՇՆՌՀԽՊԽՋՍՄՌՋՌՀԽՀՁԿՀԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆ

ՌՀԹՌԼՇԽՋՆՇՌՊԽՋՍՄՌՁՆՁՆԻՊԽԹՋԽԼՅՇՊՌԹՄՁՌՑՇՊ

ՋՁԿՆՋՇԾՇՎԽՊՌՅՇՊԺՁԼՁՌՑԻՇՅՈԹՊԽԼՌՇԻՇՆՌՊՇՄՋՇՊ

ՌՀԽԼԽՊՁՎԽԼՀՊԩԠՅԹՑԺԽՋԽՄԽԻՌԽԼԹՋ

ՌՀԽՀՁԿՀԽՋՌԽՐՈՇՋՍՊԽԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԹՑ

ՌԽՋՌ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԡԽԾՁՆՁՌՁՎԽ԰ՌՍԼՑԠՇՆԼՁՌՁՇՆՋ

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԱԽՋՌԼՍՊԹՌՁՇՆ ԼԹՑՋ ԡՍԽՌՇՋԻՀԽԼՍՄՁՆԿԻՇՆԾՄՁԻՌՋՌՀԽԽՐՈՇՋՍՊԽ

ՏԹՋՅԹՁՆՌԹՁՆԽԼԾՇՊԹՈԽՊՁՇԼՇԾԼԹՑՋԹՋՇՈՈՇՋԽԼՌՇՌՀԽՋՌԹՆԼԹՊԼԼԹՑՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽԼՍՊԹՌՁՇՆՇԾՌՀԽ

ԼԽԾՁՆՁՌՁՎԽՌԽՋՌԺԽԼԹՑՋ

ԪԽՌՀՇԼԾՇՊՋԽՄԽԻՌՁՆԿՌՀԽՀՁԿՀԽՋՌՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀԽԼԽԾՁՆՁՌՁՎԽՌԽՋՌ

ԟԹՋԽԼՇՆԻՇՆՋՍՄՌԹՌՁՇՆՏՁՌՀՋՈՇՆՋՇՊ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՀՁԿՀԽՋՌՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋԽՁՌՀԽՊՌՀԽՋՇՄՍԺՁՄՁՌՑՄՁՅՁՌՇԾՌՀԽ

ՌԽՋՌԻՇՅՈՇՍՆԼՅԿԩՇՊԼԽՅՇՆՋՌՊԹՌԽՋ

ԹԼԽՉՍԹՌԽԽՎՁԼԽՆԻԽՇԾՌՇՐՁԻՁՌՑ
ԽԿՌՀԽ

ՀՇՍՊԩԠՏՀՁԻՀԽՎԽՊԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋՄՇՏԽՋՌ

ԯԽԾԽՊԽՆԻԽՋՌՍԼՑԻՁՌԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

ԫԞ

԰ԽՈԹՊԹՌՁՇՆՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԱԽՆԾՇՄԼ ԢԭԞՋՍԿԿԽՋՌՋՌՀԹՌԹԻՇՆԻԽՆՌՊԹՌՁՇՆՋԽՈԹՊԹՌՁՇՆՇԾ

ԺԽՌՏԽԽՆ
ՇՊՌՀՊԽԽԾՇՄԼԹՆԼ
ՇՊՌԽՆ

ԾՇՄԼՁՋՋԻՁԽՆՌՁԾՁԻԹՄՄՑԹԻԻԽՈՌԹԺՄԽ 

ԫՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋ  ԱՀԽՀՁԿՀԻՇՆԻԽՆՌՊԹՌՁՇՆՌՊԽԹՌՅԽՆՌՏԹՋ

ՌԽՊՅՁՆԹՌԽԼՇՆԡԹՑԼՍԽՌՇՀՁԿՀՅՇՊՌԹՄՁՌՑ

ԢԭԞՊԽԻՇՅՅԽՆԼՋԹՅՁՆՁՅՍՅՇԾ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԹԻՇՆՌՊՇՄՈՄՍՋՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ՁԾԹՈՈՊՇՈՊՁԹՌԽ

ԞՊԽՆՇՅՁՆԹՄԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԹԼՂՍՋՌԽԼԾՇՊՈՍՊՁՌՑ!

ԶԽՋ 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԦՆԼՁԻԹՌԽՌՀԽՌՑՈԽՇԾՎԹՄՍԽՋՈՊԽՋԽՆՌԽԼԾՇՊՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԪԽԹՆՅԽԹՋՍՊԽԼ ԞՎԽՊԹԿԽՊԽԻՇՎԽՊՁԽՋՊԹՆԿԽԼԾՊՇՅՌՇ

ՇԾՆՇՅՁՆԹՄ

ԩՁՅՁՌՇԾՉՍԹՆՌՁԾՁԻԹՌՁՇՆ
ԩԬԮ ՅԿ

ԹՁԩ

ԱՀԽԩԬԮԾՇՊՌՀԽԹՆԹՄՑՌՁԻՈԽՊՁՇԼԼԽՈԽՆԼԽԼՇՆՌՀԽՊԽԿՊԽՋՋՁՇՆԹՆԹՄՑՋՁՋՈԽՊԾՇՊՅԽԼՇՆՌՀԹՌԼԹՑ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԾՇՊԻՀԽՅՁԻԹՄՌԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋԺԽՄՇՏՌՀԽԩԬԮԹՆԹՄՑՋԽՋԺԽ

ԻՇՆԼՍԻՌԽԼՇՆՌՀԽՋՌՇԻՃՋՇՄՍՌՁՇՆՋ

ԩԽՎԽՄՇԾԼԽՌԽԻՌՁՇՆ
ԩԬԡ ԫՇՌՊԽՈՇՊՌԽԼԣՊԽՉՍԽՆԻՑՇԾՅԽԹՋՍՊԽՅԽՆՌ ԼԹՑՋ  ԦՌՁՋՊԽԻՇՅՅԽՆԼԽԼՌՀԹՌՌԽՋՌՁՌԽՅԻՇՆԻԽՆՌՊԹՌՁՇՆ

ԺԽՅԽԹՋՍՊԽԼՈՊՁՇՊՌՇՌՀԽԹԼԼՁՌՁՇՆՇԾԾՁՋՀՁՆԹՄՄ

ՌԹՆՃՋԹՆԼԹՌՄԽԹՋՌՏԽԽՃՄՑՌՀԽՊԽԹԾՌԽՊՁՆՌՏՇ

ՊԽՈՄՁԻԹՌԽՋՈԽՊՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

ԴԹՋՌՀԽՊԹՆԼՇՅՁՒԽԼԻՇՅՈՄԽՌԽԺՄՇԻՃԼԽՋՁԿՆՍՋԽԼ!

ԶԽՋ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌԹՄՄԾՁՋՀԺԽՊԹՆԼՇՅՄՑ

ԹՋՋՁԿՆԽԼՌՇՌԹՆՃՋԼՍՊՁՆԿՈՊԽԽՐՈՇՋՍՊԽԱԹՆՃՋ

ԹՊԽՌՀԽՆՊԹՆՃԽԼԹԻԻՇՊԼՁՆԿՌՇՈՊԽԽՐՈՇՋՍՊԽ

ԾԽԻՍՆԼՁՌՑԹՆԼՌՀԽՌԹՆՃՋՏՁՌՀՌՀԽՀՁԿՀԽՋՌ

ԾԽԻՍՆԼՁՌՑԹՊԽՊԹՆԼՇՅՄՑԹՋՋՁԿՆԽԼՌՇԹԼԽԾՁՆՁՌՁՎԽ

ՌԽՋՌՌՊԽԹՌՅԽՆՌԹՆԼԺՄՇԻՃԾՁՊՋՌԢԹԻՀԺՄՇԻՃ

ԻՇՆՌԹՁՆՋՇՆԽՊԽՈՄՁԻԹՌԽՇԾԽԹԻՀՌՊԽԹՌՅԽՆՌ

ՁՆԻՄՍԼՁՆԿԻՇՆՌՊՇՄՋ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆԻՇՆՌՊՇՄ  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԭԹՊԹՅԽՌԽՊ ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՁՆՋՇՄՎԽՆՌԻՇՆՌՊՇՄ
ՁԾԹՈՈՄՁԻԹԺՄԽ

  ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԽՍՋԽՇԾԹԻՇՆԻՍՊՊԽՆՌ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏՀԽՆԹՋՇՄՍԺՁՄՁՒՁՆԿԹԿԽՆՌՁՋՍՋԽԼ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՊԽՈՄՁԻԹՌԽՋՈԽՊՌԽՋՌՁՌԽՅՌՊԽԹՌՅԽՆՌՄԽՎԽՄ

  ԢԭԞՊԽԻՇՅՅԽՆԼՋՊԽՈՄՁԻԹՌԽՋ

ԫՍՅԺԽՊՇԾՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

 ՅԹՄԽՋԹՆԼԾԽՅԹՄԽՋՏԽՊԽՍՋԽԼՁՆ

ԻՇՆՌՊՇՄՌԹՆՃՋԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌԹՆՃ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽ 

ԫՍՅԺԽՊՇԾԾԽՅԹՄԽԾՁՋՀՈԽՊՊԽՈՄՁԻԹՌԽԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

 ՅԹՄԽՋԹՆԼԾԽՅԹՄԽՋՏԽՊԽՍՋԽԼՁՆ

ԻՇՆՌՊՇՄՌԹՆՃՋԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՌԹՆՃ

ԢԭԞՊԽԻՇՅՅԽՆԼՋԾԽՅԹՄԽՋՈԽՊՊԽՈՄՁԻԹՌԽ

ԴԹՋԹՋՇՄՎԽՆՌՍՋԽԼ! ԶԽՋ԰ՇՄՎԽՆՌՌՑՈԽ
ՁԾԹՈՈՄՁԻԹԺՄԽ ԡԪԣԪԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՁԾԹՈՈՄՁԻԹԺՄԽ

Յԩԩ ԱՀԽՅԹՐՁՅՍՅՋՇՄՎԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՁՆՌՀՁՋ

ՋՌՍԼՑԽՐԻԽԽԼԽԼՌՀԽՅՄԩՊԽԻՇՅՅԽՆԼԽԼԺՑԢԭԞ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՌՀԽՋՇՄՎԽՆՌՆՇՌԽՐԻԽԽԼ

ՅՄԩԬԢԠԡՊԽԻՇՅՅԽՆԼՋՌՀԹՌՋՇՄՎԽՆՌ

ՀԹՎԽՆՇԽԾԾԽԻՌՇՆՋՍՊՎՁՎԹՄՆՇՊՈՊՇԼՍԻԽԹՆՑՇՌՀԽՊ

ԹԼՎԽՊՋԽԽԾԾԽԻՌՋԹՆԼՌՀԹՌԻՇՆԻԽՆՌՊԹՌՁՇՆՆՇՌԺԽ

ԿՊԽԹՌԽՊՌՀԹՆՅՄԩ



ԴԹՋԹՈՇՋՁՌՁՎԽԻՇՆՌՊՇՄՍՋԽԼ! ԫՇ

ԥՍՌԻՀՁՆՋՇՆԱԥ԰ՀՁՄՄԹԺԽԽՊԫԴՁՆՌԽՊԪԧԭՁԻՃԾՇՊԼԡԟ
ԞԻՍՌԽԹՆԼԻՀՊՇՆՁԻԽԾԾԽԻՌՋՇԾԻԹՊՊՁԽՊՋՇՄՎԽՆՌՋՁՆԹՉՍԹՌՁԻՇՊԿԹՆՁՋՅՋԞԻՊՁՌՁԻԹՄՊԽՎՁԽՏԯԽՎՁԽՏԞՉՍԹՌՁԻ

ԱՇՐՁԻՇՄՇԿՑՈՈ-

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԳԹՄՍԽ
Ջ ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

 ԫԞ


Ջ
ՁԾ ԫԞ

ՀՊՋՄՁԿՀՌՀՊՋԼԹՊՃ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՈՀՇՌՇՈԽՊՁՇԼ
ՄՁԿՀՌԼԹՊՃ

ԹԻԽ ՌՇՄՍՐ ԩՁԿՀՌՏԹՋՈՊՇՎՁԼԽԼԺՑ԰ՑՄՎԹՆՁԹԬՃՌՊՇՆն

ԾՄՍՇՊԽՋԻԽՆՌԺՍՄԺՋԹՆԼՁՆՌԽՆՋՁՌՑՏԹՋՅԽԹՋՍՊԽԼՏՁՌՀԹԳԴԯՄՁԿՀՌՅԽՌԽՊ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՄՁԿՀՌՁՆՌԽՆՋՁՌՑ-ՄՍՐ


ԹՌՏԹՌԽՊ0ՋՋՍՊԾԹԻԽ

԰ՌՇԻՃՋՇՄՍՌՁՇՆՏԹՋՇԺՋԽՊՎԽԼՌՇԺԽԻՄԽԹՊԹՆԼ

ՑԽՄՄՇՏՏՁՌՀՆՇՎՁՋՁԺՄԽՍՆԼՁՋՋՇՄՎԽԼՌԽՋՌՋՍԺՋՌԹՆԻԽԾՇՄՄՇՏՁՆԿՈՊԽՈԹՊԹՌՁՇՆԱՀՊՇՍԿՀՇՍՌՌՀԽՋՌՍԼՑՈԽՊՁՇԼԹՄՄԽՐՈՇՋՍՊԽՋՇՄՍՌՁՇՆՋՏԽՊԽՇԺՋԽՊՎԽԼՌՇԺԽԻՄԽԹՊԹՆԼԻՇՄՇՊՄԽՋՋ

ՍՅԽՆՌՇՆԞՉՍԹՌՁԻԱՇՐՁԻՁՌՑԱԽՋՌՁՆԿՇԾԡՁԾԾՁԻՍՄՌ԰ՍԺՋՌԹՆԻԽՋԹՆԼԪՁՐՌՍՊԽՋԢՆՎՁՊՇՆՅԽՆՌԹՄԥԽԹՄՌՀԹՆԼ԰ԹԾԽՌՑԭՍԺՄՁԻԹՌՁՇՆՋ԰ԽՊՁԽՋՇՆԱԽՋՌՁՆԿԹՆԼ

ՆԻԽ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽ԰ՍՅՅԹՊՑՇԾԱՊԽԹՌՅԽՆՌԠՇՆԻԽՆՌՊԹՌՁՇՆՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌԦԡ

ԫՇՅՁՆԹՄ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԪԽԹՋՍՊԽԼ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ


ՅԿԹՁԩ

ԪԽԹՆԠԳ
 ԡԽՌԹՁՄՋՇՊԯԽՅԹՊՃՋ ԤՍՁԼԽՄՁՆԽԯԽԻՇՅՅԽՆԼԹՌՁՇՆՋ

ԠՇՆՌՊՇՄ
ԼՁՄՍՌՁՇՆՏԹՌԽՊՇՆՄՑ

 ԩԬԮ ԫԞ

ԢԭԞ ՊԽԻՇՅՅԽՆԼՋ ՌՀԹՌ ՌԽՋՌ ՁՌԽՅ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ

ԺԽ ՅԹՁՆՌԹՁՆԽԼ ԹՌ Թ ԻՇԽԾԾՁԻՁԽՆՌ ՇԾ ՎԹՊՁԹՌՁՇՆ 
ԠԳ

 ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ  ԩԬԮ ԫԞ

ԱՊԽԹՌՅԽՆՌ   ԱՊԽԹՌՅԽՆՌ   ԱՊԽԹՌՅԽՆՌ   

ԞԺԺՊԽՎՁԹՌՁՇՆՋԠԳԠՇԽԾԾՁԻՁԽՆՌՇԾՎԹՊՁԹՌՁՇՆ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

Ԣ ԬԺՋԽՊՎԹՌՁՇՆՋ

ԟՁՇՄՇԿՁԻԹՄԢՆԼՈՇՁՆՌՋ ԢՆԼՈՇՁՆՌՋ ՁՆԻՄՍԼԽԼԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՒԹՌՁՇՆ ՋՍԻԻԽՋՋ ՋՍՊՎՁՎԹՄ ՊԹՌԽՋՏԽՁԿՀՌ ՆՍՈՌՁԹՄ ՌՍԺԽՊԻՄԽ ՋԻՇՊԽԳԱԤ ԻՇՆԻԽՆՌՊԹՌՁՇՆՋ ԹՆԼ

Ԥ԰Ԧ ԰ԽՐ ՋՌԽՊՇՁԼՋ ՏԽՊԽ ՊԽՈՇՊՌԽԼՄՑ ՅԽԹՋՍՊԽԼ ԺՍՌ ՆՇ ՊԽՋՍՄՌՋ ՏԽՊԽ ՈՊՇՎՁԼԽԼ ԰ԽԻՇՆԼԹՊՑ ՋԽՐ ԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋ ԹՆԼ

ԺԽՀԹՎՁՇՊԹՄԻՄՁՆՁԻԹՄՋՁԿՆՋՏԽՊԽՊԽՈՇՊՌԽԼ

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԴԽՊԽՊԹՏ
ՁՆԼՁՎՁԼՍԹՄԼԹՌԹՈՊՇՎՁԼԽԼ!ԶԽՋ

ԢԭԞՊԽԻՇՅՅԽՆԼՋՌՀԹՌՇԺՋԽՊՎԹՌՁՇՆՋՇԾՋՍՊՎՁՎԹՄԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋՋԽԻՇՆԼԹՊՑՋԽՐԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼՇՌՀԽՊԻՄՁՆՁԻԹՄՋՁԿՆՋՇԻԻՍՊԹՌՄԽԹՋՌԼԹՁՄՑԞՌ

ՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ
ԡԹՑԹԼԼՁՌՁՇՆԹՄՇԺՋԽՊՎԹՌՁՇՆՋՁՆԻՄՍԼԽԺՇԼՑՏԽՁԿՀՌԹՆԼՄԽՆԿՌՀՆՍՈՌՁԹՄՌՍԺԽՊԻՄԽՋԻՇՊԽԿՇՆԹԼԹՄՋՌԹԿՁՆԿԹՆԼՀՁՋՌՇՈԹՌՀՇՄՇԿՑՈՄԹՋՅԹ

ՎՁՌԽՄՄՇԿԽՆՁՆԹՆԼՈՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼՋ
ՌԽՋՌՇՋՌԽՊՇՆԽԹՆԼȕԽՋՌՊԹԼՁՇՄՁԾՅԽԹՋՍՊԽԼԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
Ԥ԰ԦՁՋԻԹՄԻՍՄԹՌԽԼՍՋՁՆԿԹՊԹՌՁՇՇԾԿՇՆԹԼՏԽՁԿՀՌ

ՌՇԺՇԼՑՏԽՁԿՀՌ
ԿՇՆԹԼՏԽՁԿՀՌՌՇՌՀԽՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌՁՆՅԿՐԹՌՌԽՋՌՌԽՊՅՁՆԹՌՁՇՆ

ԠՄՁՆՁԻԹՄՋՁԿՆՋՇԾՇՎԽՊՌՌՇՐՁԻՁՌՑՅԹՑՁՆԻՄՍԼԽ
ԺՍՌԹՊԽՆՇՌՄՁՅՁՌԽԼՌՇՀԽՅՇՊՊՀԹԿԽԻԽՋՋԹՌՁՇՆՇԾԾԽԽԼՁՆԿԹՆԼՇՌՀԽՊԹԺՆՇՊՅԹՄԺԽՀԹՎՁՇՊ

ԦԦ ԯԢ԰ԲԩԱ԰ԞԫԡԡԦ԰ԠԲ԰԰ԦԬԫ

Ԟ ԯԽՋՍՄՌՋ

ԱՀՊՇՍԿՀՇՍՌՌՀԽՌԽՋՌՆՇՅԹՄԽՅՇՊՌԹՄՁՌՁԽՋՏԽՊԽՇԺՋԽՊՎԽԼՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՅԹՄԽՋՍՊՎՁՎԹՄՏԹՋՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԣԽՅԹՄԽՋՍՊՎՁՎԹՄՏԹՋՁՆԺՇՌՀԻՇՆՌՊՇՄԿՊՇՍՈՋԹՆԼՏԹՋԹՆԼՊԽՋՈԽԻՌՁՎԽՄՑԹՌՌՀԽԹՆԼՅԿԹՁԩՄԽՎԽՄՋԱՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՏԹՋՌԽՊՅՁՆԹՌԽԼՇՆԡԹՑԼՍԽՌՇՀՁԿՀՅՇՊԺՁԼՁՌՑՁՆԻՄՍԼՁՆԿՄԽՌՀԹՊԿՑԹՆԼՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅԞՄՄԾՁՋՀՁՆՌՀՁՋՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈՏԽՊԽԽՍՌՀԹՆՁՒԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԞԼՍՄՌԣՁՋՀ԰ՍՊՎՁՎԹՄՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԰ՍՊՎՁՎՁՆԿ ԰ՍՊՎՁՎԹՄ ԫ ԰ՍՊՎՁՎՁՆԿ ԰ՍՊՎՁՎԹՄ

ԠՇՆՌՊՇՄ
ԩԬԮ      ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄԩԬԮ                        

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

ԪԽԹՆՅԹՄԽԺՇԼՑՏԽՁԿՀՌՏԹՋԹՆԼԿԹՆԼՅԽԹՆԾԽՅԹՄԽԺՇԼՑՏԽՁԿՀՌՏԹՋԹՆԼԿՁՆՌՀԽ

ԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑԪԽԹՆՅԹՄԽՄԽՆԿՌՀՏԹՋ

ԹՆԼՅՅԹՆԼՅԽԹՆԾԽՅԹՄԽՄԽՆԿՌՀՏԹՋԹՆԼՅՅՁՆՌՀԽԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑԪԹՄԽՎԹՄՍԽՋԽՐԻՄՍԼԽՅԽԹՋՍՊԽՅԽՆՌՋՇԾԾՁՋՀՁՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋՌՀԹՌՏԽՊԽՅՁՋՁԼԽՆՌՁԾՁԽԼԹՋԾԽՅԹՄԽԾՁՋՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԱՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՏԹՋՌԽՊՅՁՆԹՌԽԼԹՌԡԹՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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            ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ

           

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

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

 ԰ԹՅՈՄԽՋՁՒԽ
ՆՊԽՈՊԽՋԽՆՌՋՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋ ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԪԽԹՆԾԽԻՍՆԼՁՌՑՎԹՄՍԽՋՏԽՊԽԹՆԼԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑԹՆԼԾԽՊՌՁՄՁՒԹՌՁՇՆ

ՋՍԻԻԽՋՋՏԹՋԹՆԼՁՆՌՀԽԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԽԹՆՅԽԹՋՍՊԽԼ

ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ

ԱԹԺՄԽԣԽԻՍՆԼՁՌՑԹՆԼԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԣԽԻՍՆԼՁՌՑ ԣԽՊՌՁՄՁՒԹՌՁՇՆ԰ՍԻԻԽՋՋ

ԪԽԹՆ չ԰ԡ ԪԽԹՆ
 չ԰ԡ

ԠՇՆՌՊՇՄ
ԩԬԮ    

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ    

    

    

 ԫԞ ԫԞ ԫԞ ԫԞ

ԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



 ԣԽԻՍՆԼՁՌՑՁՋԻԹՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋՈԽՊՋՍՊՎՁՎՁՆԿԾԽՅԹՄԽՈԽՊՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑՈԽՊՊԽՈՄՁԻԹՌԽ



 ԣԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋ
ՁՋԻԹՄԻՍՄԹՌԽԼԹՋՌՀԽՆՍՅԺԽՊՇԾԽՅԺՊՑՇՋԼՁՎՁԼԽԼԺՑՌՀԽՆՍՅԺԽՊՇԾԽԿԿՋՅՍՄՌՁՈՄՁԽԼԺՑ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

ԪԽԼՁԹՆՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՋՏԽՊԽԹՆԼՁՆՌՀԽԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԽԹՆ

ՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑԱՀԽՋԽՎԹՄՍԽՋԽՐԻՄՍԼԽՅԽԹՋՍՊԽՅԽՆՌՋՇԾ

ԾՁՋՀՁՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋՌՀԹՌՏԽՊԽՅՁՋՁԼԽՆՌՁԾՁԽԼԹՋԾԽՅԹՄԽԾՁՋՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆԫՇ

ՌՍԺԽՊԻՄԽՋՏԽՊԽՇԺՋԽՊՎԽԼՇՆԾԽՅԹՄԽԾՁՋՀ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԫՍՈՌՁԹՄԱՍԺԽՊԻՄԽ԰ԻՇՊԽՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆԱՍԺԽՊԻՄԽ

԰ԻՇՊԽ Ն ԪԽԼՁԹՆԱՍԺԽՊԻՄԽ԰ԻՇՊԽ

ԠՇՆՌՊՇՄ
ԩԬԮ    

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ    

    

    

 ԫԞ ԫԞ ԫԞ ԫԞ

ԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ

԰ԹՅՈՄԽՋՁՒԽ
ՆՊԽՈՊԽՋԽՆՌՋՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

ԪԽԹՆՅԹՄԽԤ԰ԦՏԹՋԹՆԼԹՆԼՅԽԹՆԾԽՅԹՄԽԤ԰ԦՏԹՋԹՆԼ

ՁՆՌՀԽԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋ

ՊԽՋՈԽԻՌՁՎԽՄՑԪԹՄԽՎԹՄՍԽՋԽՐԻՄՍԼԽՅԽԹՋՍՊԽՅԽՆՌՋՇԾԾՁՋՀՁՆՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄՋՌՀԹՌՏԽՊԽ

ՅՁՋՁԼԽՆՌՁԾՁԽԼԹՋԾԽՅԹՄԽԾՁՋՀԹՌՌԽՋՌՁՆՁՌՁԹՌՁՇՆ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐ
Ԥ԰ԦՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն

ԪԽԹՆԤ԰Ԧ




չ԰ԡ Ն

ԪԽԹՆԤ԰Ԧ




չ԰ԡ

ԠՇՆՌՊՇՄ
ԩԬԮ      

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ      

      

      

 ԫԞ   ԫԞ  

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ

 ԤՇՆԹԼՇՋՇՅԹՌՁԻՁՆԼԽՐ
ՁՋԻԹՄԻՍՄԹՌԽԼԹՋԿՇՆԹԼՏԽՁԿՀՌ
ՌՇՌՀԽՆԽԹՊԽՋՌՅԿԺՇԼՑՏԽՁԿՀՌ
ՅԿՐ

԰ԹՅՈՄԽՋՁՒԽ
ՆՊԽՈՊԽՋԽՆՌՋՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

ԪԽԼՁԹՆՅԹՄԽԿՇՆԹԼԹՄՋՌԹԿԽՏԹՋԹՆԼԹՆԼՅԽԼՁԹՆԾԽՅԹՄԽԿՇՆԹԼԹՄՋՌԹԿԽՏԹՋԹՆԼՁՆ

ՌՀԽԻՇՆՌՊՇՄՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԽԹՆՅԽԹՋՍՊԽԼԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋՊԽՋՈԽԻՌՁՎԽՄՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԤՇՆԹԼԹՄ԰ՌԹԿՁՆԿՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն ԪԽԼՁԹՆ԰ՌԹԿԽ Ն ԪԽԼՁԹՆ԰ՌԹԿԽ

ԠՇՆՌՊՇՄ
ԩԬԮ    

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ    

    

    

 ԫԞ  ԫԞ 

ԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



 ԱՀԽ ԿՍՁԼԽՄՁՆԽ ՊԽԻՇՅՅԽՆԼՋ ՌՀԽ ԾՇՄՄՇՏՁՆԿ ԿՇՆԹԼԹՄ ՋՌԹԿՁՆԿ ՋԻԹՄԽ ԾՇՊ ՅԹՄԽ ԾԹՌՀԽԹԼ ՅՁՆՆՇՏ ՍՆԼԽՎԽՄՇՈԽԼ ԽԹՊՄՑ

ՋՈԽՊՅԹՌՇԿԽՆՁԻՅՁԼՋՈԽՊՅԹՌՇԿԽՆՁԻՄԹՌԽՋՈԽՊՅԹՌՇԿԽՆՁԻՋՈԽՆՌ



 ԱՀԽ ԿՍՁԼԽՄՁՆԽ ՊԽԻՇՅՅԽՆԼՋ ՌՀԽ ԾՇՄՄՇՏՁՆԿ ԿՇՆԹԼԹՄ ՋՌԹԿՁՆԿ ՋԻԹՄԽ ԾՇՊ ԾԽՅԹՄԽ ԾԹՌՀԽԹԼ ՅՁՆՆՇՏ ՍՆԼԽՎԽՄՇՈԽԼ ԽԹՊՄՑ

ԼԽՎԽՄՇՈՅԽՆՌՅՁԼԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՄԹՌԽԼԽՎԽՄՇՈՅԽՆՌՀՑԼՊԹՌԽԼՈՇՋՌՇՎՍՄԹՌՇՊՑ

԰ԹՅՈՄԽՋՁՒԽ
ՆՊԽՈՊԽՋԽՆՌՋՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

ԪՁՆՁՅԹՄՌԽՋՌՁԻՍՄԹՊԼԽԿԽՆԽՊԹՌՁՇՆՏԹՋՆՇՌԽԼՁՆՇԾՇԾԹՆԼՇԾՅԹՄԽՋՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄ

ԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑԻՇՅՈԹՊԽԼՌՇՆՇՆԽՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԣՇՍՊ

ՅԹՄԽՋՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՀԹԼԹՄՌԽՊԽԼՈՊՇՈՇՊՌՁՇՆՋՇԾՋՈԽՊՅԹՌՇՒՇԹՇՊՋՈԽՊՅԹՌՇԻՑՌԽՋ


ՅՁՆՁՅԹՄՌՇՅՇԼԽՊԹՌԽԻՇՅՈԹՊԽԼՌՇՆՇՆԽՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՄԽՎԽՄԹՆԼՇՆՄՑ

ՅՁՆՁՅԹՄՁՆԻՁԼԽՆՌՏԹՋՇԺՋԽՊՎԽԼՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԞՋՁՆԿՄԽՅԹՄԽՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈ

ՀԹԼՌՀԽՈՊԽՋԽՆԻԽՇԾՌԽՋՌՁՋՇՎԹԻՇՅՈԹՊԽԼՌՇՆՇՆԽՁՆՌՀԽՇՌՀԽՊՌՊԽԹՌԽԼՄԽՎԽՄԹՆԼԻՇՆՌՊՇՄՋ԰ՁՐՅԹՄԽՋ

ԼՁՋՈՄԹՑԽԼՅՁՄԼՌՇՅՇԼԽՊԹՌԽՁՆՌԽՊՋՌՁՌՁԹՄԻԽՄՄՀՑՈԽՊՌՊՇՈՀՑՀՑՈԽՊՈՄԹՋՁԹԻՇՅՈԹՊԽԼՌՇԾՇՍՊՅՁՆՁՅԹՄՁՆԻՁԼԽՆՌՋ

ԽԹԻՀՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՄԽՎԽՄԹՆԼՇՆՄՑՇՆԽՁՆԻՁԼԽՆՌՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԟԹՋԽԼՇՆՌՀԽՋԽԾՁՆԼՁՆԿՋՌՀԽՊԽՏԹՋՋՇՅԽԽՎՁԼԽՆԻԽԾՇՊՈՊՇՆԹՅՁԼԽՊԽՄԹՌԽԼՀՁՋՌՇՄՇԿՁԻԹՄԽԾԾԽԻՌՋՁՆՅԹՄԽ

ԾԹՌՀԽԹԼՅՁՆՆՇՏՋԹՌՌՀԽՅԿԹՁԩՄԽՎԽՄ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԞՋՄՁԿՀՌՄՑԿՊԽԹՌԽՊՈՊՇՈՇՊՌՁՇՆՇԾԾԽՅԹՄԽՋ
ՇԾՋՀՇՏԽԼՅՁՄԼՁՆԻՊԽԹՋԽԼՇՇԻՑՌԽԹՌՊԽՋՁԹԹՌՌՀԽՅԿ

ԹՁԩՄԽՎԽՄԻՇՅՈԹՊԽԼՌՇՇԾԹՆԼՇԾՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՅԿԹՁԩՄԽՎԽՄՋ

ՊԽՋՈԽԻՌՁՎԽՄՑՌՀԽՊԽՏԹՋՇԾՋՀՇՏՁՆԿՅՁՆՁՅԹՄՇՇԻՑՌԽԹՌՊԽՋՁԹՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԪՁՆՁՅԹՄԼԽԻՊԽԹՋԽԼ

ՑՇՄՃԾՇՊՅԹՌՁՇՆՏԹՋՈՊԽՋԽՆՌՁՆՇՆԽՇԾԾԽՅԹՄԽՋՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԻՇՅՈԹՊԽԼՌՇՆՇՆԽ

ՁՆՌՀԽԻՇՆՌՊՇՄՋԹՆԼՄՇՏԽՊԽՐՈՇՋՍՊԽՄԽՎԽՄԪՁՆՁՅԹՄՇՊՅՁՄԼԿՊԹՆՍՄՇՅԹՌՇՍՋՁՆԾՄԹՅՅԹՌՁՇՆՏԹՋՈՊԽՋԽՆՌՁՆՇՆԽ

ՁՆԼՁՎՁԼՍԹՄԽԹԻՀԾՊՇՅՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼՌՀԽՅԿԹՁԩՄԽՎԽՄԻՇՅՈԹՊԽԼՌՇՌՀՊԽԽՁՆԻՁԼԽՆՌՋՇԾ

ՅՁՆՁՅԹՄԿՊԹՆՍՄՇՅԹՌՇՍՋՁՆԾՄԹՅՅԹՌՁՇՆԹՌՌՀԽՅԿԹՁԩՄԽՎԽՄԱՀԽՋՌՍԼՑԹՍՌՀՇՊԻՇՆԻՄՍԼԽԼՌՀԹՌՌՀԽՊԽՏԹՋ

ՆՇՁՆԼՁԻԹՌՁՇՆՇԾԹՈՊՇՆԹՅՁԼԽՊԽՄԹՌԽԼԽԾԾԽԻՌՇՆՌՀԽՀՁՋՌՇՄՇԿՁԻԹՄԾՁՆԼՁՆԿՋՇԾԾԽՅԹՄԽԾԹՌՀԽԹԼՅՁՆՆՇՏՋՁՆՌՀՁՋ

ՋՌՍԼՑ

ԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ

ԭՊԽՋԽՆԻԽՇԾ

ԱԽՋՌՁՋԬՎԹ

ԦՆԻՊԽԹՋԽԼ

ԱԽՋՌՁԻՍՄԹՊ

ԡԽԿԽՆԽՊԹՌՁՇՆ

ԦՆՌԽՊՋՌՁՌՁԹՄԠԽՄՄ

ԥՑՈԽՊՌՊՇՈՀՑ

ԥՑՈԽՊՈՄԹՋՁԹ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԩԬԮ         

        

        

        

        

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ


ԩԬԮ

        

        

        

        

        

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ

ԭՊԽՋԽՆԻԽՇԾ

ԱԽՋՌՁՋԬՎԹ

ԦՆԻՊԽԹՋԽԼ

ԱԽՋՌՁԻՍՄԹՊ

ԡԽԿԽՆԽՊԹՌՁՇՆ

ԦՆՌԽՊՋՌՁՌՁԹՄԠԽՄՄ

ԥՑՈԽՊՌՊՇՈՀՑ

ԥՑՈԽՊՈՄԹՋՁԹ

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

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԞԼԼՁՌՁՇՆԹՄԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑԬԺՋԽՊՎԹՌՁՇՆՋՁՆԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԡԽԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ

ԦՆԻՊԽԹՋԽԼԳԹՋԻՍՄԹՊ

ՇՊԦՆՌԽՊՋՌՁՌՁԹՄ

ԭՊՇՌԽՁՆԹԻԽՇՍՋԣՄՍՁԼ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԤՇՆԹԼ

ԡԽՎԽՄՇՈՅԽՆՌ

ԞՄՌԽՊԽԼԭՊՇՈՇՊՌՁՇՆՋՇԾ

԰ՈԽՊՅԹՌՇԻՑՌԽՋՇՊ

԰ՈԽՊՅԹՌՁԼՋ

ԤՊԹՆՍՄՇՅԹՌՇՍՋ

ԦՆԾՄԹՅՅԹՌՁՇՆ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԩԬԮ           

          

                              

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ           

          

                              

           

          

                              

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱՊԽԹՌՅԽՆՌ
ՅԿԹՁԩ#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԡԽԻՊԽԹՋԽԼ

ԭՊՇՈՇՊՌՁՇՆՇԾ

԰ՈԽՊՅԹՌՇԿՇՆՁԹ

ԦՆԻՊԽԹՋԽԼԳԹՋԻՍՄԹՊ

ՇՊԦՆՌԽՊՋՌՁՌՁԹՄ

ԭՊՇՌԽՁՆԹԻԽՇՍՋԣՄՍՁԼ

ԞՋՑՆԻՀՊՇՆՇՍՋ

ԤՇՆԹԼ

ԡԽՎԽՄՇՈՅԽՆՌ

ԞՄՌԽՊԽԼԭՊՇՈՇՊՌՁՇՆՋՇԾ

԰ՈԽՊՅԹՌՇԻՑՌԽՋՇՊ

԰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

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԤՇՆԹԼԹՄԥՁՋՌՇՈԹՌՀՇՄՇԿՑՁՆԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆԻՊԽԹՋԽԼԬՇԻՑՌԽ

ԞՌՊԽՋՁԹ

ԭԽՊՁԾՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

ԥՑՈԽՊՌՊՇՈՀՑ

ԡԽԻՊԽԹՋԽԼԶՇՄՃ

ԣՇՊՅԹՌՁՇՆ

Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԩԬԮ       

      

      

      

      

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ       

      

      

      

      

       

      

      

      

      

       

      

      

      

      

Page 153 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆԻՊԽԹՋԽԼԬՇԻՑՌԽ

ԞՌՊԽՋՁԹ

ԭԽՊՁԾՇՄՄՁԻՍՄԹՊԠԽՄՄ

ԥՑՈԽՊՈՄԹՋՁԹ

ԥՑՈԽՊՌՊՇՈՀՑ

ԡԽԻՊԽԹՋԽԼԶՇՄՃ

ԣՇՊՅԹՌՁՇՆ

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



 ԤՇՆԹԼԹՄՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻՇԺՋԽՊՎԹՌՁՇՆՋԹՊԽԿՊԹԼԽԼ-ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌՊԽՅԹՊՃԹԺՄԽԪՁՆՁՅԹՄ

ԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

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

        

        

        

        

        

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ


ԩԬԮ

        

        

        

        

        

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆ

ՅԽԹՋՍՊԽԼ%

ԞԼԼՁՌՁՇՆԹՄԡՁԹԿՆՇՋՌՁԻԬԺՋԽՊՎԹՌՁՇՆՋ

԰ԽՎԽՊՁՌՑ

ԦՆՌԽՊՋՌՁՌՁԹՄԣՁԺՊՇՋՁՋ

ԢԿԿԡԽԺՊՁՋՁՆ

ԬՎՁԼՍԻՌ

ԤՊԹՆՍՄՇՅԹՌՇՍՋ

ԦՆԾՄԹՅՅԹՌՁՇՆ

ԡԽԻՊԽԹՋԽԼԭՇՋՌ

ԬՎՍՄԹՌՇՊՑԣՇՄՄՁԻՄԽՋ

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



 ԤՇՆԹԼԹՄ ՀՁՋՌՇՈԹՌՀՇՄՇԿՑԼՁԹԿՆՇՋՌՁԻ ՇԺՋԽՊՎԹՌՁՇՆՋ ԹՊԽ ԿՊԹԼԽԼ- ԺԹՋԽԼՇՆՋԽՎԽՊՁՌՑԫՇՌ ՊԽՅԹՊՃԹԺՄԽ ԪՁՆՁՅԹՄ

ԪՁՄԼԪՇԼԽՊԹՌԽ԰ԽՎԽՊԽ԰ԽԽԞՈՈԽՆԼՁՐԢՇԾՌՀԽՌԽՋՌԿՍՁԼԽՄՁՆԽԾՇՊՊԽԾԽՊԽՆԻԽ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

ԪԽԹՆ ՅԹՄԽ ԳԱԤ ՏԹՋ    ԹՆԼ  ՆԿՅԩ ԹՆԼ ԾԽՅԹՄԽ ԳԱԤ ՏԹՋ Ր

 Ր

Ր ԹՆԼ Ր

 ՆԿՅԩ ՁՆ ՌՀԽ ԻՇՆՌՊՇՄ ՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄ ԹՆԼ ՅԽԹՆՅԽԹՋՍՊԽԼ  ԹՆԼ  ՅԿ

ԹՁԩ ՌՊԽԹՌՅԽՆՌ ՄԽՎԽՄՋ ՊԽՋՈԽԻՌՁՎԽՄՑ ԪԹՄԽ ՎԹՄՍԽՋ ԽՐԻՄՍԼԽ ՅԽԹՋՍՊԽՅԽՆՌՋ ՇԾ ԾՁՋՀ ՁՆ ՌՀԽ ՆԽԿԹՌՁՎԽ ԹՆԼ

ՋՇՄՎԽՆՌ ԻՇՆՌՊՇՄՋ ՌՀԹՌ ՏԽՊԽ ՅՁՋՁԼԽՆՌՁԾՁԽԼ ԹՋ ԾԽՅԹՄԽ ԾՁՋՀ ԹՌ ՌԽՋՌ ՁՆՁՌՁԹՌՁՇՆ ԰ՌԽՊՇՁԼ ՄԽՎԽՄՋ ՏԽՊԽ ՊԽՈՇՊՌԽԼՄՑ

ՅԽԹՋՍՊԽԼԾՊՇՅՈՄԹՋՅԹՋԹՅՈՄԽՋԺՍՌՌՀԽՊԽՋՍՄՌՋՏԽՊԽՆՇՌՈՊՇՎՁԼԽԼՁՆՌՀԽՋՌՍԼՑՊԽՈՇՊՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԭՄԹՋՅԹԳՁՌԽՄՄՇԿԽՆՁՆ
ԳԱԤ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

Ն

ԪԽԹՆ


ՆԿՅԩ

ՈՄԹՋՅԹ

չ԰ԡ Ն

ԪԽԹՆ


ՆԿՅԩ

ՈՄԹՋՅԹ

չ԰ԡ

ԠՇՆՌՊՇՄ
ԩԬԮ     Ր Ր

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ     Ր Ր

     Ր Ր

     Ր Ր

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ԰ԡ԰ՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆ

԰ԹՅՈՄԽՋՁՒԽ
ՆՊԽՈՊԽՋԽՆՌՋՌՀԽՆՍՅԺԽՊՇԾՁՆԼԽՈԽՆԼԽՆՌՊԽՈՄՁԻԹՌԽՋ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

Page 156 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԭՄԹՋՅԹ԰ԽՐ԰ՌԽՊՇՁԼՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՀՁՋՌԹԺՄԽՁՋՇՅՁՌՌԽԼԺԽԻԹՍՋԽՊԽՋՍՄՌՋԾՇՊՈՄԹՋՅԹՋԽՐՋՌԽՊՇՁԼԻՇՆԻԽՆՌՊԹՌՁՇՆՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼ

ԫՇԹԺՆՇՊՅԹՄՇԺՋԽՊՎԹՌՁՇՆՋՁՆԺԽՀԹՎՁՇՊՇՊԹՈՈԽԹՊԹՆԻԽՁՆԻՄՍԼՁՆԿՋԽԻՇՆԼԹՊՑՋԽՐԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋՏԽՊԽՆՇՌԽԼՁՆՌՀԽԻՇՆՌՊՇՄՋՇՊԹՆԼՅԿ

ԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄՋԺՑՌՀԽՋՌՍԼՑԹՍՌՀՇՊԩԽՌՀԹՊԿՑԹՆԼՄՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅՇԺՋԽՊՎԽԼԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՄԽԼՌՇՌՀԽՌԽՊՅՁՆԹՌՁՇՆՇԾՌՀՁՋԿՊՇՍՈԹՌՋՌՍԼՑԡԹՑ

ԱԹԺՄԽ԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋՁՆԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

԰ԽԻՇՆԼԹՊՑ԰ԽՐԠՀԹՊԹԻՌԽՊՁՋՌՁԻՋԹՆԼԠՄՁՆՁԻԹՄ԰ՁԿՆՋ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ

ԱՑՈԽ Ն ԦՆԻՁԼԽՆԻԽ ԱՑՈԽ Ն ԦՆԻՁԼԽՆԻԽ

ԠՇՆՌՊՇՄ
ԩԬԮ ԫՇՆԽՊԽՈՇՊՌԽԼ   ԫՇՆԽՊԽՈՇՊՌԽԼ  ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ ԫՇՆԽՊԽՈՇՊՌԽԼ   ԫՇՆԽՊԽՈՇՊՌԽԼ   ԫՇՆԽՊԽՈՇՊՌԽԼ   ԫՇՆԽՊԽՈՇՊՌԽԼ   ԫՇՆԽՊԽՈՇՊՌԽԼ   ԩՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅՇՆԡԹՑՋ  

ԩԽՌՀԹՊԿՑ   ԩԽՌՀԹՊԿՑ  ԫԞ

ԩՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅ   ԩՇՋՋՇԾԽՉՍՁՄՁԺՊՁՍՅ  

ԦՆԻՁԼԽՆԻԽՁՋԽՋՌՁՅԹՌԽԼԺԹՋԽԼՇՆԼԹՌԹՈՊՇՎՁԼԽԼԺՑՊԽՈՄՁԻԹՌԽՊԹՌՀԽՊՌՀԹՆԺՑՁՆԼՁՎՁԼՍԹՄԾՁՋՀ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԟ ԰ՌՍԼՑԞՍՌՀՇՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

ԱՀԽՋՌՍԼՑԹՍՌՀՇՊԹՆԹՄՑՒԽԼՋՍՊՎՁՎԹՄՏԽՁԿՀՌՌՍԺԽՊԻՄԽՋԻՇՊԽԤ԰ԦԾԽՊՌՁՄՁՌՑ
ԽԿԿՋՌՀԹՌՏԽՊԽԾԽՊՌՁՄԽ

ԾԽԻՍՆԼՁՌՑ
ԽԿԿՋԾԽՅԹՄԽՊԽՈՊՇԼՍԻՌՁՎԽԼԹՑԹՆԼԳԱԤԡԹՌԹԾՇՊԿՊՇՏՌՀՌՍԺԽՊԻՄԽՋԻՇՊԽԤ԰ԦԹՆԼ

ԳԱԤՏԽՊԽԹՆԹՄՑՒԽԼՋԽՈԹՊԹՌԽՄՑԺՑՋԽՐԣՇՊԹՄՄՈԹՊԹՅԽՌԽՊՋՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈՋ

ՏԽՊԽԻՇՅՈԹՊԽԼՍՋՁՆԿԹՌԱԽՋՌ
ĮՆՇԼՁԾԾԽՊԽՆԻԽՏԹՋԼԽՌԽԻՌԽԼԾՇՊԹՆՑԽՆԼՈՇՁՆՌՋՇՌՊԽԹՌՅԽՆՌ

ԿՊՇՍՈՋՏԽՊԽԻՇՅՈԹՊԽԼՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ

ԡԽՋԻՊՁՈՌՁՎԽՋՌԹՌՁՋՌՁԻՋ
ՅԽԹՆՋՌԹՆԼԹՊԼԼԽՎՁԹՌՁՇՆԽՌԻՏԽՊԽԼԽՌԽՊՅՁՆԽԼԾՇՊԽԹԻՀԽՆԼՈՇՁՆՌ԰ՁԿՆՁԾՁԻԹՆՌ

ԽԾԾԽԻՌՋՏԽՊԽԼԽՌԽԻՌԽԼԾՇՊՈԹՆԼԹՆԹՄՑՋԽՋՏԽՊԽԻՇՆԼՍԻՌԽԼՍՋՁՆԿԠԢԱԦ԰TMԳԽՊՋՁՇՆ

ԢԾԾԽԻՌՋՇՆՋՍՊՎՁՎԹՄՏԽՊԽԼԽՌԽՊՅՁՆԽԼՍՋՁՆԿԹԣՁՋՀԽՊ0ՋԽՐԹԻՌՌԽՋՌ
ՏՁՌՀԟՇՆԾԽՊՊՇՆՁԥՇՄՅԹԼՂՍՋՌՅԽՆՌ

ԡԹՌԹՏԽՊԽՌԽՋՌԽԼՌՇԻՇՆԾՁՊՅՆՇՊՅԹՄՁՌՑՍՋՁՆԿ԰ՀԹՈՁՊՇԴՁՄՃ0ՋՌԽՋՌԹՆԼՌՇԻՇՆԾՁՊՅՀՇՅՇԿԽՆԽՁՌՑՇԾ

ՎԹՊՁԹՆԻԽՋՍՋՁՆԿԟԹՊՌՄԽՌՌ0ՋՌԽՋՌ
ĮԡԹՌԹՌՀԹՌՋԹՌՁՋԾՁԽԼՌՀԽՋԽԹՋՋՍՅՈՌՁՇՆՋԺՍՌԼՁԼՆՇՌԽՐՀՁԺՁՌԹ

ՅՇՆՇՌՇՆՁԻՌՊԽՆԼՏԽՊԽԻՇՅՈԹՊԽԼՍՋՁՆԿԡՍՆՆԽՌՌ0ՋՌԽՋՌԱՀԽՆՇՆՈԹՊԹՅԽՌՊՁԻԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌ

ՏԹՋՍՋԽԼՏՀԽՆԼԹՌԹԼՁԼՆՇՌՅԽԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾՆՇՊՅԹՄՁՌՑԹՆԼՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՋՇՊԾՇՊ

ԼԹՌԹՏՀՁԻՀՏԽՊԽԼԽՌԽՊՅՁՆԽԼՌՇԺԽԽՅՈՁՊՁԻԹՄՄՑՅՇՆՇՌՇՆՁԻԱՀԽՋԽՅԽՌՀՇԼՋԹՈՈԽԹՊՌՇԺԽԻՇՆՋՁՋՌԽՆՌ

ՏՁՌՀՌՀԽՅԽՌՀՇԼՋՊԽԻՇՅՅԽՆԼԽԼՁՆՌՀԽԬԠ԰ԭԭԿՍՁԼԽՄՁՆԽ

ԞԼՍՄՌՋՍՊՎՁՎԹՄՏԹՋՆՇՌՋՁԿՆՁԾՁԻԹՆՌՄՑԼՁԾԾԽՊԽՆՌԻՇՅՈԹՊԽԼՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄՋ
Ո ԣՁՋՀԽՊ0ՋԢՐԹԻՌ

ՌԽՋՌԾՇՊՅԹՄԽՋԾԽՅԹՄԽՋՇՊԻՇՅԺՁՆԽԼՋԽՐԽՋԱՀԽՊԽՏԽՊԽՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՊԽԼՍԻՌՁՇՆՋԼԽՌԽԻՌԽԼ

ԾՇՊԾԽՊՌՁՄՁՌՑԹՆԼԾԽԻՍՆԼՁՌՑԻՇՅՈԹՊԽԼՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ
ՈԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԹՌՌՀԽ

ՅԿԹՁԩՄԽՎԽՄԱՀԽՊԽՏԽՊԽՆՇՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋԼԽՌԽԻՌԽԼԾՇՊԹՆՑՊԽՅԹՁՆՁՆԿԽՆԼՈՇՁՆՌՊԽՄԹՌՁՎԽՌՇ

ՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄ
Ո ԡՍՆՆԽՌՌ0ՋՇՊԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԞՄՌՀՇՍԿՀՆՇՌԹՆԹՄՑՒԽԼ

ՋՌԹՌՁՋՌՁԻԹՄՄՑՌՀԽՋՌՍԼՑԹՍՌՀՇՊՆՇՌԽԼՈՇՌԽՆՌՁԹՄՄՑԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՄԹՌԽԼՄԽՋՁՇՆՋՁՆԻՄՍԼՁՆԿԼԽԻՊԽԹՋԽԼ

ՈՊՇՈՇՊՌՁՇՆՋՇԾՋՈԽՊՅԹՌՇՒՇԹՁՆԻՊԽԹՋԽԼՁՆՌԽՊՋՌՁՌՁԹՄՈՊՇՌԽՁՆԹԻԽՇՍՋԾՄՍՁԼՁՆՌԽՊՋՌՁՌՁԹՄԻԽՄՄՀՑՈԽՊՈՄԹՋՁԹԹՆԼ

ՁՆԻՊԽԹՋԽԼՌԽՋՌՁԻՍՄԹՊԼԽԿԽՆԽՊԹՌՁՇՆԹՌՌՀԽՅԿԹՁԩՄԽՎԽՄԱՀԽՊԽՏԽՊԽՆՇՇԺՎՁՇՍՋՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼ

ՄԽՋՁՇՆՋՈՊԽՋԽՆՌՁՆԾԽՅԹՄԽԾՁՋՀԱՀԽՋՌՍԼՑԹՍՌՀՇՊԼՁԼՆՇՌՊԽՈՇՊՌՇԺՋԽՊՎՁՆԿԹՆՑՆՇՌԹԺՄԽԻՄՁՆՁԻԹՄՋՁԿՆՋՇՊ

ԺԽՀԹՎՁՇՊԹՄԽԾԾԽԻՌՋՁՆԻՄՍԼՁՆԿՋԽԻՇՆԼԹՊՑՋԽՐՍԹՄԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋԱՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՄՑՇԺՋԽՊՎԽԼ

ՌՀԽՈՊԽՋԽՆԻԽՇԾՌՀԽԼՇՊՋԹՄՆԹՈԽՈԹԼՁՆՅԹՄԽՋԹՆԼԻՇՄՄԽԻՌԽԼՈՄԹՋՅԹՋԹՅՈՄԽՋԾՇՊՅԽԹՋՍՊԽՅԽՆՌՇԾ

ՋԽՐՋՌԽՊՇՁԼՋԺՍՌՊԽՋՍՄՌՋՇԾՌՀԽՋԽԹՆԹՄՑՋԽՋՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼՁՆՌՀԽՋՌՍԼՑ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

Ԡ ԯԽՎՁԽՏԽՊ0ՋԞՆԹՄՑՋՁՋԹՆԼԠՇՆԻՄՍՋՁՇՆՋ

԰ՌԹՌՁՋՌՁԻԹՄԪԽՌՀՇԼՋԱՀԽՊԽՎՁԽՏԽՊՎՁՋՍԹՄՄՑԹՋՋԽՋՋԽԼՋՍՊՎՁՎԹՄ
ՅՇՊՌԹՄՁՌՑԼԹՌԹԣԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՌՑ

ՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՅԹՄԽՈՄԹՋՅԹԳԱԤԹՆԼԾԽՅԹՄԽՄԽՆԿՌՀՏԽՊԽԻՇՆՋՁՋՌԽՆՌՏՁՌՀԹՅՇՆՇՌՇՆՁԻ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԹՆԼՏԽՊԽՌՀԽՊԽԾՇՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌՊԽՆԼՌԽՋՌԱՀԽ

ՊԽՅԹՁՆՁՆԿԽՆԼՈՇՁՆՌՋՏԽՁԿՀՌՅԹՄԽՄԽՆԿՌՀԾԽՅԹՄԽՈՄԹՋՅԹԳԱԤԹՆԼԤ԰ԦԼԹՌԹՏԽՊԽՆՇՌԻՇՆՋՁՋՌԽՆՌ

ՏՁՌՀԹՅՇՆՇՌՇՆՁԻԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽԞՄՄԼԹՌԹՏԽՊԽՌԽՋՌԽԼԾՇՊՆՇՊՅԹՄՁՌՑՍՋՁՆԿ԰ՀԹՈՁՊՇԴՁՄՃՋՌԽՋՌ

ԹՆԼԾՇՊՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽՍՋՁՆԿԩԽՎԽՆԽ0ՋՌԽՋՌ
԰Ԟ԰ԱՀԽՋԽԼԹՌԹՅԽՌՌՀԽԹՋՋՍՅՈՌՁՇՆՋՇԾ

ՆՇՊՅԹՄՁՌՑԹՆԼՀՇՅՇԿԽՆԽՁՌՑՇԾՎԹՊՁԹՆԻԽԹՆԼՏԽՊԽՌՀԽՊԽԾՇՊԽԹՆԹՄՑՒԽԼՍՋՁՆԿՌՀԽՈԹՊԹՅԽՌՊՁԻԡՍՆՆԽՌՌ0Ջ

ՌԽՋՌ

ԫՇՋՍՊՎՁՎՁՆԿԾԽՅԹՄԽՋՏԽՊԽԾՇՍՆԼՌՇՀԹՎԽՌՍԺԽՊԻՄԽՋԹՆԼՋԽՐՋՌԽՊՇՁԼՋՏԽՊԽՆՇՌՅԽԹՋՍՊԽԼԲՆՄԽՋՋ

ՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋՏԽՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈԱՀԽՊԽՎՁԽՏԽՊ0Ջ

ԹՆԹՄՑՋՁՋՏԹՋԻՇՆԼՍԻՌԽԼՍՋՁՆԿ԰Ԟ԰ԱՀԽՊԽՎՁԽՏԽՊԹԼԼՁՌՁՇՆԹՄՄՑԻՇՅՈԹՊԽԼՌՀԽՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌ

ԻՇՆՌՊՇՄԿՊՇՍՈՋԾՇՊԹՄՄԽՆԼՈՇՁՆՌՋՍՋՁՆԿԹՌՏՇՋՁԼԽԼ԰ՌՍԼԽՆՌ0ՋՌՌԽՋՌՁՆԢՐԻԽՄՆՇՋՁԿՆՁԾՁԻԹՆՌԼՁԾԾԽՊԽՆԻԽՋ

ԺԽՌՏԽԽՆՌՀԽԻՇՆՌՊՇՄՋՏԽՊԽԼԽՌԽԻՌԽԼ
Ո ԱՀԽՊԽՎՁԽՏԽՊԻՇՅՈԹՊԽԼԹՄՄՈՊՇՆԹՅՁԼԽՌՊԽԹՌԽԼԿՊՇՍՈՋ

ՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԠՇՆԻՄՍՋՁՇՆՋԣԽՊՌՁՄՁՌՑՋՀՇՏԽԼԹՋՁԿՆՁԾՁԻԹՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆԼԽՈԽՆԼԽՆՌՊԽԼՍԻՌՁՇՆ
ՈԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹՇԾԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄԻՇՅՈԹՊԽԼՌՇՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄԣԽԻՍՆԼՁՌՑ

ԾՇՄՄՇՏԽԼԹԻՇՆԻԽՆՌՊԹՌՁՇՆԼԽՈԽՆԼԽՆՌՊԽԼՍԻՌՁՇՆՇԾԹՆԼԹՌՌՀԽԹՆԼՅԿԹՁԩ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՋՊԽՋՈԽԻՌՁՎԽՄՑՀՇՏԽՎԽՊՌՀԽՋԽՊԽԼՍԻՌՁՇՆՋՏԽՊԽՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌ
ՈԹՆԼ

ՈՊԽՋՈԽԻՌՁՎԽՄՑԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԱՀԽՊԽԼՍԻՌՁՇՆԹՌՌՀԽՅԿԹՁԩԻՇՆԻԽՆՌՊԹՌՁՇՆՁՋ

ԻՇՆՋՁԼԽՊԽԼԺՑՌՀԽՊԽՎՁԽՏԽՊՌՇԺԽԺՁՇՄՇԿՁԻԹՄՄՑՊԽՄԽՎԹՆՌԼՍԽՌՇՌՀԽՅԹԿՆՁՌՍԼԽՇԾԽԾԾԽԻՌԹՆԼՌՀԽ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋՁՎԽՈԹՌՌԽՊՆԞԼԼՁՌՁՇՆԹՄՄՑՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՋՏԽՊԽՋՁԿՆՁԾՁԻԹՆՌՄՑԿՊԽԹՌԽՊ


ՈԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԺՑՁՆՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԹՆԼԺՑԹՌՌՀԽ

ՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈԱՀԽՊԽՏԽՊԽՊԽԼՍԻԽԼՈՊՇՈՇՊՌՁՇՆՋՇԾՋՈԽՊՅԹՌՇՒՇԹՁՆԻՊԽԹՋԽԼՌԽՋՌՁԻՍՄԹՊ

ԼԽԿԽՆԽՊԹՌՁՇՆԹՆԼՁՆԻՊԽԹՋԽԼՁՆԻՁԼԽՆՌՋՇԾՁՆՌԽՊՋՌՁՌՁԹՄՈՊՇՌԽՁՆԹԻԽՇՍՋԾՄՍՁԼԹՆԼՁՆՌԽՊՋՌՁՌՁԹՄԻԽՄՄՀՑՈԽՊՈՄԹՋՁԹ

ԹՌՌՀԽՅԿԹՁԩՄԽՎԽՄՊԽՄԹՌՁՎԽՌՇՌՀԽԻՇՆՌՊՇՄԿՊՇՍՈՋ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԪԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ Ԥ԰Ԧ

ԤՇՆԹԼԹՄ

԰ՌԹԿՁՆԿԹՆԼ

ԥՁՋՌՇ

ԭՄԹՋՅԹԳԱԤ ԭՄԹՋՅԹԱ ԭՄԹՋՅԹԢ

ԪԽԼՁԹՆ Ո ԡՁԾԾ Ո

ԢԾԾԽԻՌ!


ԶԽՋԫՇ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ ԭ

ԠՇՆՌՊՇՄ
ԩԬԮ  ԫԞ  ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ     ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ     ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ     ԶԽՋ   ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԡՍՆՆԽՌՌ0Ջ ԫԞ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՆԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԠՇՅՈԹՊՁՋՇՆՋՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՊԽԺԹՋԽԼՇՆԹՌՏՇՋՁԼԽԼ԰ՌՍԼԽՆՌ0ՋՌՌԽՋՌ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԯԽՈՊՇԼՍԻՌՁՎԽԹՆԼԥԭԤԢՆԼՈՇՁՆՌՋԾՇՊԣԽՅԹՄԽԣԹՌՀԽԹԼԪՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋՁՆՌՀԽԣ԰ԱԯԞՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԣԽԻՍՆԼՁՌՑ ԣԽՊՌ԰ՍԻԻԽՋՋ ԱՍԺԽՊԻՄԽ԰ԻՇՊԽ Ԥ԰Ԧ

ԤՇՆԹԼԹՄ

԰ՌԹԿՁՆԿԹՆԼ

ԥՁՋՌՇ

ԭՄԹՋՅԹԳԱԤ ԭՄԹՋՅԹԱ ԭՄԹՋՅԹԢ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԪԽԼՁԹՆ Ո



ԡՁԾԾ Ո

ԢԾԾԽԻՌ!


ԶԽՋԫՇ



ԡՁԾԾ Ո



ԡՁԾԾ

Ո ԡՁԾԾ ԭ

ԠՇՆՌՊՇՄ
ԩԬԮ  ԫԞ  ԫԞ  ԫԞ  ԫԞ ԫԞ  ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ      ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ      ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ      ԫԞ   ԫՇ   ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ

ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ

ԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹ

ԫԞ ԡՍՆՆԽՌՌ0Ջ ԫԞ ԡՍՆՆԽՌՌ0Ջ ԫԞ ԫԞ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԢȕԽՋՌՊԹԼՁՇՄԣԽՊՌԣԽՊՌՁՄՁՒԹՌՁՇՆԤ԰ԦԤՇՆԹԼՇ԰ՇՅԹՌՁԻԦՆԼԽՐԥՁՋՌՇԥՁՋՌՇՈԹՌՀՇՄՇԿՑԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽԱԱԽՋՌՇՋՌԽՊՇՆԽԳԱԤԳՁՌԽՄՄՇԿԽՆՁՆ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼԽԾԾԽԻՌՋԹՆԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊԻՇՆՌՊՇՄԠՇՆԻՄՍՋՁՇՆՋՊԽԿԹՊԼՁՆԿ

ՀՁՋՌՇՈԹՌՀՇՄՇԿՑՅԹՑԺԽՀԽԹՎՁՄՑՏԽՁԿՀՌԽԼԺՑՌՀԽԽՐՈԽՊՌՇՈՁՆՁՇՆՇԾԹԺՇԹՊԼԻԽՊՌՁԾՁԽԼՈԹՌՀՇՄՇԿՁՋՌ

 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ ԠՇՅՈԹՊՁՋՇՆՋՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՊԽԺԹՋԽԼՇՆԹՌՏՇՋՁԼԽԼ԰ՌՍԼԽՆՌ0ՋՌՌԽՋՌ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱԹԺՄԽԤՊՇՏՌՀԢՆԼՈՇՁՆՌՋՁՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑ
ԣ԰ԱԯԞՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԱՊԽԹՌՅԽՆՌ


ՅԿԹՁԩ

#ՅԽԹՆՅԽԹՋՍՊԽԼ%

ԟՇԼՑԴԽՁԿՀՌ ԩԽՆԿՌՀ

ԪԹՄԽՋ ԣԽՅԹՄԽՋ ԪԹՄԽՋ ԣԽՅԹՄԽՋ

ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո ԡՁԾԾ Ո

ԠՇՆՌՊՇՄ
ԩԬԮ  ԫԞ  ԫԞ  ԫԞ  ԫԞ

԰ՇՄՎԽՆՌԻՇՆՌՊՇՄ
ԩԬԮ        

        

        

 ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ ԫԞ

԰ՌԹՌՁՋՌՁԻԹՄԱԽՋՌ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԡՍՆՆԽՌՌ0Ջ ԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹ

ԞԺԺՊԽՎՁԹՌՁՇՆՋԡՁԾԾԡՁԾԾԽՊԽՆԻԽԫԞԫՇՌԹՈՈՄՁԻԹԺՄԽ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՁՆԼՁԻԹՌԽԼՈԽՊԻԽՆՌ
ԼՁԾԾԽՊԽՆԻԽՋԹՊԽՊԽՈՇՊՌԽԼԺԹՋԽԼՇՆԻՇՅՈԹՊՁՋՇՆՌՇՌՀԽՆԽԿԹՌՁՎԽ
ԻՄԽԹՆՏԹՌԽՊ

ԻՇՆՌՊՇՄ



 ԲՆՄԽՋՋՇՌՀԽՊՏՁՋԽՋՈԽԻՁԾՁԽԼԽԾԾԽԻՌՋԹՊԽԻՇՆՋՁԼԽՊԽԼՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌԹՌՈ



 ԠՇՅՈԹՊՁՋՇՆՋՌՇՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՊԽԺԹՋԽԼՇՆԹՌՏՇՋՁԼԽԼ԰ՌՍԼԽՆՌ0ՋՌՌԽՋՌ

ԩԬԮՅԿԹՁԩ
ԹՎԽՊԹԿԽՎԹՄՍԽ

ԡ ԰ՌՍԼՑԡԽԾՁԻՁԽՆԻՁԽՋ

ԱՀԽՊԽՏԽՊԽԹՆՍՅԺԽՊՇԾԼԽՎՁԹՌՁՇՆՋԼԽՋԻՊՁԺԽԼՁՆ԰ԽԻՌՁՇՆԦԪԹՌԽՊՁԹՄՋԹՆԼԪԽՌՀՇԼՋՇԾՌՀՁՋԡԢԯ

ՊԽԿԹՊԼՁՆԿՌՀԽՆՍՅԺԽՊՇԾՌԽՋՌԻՇՆԻԽՆՌՊԹՌՁՇՆՋԹՆԼԾԹՁՄՍՊԽՌՇՊԽՈՇՊՌԻԽՊՌԹՁՆՏԹՌԽՊԻՀԹՊԹԻՌԽՊՁՋՌՁԻՋԞՄՇՆԿ

ՏՁՌՀՌՀԽՋԽԼԽՎՁԹՌՁՇՆՋՋԽՎԽՊԹՄՎԹՄՁԼՁՌՑԹՆԼՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹՊԽԿԹՊԼՁՆԿՋՍՊՎՁՎԹՄԾԽՊՌՁՄՁՒԹՌՁՇՆՋՍԻԻԽՋՋ

ՌԽՅՈԽՊԹՌՍՊԽԹՆԼԼՁՋՋՇՄՎԽԼՇՐՑԿԽՆԻՇՆՌԽՆՌ
ՋՈԽԻՁԾՁԽԼԺՑՌՀԽԬԠ԰ԭԭԿՍՁԼԽՄՁՆԽՏԽՊԽՆՇՌ

ՅԽՌԾՇՊՌՀՁՋՋՌՍԼՑ

 ԱՀԽՋՍՊՎՁՎԹՄՎԹՄՁԼՁՌՑԻՊՁՌԽՊՁՇՆՇԾՏԹՋՆՇՌՅԽՌՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԞՎԽՊԹԿԽՋՍՊՎՁՎԹՄՁՆՌՀԽ

ՋՇՄՎԽՆՌԻՇՆՌՊՇՄՏԹՋԞՎԽՊԹԿԽՋՍՊՎՁՎԹՄՁՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՏԹՋԱՀԽՀՁԿՀԽՋՌ

ԻՇՆԻԽՆՌՊԹՌՁՇՆՏԹՋՆՇՅՁՆԹՄՄՑՅԿԹՁԩՏՁՌՀԹՅԽԹՆՅԽԹՋՍՊԽԼԻՇՆԻԽՆՌՊԹՌՁՇՆՇԾՅԿԹՁԩ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԱՀՁՋՀՁԿՀԽՋՌՄԽՎԽՄՊԽՋՍՄՌԽԼՁՆՅՇՊԺՁԼՁՌՑԹՆԼՌԽՊՅՁՆԹՌՁՇՆՇԾՌՀՁՋՄԽՎԽՄԾՊՇՅՌՀԽՋՌՍԼՑՇՆԡԹՑԞ

ՊԹՆԿԽԾՁՆԼՁՆԿՋՌՍԼՑՏԹՋՆՇՌՊԽՈՇՊՌԽԼ

 ԱՏՇՇԾՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌԹՆՃՋԹՆԼՇՆԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՀԹԼՅԹՄԽՋԹՆԼԾԽՅԹՄԽՋԬԠ԰ԭԭ

ՊԽԻՇՅՅԽՆԼՋՌՏՇՅԹՄԽՋԹՆԼԾՇՍՊԾԽՅԹՄԽՋՁՆԽԹԻՀՌԹՆՃԱՀԽՋՌՍԼՑԹՍՌՀՇՊՊԽՈՇՊՌԽԼՌՀԹՌ

ԹՄՄԽՆԼՈՇՁՆՌՋՏԽՊԽԹԼՂՍՋՌԽԼԾՇՊՌՀԽՊԽԼՍԻԽԼՆՍՅԺԽՊՇԾԾԽՅԹՄԽՋ

 ԡՁՋՋՇՄՎԽԼՇՐՑԿԽՆԼՊՇՈՈԽԼԺԽՄՇՏՁՆՌՀԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄԹՆԼԺՇՌՀՈՊՇՆԹՅՁԼԽՌՊԽԹՌԽԼՄԽՎԽՄՋ

ՏՁՌՀՅՁՆՁՅԹՊԹՆԿՁՆԿԾՊՇՅ

 ԦՆՁՌՁԹՄՅԹՄԽԹՆԼԾԽՅԹՄԽԾՁՋՀՏԽՁԿՀՌՋԽՐԻԽԽԼԽԼՌՀԽՊԽԻՇՅՅԽՆԼԽԼՅԹՐՁՅՍՅՎԹՊՁԹՌՁՇՆԹՊՇՍՆԼՌՀԽ

ՋԹՅՈՄԽՅԽԹՆ
ՁԽչՁՆՁՌՁԹՄՅԹՄԽԾՁՋՀՏԽՁԿՀՌՋՎԹՊՁԽԼչԹՆԼՁՆՁՌՁԹՄԾԽՅԹՄԽՏԽՁԿՀՌՋՎԹՊՁԽԼ

չՇԾՌՀԽՋԹՅՈՄԽՅԽԹՆ

 ԱՀԽՍՆՁՇՆՁՒԽԼԹՅՅՇՆՁԹԹՆԼՊԽՋՁԼՍԹՄԻՀՄՇՊՁՆԽՁՆՌՀԽՌԽՋՌՏԹՌԽՊՏԽՊԽՆՇՌՊԽՈՇՊՌԽԼԱՀԽԬԠ԰ԭԭ

ՈԽՊԾՇՊՅԹՆԻԽԻՊՁՌԽՊՁԹԽՋՌԹԺՄՁՋՀՅԹՐՁՅՍՅՄԽՎԽՄՋԾՇՊՌՀԽՋԽՎԹՄՍԽՋԹՆԼՁՌՁՋՍՆԻՄԽԹՊՁԾՌՀԽ

ՅԹՐՁՅՍՅՄՁՅՁՌՋՏԽՊԽԽՐԻԽԽԼԽԼ

 ԬՆՌԽՋՌԡԹՑՌՀԽՅԹՐՁՅՍՅՌԽՅՈԽՊԹՌՍՊԽՏԹՋՊԽԻՇՊԼԽԼՌՇԺԽոԠԾԹՄՄՁՆԿՇՍՌՋՁԼԽՌՀԽՊԽՉՍՁՊԽԼ

ՊԹՆԿԽՇԾչոԠ

ԱՀԽՋԽԼԽՎՁԹՌՁՇՆՋԼՇՆՇՌՋՍԺՋՌԹՆՌՁՎԽՄՑՁՅՈԹԻՌՌՀԽՊԽՋՍՄՌՋՇՊՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀՁՋՋՌՍԼՑ

Ԣ ԯԽՎՁԽՏԽՊ0ՋԠՇՅՅԽՆՌՋ

ԱՀԽՋՌՍԼՑԹՍՌՀՇՊ0ՋԹՆԹՄՑՋՁՋԻՇՅՈԹՊՁՆԿՈՊՇՆԹՅՁԼԽՌՊԽԹՌԽԼԻՇՆԼՁՌՁՇՆՋՌՇՌՀԽՈՇՇՄԽԼԻՇՆՌՊՇՄՊԽՎԽԹՄԽԼ

ՋՇՅԽԼՁԾԾԽՊԽՆԻԽՋԻՇՅՈԹՊԽԼՌՇՌՀԽՊԽՋՍՄՌՋՇԾՌՀԽՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋՁՋԺԹՋԽԼՇՆՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄ

ԱՀԽՇՆՄՑՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋԼԽՌԽԻՌԽԼԺՑՌՀԽՋՌՍԼՑԹՍՌՀՇՊ0ՋԹՆԹՄՑՋՁՋՏԽՊԽԾՇՊԾԽՊՌՁՄՁՌՑԹՆԼԾԽԻՍՆԼՁՌՑԹՌ

ՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌՄԽՎԽՄԱՀԽՊԽՎՁԽՏԽՊ0ՋԹՆԹՄՑՋՁՋԼԽՌԽԻՌԽԼՌՀԽՋԽԽԾԾԽԻՌՋԹՆԼԾՍՊՌՀԽՊԼԽՌԽԻՌԽԼ

ՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌՋ
ՈՇՆՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽԟՇՌՀՌՀԽՋՌՍԼՑԹՍՌՀՇՊԹՆԼՌՀԽՊԽՎՁԽՏԽՊԹԿՊԽԽԼ

ՌՀԹՌՀՁՋՌՇՈԹՌՀՇՄՇԿՁԻԹՄԽԾԾԽԻՌՋՏԽՊԽՇԺՋԽՊՎԽԼՁՆՅԹՄԽԾՁՋՀԹՌՌՀԽՅԿԹՁԩՄԽՎԽՄ

ԱՀԽՊԽՏԽՊԽԾՇՍՊԽՆԼՈՇՁՆՌՋԽՐՀՁԺՁՌՁՆԿԹՅՇՆՇՌՇՆՁԻԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՋՈՇՆՋԽՏՀՁԻՀԹՄՋՇՋԹՌՁՋԾՁԽԼ

ՈԹՊԹՅԽՌՊՁԻԹՋՋՍՅՈՌՁՇՆՋ
ՁԽԾԽԻՍՆԼՁՌՑԾԽՊՌՁՄՁՌՑՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽԹՆԼՅԹՄԽԳԱԤԱՀԽԬԠ԰ԭԭ

ԿՍՁԼԹՆԻԽՊԽԻՇՅՅԽՆԼՋՍՋԽՇԾՌՀԽՆՇՆՈԹՊԹՅԽՌՊՁԻԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌՌՇԼԽՌԽԻՌ

ՌՊԽԹՌՅԽՆՌՊԽՄԹՌԽԼԽԾԾԽԻՌՋԾՇՊԹՆՑՅՇՆՇՌՇՆՁԻՊԽՋՈՇՆՋԽՏՀՁՄԽՌՀԽՀՁՋՌՇՊՁԻԹՄԢԣԢԡՅԽՌՀՇԼՋՍԿԿԽՋՌՋՍՋԽ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ՇԾԴՁՄՄՁԹՅ0ՋՌԽՋՌՏՀԽՆՈԹՊԹՅԽՌՊՁԻԹՋՋՍՅՈՌՁՇՆՋԹՊԽՋԹՌՁՋԾՁԽԼԣՇՊՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽԹՆԼՅԹՄԽԳԱԤ

ԺՇՌՀՌԽՋՌՋՊԽՋՍՄՌԽԼՁՆՌՀԽՋԹՅԽԻՇՆԻՄՍՋՁՇՆՋԥՇՏԽՎԽՊԾՇՊԾԽՊՌՁՄՁՌՑԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹԼԽՌԽԻՌԽԼԹ

ՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌԹՌՌՀԽՅԿԹՁԩԻՇՆԻԽՆՌՊԹՌՁՇՆՏՀԽՆԴՁՄՄՁԹՅ0ՋՌԽՋՌԼՁԼՆՇՌԹՆԼԾՇՊԾԽԻՍՆԼՁՌՑ

ԴՁՄՄՁԹՅ0ՋՌԽՋՌԼԽՌԽԻՌԽԼԹՋՁԿՆՁԾՁԻԹՆՌԽԾԾԽԻՌԹՌՌՀԽՅԿԹՁԩԻՇՆԻԽՆՌՊԹՌՁՇՆՏՀԽՆԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹԼՁԼՆՇՌ

ԞՄՋՇՇԾՆՇՌԽՁՆՌՀՁՋՋՌՍԼՑՁՋՌՀԹՌՌՀԽՋՌԹՌՁՋՌՁԻԹՄՋՁԿՆՁԾՁԻԹՆԻԽՇԾՌՀԽՅԹՄԽՌՍԺԽՊԻՄԽՊԽՋՍՄՌՋԼԽՈԽՆԼՋՇՆ

ՏՀԽՌՀԽՊՌՀԽԼԹՌԹՁՋՂՍԼԿԽԼՌՇԾՇՄՄՇՏԹՅՇՆՇՌՇՆՁԻՌՊԽՆԼԱՀԽՊԽՎՁԽՏԽՊԺԽՄՁԽՎԽԼԹՌՊԽՆԼՏԹՋՈՊԽՋԽՆՌ

ԹՆԼՊԽՈՇՊՌԽԼՌՀԽՊԽՋՍՄՌՋԾՊՇՅՌՀԽԧՇՆԻՃՀԽԽՊԽԱԽՊՈՋՌՊԹՌԽՋՌԹԻԻՇՊԼՁՆԿՄՑԦԾԡՍՆՆԽՌՌ0ՋՌԽՋՌՁՋՍՋԽԼԾՇՊ

ՌՀԽԹՆԹՄՑՋՁՋՌՀԽՁՆԻՊԽԹՋԽՋՁՆՌՀԽՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋԹՊԽՆՇՌՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌ
ՈԹՆԼ

ՈԾՇՊՌՀԽԹՆԼՅԿԹՁԩՌՊԽԹՌՅԽՆՌԿՊՇՍՈՋՊԽՋՈԽԻՌՁՎԽՄՑ

ԱՏՇՇԾՌՀԽՆԽԿԹՌՁՎԽԻՇՆՌՊՇՄՌԹՆՃՋԹՆԼՇՆԽՋՇՄՎԽՆՌԻՇՆՌՊՇՄՀԹԼՅԹՄԽՋԹՆԼԾԽՅԹՄԽՋԼՍԽՌՇ

ՅՁՋՁԼԽՆՌՁԾՁԻԹՌՁՇՆՇԾՅԹՄԽԾՁՋՀԹՌՋՌՍԼՑՁՆՁՌՁԹՌՁՇՆԯԽՋՍՄՌՋՈՊԽՋԽՆՌԽԼՁՆՌՀՁՋԡԢԯԽՐԻՄՍԼԽՌՀԽՋԽԾՁՋՀԾՊՇՅ

ՋՍՅՅԹՊՑՋՌԹՌՁՋՌՁԻՋԹՆԼՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋՁՋԦՆԻՄՍԼՁՆԿՌՀԽՋԽԾՁՋՀՁՆՌՀԽՋՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋՁՋԾՇՊՌՀԽՅԹՄԽ

ԽՆԼՈՇՁՆՌՋԼՇԽՋՄԽԹԼՌՇՋՄՁԿՀՌՄՑԼՁԾԾԽՊԽՆՌԻՇՆԻՄՍՋՁՇՆՋԾՇՊՌՏՇԽՆԼՈՇՁՆՌՋ
ԾՇՊՅԹՄԽՌՍԺԽՊԻՄԽՋԻՇՊԽՌՀԽ

ՁՆԻՊԽԹՋԽԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆԺԽԻՇՅԽՋՆՇՆՋՁԿՆՁԾՁԻԹՆՌ
ՈԧՇՆԻՃՀԽԽՊԽ

ԱԽՊՈՋՌՊԹԱՀԽԽԾԾԽԻՌԹՌՌՀԽՅԿԹՁԩՌՊԽԹՌՅԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆՊԽՅԹՁՆՋՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌ

ԞՆԼ
ԾՇՊՅԹՄԽՄԽՆԿՌՀԹՋՌԹՌՁՋՌՁԻԹՄՄՑՋՁԿՆՁԾՁԻԹՆՌՁՆԻՊԽԹՋԽՇԾՁՋԼԽՌԽԻՌԽԼԹՌՌՀԽՅԿԹՁԩ

ՌՊԽԹՌՅԽՆՌԻՇՆԻԽՆՌՊԹՌՁՇՆ
ՈԡՍՆՆԽՌՌ0ՋԱՀԽՁՆԻՊԽԹՋԽԹՌՅԿԹՁԩՊԽՅԹՁՆՋՆՇՆՋՁԿՆՁԾՁԻԹՆՌ

ԱՀԽՋԽԼՁԾԾԽՊԽՆԻԽՋԹՊԽՋՄՁԿՀՌԹՆԼՋՀՇՍՄԼՆՇՌՋՍԺՋՌԹՆՌՁԹՄՄՑԹՄՌԽՊՌՀԽՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽՋՌՍԼՑՊԽՋՍՄՌՋ

԰ՌԹՌՁՋՌՁԻԹՄԹՆԹՄՑՋՁՋՇԾՌՀԽՅԹՄԽՋՈԽԻՁԾՁԻԽՆԼՈՇՁՆՌՋՁՆԻՄՍԼՁՆԿԼԹՌԹԾՊՇՅՌՀԽՅՁՋՋԽՐԽԼՅԹՄԽՋՁՋ

ՈՊԽՋԽՆՌԽԼԹՌՌՀԽԽՆԼՇԾՌՀԽՋՌԹՌՁՋՌՁԻԹՄՊԽՋՍՄՌՋՁՆԞՈՈԽՆԼՁՐԦ

ԟԽԻԹՍՋԽՀՁԿՀՎԹՊՁԹԺՁՄՁՌՑՁՆՌՀԽԽՆԼՈՇՁՆՌՅԹՃԽՋՅԹՄԽԳԱԤՊԽՋՍՄՌՋԼՁԾԾՁԻՍՄՌՌՇՁՆՌԽՊՈՊԽՌՌՀՁՋԽՆԼՈՇՁՆՌՁՋ

ՈՊԽՋԽՆՌԽԼԿՊԹՈՀՁԻԹՄՄՑՁՆՌՀԽԺՇՐՈՄՇՌՋԺԽՄՇՏԦՆԻՄՍԼՁՆԿՇՊԽՐԻՄՍԼՁՆԿՌՀԽՅՁՋՋԽՐԽԼՅԹՄԽԾՁՋՀՁՆՌՀԽ

ՆԽԿԹՌՁՎԽԹՆԼՋՇՄՎԽՆՌԻՇՆՌՊՇՄԿՊՇՍՈՋԼՇԽՋՆՇՌԻՀԹՆԿԽՌՀԽՁՆՌԽՊՈՊԽՌԹՌՁՇՆՇԾՌՀԽԽՆԼՈՇՁՆՌ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

Pronamide, Male Vtg Excluding Mis-sexed Males

NC SC 0.094 1.1

0

1000

2000

3000

vtg

conc

Pronamide, Male Vtg Including Mis-sexed Males

NC SC 0.094 1.1

0

1000

2000

3000

vtg

conc

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԦԦԦ ԯԢԣԢԯԢԫԠԢ԰

ԞՆՃՄԽՑԤԱԧԽՆՋԽՆԨԪԨԹՀՄԪԡԨՇՊՌԽԧԧԹՆԼԪԹՃՑՆԽՆԢԞԡԽՋԻՊՁՈՌՁՇՆԹՆԼԽՎԹՄՍԹՌՁՇՆՇԾ

ԹՋՀՇՊՌՌԽՊՅՊԽՈՊՇԼՍԻՌՁՇՆՌԽՋՌՏՁՌՀՌՀԽԾԹՌՀԽԹԼՅՁՆՆՇՏ
ԭՁՅԽՈՀԹՄԽՋՈՊՇՅԽՄԹՋԢՆՎՁՊՇՆԱՇՐՁԻՇՄԠՀԽՅ



ԞԭԥԞԞԴԴԞԴԭԠԣ԰ՌԹՆԼԹՊԼԪԽՌՀՇԼՋԾՇՊՌՀԽԢՐԹՅՁՆԹՌՁՇՆՇԾԴԹՌԽՊԹՆԼԴԹՋՌԽՏԹՌԽՊՌՀԢԼՁՌՁՇՆ

ԴԹՋՀՁՆԿՌՇՆԡԠ

Ԟ԰ԱԪԠՇՅՅՁՌՌԽԽԢՇՆԟՁՇՄՇԿՁԻԹՄԢԾԾԽԻՌՋԹՆԼԢՆՎՁՊՇՆՅԽՆՌԹՄԣԹՌԽ԰ՌԹՆԼԹՊԼԤՍՁԼԽԾՇՊԠՇՆԼՍԻՌՁՆԿ

ԢԹՊՄՑԩՁԾԽ԰ՌԹԿԽԱՇՐՁԻՁՌՑԱԽՋՌՋՏՁՌՀԣՁՋՀԽՋԞ԰ԱԪԡԽՋՁԿՆԹՌՁՇՆԢԞՅԽՊՁԻԹՆ԰ՇԻՁԽՌՑԾՇՊԱԽՋՌՁՆԿԹՆԼ

ԪԹՌԽՊՁԹՄՋԟԹՊՊԥԹՊԺՇՊԡՊՁՎԽԭԬԟՇՐԠԴԽՋՌԠՇՆՋՀՇՀՇԻՃԽՆԭԽՆՆՋՑՄՎԹՆՁԹ

ԣՄԽՁՋԻՀԽՊԪԹՊՃԢԳԹՄՁԼԹՌՁՇՆՇԾՌՀԽԞՆԹՄՑՌՁԻԹՄԪԽՌՀՇԼԾՇՊՌՀԽԡԽՌԽՊՅՁՆԹՌՁՇՆՇԾԱԽՋՌՇՋՌԽՊՇՆԽԹՆԼԢՋՌՊԹԼՁՇՄՁՆ

԰ԽՊՍՅ԰ՅՁՌՀԽՊՋԳՁՋԻՁԽՆՌ԰ՌՍԼՑԫՍՅԺԽՊԣՁՆԹՄՊԽՈՇՊՌԼԹՌԽԧԹՆՍԹՊՑ

ԦՎԽՋԪՁԻՀԹԽՄԠԢԱԦ԰ԠՇՅՈՊԽՀԽՆՋՁՎԽԢՆՎՁՊՇՆՅԽՆՌԹՄԱՇՐՁԻՁՌՑԦՆԾՇՊՅԹՌՁՇՆ԰ՑՋՌԽՅԱԪԲՋԽՊ0ՋԤՍՁԼԽ

ԱՁԼԽՈՇՇՄ԰ԻՁԽՆՌՁԾՁԻ԰ՇԾՌՏԹՊԽԪԻԨՁՆՄԽՑՎՁՄՄԽԠԹՄՁԾՇՊՆՁԹ

ԪՇՍՆՌԡԦԹՆԼԴԞԟՊՍՆԿՋԞՋՁՅՈՄՁԾՁԽԼԼՇՋՁՆԿԹՈՈԹՊԹՌՍՋԾՇՊԾՁՋՀՌՇՐՁԻՇՄՇԿՑՋՌՍԼՁԽՋԴԹՌԽՊ

ԯԽՋԽԹՊԻՀ

԰ՈՊԹԿՍԽԧԟԪԽԹՋՍՊԽՅԽՆՌՇԾՈՇՄՄՍՌԹՆՌՌՇՐՁԻՁՌՑՌՇԾՁՋՀԟՁՇԹՋՋԹՑՅԽՌՀՇԼՋԾՇՊԹԻՍՌԽՌՇՐՁԻՁՌՑԴԹՌԽՊ

ԯԽՋ

ԬԢԠԡԤՍՁԼԽՄՁՆԽԾՇՊԱԽՋՌՁՆԿՇԾԠՀԽՅՁԻԹՄՋԡԹՈՀՆՁԹՅԹԿՆԹԯԽՈՊՇԼՍԻՌՁՇՆԱԽՋՌԤՍՁԼԽՄՁՆԽ

ԞԼՇՈՌԽԼ԰ԽՈՌԽՅԺԽՊ

ԬԢԠԡ
ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑԬԢԠԡԤՍՁԼԽՄՁՆԽԾՇՊՌՀԽՌԽՋՌՁՆԿԠՀԽՅՁԻԹՄՋԱԽՋՌԫՇ

ԭԹՊՁՋԣՊԹՆԻԽՈՈ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

Բ԰ԢԭԞԠԣԯԭԹՊՌԣԽԼԽՊԹՄԦՆՋԽԻՌՁԻՁԼԽԣՍՆԿՁԻՁԼԽԹՆԼԯՇԼԽՆՌՁԻՁԼԽԞԻՌԤՇՇԼԩԹԺՇՊԹՌՇՊՑ

ԭՊԹԻՌՁԻԽՋ԰ՌԹՆԼԹՊԼՋԣՁՆԹՄԯՍՄԽԬԾԾՁԻԽՇԾՌՀԽԣԽԼԽՊԹՄԯԽԿՁՋՌԽՊԫԹՌՁՇՆԹՄԞՊԻՀՁՎԽՋԹՆԼԯԽԻՇՊԼՋ

ԞԼՅՁՆՁՋՌՊԹՌՁՇՆԲ԰ԤՇՎԽՊՆՅԽՆՌԭՊՁՆՌՁՆԿԬԾԾՁԻԽԴԹՋՀՁՆԿՌՇՆԡԠ

Բ԰ԢԭԞԬԾԾՁԻԽՇԾԭՊԽՎԽՆՌՁՇՆԭԽՋՌՁԻՁԼԽՋԹՆԼԱՇՐՁԻ԰ՍԺՋՌԹՆԻԽՋԢԻՇՄՇԿՁԻԹՄԢԾԾԽԻՌՋԤՍՁԼԽՄՁՆԽԬԭԭԱ԰

԰ՈԽԻՁԹՄԠՇՆՋՁԼԽՊԹՌՁՇՆԾՇՊԠՇՆԼՍԻՌՁՆԿԞՉՍԹՌՁԻԩԹԺՇՊԹՌՇՊՑ԰ՌՍԼՁԽՋ՟ԭՍԺՄՁԻԡՊԹԾՌՠԢԭԞԠ

ԞՈՊՁՄԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑԴԹՋՀՁՆԿՌՇՆԡԠ

԰ՅՁՌՀԽՊՋԳՁՋԻՁԽՆՌ԰ՌՍԼՑԫՇԭԹԿԽ

Բ԰ԢԭԞ԰ՀՇՊՌՌԽՊՅՅԽՌՀՇԼՋԾՇՊԽՋՌՁՅԹՌՁՆԿՌՀԽԻՀՊՇՆՁԻՌՇՐՁԻՁՌՑՇԾԽԾԾՄՍԽՆՌՋԹՆԼՊԽԻԽՁՎՁՆԿՏԹՌԽՊՋՌՇ

ՅԹՊՁՆԽԹՆԼԽՋՌՍԹՊՁՆԽՇՊԿԹՆՁՋՅՋԱՀՁՊԼԽԼՁՌՁՇՆԬԾԾՁԻԽՇԾԴԹՌԽՊԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑ

ԴԹՋՀՁՆԿՌՇՆԡԠԢԭԞԯ

Բ԰ԢԭԞԬԾԾՁԻԽՇԾԭՊԽՎԽՆՌՁՇՆԭԽՋՌՁԻՁԼԽՋԹՆԼԱՇՐՁԻ԰ՍԺՋՌԹՆԻԽՋԢՆԼՇԻՊՁՆԽԡՁՋՊՍՈՌՇՊ԰ԻՊԽԽՆՁՆԿ

ԭՊՇԿՊԹՅԱԽՋՌԤՍՁԼԽՄՁՆԽԬԭԭԱ԰ԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑԢԭԞԠ

ԬԻՌՇԺԽՊԲ԰ԢՆՎՁՊՇՆՅԽՆՌԹՄԭՊՇՌԽԻՌՁՇՆԞԿԽՆԻՑԴԹՋՀՁՆԿՌՇՆԡԠ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԞԭԭԢԫԡԦԵԦԬԲԱԭԲԱԬԣԯԢԳԦԢԴԢԯ0԰԰ԱԞԱԦ԰ԱԦԠԞԩԳԢԯԦԣԦԠԞԱԦԬԫ

ԠՇՆՌՊՇՄԠՇՅՈԹՊՁՋՇՆՋ

ԪՇՊՌ
ԹՄՄ ԪՇՊՌ
ՅԹՄԽ ԪՇՊՌ
ԾԽՅԹՄԽ ԣԽԻՍՆԼՁՌՑ ԣԽՊՌ

ԫԽԿԠՇՆՌՊՇՄ     

    

        

ԞՎԽՊԹԿԽ     ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ     

    

    

    

ԞՎԽՊԹԿԽ     ՌՌԽՋՌՈՎԹՄՍԽ     

ԴՌ
ԹՄՄՅԹՄԽՋ

ԴՌ
ՅԹՄԽԽՐԻՄՍԼՁՆԿՅՁՋՋԽՐԽԼ ԩԽՆԿՌՀ
ԹՄՄՅԹՄԽՋ

ԩԽՆԿՌՀ
ՅԹՄԽԽՐԻՄՍԼՁՆԿՅՁՋՋԽՐԽԼ ԴՌ
ԾԽՅԹՄԽ ԩԽՆԿՌՀ
ԾԽՅԹՄԽ

ԫԽԿԠՇՆՌՊՇՄ      

     

     

     

ԞՎԽՊԹԿԽ      

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԠՇՆՌՊՇՄԠՇՅՈԹՊՁՋՇՆՋ

԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ      

               

ԞՎԽՊԹԿԽ      ՌՌԽՋՌՈՎԹՄՍԽ      

Ԥ԰Ԧ
ԹՄՄՅԹՄԽՋ

Ԥ԰Ԧ
ՅԹՄԽԽՐԻՄՍԼՁՆԿՅՁՋՋԽՐԽԼ Ԥ԰Ԧ
ԾԽՅԹՄԽ

ԱՍԺԽՊԻՄԽ
ԹՄՄՅԹՄԽ

ԱՍԺԽՊԻՄԽ
ՅԹՄԽԽՐԻՄՍԼՁՆԿՅՁՋՋԽՐԽԼ ԳԱԤ
ԹՄՄՅԹՄԽՋ

ԳԱԤ
ՅԹՄԽԽՐԻՄՍԼՁՆԿՅՁՋՋԽՐԽԼ ԳԱԤ
ԣԽՅԹՄԽ

ԫԽԿԠՇՆՌՊՇՄ        

                     

ԞՎԽՊԹԿԽ        ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ        

       

       

       

ԞՎԽՊԹԿԽ        ՌՌԽՋՌՈՎԹՄՍԽ        ՌՌԽՋՌՋԹՊԽՋՁԼԽԼ

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԳԽՊՁԾՁԻԹՌՁՇՆՇԾԞՆԹՄՑՌՁԻԹՄԳԹՊՁԹՌՁՇՆ   



ԫՇՅՁՆԹՄ ԪԽԹՋՍՊԽԼ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ
ՅԿԹՁԩ ԱՁՅԽ
ԡԹՑ ԠՇՆԻԽՆՌՊԹՌՁՇՆ
ՅԿԹՁԩ  

ԯԽՈ ԯԽՈ ԞՎԿ

ԫԽԿԹՌՁՎԽԹՆԼ԰ՇՄՎԽՆՌԠՇՆՌՊՇՄ    

   

   

   

   

  ԪԽԹՆ 

԰ՌԹՆԼԹՊԼԡԽՎ 

ԠԳ
 

 

    

   

   

   

   

  ԪԽԹՆ 

԰ՌԹՆԼԹՊԼԡԽՎ 

ԠԳ
 

 

    

    

   

   

   

  ԪԽԹՆ 

԰ՌԹՆԼԹՊԼԡԽՎ 

ԠԳ
 

 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

ԳԽՊՁԾՁԻԹՌՁՇՆՇԾԞՆԹՄՑՌՁԻԹՄԳԹՊՁԹՌՁՇՆ   



ԫՇՅՁՆԹՄ ԪԽԹՋՍՊԽԼ

ԠՇՆԻԽՆՌՊԹՌՁՇՆ
ՅԿԹՁԩ ԱՁՅԽ
ԡԹՑ ԠՇՆԻԽՆՌՊԹՌՁՇՆ
ՅԿԹՁԩ  

ԯԽՈ ԯԽՈ ԞՎԿ

    

   

    

   

   

  ԪԽԹՆ 

԰ՌԹՆԼԹՊԼԡԽՎ 

ԠԳ
 

 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

ANALYSIS RESULTS FOR VARIABLE VAR01 ( F 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 

 0.841 0.028 1.419 0.291 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 1.32 0.05 0.03 4.02 1.24, 1.41 

 Dose1 4 1.38 0.16 0.08 11.88 1.12, 1.64 

 Dose2 4 1.37 0.16 0.08 11.52 1.12, 1.62 

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

 Ctrl 1.34 1.24 1.36 . . 

 Dose1 1.44 1.13 1.49 104.08 -4.08 

 Dose2 1.40 1.15 1.52 103.59 -3.59 

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

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 

 2 9 0.19 0.829 

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 1.32 . 1.36 . . . . . . 

 Dose1 1.38 0.799 1.36 0.722 . . . . . 

 Dose2 1.37 0.839 1.36 0.756 0.997 . . . . 

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

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 1.88 0.390 

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 1.34 . . 

 Dose1 1.44 0.346 0.876 

 Dose2 1.40 0.346 0.847 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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

 Analysis of Variance (ANOVA) - overall F-test 

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ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Numerator df Denominator df F-stat P-value 

 2 9 0.19 0.829 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -1.32 . -1.32 . . . . . . 

 Dose1 -1.38 0.799 -1.37 0.362 . . . . . 

 Dose2 -1.37 0.839 -1.37 0.386 0.997 . . . . 

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

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 1.88 0.390 

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 -1.34 . . 

 Dose1 -1.44 0.346 0.124 

 Dose2 -1.40 0.346 0.153 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.916 0.253 0.189 0.831 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 2.64 0.48 0.24 18.18 1.88, 3.41 

 Dose1 4 3.13 0.42 0.21 13.39 2.46, 3.79 

 Dose2 4 3.03 0.45 0.22 14.80 2.32, 3.74 

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

 Ctrl 2.62 2.14 3.20 . . 

 Dose1 3.13 2.62 3.62 118.22 -18.22 

 Dose2 2.97 2.55 3.63 114.58 -14.58 

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

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 1.28 0.323 

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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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 2.64 . 2.93 . . . . . . 

 Dose1 3.13 0.272 2.93 0.877 . . . . . 

 Dose2 3.03 0.408 2.93 0.901 0.951 . . . . 

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

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 2.58 0.276 

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 2.62 . . 

 Dose1 3.13 0.235 0.926 

 Dose2 2.97 0.346 0.847 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 1.28 0.323 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -2.64 . -2.64 . . . . . . 

 Dose1 -3.13 0.272 -3.08 0.122 . . . . . 

 Dose2 -3.03 0.408 -3.08 0.130 0.951 . . . . 

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

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 2.58 0.276 

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 -2.62 . . 

 Dose1 -3.13 0.235 0.074 

 Dose2 -2.97 0.346 0.153 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

Page 174 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.911 0.219 1.775 0.224 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 49.68 0.42 0.21 0.85 49.01, 50.36 

 Dose1 4 49.16 0.70 0.35 1.42 48.05, 50.26 

 Dose2 4 49.08 1.33 0.66 2.71 46.96, 51.19 

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

 Ctrl 49.78 49.11 50.06 . . 

 Dose1 49.26 48.24 49.87 98.94 1.06 

 Dose2 49.54 47.16 50.07 98.78 1.22 

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

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 0.54 0.602 

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 49.68 . 49.68 . . . . . . 

 Dose1 49.16 0.634 49.16 0.256 . . . . . 

 Dose2 49.08 0.555 49.08 0.233 0.991 . . . . 

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

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 1.51 0.469 

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 49.78 . . 

 Dose1 49.26 0.235 0.074 

 Dose2 49.54 0.889 0.255 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 175 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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

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 0.54 0.602 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -49.68 . -49.30 . . . . . . 

 Dose1 -49.16 0.634 -49.30 0.800 . . . . . 

 Dose2 -49.08 0.555 -49.30 0.830 0.991 . . . . 

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

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 1.51 0.469 

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 -49.78 . . 

 Dose1 -49.26 0.235 0.926 

 Dose2 -49.54 0.889 0.745 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.971 0.917 0.176 0.841 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 59.77 2.64 1.32 4.42 55.57, 63.98 

 Dose1 4 63.77 2.17 1.09 3.41 60.31, 67.23 

 Dose2 4 61.67 2.95 1.47 4.78 56.98, 66.36 

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

 Ctrl 58.80 57.86 63.63 . . 

 Dose1 64.52 60.59 65.45 106.68 -6.68 

 Dose2 62.76 57.33 63.84 103.17 -3.17 

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

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

 Analysis of Variance (ANOVA) - overall F-test 

Page 176 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Numerator df Denominator df F-stat P-value 

 2 9 2.35 0.151 

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 59.77 . 61.77 . . . . . . 

 Dose1 63.77 0.102 61.77 0.908 . . . . . 

 Dose2 61.67 0.510 61.67 0.921 0.517 . . . . 

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

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 4.50 0.105 

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 58.80 . . 

 Dose1 64.52 0.103 0.978 

 Dose2 62.76 0.678 0.721 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 2.35 0.151 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -59.77 . -59.77 . . . . . . 

 Dose1 -63.77 0.102 -62.72 0.085 . . . . . 

 Dose2 -61.67 0.510 -62.72 0.091 0.517 . . . . 

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

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 4.50 0.105 

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 -58.80 . . 

 Dose1 -64.52 0.103 0.022 

Page 177 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Dose2 -62.76 0.678 0.279 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.955 0.718 3.687 0.068 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 1158044 376768.3 188384.1 32.53 558521.6, 1757566 

 Dose1 4 1021250 148782.8 74391.41 14.57 784503.6, 1257997 

 Dose2 4 1062088 309213.6 154606.8 29.11 570060.2, 1554116 

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

 Ctrl 1199186 753299.0 1480506 . . 

 Dose1 1043868 838713.0 1158553 88.19 11.81 

 Dose2 1014884 750273.0 1468312 91.71 8.29 

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

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 0.23 0.801 

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 1158044 . 1158044 . . . . . . 

 Dose1 1021250 0.743 1041669 0.351 . . . . . 

 Dose2 1062088 0.860 1041669 0.375 0.979 . . . . 

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

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 0.62 0.735 

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 1199186 . . 

 Dose1 1043868 0.889 0.386 

 Dose2 1014884 0.494 0.232 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

Page 178 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 0.23 0.801 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -1158044 . -1080461 . . . . . . 

 Dose1-1021250 0.743 -1080461 0.729 . . . . . 

 Dose2-1062088 0.860 -1080461 0.763 0.979 . . . . 

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

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 0.62 0.735 

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 -1199186 . . 

 Dose1 -1043868 0.889 0.614 

 Dose2 -1014884 0.494 0.768 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.907 0.196 2.712 0.120 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 786.00 851.85 425.92 108.38 -569.48, 2141.48 

 Dose1 4 434.25 618.14 309.07 142.35 -549.35, 1417.85 

 Dose2 4 239.50 271.42 135.71 113.33 -192.39, 671.39 

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

 Ctrl 581.00 95.00 1887.00 . . 

 Dose1 187.00 14.00 1349.00 55.25 44.75 

 Dose2 121.00 71.00 645.00 30.47 69.53 

Page 179 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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

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 0.78 0.487 

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 786.00 . 786.00 . . . . . . 

 Dose1 434.25 0.657 434.25 0.268 . . . . . 

 Dose2 239.50 0.398 239.50 0.158 0.900 . . . . 

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

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 1.13 0.569 

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 581.00 . . 

 Dose1 187.00 0.678 0.282 

 Dose2 121.00 0.346 0.170 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 0.78 0.487 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -786.00 . -486.58 . . . . . . 

 Dose1 -434.25 0.657 -486.58 0.822 . . . . . 

 Dose2 -239.50 0.398 -486.58 0.851 0.900 . . . . 

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

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 1.13 0.569 

MannWhit - testing each trt median signif. different from control 

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

Page 180 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl -581.00 . . 

 Dose1 -187.00 0.678 0.718 

 Dose2 -121.00 0.346 0.830 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.938 0.478 0.154 0.859 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 15.28 1.74 0.87 11.39 12.51, 18.04 

 Dose1 4 15.37 1.78 0.89 11.57 12.54, 18.20 

 Dose2 4 13.59 1.54 0.77 11.32 11.14, 16.03 

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

 Ctrl 15.34 13.26 17.17 . . 

 Dose1 15.78 12.97 16.95 100.62 -0.62 

 Dose2 13.44 11.89 15.57 88.94 11.06 

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

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 1.41 0.292 

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 15.28 . 15.32 . . . . . . 

 Dose1 15.37 0.995 15.32 0.600 . . . . . 

 Dose2 13.59 0.312 13.59 0.120 0.338 . . . . 

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

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 2.35 0.309 

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 15.34 . . 

 Dose1 15.78 1.000 0.500 

Page 181 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Dose2 13.44 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) 

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

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 1.41 0.292 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -15.28 . -14.74 . . . . . . 

 Dose1 -15.37 0.995 -14.74 0.753 . . . . . 

 Dose2 -13.59 0.312 -14.74 0.786 0.338 . . . . 

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

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 2.35 0.309 

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 -15.34 . . 

 Dose1 -15.78 1.000 0.500 

 Dose2 -13.44 0.235 0.906 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.954 0.702 1.814 0.218 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 1.61 0.32 0.16 19.63 1.11, 2.11 

 Dose1 4 1.29 0.12 0.06 9.56 1.09, 1.48 

 Dose2 4 1.40 0.36 0.18 25.92 0.82, 1.98 

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

 Ctrl 1.59 1.26 2.00 . . 

Page 182 of 285
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 Dose1 1.29 1.14 1.44 79.97 20.03 

 Dose2 1.35 1.03 1.88 87.11 12.89 

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

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 1.30 0.320 

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 1.61 . 1.61 . . . . . . 

 Dose1 1.29 0.244 1.35 0.133 . . . . . 

 Dose2 1.40 0.514 1.35 0.142 0.841 . . . . 

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

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 2.42 0.298 

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 1.59 . . 

 Dose1 1.29 0.235 0.074 

 Dose2 1.35 0.346 0.121 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 1.30 0.320 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -1.61 . -1.43 . . . . . . 

 Dose1 -1.29 0.244 -1.43 0.869 . . . . . 

 Dose2 -1.40 0.514 -1.43 0.894 0.841 . . . . 

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

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 2.42 0.298 

Page 183 of 285
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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 -1.59 . . 

 Dose1 -1.29 0.235 0.926 

 Dose2 -1.35 0.346 0.879 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 0.00 0.00 0.00 . . , . 

 Dose1 4 0.00 0.00 0.00 . . , . 

 Dose2 4 0.00 0.00 0.00 . . , . 

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

 Ctrl 0.00 0.00 0.00 . . 

 Dose1 0.00 0.00 0.00 . . 

 Dose2 0.00 0.00 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 

 . . . 9 . . . . . . . 

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 0.00 . . . . . . . . 

 Dose1 0.00 . . . . . . . . 

 Dose2 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 

 2 0.00 1.000 

MannWhit - testing each trt median signif. different from control 

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

Page 184 of 285
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 Level Median MannWhit p-value Jonckheere p-value 

 Ctrl 0.00 . . 

 Dose1 0.00 1.000 . 

 Dose2 0.00 1.000 . 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose1 

 Jonckheere Dose1 

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

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 

 . . . 9 . . . . . . . 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 0.00 . . . . . . . . 

 Dose1 0.00 . . . . . . . . 

 Dose2 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 

 2 0.00 1.000 

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 0.00 . . 

 Dose1 0.00 1.000 . 

 Dose2 0.00 1.000 . 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams Dose1 

 Jonckheere Dose1 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.976 0.962 0.758 0.496 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 29.00 2.80 1.40 9.65 24.55, 33.45 

Page 185 of 285
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 Dose1 4 33.50 1.87 0.94 5.58 30.52, 36.48 

 Dose2 4 33.63 3.73 1.86 11.09 27.69, 39.56 

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

 Ctrl 29.75 25.00 31.50 . . 

 Dose1 33.75 31.00 35.50 115.52 -15.52 

 Dose2 32.50 30.50 39.00 115.95 -15.95 

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

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 3.30 0.084 

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 29.00 . 32.04 . . . . . . 

 Dose1 33.50 0.097 32.04 0.955 . . . . . 

 Dose2 33.63 0.089 32.04 0.967 0.998 . . . . 

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

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 5.81 0.055 

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 29.75 . . 

 Dose1 33.75 0.103 0.978 

 Dose2 32.50 0.103 0.961 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 3.30 0.084 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -29.00 . -29.00 . . . . . . 

 Dose1 -33.50 0.097 -33.50 0.032 . . . . . 

 Dose2 -33.63 0.089 -33.63 0.031 0.998 . . . . 

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

Page 186 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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 5.81 0.055 

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 -29.75 . . 

 Dose1 -33.75 0.103 0.022 

 Dose2 -32.50 0.103 0.039 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams Dose1 

 Jonckheere Dose1 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.911 0.220 1.797 0.220 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 21.04 10.63 5.31 50.50 4.13, 37.95 

 Dose1 4 16.88 2.54 1.27 15.04 12.84, 20.92 

 Dose2 4 10.26 6.49 3.24 63.19 -0.06, 20.58 

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

 Ctrl 17.87 12.30 36.12 . . 

 Dose1 17.77 13.15 18.84 80.23 19.77 

 Dose2 8.94 3.89 19.28 48.78 51.22 

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

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 2.20 0.167 

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 21.04 . 21.04 . . . . . . 

 Dose1 16.88 0.651 16.88 0.265 . . . . . 

 Dose2 10.26 0.117 10.26 0.041 0.442 . . . . 

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

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

 Kruskal-Wallis test - equality among treatment groups 

 Degrees of Freedom TestStat P-value 

Page 187 of 285
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 2 3.04 0.219 

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 17.87 . . 

 Dose1 17.77 0.889 0.386 

 Dose2 8.94 0.156 0.054 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams Dose2 

 Jonckheere >highest dose (no sign. differences) 

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

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 2.20 0.167 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -21.04 . -16.06 . . . . . . 

 Dose1 -16.88 0.651 -16.06 0.887 . . . . . 

 Dose2 -10.26 0.117 -16.06 0.910 0.442 . . . . 

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

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 3.04 0.219 

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 -17.87 . . 

 Dose1 -17.77 0.889 0.614 

 Dose2 -8.94 0.156 0.946 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

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 

 0.828 0.020 2.840 0.111 USE PARAMETRIC TESTS 

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

Page 188 of 285
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BASIC SUMMARY STATISTICS 

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

 Ctrl 4 96.78 1.20 0.60 1.24 94.86, 98.69 

 Dose1 4 94.60 2.95 1.47 3.12 89.91, 99.29 

 Dose2 4 92.30 5.35 2.67 5.80 83.79, 100.81 

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

 Ctrl 97.00 95.20 97.90 . . 

 Dose1 95.60 90.30 96.90 97.75 2.25 

 Dose2 94.70 84.30 95.50 95.38 4.62 

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

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 1.55 0.264 

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 96.78 . 96.78 . . . . . . 

 Dose1 94.60 0.616 94.60 0.247 . . . . . 

 Dose2 92.30 0.190 92.30 0.070 0.651 . . . . 

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

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 4.89 0.087 

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 97.00 . . 

 Dose1 95.60 0.283 0.096 

 Dose2 94.70 0.103 0.012 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere Dose2 

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

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 1.55 0.264 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -96.78 . -94.56 . . . . . . 

 Dose1 -94.60 0.616 -94.56 0.869 . . . . . 

Page 189 of 285
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 Dose2 -92.30 0.190 -94.56 0.894 0.651 . . . . 

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

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 4.89 0.087 

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 -97.00 . . 

 Dose1 -95.60 0.283 0.904 

 Dose2 -94.70 0.103 0.988 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

ANALYSIS RESULTS FOR VARIABLE VAR13 ( F testosterone (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 

 0.828 0.020 2.840 0.111 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 0 . . . . . , . 

 Dose1 0 . . . . . , . 

 Dose2 0 . . . . . , . 

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

 Ctrl . . . . . 

 Dose1 . . . . . 

 Dose2 . . . . . 

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

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 1.55 0.264 

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 . . . 

 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

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

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

 Analysis of Variance (ANOVA) - overall F-test 

Page 190 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

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 Numerator df Denominator df F-stat P-value 

 2 9 1.55 0.264 

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 . . . 

 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

ANALYSIS RESULTS FOR VARIABLE VAR14 ( M testosterone (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 

 0.828 0.020 2.840 0.111 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 0 . . . . . , . 

 Dose1 0 . . . . . , . 

 Dose2 0 . . . . . , . 

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

 Ctrl . . . . . 

 Dose1 . . . . . 

 Dose2 . . . . . 

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

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 1.55 0.264 

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 . . . 

 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

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

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 1.55 0.264 

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 . . . 

Page 191 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

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 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

ANALYSIS RESULTS FOR VARIABLE VAR15 ( F 17b-estradiol (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 

 0.828 0.020 2.840 0.111 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 0 . . . . . , . 

 Dose1 0 . . . . . , . 

 Dose2 0 . . . . . , . 

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

 Ctrl . . . . . 

 Dose1 . . . . . 

 Dose2 . . . . . 

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

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 1.55 0.264 

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 . . . 

 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

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

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 1.55 0.264 

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 . . . 

 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Excluded 

ANALYSIS RESULTS FOR VARIABLE VAR16 ( M 17b-estradiol (ng/mL) ) 

TESTS OF ASSUMPTIONS FOR PARAMETRIC ANALYSIS 

Page 192 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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 

 0.828 0.020 2.840 0.111 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 0 . . . . . , . 

 Dose1 0 . . . . . , . 

 Dose2 0 . . . . . , . 

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

 Ctrl . . . . . 

 Dose1 . . . . . 

 Dose2 . . . . . 

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

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 1.55 0.264 

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 . . . 

 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

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

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 1.55 0.264 

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 . . . 

 Dose1 . . . 

 Dose2 . . . 

 Jonckheere Dose1 

Page 193 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Included 

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 

 0.957 0.743 0.050 0.952 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 2.52 0.32 0.16 12.65 2.01, 3.02 

 Dose1 4 3.13 0.42 0.21 13.39 2.46, 3.79 

 Dose2 4 3.03 0.45 0.22 14.80 2.32, 3.74 

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

 Ctrl 2.56 2.14 2.81 . . 

 Dose1 3.13 2.62 3.62 124.24 -24.24 

 Dose2 2.97 2.55 3.63 120.42 -20.42 

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

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 2.70 0.120 

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 2.52 . 2.89 . . . . . . 

 Dose1 3.13 0.102 2.89 0.941 . . . . . 

 Dose2 3.03 0.173 2.89 0.955 0.938 . . . . 

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

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 4.31 0.116 

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 2.56 . . 

 Dose1 3.13 0.156 0.958 

 Dose2 2.97 0.156 0.928 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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

 Analysis of Variance (ANOVA) - overall F-test 

Page 194 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

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 Numerator df Denominator df F-stat P-value 

 2 9 2.70 0.120 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -2.52 . -2.52 . . . . . . 

 Dose1 -3.13 0.102 -3.08 0.045 . . . . . 

 Dose2 -3.03 0.173 -3.08 0.048 0.938 . . . . 

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

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 4.31 0.116 

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 -2.56 . . 

 Dose1 -3.13 0.156 0.042 

 Dose2 -2.97 0.156 0.072 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams Dose1 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Included 

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 

 0.909 0.209 0.609 0.565 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 59.46 1.68 0.84 2.82 56.79, 62.12 

 Dose1 4 63.77 2.17 1.09 3.41 60.31, 67.23 

 Dose2 4 61.67 2.95 1.47 4.78 56.98, 66.36 

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

 Ctrl 58.84 58.28 61.87 . . 

 Dose1 64.52 60.59 65.45 107.25 -7.25 

 Dose2 62.76 57.33 63.84 103.72 -3.72 

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

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 3.44 0.078 

Page 195 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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 59.46 . 61.63 . . . . . . 

 Dose1 63.77 0.049 61.63 0.940 . . . . . 

 Dose2 61.67 0.343 61.63 0.955 0.442 . . . . 

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

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 5.12 0.077 

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 58.84 . . 

 Dose1 64.52 0.103 0.978 

 Dose2 62.76 0.346 0.810 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 3.44 0.078 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -59.46 . -59.46 . . . . . . 

 Dose1 -63.77 0.049 -62.72 0.046 . . . . . 

 Dose2 -61.67 0.343 -62.72 0.048 0.442 . . . . 

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

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 5.12 0.077 

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 -58.84 . . 

 Dose1 -64.52 0.103 0.022 

 Dose2 -62.76 0.346 0.190 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

Page 196 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

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 Williams Dose1 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Included 

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 

 0.903 0.176 1.254 0.331 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 936.25 749.44 374.72 80.05 -256.27, 2128.77 

 Dose1 4 434.25 618.14 309.07 142.35 -549.35, 1417.85 

 Dose2 4 239.50 271.42 135.71 113.33 -192.39, 671.39 

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

 Ctrl 881.50 95.00 1887.00 . . 

 Dose1 187.00 14.00 1349.00 46.38 53.62 

 Dose2 121.00 71.00 645.00 25.58 74.42 

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

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 1.52 0.269 

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 936.25 . 936.25 . . . . . . 

 Dose1 434.25 0.404 434.25 0.151 . . . . . 

 Dose2 239.50 0.210 239.50 0.078 0.886 . . . . 

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

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 1.94 0.379 

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 881.50 . . 

 Dose1 187.00 0.494 0.193 

 Dose2 121.00 0.235 0.106 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Page 197 of 285
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ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

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

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 1.52 0.269 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -936.25 . -536.67 . . . . . . 

 Dose1 -434.25 0.404 -536.67 0.889 . . . . . 

 Dose2 -239.50 0.210 -536.67 0.912 0.886 . . . . 

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

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 1.94 0.379 

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 -881.50 . . 

 Dose1 -187.00 0.494 0.807 

 Dose2 -121.00 0.235 0.894 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Included 

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 

 0.915 0.251 1.536 0.267 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 1.61 0.38 0.19 23.45 1.01, 2.20 

 Dose1 4 1.29 0.12 0.06 9.56 1.09, 1.48 

 Dose2 4 1.40 0.36 0.18 25.92 0.82, 1.98 

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

 Ctrl 1.51 1.26 2.14 . . 

 Dose1 1.29 1.14 1.44 80.22 19.78 

 Dose2 1.35 1.03 1.88 87.38 12.62 

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

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

 Analysis of Variance (ANOVA) - overall F-test 

Page 198 of 285
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 Numerator df Denominator df F-stat P-value 

 2 9 1.07 0.382 

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 1.61 . 1.61 . . . . . . 

 Dose1 1.29 0.299 1.35 0.159 . . . . . 

 Dose2 1.40 0.574 1.35 0.169 0.862 . . . . 

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

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 2.42 0.298 

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 1.51 . . 

 Dose1 1.29 0.235 0.074 

 Dose2 1.35 0.346 0.121 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 1.07 0.382 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -1.61 . -1.43 . . . . . . 

 Dose1 -1.29 0.299 -1.43 0.851 . . . . . 

 Dose2 -1.40 0.574 -1.43 0.878 0.862 . . . . 

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

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 2.42 0.298 

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 -1.51 . . 

 Dose1 -1.29 0.235 0.926 

Page 199 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Dose2 -1.35 0.346 0.879 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

Pronamide FSTRA 101701 48619106 Mis-sexed Males Included 

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 

 0.958 0.757 1.240 0.335 USE PARAMETRIC TESTS 

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

BASIC SUMMARY STATISTICS 

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

 Ctrl 4 28.63 3.15 1.57 10.99 23.62, 33.63 

 Dose1 4 33.50 1.87 0.94 5.58 30.52, 36.48 

 Dose2 4 33.63 3.73 1.86 11.09 27.69, 39.56 

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

 Ctrl 29.00 25.00 31.50 . . 

 Dose1 33.75 31.00 35.50 117.03 -17.03 

 Dose2 32.50 30.50 39.00 117.47 -17.47 

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

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 3.57 0.072 

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 28.63 . 31.92 . . . . . . 

 Dose1 33.50 0.084 31.92 0.960 . . . . . 

 Dose2 33.63 0.077 31.92 0.971 0.998 . . . . 

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

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 4.72 0.094 

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 29.00 . . 

 Dose1 33.75 0.125 0.970 

 Dose2 32.50 0.156 0.938 

 DECREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. LESS THAN CONTROL 

Page 200 of 285
ԡԹՌԹԢՎԹՄՍԹՌՁՇՆԯԽԻՇՊԼՇՆՌՀԽԣՁՋՀ԰ՀՇՊՌԱԽՊՅԯԽՈՊՇԼՍԻՌՁՇՆԞՋՋԹՑՏՁՌՀԭՊՇՆԹՅՁԼԽ

ԢԭԞԪԯԦԡԫՍՅԺԽՊ

ԭԹԿԽ  οԾ 

 Williams >highest dose (no sign. differences) 

 Jonckheere >highest dose (no sign. differences) 

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

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 3.57 0.072 

Dunnett - testing each trt mean signif. different than control 

Williams - test assumes dose-response relationship, testing INCREASING 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 -28.63 . -28.63 . . . . . . 

 Dose1 -33.50 0.084 -33.50 0.028 . . . . . 

 Dose2 -33.63 0.077 -33.63 0.027 0.998 . . . . 

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

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 4.72 0.094 

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 -29.00 . . 

 Dose1 -33.75 0.125 0.030 

 Dose2 -32.50 0.156 0.062 

 INCREASING TREND TEST SUMMARY LOWEST CONCENTRATION SIGNIF. GREATER THAN CONTROL 

 Williams Dose1 

 Jonckheere >highest dose (no sign. differences) 

Page 201 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE)

Study Type: OCSPP 890.1400, In vivo Hershberger Assay

EPA Contract No. EP10H001452 

Task Assignment No. 3-14-2012 (MRID 48673401) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

CSS-Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer: Signature:

Michelle Sharpe-Kass, M.S. Date: 8/21/2012

Secondary Reviewer: Signature:

Scott D. Studenberg, Ph.D., D.A.B.T. Date: 8/29/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 9/04/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 9/04/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 202 of 285
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 203 of 285
PRONAMIDE /101701 

Primary Reviewer: _Kh_in~O~o~M~·~D~·-------­

Health Effects Division 

Secondary Reviewer: Greg Akerman, Ph.D. 

Health Effects Division 

In vivo Hershberger Assay (2012)/ Page 1 of 17 

OCSPP 890.1400/ OECD 441 

Signature: _l=-~=·=· ,.....----

Date: c./z.."t/1.o\~ 

Signature: *Oii ,A-:== 

Date: c../~lt.:r 

Template version 10/2011 

DATA EVALUATION RECORD 

STUDY TYPE: Jn Vivo Hershberger Assay (Rat); OCSPP 890.1400; OECD 441 

PCCODE: 101701 DP BARCODE: D403721 

TXR#: 0056255 CAS No: 23950-58-5 

TEST MATERIAL (PURITY): Pronamide (95.7% a.i.) 

SYNONYMS: Propyzamide, 3,5-Dichloro-N-(l, 1-dimethyl-2-propynyl)benzamide 

CITATION: Marty, M.S., Marshall, V.A., Zhang, F. (2012). Pronamide Technical: 

Hershberger Assay in Castrated Adult Male Crl:CD(SD) Rats. Toxicology & 

Environmental Research and Consulting, Midland, MI. Laboratory Report No. 

101010, June 22, 2012. MRID 48673401. Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 46268 

TEST ORDER#: CON -101701-37 

EXECUTIVE SUMMARY: In a Hershberger Assay (MRID 48673401) screening for 

androgenic activity, pronamide (95.7% purity, Lot# TA0788R301 , TSN003588-0002) in 

0.5% aqueous methylcellulose (MC) was administered daily via oral gavage to groups of seven, 

55-day old, castrated male Crl:CD(SD) rats at dose levels of 0 (vehicle), 40, 200 or 1000 (limit 

dose) mg/kg/day. The test included an androgenic positive control group consisting of seven 

castrated rats exposed orally to the vehicle control plus 0.4 mg/kg/day of testosterone propionate 

(TP) by s.c. injection. 

To screen for potential anti-androgenic activity, pronamide (95 .7% a.i.) in 0.5% MC was 

administered daily via oral gavage to groups of seven, 55-day old, castrated male Crl:CD(SD) 

rats at dose levels of 0 (vehicle), 40, 200 or 1000 mg/kg/day, in conjunction with a daily dose of 

TP at 0.4 mg/kg/day by s.c. injection. The anti-androgenic positive control group consisted of 

seven castrated rats exposed to 3 mg/kg/day flutamide (FT) in com oil by oral gavage and 0.4 

mg/kg/day TP by s.c. injection. The positive control animals for the androgen agonist assay 

served as the anti-androgenic negative controls. 

For both components of the assay, body weights and food consumption were determined daily. 

The animals were dosed for 10 consecutive days and terminated approximately 24 hours after the 

final dose administration. At necropsy, the five androgen-dependent tissues, adrenal glands, 

kidneys, and liver were collected and weighed. Blood was collected for measurement of serum 

Page 204 of 285
In vivo Hershberger Assay (2012)/ Page 2 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

testosterone, and livers from control group and the 200 and 1000 mg/kg/day groups were 

collected for microsomal analysis of testosterone metabolism. 

All rodents survived until termination with the exception of one rat in the 1000 mg/kg/day group, 

which was found dead on Day 11 from an apparent gavage dosing error. There were no 

treatment-related clinical signs in animals dosed at ≤200 mg/kg/day in either assay. In the 1000 

mg/kg/day group, the only treatment-related observation was perineal (urine) soiling in three 

animals in the androgenic portion of the study over Days 3-8 and in one animal in the antiandrogenic portion of the study during Days 7-10. 

In the androgen agonist assay, there were no treatment-related effects on body weights in any 

dose group, or on body weight gain in the low- and mid-dose groups. In the high-dose group, 

body weight gains were decreased by 79% for Days 1-4, 47% for Days 1-7 and 20% for Day 1-

11. However, after inspection of individual body weights, with particular attention to the rat 

which died on Day 11 due to a gavage error (effects observed beginning on Day 2), that had a 

negative body weight gain over Days 1-4 and gained only 11 grams by Day 7, it is clear that this 

animal drove the low response. Food consumption in this group was also decreased (p<0.05) by 

27% during Days 1-4. In the mid-dose group, food consumption was decreased (p<0.05) by 

11% during Days 1-4, but was increased (p<0.05) by 9% for Days 4-7. Absolute liver weights 

were increased (p<0.05) in the mid- and high-dose groups by 56% and 125%, respectively, and 

adrenal gland weights were also increased (p<0.05) by 35% in the high-dose group. There were 

no other pronamide-related effects in the androgen assay. There were no statistically significant 

weight increases in androgen-dependent tissue weights at up to the limit dose (1,000 mg/kg/day). 

Animals in the positive control (vehicle + TP) group had accessory sex organ weight increases 

(p<0.05) as follows: 446% in Cowper’s glands; 71% in glans penis; 187% in levator anibulbocavernosus muscle complex (LABC); 533% in ventral prostate; and 1211% in the seminal 

vesicles with coagulating glands. 

In the anti-androgen assay, body weights were decreased (p<0.05) by 11% and 9% on Days 7 

and 11, respectively, in the high-dose group, but there were no treatment-related effects on body 

weight at the mid- or low-dose. Body weight gains were initially decreased by 40% in the middose group, but were not significantly different over the entire study (Days 1-11). In the highdose group, body weight gains were decreased (<0.05) by 77% and 71% for Days 1-4 and 1-7, 

respectively, and by 38% over Days 1-11. Food consumption was also decreased (p<0.05) by 

10-32% over the entire study in the high-dose group, and by 6-14% in the positive FT+TP 

control group. As in the androgenic assay, absolute liver weights were increased (p<0.05) in a 

dose-dependent manner by 49 and 102% in the mid- and high-dose groups, respectively, and 

adrenal gland weights were increased (p<0.05) by 59% in the high-dose group. No significant 

weight changes were observed in accessory sex tissues in the low-dose group or in the Cowper’s

gland and glans penis in the mid- and high-dose groups. However, dose-dependent decreases 

(p<0.05) in weight were observed in the LABC (↓22% and ↓51%), ventral prostate (↓24% and 

↓50%) and seminal vesicles (↓35% and ↓42%) in the mid- and high-dose groups. In addition, 

animals in the positive control (FT+TP) group had the expected decreases (p<0.05) in accessory 

sex organ weight as follows: 58% in Cowper’s glands; 25% in glans penis; 57% in LABC; 74% 

in ventral prostate; and 81% in seminal vesicles with coagulating glands. There were dosedependent decreases observed in three androgen-dependent tissues. 

Percent CVs for the vehicle control and the high-dose groups for both assays were compared to 

the performance criteria in the Guidelines. In the androgenic assay, all %CV values were less 

Page 205 of 285
In vivo Hershberger Assay (2012)/ Page 3 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

than the maximum permissible values. In the anti-androgenic assay, the following values were 

greater than the maximum permissible values: Cowper’s glands in the high-dose group (CV 

42% vs. 35% maximum); LABC in the low-, mid- and high-dose groups (CV 21-29% vs. 20% 

maximum); ventral prostate in the mid- and high-dose groups (CV 41-44% vs. 40% maximum); 

and seminal vesicles in the mid-dose group (CV 45% vs. 40% maximum). Although CV values 

for numerous accessory sex tissues were above the allowable maximum values, these deviations 

do not interfere with the interpretation of the study as there was a significant effect in three target 

tissues in the anti-androgenic assay. 

The results of the microsomal assay indicate that pronamide treatment can induce the liver 

enzymes responsible for testosterone metabolism, which could possibly result in reduced 

testosterone levels and subsequent decreases in the weights of androgen sensitive tissues. 

However, the serum testosterone data from the anti-androgen assay do not clearly support this 

conclusion. Although there was an apparent 50% decrease (not significant, NS) in serum 

testosterone levels in the high-dose group, there was also an apparent 14% increase (NS) in 

serum testosterone in the mid-dose group, which also showed significant decreases in weights of 

androgen sensitive tissues. The utility of the available serum testosterone data is limited due to 

the large within-group variability (CVs 47-89%). 

Pronamide was negative for androgenic activity in the Hershberger assay 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, pronamide was positive for anti-androgenicity 

in the Hershberger assay as statistically significant decreases in organ weights were seen in three 

of the five androgen sensitive tissues in the androgen antagonist assay. 

The assay satisfies the EDSP Tier 1 Test Order requirements for a Hershberger assay (OCSPP 

890.1400). 

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

Assurance statements were provided. 

Page 206 of 285
In vivo Hershberger Assay (2012)/ Page 4 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Toxicology & Environmental Research and Consulting

Location: Midland, MI

Study Director: Marshall, V.A.

Other Personnel: Marty, M.S., Lead Scientist

Zhang, F., Research Scientist

Study Period: February 23, 2010 - June 22, 2012

2. Test Substance: Pronamide

Description: Off-white powder

Source: Dow AgroSciences, LLC, Indianapolis, IN (Cat # not reported)

Lot/Batch #: TA0788R301, TSN003588-0002 (No expiration date; test substance 

recertification - August 19, 2011

Purity: 95.7%

Stability: The stability of pronamide in 0.5% aqueous cellulose at 0.250, 2.50 and 250 

mg/ml was determined in a previous study: ≤12 days

CAS #: 23950-58-5

Structure:

Cl

Cl

O

N

H

CH3

CH3 CH

3. Reference Androgen: Testosterone propionate (TP)

Supplier: Sigma-Aldrich (St. Louis, MO)

Lot/Batch #: Lot # and Expiration date were not provided

Purity: ≥98%

CAS #: 57-85-2

4. Reference Anti-androgen: Flutamide (FT)

Supplier: Sigma-Aldrich (St. Louis, MO)

Lot/Batch #: Lot # and Expiration date were not provided

Purity: ≥99%

CAS #: 13311-84-7

5. Solvent/Vehicle Control: Aqueous methylcellulose (MC; MethocelTM)

Supplier: Not provided

Lot/Batch #: Not provided

Rationale (if other than water): Not provided

Final concentration: 0.5%

Page 207 of 285
In vivo Hershberger Assay (2012)/ Page 5 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

6. Test Animals:

Species: Rat (males only)

Strain: Crl:CD(SD)

Age/weight at dose initiation: Post-natal day (PND) 55/194-256.4 g 

Source: Charles River, Raleigh, NC

Housing: 2-3/cage, stainless steel cages, wire mesh floor suspended over absorbent 

paper

Diet: LabDiet Certified Rodent Diet #5002, ad libitum

Phytoestrogen content not reported

Water: Tap Water ad libitum

Environmental conditions: Temperature:

Humidity:

Air changes:

Photoperiod:

22 ± 3 oC

40-70% 

12-15/hr

12 hrs light/12 hrs dark

Acclimation period: 10 days post-castration

B. STUDY DESIGN

1. In-life Dates: Start: July 4/5, 2010 End: July 14/15, 2010 

2. Study Design: In a Hershberger Assay conducted to screen for potential androgenic 

activity, the test substance was administered in 0.5% aqueous MC daily via oral gavage to 

castrated male rats, which also received a s.c. injection of corn oil. The positive control 

group received the vehicle plus TP (0.4 mg/kg/day) in corn oil by s.c. Positive androgenic 

activity is defined as a significant increase in two or more target organ weights compared to 

the vehicle control. Negative control groups for androgenic activity consisted of 0.5% 

aqueous MC alone and 0.5% aqueous MC with an s.c. injection of corn oil only. 

To screen for the potential anti-androgenic activity, the test substance was also administered 

daily via oral gavage to castrated male rats in conjunction with a daily dose of TP (0.4 

mg/kg/day) by s.c. injection. A positive control group received flutamide (FT) at 3 

mg/kg/day in corn oil by oral gavage plus TP at 0.4 mg/kg/day by s.c. injection. 

Anti-androgenic activity is indicated by a statistically significant decrease in two or more 

target organ weights of the treated groups (test substance + TP) compared to the negative 

control. For anti-androgenic test, the negative control (vehicle control + TP) was the same 

group of animals that served as the positive control in the androgenic assay. 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: Rats were castrated at Charles River Laboratories at 45 days of age and 

received by the test laboratory at 49 or 50 days of age. The dose administration period was 

from PND 55 through PND 64, which allowed 10 days after castration for recovery and 

regression of accessory sex organ weights prior to initiation of dosing. Rats were 

euthanized on PND 65 approximately 24 hours after the last dose and necropsied for organ 

weight measurements.

4. Animal Assignment: Animals were assigned, stratified by body weight, to the test groups 

noted in Table 1. Statistical analysis indicated that there were no significant differences in 

group means at study initiation. Furthermore, the body weight of each animal was within 

20% of the overall mean. 

Page 208 of 285
In vivo Hershberger Assay (2012)/ Page 6 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

TABLE 1. Study Designa

Test group Dose (mg/kg/day) # of Males

Androgen Agonist Assay

Vehicle control (no s.c. injection) 0 7

Vehicle control, negative controlb 0 7

Low (Pronamide)b 40 7

Mid (Pronamide)b 200 7

High (Pronamide)

b 1000 7

Positive control (Vehicle + TPc) 0 + 0.4 7

Anti-Androgen Assay

Low (Pronamide + TPc) 40 + 0.4 7

Mid (Pronamide + TPc) 200 + 0.4 7

High (Pronamide + TPc) 1000 + 0.4 7

Flutamided + TP, positive control 3 + 0.4 7

a Data were obtained from page 17 of the study report.

b Gavage administration of test compound plus s.c. administration of corn oil vehicle.

c Testosterone propionate administered by s.c. in corn oil.

d The animals in the positive control group for the androgenic assay also served as the negative control group for 

the anti-androgenic assay.

e Administered in corn oil by oral gavage. 

5. Dose Selection Rationale: The dose levels were selected based on the results from a rangefinding study that was included in the report. Five castrated male rats/dose group were 

administered pronamide in 0.5% aqueous methylcellulose by oral gavage in a two-phase 

range-finding study. The first phase consisted of dose levels of 0, 25, 100, 250, and 500 

mg/kg/day, and the second phase included higher dose levels of 0, 600, 800, and 1000 

mg/kg/day. The second phase was added due to the lack of clear, treatment-related body 

weight effects in the first phase of the range-finding study. Because the high-dose level of 

1000 mg/kg/day pronamide was well tolerated in study animals and produced an 

approximate 10% decrease in body weights after administration of 10 daily doses by 

gavage, it was selected as the high dose in the Hershberger assay. 

6. (a) Dose Preparation: Pronamide technical was administered as a suspension in 0.5% 

aqueous MC at a dose volume of 10 mL/kg body weight. FT was administered in corn oil at 

a dose volume of 5 mL/kg body weight. The TP dosing solution was prepared in laboratory 

grade stripped corn oil and administered at a dose volume of 0.5 mL/kg to achieve the 

targeted dose (0.4 mg/kg). Dosing solutions were prepared in accordance with established 

stability limits. Dose volumes were adjusted daily based on body weights. Homogeneity 

and dose confirmation analyses were determined pre-exposure on all pronamide technical 

dose solutions from the first mix. 

(b) Dose Analysis: 

Results

Homogeneity (%RSD): 0.2-0.9% 

Page 209 of 285
In vivo Hershberger Assay (2012)/ Page 7 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

Stability: Not Tested (Stability was determined previously as ≤12 days for pronamide in 

0.5% METHOCELTM at concentrations of 0.25-250 mg/mL.1

Concentration (% of nominal): 97.7-100.1% 

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 by oral 

gavage (10 mL/kg) for 10 days. TP was given via s.c. injection at 0.5 mL/kg and FT was 

administered by oral gavage at 5 mL/kg. Dose volumes were adjusted daily based on the 

concurrent body weight measurement. 

8. Statistics: Body weights, body weight gains, organ weights (absolute), testosterone levels, 

testosterone metabolites (excluding estrone), and feed consumption were evaluated by 

Bartlett’s test (α = 0.01) for equality of variances. Based on the outcome of Bartlett's test, a 

parametric or non-parametric analysis of variance (ANOVA) was performed. Variables that 

required transformation prior to analysis included DHT and estradiol, which were log 

transformed, and 6-alpha-hydroxytestosterone and 16-beta-hydroxytestosterone, which were 

square root transformed. If the ANOVA was significant at α = 0.05, analysis by two-sided 

(body weights/gains, liver, kidney and adrenal weights; testosterone metabolites (excluding 

estrone) or one-sided Dunnett's test (androgen-sensitive tissue weights and testosterone 

levels) (α = 0.05) or the Wilcoxon Rank-Sum test (α = 0.05) with Bonferroni's correction 

was performed, respectively. A coefficient of variation (CV) was calculated for the control 

organ weights and compared with acceptance criteria provided in the OECD test guideline. 

The statistical analyses were considered adequate by the reviewers. 

C. METHODS

1. Clinical Examinations: Cage-side checks for mortality, moribundity, and clinical signs of 

toxicity were conducted twice daily, and a hand-held examination was conducted once daily 

approximately one hour after dosing. Detailed physical examinations were performed prior 

to initiation of dosing and at termination.

2. Body Weight: Animals were weighed at randomization, study initiation and daily 

throughout the dosing period. 

3. Food Consumption: Food consumption was measured for each cage by subtracting the 

amount of food remaining in the cage from the amount supplied. Values were reported as 

group mean daily food consumption (g/animal/day) for the following intervals: Days 1-4, 4-

7, and 7-11. 

 

1 Dryzga, M. D. and Yano, B. L. (2005). Pronamide Technical: 28-Day Dermal Toxicity Study in F344/DuCrl Rats. 

Report of Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, 

Michigan.

Page 210 of 285
In vivo Hershberger Assay (2012)/ Page 8 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

4. Serum Hormone Measurements: At study termination (Day 11), each animal was 

anesthetized with isoflurane/O2, and blood was collected via cardiac puncture for serum 

hormone analyses. The initial quantitative analyses of testosterone were conducted by 

liquid chromatography/positive atmospheric pressure photoionization tandem mass 

spectrometry (LC/APPI-MS/MS). Secondary analyses of samples from the anti-androgen 

assay (TP control group, and low-, mid- and high-doses + TP groups) were determined by

radioimmunoassay (RIA) with the Coat-A-Count total Testosterone RIA kit (Siemens 

Diagnostics, California) conducted at AniLytics Incorporated (Gaithersburg, MD). 

5. Dissection and Measurement of Tissue and Organ Weights: On PND 65 (approximately 

24 hours after the final administration of the test substance), all surviving animals were 

euthanized by decapitation following anesthesia with isoflurane/O2, exsanguinated, and 

subjected to a gross necropsy. The five mandatory androgen-dependent organs (ventral 

prostate, seminal vesicles, levator ani-bulbocavernous muscle complex [LABC], Cowper’s 

gland, and glans penis) were excised, trimmed free of adhering tissue, and weighed fresh 

(unfixed) according to the standard operating procedures detailed in the U.S. EPA Guideline 

(OCSPP 890.1400). Additionally, the liver, kidneys, and adrenals were weighed, and all 

tissues were prepared for microscopic examination. 

6. Microsomal Preparation and Testosterone Metabolite Formation: To evaluate 

testosterone metabolizing capacity, microsomes were isolated from liver tissue of control 

and pronamide-treated animals (200 and 1000 mg/kg/day groups). Frozen samples were 

homogenized in a Tris-buffered KCl solution containing EDTA and an antioxidant. 

Samples were centrifuged to pelletize microsomes, and resultant pellets were resuspended in 

a pyrophosphate solution to remove nucleic acid polymers and recentrifuged. Pelleted 

microsomes were then suspended in a Tris-buffered 20% glycerol solution containing an 

antioxidant. Microsomes were aliquoted in multiple cryo-tubes and stored at -80 °C until 

used. Rat liver microsomes (1 mg/mL) were incubated for 30 minutes with testosterone 

(0.25 mM) in the presence of cofactor NADPH (1 mM) in 0.1 M phosphate buffer, pH 7.3 at 

37°C. The reaction was stopped by transferring the vials to ice and adding 10% kill solution 

(2% formic acid in CH3CN). The supernatant was analyzed for hydroxylated testosterone 

metabolites and androstenedione by LC/MS-MS. Other potential metabolites were 

quantified by a method developed in house (not reported) 

II. RESULTS

A. OBSERVATIONS

1. Mortality: All rodents survived until schedule sacrifice with the exception of one rat 

(animal #5049) in the 1000 mg/kg/day group, which was found dead on Day 11 prior to the 

scheduled necropsy. Necropsy revealed clotted blood in the thoracic cavity and the visceral 

and parietal pleura had adhesions of fibrin and clotted blood which were consistent with a 

gavage dosing error. Organ weights were not collected and tissues were not preserved from 

this animal, because its death was deemed unrelated to pronamide treatment. 

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2. Clinical Signs of Toxicity: One animal in the 1000 mg/kg/day group, which was found 

dead on Day 11, began showing clinical signs of toxicity on Day 2. Clinical observations 

over the Days 3-10 (excluding Days 7 and 9) included uncoordinated gait, splayed hind 

limbs, soft/limp muscle tension, decreased, activity, urine perineal soiling, 

perioral/periocular/perinasal red soiling, dehydration and labored respiration without mouth 

breathing. These observations were considered secondary to an apparent error during 

gavage dosing. The only treatment-related observation occurred in selected high-dose 

animals, which consisted of perineal (urine) soiling seen in three animals in the androgenic 

portion of the study over Days 3-8, and one animal in the anti-androgenic portion of the 

study during Days 7-10. 

B. BODY WEIGHT AND WEIGHT GAIN: Body weight and body weight gain data for the 

androgen agonist assay are presented in Table 2. There were no differences in body weights 

of the pronamide treated groups compared to the control. However, body weight gains were 

decreased (p<0.05) by 78% for Days 1-4 and by 47% for Days 1-7 in the high-dose group, 

although the overall body weight grain (Day 1-11) for the high-dose group was comparable 

to the control. As expected, the positive TP control group had an overall increase in body 

weight gain of 23% compared to the control. 

TABLE 2. Group Mean Body Weights and Cumulative Body Weight Gains (g) in the Androgen Agonist 

Assaya

Study Day #

Dose (mg/kg/day)

Vehicle 

Control

Positive Control

Vehicle + TP (0.4) Pronamide (40) Pronamide (200) Pronamide (1000)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 7 223.9 8.5 7 221.3 12.9 7 225.5 7.1 7 229.5 12.6 7 225.7 5.4

4 7 241.6 11.1 7 246.6 15.7 7 244.7 9.1 7 240.2 15.4 7 229.5 11.1

7 7 262.3 14.1 7 271.2 18.3 7 266.0 11.7 7 267.8 19.7 7 246.0 12.2

11 7 290.7 18.8 7 303.6 19.1 7 293.8 15.8 7 298.5 21.6 6 279.3 16.7

BWG 

(Days 1-4)

7 17.8 3.7 7 25.2*

(↑42)

5.2 7 19.2 3.5 7 10.6 7.1 7 3.9*

(↓78)

8.7

BWG

(Days 1-7)

7 38.4 7.0 7 49.9*

(↑30)

10.3 7 40.4 6.5 7 38.3 8.2 7 20.3*

(↓47)

8.6

BWG

(Days 1-11)

7 66.9 12.4 7 82.2*

(↑23)

12.5 7 68.3 10.8 7 69.0 9.8 6 53.6 13.5

a Data were obtained from Table 4 on pages 48-49 and Table 5 on pages 53-54 of the study report. Percent 

differences from vehicle controls, calculated by the reviewers, are included in parentheses.

N Number of animals in the group

SD Standard Deviation

* Significantly different from controls at p<0.05

Body weight and body weight gain data for the anti-androgen assay are presented in Table 

3. Body weights in the low- and mid-dose groups were comparable to the TP control, but 

body weights in the high-dose group were decreased (p<0.05) by 11% and 9% on Days 7 

and 11, respectively. Initially (Days 1-4), body weight gains were decreased by 38 and 77% 

in the mid- and high-dose groups, and the reduction in weight grain was maintained in the 

high-dose group, in which the overall (Days 1-11) weight grain was reduced by 38% 

compared to the control. 

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TABLE 3. Group Mean Body Weights and Cumulative Body Weight Gains (g) in the Anti-Androgen Assaya

Study Day #

Dose (mg/kg/day)

Vehicle Control 

+ TP (0.4)

Positive Control

TP + FT (0.4 + 3)

Pronamide + TP

(40 + 0.4)

Pronamide + TP

(200 + 0.4)

Pronamide + TP

(1000 + 0.4)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 7 221.3 12.9 7 223.6 11.5 7 225.2 9.8 7 223.5 11.8 7 226.5 6.7

4 7 246.6 15.7 7 243.4 7.9 7 249.4 11.2 7 239.2 11.6 7 232.3 11.6

7 7 271.2 18.3 7 265.8 12.6 7 276.2 13.7 7 268.8 14.6 7 241.1*

(↓11)

16.6

11 7 303.6 19.1 7 293.7 14.4 7 306.4 17.0 7 301.3 16.3 7 277.7*

(↓9)

14.9

Body Weight 

Gain (Days 1-4)

7 25.2 5.2 7 19.8 10.0 7 24.2 3.1 7 15.7*

(↓38)

4.0 7 5.8*

(↓77)

9.9

Body Weight 

Gain (Days 1-7)

7 49.9 10.3 7 42.2 7.5 7 50.9 5.4 7 45.3 8.3 7 14.6*

(↓62%)

15.6

Body Weight 

Gain 

(Days 1-11)

7 82.2 12.5 7 70.0 9.2 7 81.1 9.3 7 77.8 11.0 7 51.2*

(↓38)

14.3

a Data were obtained from Table 4 on pages 50-51 and Table 5 on pages 55-56 of the study report. Percent 

differences from negative controls, calculated by the reviewers, are included in parentheses.

N Number of animals in the group

SD Standard Deviation

* Significantly different from controls at p<0.05

C. FOOD CONSUMPTION: Food consumption data for the androgenic assay are presented 

in Table 4. In the mid-dose group, food consumption was decreased (p<0.05) by 11% 

during Days 1-4, but was increased (p<0.05) by 9% for Days 4-7. In the high-dose group, 

food consumption was decreased (p<0.05) by 27% during Days 1-4. Food consumption was 

increased (p<0.05) in the positive control group on Days 4-7 (↑9%) and Days 7-11 (↑8%). 

TABLE 4. Food Consumption (g/animal/day) in the Androgen Agonist Assaya

Study Day 

Interval

Dose (mg/kg/day)

Vehicle Control Positive Control

Vehicle + TP (0.4) Pronamide (40) Pronamide (200) Pronamide (1000)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1-4 7 19.8 0.9 7 20.9 0.2 7 20.3 0.7 7 17.7*

(↓11)

1.8 7 14.5*

(↓27)

1.6

4-7 7 20.6 0.9 7 22.5*

(↑9)

0.9 7 21.7 0.7 7 22.5*

(↑9)

1.6 7 19.6 0.8

7-11 7 21.4 1.0 7 23.2*

(↑8)

1.1 7 21.8 1.3 7 22.2 1.6 7 20.1 3.2

a Data were obtained from pages 58 and 59 of the study report. Percent differences from vehicle controls, 

calculated by the reviewers, are included in parentheses.

N Number of animals in the group

SD Standard Deviation

* Significantly different from controls at p<0.05

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Food consumption data for the anti-androgen assay are presented in Table 5. In the lowdose group, food consumption was decreased (p<0.05) by 3% during Days 1-4. In the highdose group, food consumption was decreased (p<0.05) by 32% for Days 1-4, 25% for Days

4-7, and 10% for Days 7-11. Food consumption was also decreased (p<0.05) in the positive 

control (FT+TP) group on Days 1-4 (↓6%), Days 4-7 (↓13%), and Days 7-11 (↓14%). 

TABLE 5. Food Consumption (g/animal/day) in the Anti-Androgen Agonist Assaya

Study Day 

Interval

Dose (mg/kg/day)

Vehicle Control + 

TP (0.4)

Positive Control

TP + FT (0.4 + 3)

Pronamide + TP

(40 + 0.4)

Pronamide + TP

(200 + 0.4)

Pronamide + TP

(1000 + 0.4)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1-4 7 20.9 0.2 7 19.7*

(↓6)

0.9 7 20.2*

(↓3)

0.4 7 18.8 1.7 7 14.3*

(↓32)

2.8

4-7 7 22.5 0.9 7 19.5*

(↓13)

0.9 7 22.5 0.5 7 23.2 1.4 7 16.9*

(↓25)

1.7

7-11 7 23.2 1.1 7 19.9*

(↓14)

0.7 7 22.2 0.6 7 22.6 1.0 7 20.9*

(↓10)

0.4

a Data were obtained from pages 60 and 61 of the study report. Percent differences from negative controls, 

calculated by the reviewers, are included in parentheses.

N Number of animals in the group

SD Standard Deviation

* Significantly different from controls at p<0.05

D. ORGAN WEIGHTS: Weights for the accessory sex organs, adrenal glands, kidneys, and 

liver from the androgen agonist assay are presented in Table 6. Absolute liver weights were

increased (p<0.05) by 56 and 125% in the mid- and high-dose groups, respectively, and 

adrenal gland weight was increased (p<0.05) by 35% in the high-dose group. No 

differences were observed in kidney weights, and the weights of all androgen-sensitive 

tissues in the pronamide-treatment groups were similar to the control. 

Rats in the positive control (vehicle + TP) group had accessory sex organ weight increases 

(p<0.05) as follows: 446% in Cowper’s glands; 71% in glans penis; 187% in LABC; 533% 

in ventral prostate; and 1211% in the seminal vesicles with coagulating glands. 

The guideline performance criteria for the androgenic assay were met for the control and 

high-dose groups. 

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TABLE 6. Accessory Sex Organ Weights from Androgen Agonist Assay in Sprague Dawley Ratsa

Organ

Dose (mg/kg/day)

Vehicle Control

(Methocel with corn oil)

Positive Control

Vehicle + TP (0.4) Pronamide (40) Pronamide (200) Pronamide (1000)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

Liver (g) 7 11.2 1.2 11 7 12.3 1.5 12 7 12.7 1.3 10 7 17.5*

(↑56) 2.3 13 6 25.2*(↑125) 2.4 10

Adrenal 

glands (g) 7 0.0614 0.006 10 7 0.0542 0.010 18 7 0.0610 0.005 8 7 0.0692 0.007 10 6 0.0826*

(↑35) 0.015 18

Kidneys (g) 7 1.9 0.144 8 7 2.0177 0.224 11 7 2.1147 0.175 8 7 2.1203 0.256 12 6 2.1011 0.164 8

Cowper’s

glands (g) 7 0.0056 0.002 29 6 0.0316*

(↑464)

0.008

6 27 7 0.0060 0.001 23 7 0.0056 0.001 20 6 0.0030 0.001 47

Glans penis 

(g) 6 0.052 0.005 10 6 0.0890*

(↑71) 0.014 16 6 0.0529 0.006 11 7 0.0566 0.008 14 6 0.0557 0.012 22

LABC (g) 7 0.1393 0.020

6 15 7 0.4002*

(↑187) 0.033 8 7 0.1379 0.031 23 7 0.1392 0.037 27 6 0.1136 0.025 22

Ventral 

prostate (g) 7 0.0246 0.007 29 6 0.1556*

(↑533) 0.021 13 7 0.0184 0.006 34 7 0.0193 0.008 41 4 0.0154 0.007 44

Seminal 

vesicles (g) b 7 0.0317 0.006 17 7 0.4155*(↑1211) 0.033 8 7 0.0335 0.007 20 7 0.0326 0.010 29 6 0.0322 0.006 17

a Data were obtained from Table 7 on pages 63-64 of the study report. Percent differences from vehicle controls, calculated by 

the reviewers, are included in parentheses.

b Seminal vesicles with coagulating glands.

N Number of animals in the group

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from controls at p<0.05

Weights for the accessory sex organs, adrenal glands, kidneys, and liver from the antiandrogen assay are presented in Table 7. As seen in the androgenic assay, absolute liver 

weights were increased (p<0.05) in the mid- and high-dose groups by 49 and 102%, 

respectively, and adrenal gland weight was increased (p<0.05) by 59% in the high-dose 

group. No differences were observed in kidney weights for any groups and the weights of 

all androgen-sensitive tissues in the low-dose + TP group similar were to the TP control. In 

the mid-dose +TP group, the following decreases (p<0.05) occurred in three of the five 

androgen sensitive tissues: 22% in the LABC, 24% in ventral prostate, and 35% in seminal 

vesicles with coagulating gland. Decreases (p<0.05) in weight from the same three tissues 

were also observed in the high-dose + TP group: 51% in LABC, 50% in ventral prostate, 

and 42% in the seminal vesicles with coagulating glands. The decrease in weights for these 

three tissues was dose-dependent. 

Rats in the positive control (FT+TP) group had the expected decreases (p<0.05) in accessory 

sex organ weight as follows: 58% in Cowper’s glands; 25% in glans penis; 57% in LABC; 

74% in ventral prostate; and 81% in seminal vesicles with coagulating glands. 

The guideline performance criteria for the anti-androgen assay were met for the control 

group and for the glans penis and seminal vesicles in the high-dose group. However, the 

maximum permissible CV values specified in the Guideline were exceeded in the mid-dose 

+ TP group for the LABC (21% vs. 20% allowable), ventral prostate (44% vs. 40% 

allowable), and seminal vesicles (45% vs. 40% allowable), and in the high-dose + TP group 

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for the Cowper’s gland (42% vs. 35% allowable), the LABC (29% vs. 20% allowable), and 

ventral prostate (41% vs. 40% allowable). 

TABLE 7. Accessory Sex Organ Weights from Anti-Androgen Assay in Sprague Dawley Ratsa

Organ

Dose (mg/kg/day)

Negative Control

Vehicle + TP (0.4)

Positive Control

TP + FT (0.4 + 3)

Pronamide + TP

(40 + 0.4)

Pronamide + TP

(200 + 0.4)

Pronamide + TP

(1000 + 0.4)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

Liver (g) 7 12.3 1.5 12 7 12.0 1.2 10 7 13.3 1.2 9 7 18.3*

(↑49) 1.9 10 7 24.8*(↑102) 2.1 8 

Adrenal 

glands (g) 7 0.0542 0.010 18 7 0.0610 0.008 12 7 0.0564 0.011 19 7 0.0627 0.008 12 7 0.0861*

(↑59) 0.010 11

Kidneys (g) 7 2.0177 0.224 11 7 1.9225 0.177 9 7 2.1151 0.215 10 7 2.1523 0.090 4 7 2.0569 0.170 8 

Cowper’s

glands (g) 6 0.0316 0.009 27 7 0.0134*

(↓58) 0.005 38 7 0.0313 0.006 20 7 0.0279 0.008 27 7 0.0228 0.0096 42 b 

Glans penis 

(g) 6 0.0890 0.014 16 7 0.0670*

(↓25) 0.012 17 7 0.0897 0.011 12 7 0.0786 0.011 15 7 0.0796 0.0115 14 

LABC (g) 7 0.4002 0.033 8 7 0.1715*

(↓57) 0.044 26 7 0.3619 0.080 22 b 7 0.3116*(↓22) 0.065 21 b 7 0.1976*(↓51) 0.058 29 b 

Ventral 

prostate (g) 7 0.1556 0.021 13 7 0.0399*

(↓74) 0.017 43 7 0.1532 0.022 14 7 0.1182*(↓24) 0.052 44 b 7 0.0785*(↓50) 0.032 41 b 

Seminal 

vesicles (g) b 7 0.4155 0.033 8 7 0.0801*

(↓81) 0.048 60 7 0.3785 0.103 27 7 0.2712*(↓35) 0.123 45 b 7 0.2399*(↓42) 0.087 36

a Data were obtained from Table 7 on pages 65-66 of the study report. Percent differences from negative controls, calculated by the 

reviewers, are included in parentheses.

b CV values exceed the maximum allowable for the anti-androgenic assay specified in Guideline 890.1400.

c Seminal vesicles with coagulating glands.

N Number of animals in the group

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from controls at p<0.05

E. SERUM HORMONE CONCENTRATIONS: Serum testosterone data (as determined by 

RIA) for the anti-androgen assay are presented in Table 8. Although there were no 

significant changes in serum testosterone, the high level of variability in the data (CVs 47-

89%) and application of exogenous TP may have masked any treatment-related effects. 

Average testosterone concentration was increased by 47 and 14% for the low- and mid-dose 

groups and decreased by 50% in the high-dose group. 

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TABLE 8 . Hormone Measurement in the Anti-Androgen Assaya

Hormone

Dose (mg/kg/day)

Vehicle Control + 

TP (0.4)

Pronamide + TP

(40 + 0.4)

Pronamide + TP

(200 + 0.4)

Pronamide + TP

(1000 + 0.4)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

N Mean SD CV 

(%)

Serum 

Testosterone

(ng/mL)

7 0.36 0.18 50 7 0.53

(↑47)

0.25 47 7 0.41

(↑14)

0.26 63 7 0.18

(↓50)

0.16 89

a Data were obtained from page 68 of the study report. Percent differences from negative controls, calculated by 

the reviewers, are included in parentheses.

N Number of animals in the group

SD Standard Deviation

CV Coefficient of Variation

F. TESTOSTERONE METABOLITE FORMATION: The quantities of hydroxylated 

testosterone metabolites produced by liver microsomes in vitro are shown in Table 9. The 

microsomes were obtained from the control, mid-dose and high-dose groups for the 

androgenic assay. 

The hydroxylation of testosterone in the 16β-position was the most sensitive to treatment, 

based on the >2600% increase in this metabolite following pronamide treatment. In addition, 

there were significant dose-dependent increases in 6α-OHT (105 and 375%) and 6β-OHT (89 

and 92%) at both dose levels. 16α-OHT was also significantly increased at the mid-dose 

level (118%), but not at the high-dose; this biphasic response has been reported previously 

and may be due to an increase in CYP2B1 with a concurrent decrease in CYP2C11. In 

contrast, the formation of DHT and estradiol were decreased significantly (75-80%) at both 

doses of pronamide. 

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TABLE 9. Testosterone Metabolite Formation from Liver Microsomes from the Androgen Assay in 

Sprague Dawley Ratsa

Testosterone Metabolites 

(pmol/min/mg microsomal 

protein)

Dose (mg/kg/day)

Vehicle Control Pronamide (200) Pronamide (1000)

Mean SD Mean SD Mean SD

2α-hydroxytestosterone 

(2α-OHT) 275.1 129.0 214.1 47.1 261.4 49.1

6α-hydroxytestosterone

(6α-OHT) b 21.0 7.9 43.1*

(↑105) 4.3 99.8*(↑375) 21.2

6β-hydroxytestosterone

(6β-OHT) 488.5 286.3 922.0*

(↑89) 127.5 936.0*(↑92) 171.3

7α-hydroxy-testosterone 

(7α-OHT) 61.8 16.4 70.1 16.5 149.2*(↑141) 37.5

16α-hydroxytestosterone

(16α-OHT) 141.0 143.1 307.3*

(↑118) 112.6 253.3 50.1

16β-hydroxytestosterone

(16β-OHT) b 7.1 2.7 198.0*

(↑2689) 27.8 249.0*(↑3407) 41.4

Androgen 84.2 57.1 115.2 30.2 105.5 19.2

Dihydrotestosterone

(DHT) 837.7 533.8 165.6*

(↓80) 100.9 199.2*(↓76) 87.5

Estradiol 882.9 548.6 181.8*

(↓79) 117.5 223.7*(↓75) 103.3

a Data were obtained from Tables 3 and 4 on pages 33-34 of the study report. Percent differences from controls, calculated 

by the reviewers, are included in parentheses.

b Analysis was performed on square root transformed data.

SD Standard Deviation

* Significantly different from controls at p<0.05

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: Based on the lack of significant, treatment-related 

increases in two accessory sex tissue weights in the androgenic portion of the assay, 

pronamide at doses ≤1000 mg/kg/day was deemed negative for androgenic activity in the 

Hershberger assay. Based on significant decreases in three accessory sexual tissue weights 

in the anti-androgenic portion of the assay, the mid- and high-dose levels of pronamide were 

deemed positive for anti-androgenic potential. However, the significant increase in liver 

weight, apparent decrease in serum testosterone level, increased testosterone metabolism 

using hepatic microsomes from pronamide-treated animals, and lack of direct interaction 

with the androgen receptor indicate that the apparent anti-androgenic response was due to 

enhanced testosterone metabolism, resulting in decreased accessory sexual tissue weights. 

These data will require careful consideration in the pronamide weight-of-evidence (WoE) 

assessment for anti-androgenicity. There were no effects on androgen-sensitive endpoints at 

40 mg/kg/day pronamide. 

B. AGENCY COMMENTS: All animals survived until scheduled sacrifice on Day 11, with 

the exception of one rat in the high-dose group, which was found dead on Day 11. Based on 

clinical signs and necropsy data, this death was the result of an apparent gavage error that 

likely occurred early during the study (Day 2). There were no treatment-related clinical 

signs in animals dosed at ≤200 mg/kg/day in either assay, and the only clinical sign 

observed in the high-dose groups was periodic perineal (urine) soiling in three animals from

the androgenic assay and in one animal from the anti-androgenic assay. 

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In the androgen agonist assay, mean body weights of all pronamide-treated animals were 

similar to the control on Days 1, 4, 7 and 11 (sacrifice). In the high-dose group, body 

weight gains were decreased by 79% for Days 1-4 and 47% for Days 1-7. However, after 

inspection of individual body weights, with particular attention to the rat which died on Day

11 due to a gavage error (effects were seen beginning on Day 2), it is clear that this animal 

drove the low response as it lost weight over Days 1-4 and gained only 11 grams by Day 7. 

When this animal was excluded from analysis, the overall body weight grain (Days 1-11) 

for the high-dose group was similar to the control. Food consumption in the high-dose 

group was initially decreased (p<0.05) during Days 1-4, but not at the later intervals. In the 

mid-dose group, food consumption was slightly decreased (p<0.05) during Days 1-4, but 

was then slightly increased for Days 4-7. Absolute liver weights were increased (p<0.05) in 

a dose-dependent manner in the mid- and high-dose groups, and adrenal gland weights were 

also increased (p<0.05) in the high-dose group. There were no treatment-related effects on 

weight of any of the accessory sex organs at dose levels up to 1000 mg/kg/day. Animals in 

the positive TP control group showed the expected increases (p<0.05) in accessory sex 

organ weights. 

In the anti-androgen assay, body weights were decreased (p<0.05) on Days 7 and 11 in the 

high-dose group, but not in the mid- or low-dose groups. Body weight gains were also

initially decreased in the mid-dose group, but weight grains recovered by Day 11. In the 

high-dose group, body weight gains were decreased (p<0.05) at all intervals as was food 

consumption. Food consumption was also decreased (p<0.05) in the positive control group 

at all intervals. As in the androgenic assay, absolute liver weights were increased (p<0.05) 

in a dose-dependent manner in the mid- and high-dose groups, and adrenal gland weights 

were increased (p<0.05) in the high-dose group. No significant weight changes were 

observed in accessory sex tissues in the low-dose group or in the Cowper’s gland and glans 

penis in the mid- and high-dose groups. However, dose-dependent decreases (p<0.05) in 

weight were observed in the LABC, ventral prostate and seminal vesicles in the mid- and 

high-dose groups. In addition, animals in the positive TP+FT control group showed the 

expected increases (p<0.05) in accessory sex organ weights. There were significant, dosedependent decreases in three androgen-dependent tissues. 

Percent CVs for the vehicle control and the high-dose treatment groups for both assays were 

compared to the performance criteria in the Guidelines. In the androgenic assay, all %CV 

values were less than the maximum permissible values. In the anti-androgenic assay, the 

following values were greater than the maximum permissible values: Cowper’s glands in 

the high-dose group (CV - 42%, maximum permissible - 35%); LABC in the low-, mid- and 

high-dose groups – 21-29%, maximum permissible – 20%); ventral prostate in the mid- and 

high-dose groups (CV = 44% and 41%,respectively, maximum permissible 40%); and 

Seminal vesicles in the mid-dose group (CV – 45%, maximum permissible – 40%). These 

deviations do not interfere with the interpretation of the study as there was a significant 

effect in three target tissues in the anti-androgenic assay. 

The results of the microsomal assay support the conclusion that treatment with pronamide 

induces metabolic enzymes responsible for testosterone metabolism, which could possibly 

result in reduced testosterone levels and subsequent decreases in the weights of androgen 

sensitive tissues. However, the serum testosterone data from the anti-androgen assay do not 

Page 219 of 285
In vivo Hershberger Assay (2012)/ Page 17 of 17

PRONAMIDE /101701 OCSPP 890.1400/ OECD 441

clearly support this conclusion. Although there was an apparent 50% decrease (NS) in 

serum testosterone levels in the high-dose group, there was also an apparent 14% increase 

(NS) in serum testosterone in the mid-dose group, which also showed significant decreases 

in weights of androgen sensitive tissues. Due to the large within-group variability (CVs 47-

89%), the utility of the serum testosterone data is limited. 

Pronamide was administered at up to the limit dose (1000 mg/kg/day); at this dose, large 

increases were observed in liver (102-125%) and adrenal (35-59%) weights, and a 38% 

decrease in body weight gain was observed in the anti-androgen assay. 

Pronamide was negative for androgenic activity in the Hershberger assay 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, pronamide was positive for antiandrogenicity in the Hershberger assay as statistically significant decreases in organ weights 

were seen in three of the five androgen sensitive tissues in the androgen antagonist assay. 

C. STUDY DEFICIENCIES: None 

Page 220 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE)

Study Type: OCSPP 890.1450, Female Pubertal Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 3-14-2012 (MRID 48673402) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

CSS-Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer: Signature:

Michelle Sharpe-Kass, M.S. Date: 8/21/2012

Secondary Reviewer: Signature:

Scott D. Studenberg, Ph.D., D.A.B.T. Date: 8/27/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 8/30/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 8/30/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 221 of 285
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 222 of 285
PRONAMIDE I 101701 

Female Pubertal Assay (2012) I Page 1 of 16 

OCSPP 890.1450/ OECD None 

DATA EVALUATION RECORD 

STUDY TYPE: Female Pubertal Assay; OCSPP 890.1450; OECD None. 

PC CODE: 101701 DP BARCODE: D403723 

TXR#: 0056255 CAS No: 23950-58-5 

TEST MATERIAL (PURITY): Pronamide (96.2% .a.i.) 

SYNONYMS: 3,5-dichloro-N-(1, l-dimethyl-2-propynyl)benzamide; Propyzamide 

CITATION: Marty, M.S., Zablonty, C.L., Stebbins, K.E. (2012). Pronamide: Pubertal 

Development and Thyroid Function in Intact Juvenile/Peripubertal Female 

Crl:CD(SD) Rats. Toxicology & Environmental Research and Consulting, 

Midland, MI. Laboratory Report No.: 111080, June 21, 2012. MRID 

48673402. Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 

TEST ORDER#: CON-101701-37 

EXECUTIVE SUMMARY: In a Female Pubertal Assay (MRID 48673402), 16 Crl:CR(SD) 

rats/dose group were treated daily via oral gavage with pronamide (96.2% purity, Lot# 

XG1088R301 , TSN003588-0004) in 0.5% aqueous methylcellulose at doses ofO (vehicle), 25, 

100, or 300 mg/kg/day from post-natal day (PND) 22 to 42. Animals were examined for vaginal 

opening (VO) daily beginning on PND 22, and age and weight at day of attainment were 

recorded. Following sacrifice on PND 42, blood was collected for clinical chemistry and 

hormone analyses; total thyroxine (T 4) and thyroid stimulating hormone (TSH) levels were 

determined using a chemiluminescent immunoassay or a radioimmunioassay (RIA). Adrenal, 

liver, pituitary, thyroid, and urogenital organs were collected and weighed, and microscopic 

examinations were performed on the ovaries, uterus, adrenal, thyroid, and kidneys. 

All rats survived the 21-day test period with the exception of one animal in the mid-dose group. 

This animal appeared dehydrated, had urine soiling, soft feces, decreased activity, and partially 

closed eye lids on PND 23, and died spontaneously on PND 24. Tissues from this animal were 

moderately autolytic at necropsy and the probable cause of death could not be determined. 

Given the lack of a dose-response relationship and previous toxicity data for pronamide, this 

death was not considered treatment related. 

No treatment-related effects were observed on body weight, body weight gain, age or weight of 

at VO at any dose. Three high-dose animals failed to achieve VO by PND 42; however, all other 

Page 223 of 285
Female Pubertal Assay (2012) / Page 2 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

study animals achieved VO during the monitoring period. Decreased body weights/body weight 

gains may have contributed to the delays in VO because each of three affected animals weighed 

19-38% less on PND 34 than the mean control body weight at the time of VO (i.e., ≤88.2 g vs. 

109.3 g). 

Administration of pronamide did not change the day of first estrus compared to the control 

group. Animals exhibited similar cycle lengths and regularity. The majority of females in the 

300 mg/kg/day group were in diestrus at necropsy. 

There were dose-dependent increases in all liver weights at mid and high doses. At 100 

mg/kg/day, absolute, adjusted and relative liver weights were increased by 13-18%, with only the 

increase in relative weight being significant (p<0.05); however, at 300 mg/kg/day, all liver 

weights were increased (p<0.05) by 53-58%. Relative kidney weights were significantly 

increased at 100 and 300 mg/kg/day (6% and 7%, respectively); however, neither absolute nor 

adjusted kidney weights were affected. Given the minimal change in absolute weights and the 

lack of associated histopathological changes in the kidney, the toxicological significance of the 

increase in kidney weights is unclear. For the thyroid, both absolute and adjusted weights were 

significantly increased by 16-18% in the mid-dose and by 26-28% in the high-dose groups. 

These increases in thyroid weight are consistent with the observed increases in serum TSH levels 

and are considered treatment related. There were dose-dependent decreases (p≤0.05) in serum 

T4 concentrations at all dose levels of pronamide (↓25, 42, and 48%) and corresponding 

increases in serum TSH concentrations at all doses [↑69% (NS), low dose; ↑123 and 338% in the 

mid- and high-dose groups, respectively]. 

 

In addition to the changes in thyroid weight and hormone levels at the high dose, there were 

treatment-related decreases (p<0.05) in follicular colloid area (Grades 2-3) and increases in 

follicular cell height (Grades 3-4), compared to the control as well as the low- and mid-dose 

groups. The combination of these thyroid effects indicates a change in thyroid function in 

response to treatment with pronamide. 

Pronamide treatment also had a significant effect on adrenal histology. In both the mid- and 

high-dose groups, there was a very slight increase in hypertrophy of the zona fasciculate region 

and an increase in cortex vacuolization, with the incidence of both effects increasing with dose. 

No significant differences were observed in the ovaries or uterus, although at the high-dose the 

ovaries of several animals (4/16) were slightly juvenile in appearance and there was a slight 

decrease in uterus size for 2/16 animals. These findings in the ovaries and uterus were almost 

exclusively associated with the three high-dose animals that did not attain VO during the study. 

Based on the large increases in liver weight (53-58%) and the histological changes noted in the 

adrenal glands at 300 mg/kg/day, the high-dose used in this study was considered an appropriate

concentration to challenge the animals. 

 

The assay satisfies the EDSP Tier 1 Test Order requirements for a Female Pubertal Assay 

(OCSPP 890.1450). 

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

Assurance statements were provided. 

Page 224 of 285
Female Pubertal Assay (2012) / Page 3 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Toxicology& Environmental Research and Consulting

Location: Midland, Michigan

Study Director: Zablotny, C.L

Other Personnel: Woolhiser, M.R.; Manager

Marty, M.S.; Lead Scientist

Stebbins, K.E.; Pathologist

Mahan, H.M.; Quality Assurance

Gallagher, K.H.; Animal technician

Passage, J.K.; Reproductive technologist

Lawson, M.A.; Pathology data

Perala, A.W.; Analytical analyses

Hall, B.K.; Document management

Lacher, J.W.; Laboratory Veterinarian

McFadden, L.G.; Statistical analyses

Study Period: June 27, 2011 to June 21, 2012

2. Test Substance: Pronamide

Description: Not reported

Source: Dow AgroSciences, LLC, Indianapolis, IN

Lot/Batch #: XG1088R301, TSN003588-0004 (Expiration date not reported)

Purity: 96.2%

Stability: Not reported

CAS #: 23950-58-5

Structure:

Cl

Cl

O

N

H

CH3

CH3 CH

3. Vehicle: Aqueous Methylcellulose (0.5%)

4. Test Animals:

Species: Rat

Strain: Crl:CD(SD

Age/Weight at 

Study Initiation: PND22/ 39.0 to 62.2 g females only

Source: Charles River (Portage, MI)

Housing: 2/cage, plastic solid bottom cages with heat-treated laboratory grade, aspen wood shavings

Diet: Teklad Diet #2016, Harlan Laboratories, ad libitum

Phytoestrogen content <325 μg of genistein equivalents/gram diet

Water: Deionized water, ad libitum

Environmental 

Conditions:

Temperature:

Humidity:

Air changes:

Photoperiod:

22±1°C

40-70% 

12-15/hr

12 hrs light/12 hrs dark 

B. STUDY DESIGN

1. In-Life Dates: Start: July 1, 2011 End: July 22, 2011 

Page 225 of 285
Female Pubertal Assay (2012) / Page 4 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

2. Mating: Time-mated pregnant dams were received from the supplier such that they would 

all reach gestation day (GD) 21 on the same day; however, litters born on either gestation 

day 21 or 22 were used for the pubertal assay. Litters with more than 10 pups were 

standardized by culling on PND 4 to 10 pups per litter. 

3. Animal Assignment: Offspring were weaned on PND 21 and weighed. Animals were 

assigned such that mean body weights and variances for all groups were similar, to the test 

groups noted in Table 1. Littermates were not assigned to the same treatment group. 

TABLE 1. Study Designa

Test group Dose (mg/kg/day) # of Females

Control 0 16

Low 25 16

Middle 100 16

High 300 16

a Data were obtained from page 18 of the study report.

4. Dose Selection Rationale: The dose levels were selected based on the results from a 

screening study, a dietary study, a probe study, and a Hershberger assay. In a screening 

study, rats were treated for 3 days by oral gavage with pronamide doses of 0, 25, 100 or 

400 mg/kg/day in 0.5% methylcellulose1. Liver-to body weight ratios were increased in 

both sexes at the high dose. In a 2-week dietary study, pronamide was found to be an 

inducer of cytochrome P450 enzymes at 239.3 mg/kg/day2

. In a probe study, male rats were 

given 0 to 1000 mg/kg/day pronamide by gavage for 15 days from PND 30-44. Terminal 

body weights were decreased by 12-15% at pronamide doses ≥600 mg/kg/day without a 

strong dose-response relationship3

. There were marked increases in absolute and relative 

liver weights at doses ≥100 mg/kg/day, which partially masked body weight decreases. In 

the uterotrophic assay4

, groups of 6 immature female rats were exposed to 0, 25, 100 or 400 

mg/kg/day pronamide from PND 19-21. There were significant decreases in terminal body 

weights at all doses of pronamide. Body weight gains in pronamide-treated animals were 

decreased; however, there were no treatment-related effects on wet or blotted uterine 

weights at any dose level.

 

Based on the probe study a high dose of 300 mg/kg/day was selected for the female pubertal 

assay as this dose was expected to cause a statistically significant reduction in terminal body 

weight gain relative to the control animals, but not exceed a 10% change in terminal body 

weight.

 

1 Deckert, F. W. and Steigerwalt, R. B. (1979). KERBTM: Screening for hepatic enzyme induction via in vitro paranitroanisole demethylation after 3 day oral pretreatment of rats. Report of Toxicology & Environmental Research 

and Consulting, The Dow Chemical Company, Midland, Michigan.

2 Harada, T. (1996). Propyzamide: Hepatic drug-metabolizing enzyme induction study in mice and rats. Report of 

Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan. 3 Marty, M. S., Marshall, V. A., and Zhang, F. (In progress). Pronamide: Hershberger assay in castrated adult male 

Crl:CD(SD) rat. Report of Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 

Midland, Michigan 4 Marty, M. S., Brooks, K. J., and Jeong, YC. (2011). Pronamide: Uterotrophic assay in the immature females 

Crl:CD(SD) rat. Report of Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 

Midland, Michigan.

Page 226 of 285
Female Pubertal Assay (2012) / Page 5 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

5. Dose Preparation and Analysis: Dose formulations were prepared by mixing appropriate 

amounts of test substance with 0.5% aqueous methylcellulose. Homogeneity (top, middle, 

bottom) and achieved concentrations were tested for the low- and high-dose formulations, 

but only two samples were collected for the mid-dose formulation. The stability of 

pronamide in 0.5% aqueous methylcellulose at 0.250, 2.50 and 250 mg/ml was determined 

in a previous study for 12 days5. 

Results of Dose Analysis 

Homogeneity (%CV): 1.4% - 4.1% 

 

Stability: No data provided 

Concentration: 93.6 - 97.3% 

The analytical data indicated that the mixing procedure was adequate and that the variation 

between nominal and actual dosage to the animals was acceptable. 

6. Dosage Administration: All doses were administered once daily by gavage, from PND 22 

through PND 42, in a volume of 4.0 mL/kg of body weight. Dosing was performed at 

approximately the same time daily. Dose volume was adjusted daily based on individual 

body weights. 

7. Statistics: The following statistical analyses were performed. Statistical significance was 

reported when p<0.05. The analyses were considered appropriate. 

Parameter Statistical test

Initial Body weight, body weight gain (Except PND 22-

25) clinical chemistries (except alanine 

aminotransferase), mean cycle length, body weight at 

VO, age at first estrus, organ weights, organ-to-body 

weight ratios (liver, kidney, adrenal, and pituitary 

weights, and serum hormones.

Homogeneous data sets were analyzed using a twoway analysis of variance (ANOVA) with block and 

treatment as main effects, followed by pairwise 

comparisons using Dunnett’s two-tailed t tests.

Body weight at VO and organ weights (thyroid, ovaries, 

uterus)

Homogeneous data sets were analyzed using a twoway analysis of covariance (ANCOVA) with PND 

21 body weight as the covariable, followed by 

pairwise comparisons using Dunnett’s two-tailed t 

tests.

Cycling status and percent cycling regularly Chi-square analysis, followed by a Fisher’s exact 

test with a Bonferroni-Holm adjustment, if 

significant

BWG from PND 22-25, alanine aminotransferase, and 

age at VO.

Bartlett's test, followed by nonparametric KruskalWallis test and a Wilcoxon rank-sum test with a 

Bonefforoni-Holm adjustment for multiple 

comparisons to control

 

5 Dryzga, M. D., and Yano, B. L. (2005). Pronamide Technical: 28-Day dermal toxicity, study in F344/DuCrl rats. 

Report of Toxicology & Environmental Research and, Consulting, The Dow Chemical Company, Midland,

Michigan.

Page 227 of 285
Female Pubertal Assay (2012) / Page 6 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

C. METHODS

1. Mortality and Clinical Examinations: All animals were examined at least twice daily 

after dosing for mortality and moribundity. Clinical examinations were conducted after 

dosing. 

2. Body Weight: Animals were weighed daily prior to dosing, and body weights were 

statistically analyzed and reported for PND 21, 22, 25, 28, 32, 35, and 42. Body weight 

gains were also analyzed over the associated intervals beginning with PND 22-25, as well as 

for the overall dosing period (PND 22-42). 

3. Vaginal Opening (VO): Beginning on PND 22, all animals were examined daily for onset 

of VO. The appearance of a small “pin hole”, a vaginal thread, and complete vaginal 

opening were recorded. Age and weight on the day of completion of VO were recorded. 

However, if any animal within any group showed incomplete opening (persistent pin holes 

and/or threads) for greater than 3 days, a separate second analysis was conducted using the 

age at which incomplete opening was first observed. Examination of the females was 

continued daily until VO was present or until euthanasia. 

4. Estrous Cyclicity: Beginning on the day of VO, and up to and including the day of 

necropsy, daily vaginal smears were obtained and evaluated for the presence of leukocytes, 

nucleated epithelial cells, or cornified epithelial cells. The vaginal smears were classified as 

diestrus (predominance of leukocytes mixed with some cornified epithelial cells), proestrus 

(predominance of clumps of round, nucleated epithelial cells), or estrus (predominance of 

cornified epithelial cells). The age at first vaginal estrus was recorded. 

5. Sacrifice and Pathology: On the afternoon of PND 41, rats were transferred to the 

necropsy holding area to avoid transport on the day of necropsy, so as not to induce stressrelated responses in other animals which may affect hormone measurements. All surviving 

animals were sacrificed by sedation with isoflurane followed by exsanguination on PND 42 

approximately 2 hours post-dosing, and all necropsies were completed by 1300 hours. 

Blood from the trunk of the animals was collected immediately into serum separation tubes, 

processed by centrifugation, and stored at −80°C for subsequent hormone and clinical

chemistry evaluations. 

a. Hormone Analysis: TSH levels were determined by RIA, and total T4 concentrations were 

determined by chemiluminescent immunoassay, at WIL Research Laboratories, LLC in 

accordance with GLP requirements. Samples were assayed in duplicate with multiple 

quality control samples. 

b. Clinical Chemistry: The following CHECKED (X) parameters were examined.

Page 228 of 285
Female Pubertal Assay (2012) / Page 7 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

ELECTROLYTES OTHER

X Calcium X Albumin

X Chloride X Creatinine*

Magnesium X Urea nitrogen*

X Phosphorus X Total cholesterol

X Potassium X Globulins

X Sodium Glucose

ENZYMES X Total bilirubin

X Alkaline phosphatase (ALP) Total protein

Cholinesterase (ChE) Triglycerides

Creatine phosphokinase Serum protein electrophoresis

Lactic acid dehydrogenase (LDH) X A/G ratio

X Alanine aminotransferase (ALT/also SGPT)

X Aspartate aminotransferase (AST/also SGOT)

Sorbitol dehydrogenase (SDH)

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. The (XX) organs, in addition, were subjected to histological 

examination 

UROGENITAL OTHER

XX Ovaries (paired, without oviducts)*+ XX Thyroid*+

XX Uterus*+ X Liver*

XX Kidneys (paired)*+ XX Adrenals (paired)*

X Pituitary*

* Weights required based on Guideline 890.1450

+ Histopathological examination required based on Guideline 890.1450

All organs collected, except the thyroid/trachea and uterus were weighed prior to fixation. 

Paired organs (kidneys, adrenals, and ovaries) were weighed together. The uterus and 

cervix were separated from the vagina and weighed, and the uterus was reweighed following 

removal of the fluid in the lumen (blotted weight). 

The ovaries and uterus were fixed in 10% buffered formalin and stored in 70% ethanol prior 

to embedding. The thyroid (with parathyroid) and kidneys were fixed in 10% buffered 

formalin for at least 24 hrs. Following fixation, the thyroid was dissected from the trachea. 

All collected tissues were routinely processed into paraffin blocks, sectioned, stained with 

hematoxylin and eosin, and examined microscopically. 

One animal died on PND 24 prior to the scheduled necropsy. It was necropsied on the same 

day, and similar procedures were followed to examine for gross lesions, but no blood 

collection, recording of terminal body and organ weights, or histopathological examination 

was conducted. 

Page 229 of 285
Female Pubertal Assay (2012) / Page 8 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

II. RESULTS 

A. MORTALITY: All rats survived the 21-day test period with the exception of one animal 

in the mid-dose (100 mg/kg/day) group. This animal appeared dehydrated, had urine 

soiling, soft feces, decreased activity and partially closed eye lids on PND 23, and died 

spontaneously on PND 24. Tissues from this animal were moderately autolytic at necropsy 

and the probable cause of death could not be determined. All other rats survived until 

scheduled sacrifice.

B. CLINICAL SIGNS OF TOXICITY: No treatment-related clinical signs of toxicity were 

observed in animals for any dose groups. Clinical observations were limited to the mid-dose 

animal that died on PND 24 and one high-dose animal that exhibited urine soiling on PND 

25 only. 

C. GENERAL GROWTH AND VAGINAL OPENING: Body weights, body weight gains, 

and age and weight at day of attainment of VO are presented in Table 2. No treatmentrelated effects were observed on body weights, body weight gains, age of attainment of VO 

or weight at day of attainment at any dose. Females in the 300 mg/kg/day group gained 

96.0 g from PND 22-42 compared with 100.6 g in the control group during this interval; 

therefore, the high-dose animals weighed 95.4% of mean control body weight on PND 42. 

After adjustment for increased liver weight, terminal body weight and body weight gains in 

the high-dose group were 94.6 and 91.7% of control values, respectively, which more 

accurately reflected the overall growth differences. 

The mean age at VO for the control animals was PND 33.8 (adjusted value 33.7); whereas, 

the pronamide-treated animals ranged from PND 34.3-35.8 (adjusted values 34.3-35.8). 

Three high-dose animals failed to achieve VO by PND 42 (Animals #7192, #7194, and 

#7195), whereas all other study animals achieved VO during the monitoring period. 

The mean age at VO, body weight at VO, and final body weight in the control group were 

within the acceptable range of the performance criteria provided in the Guideline (890.1450). 

Page 230 of 285
Female Pubertal Assay (2012) / Page 9 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

TABLE 2. General Growth and Vaginal Opening (VO)a

Parameter 

Evaluated

Vehicle Control Pronamide

(25 mg/kg/day)

Pronamide

(100 mg/kg/day)

Pronamide

(300 mg/kg/day)

N Mean SD

CV 

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%)

Initial body weight

(PND 22; g) U 16 51.05 6.09 11.93 16 50.78 6.41 12.62 16 51.19 5.20 10.16 16 51.16 5.67 11.09

Body weight at 

vaginal opening 

(g)

U 16 109.28 10.98 10.05 16 107.56 13.76 12.79 15 109.01 14.23 13.06 13 110.79 14.31 12.91

A 16 109.76 2.741 NA 16 108.40 2.744 NA 15 108.92 2.826 NA 13 109.27 3.053 NA

Final body weight

(g)

U 16 151.66 13.30 8.77 16 143.29 16.21 11.31 15 147.94 17.78 12.02 16 147.19 21.43 14.56

A 16 151.77 3.428 NA 16 143.91 3.429 NA 15 147.26 3.542 NA 16 147.10 3.428 NA

Final body weight 

(% of control)

U NA NA NA NA NA 94.5 10.07 11.3 NA 97.5 11.7 12.0 NA 97.1 14.1 14.6

A NA NA NA NA NR NR NR NR NR NR NR NR NR NR NR NR

Body weight gain

(final – initial; g)

U 16 100.61 10.69 10.63 16 92.51 13.85 14.97 15 96.46 15.08 15.63 16 96.03 17.54 18.26

A NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR

Age at vaginal 

opening (PND)

U 16 33.8 1.5 4.4 16 34.3 1.4 3.9 15 34.3 1.6 4.6 16 35.8 4.1 11.4

A 16 33.7 0.41 NA 16 34.3 0.41 NA 15 34.3 0.43 NA 16 35.8 0.59 NA

Proportion unopened 

(#/N)

0 NA 0 NA 0 NA 3 NA

a Data were obtained from page 55 of the study report. Percent differences from controls, calculated by the reviewers, are included in 

parentheses.

U Unadjusted for body weight on PND 22

A Adjusted for body weight on PND 22

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

NA Not applicable

NR Not Required as part of the test guideline

D. ORGAN WEIGHTS: Organ weights at necropsy are presented in Table 3. There were

significant increases (p<0.05) in absolute, adjusted and relative liver weights (↑53-58%) at 

300 mg/kg/day and there was a significant increase of 18% in relative liver weight at 100 

mg/kg/day. Increases of 13-14% (NS) were also observed in absolute and adjusted liver 

weights at 100 mg/kg/day. All liver weights at 25 mg/kg/day were similar to the control. 

Relative kidney weights were increased (p<0.05) by 6 and 7%, respectively, at 100 and 300 

mg/kg/day; however, neither absolute nor adjusted kidney weights were statistically 

different from controls at these dose levels. Both absolute and adjusted thyroid weights 

were dose-dependently increased (p<0.05) in the mid-and high-dose groups by 16-18% and 

26-28%, respectively. There were no other significant, treatment-related effects on organ 

weights at any dose of pronamide. 

The unadjusted values for all organ weights in the control group were within the acceptable 

range of the performance criteria provided in the Guideline (890.1450).

Page 231 of 285
Female Pubertal Assay (2012) / Page 10 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

TABLE 3. Organ Weights at Necropsya

Organ

Vehicle Control Pronamide

(25 mg/kg/day)

Pronamide

(100 mg/kg/day)

Pronamide

(300 mg/kg/day)

N Mean SD

CV 

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%)

Liver

(g) U 16 6.89 0.81 11.68 16 6.69 0.94 14.13 15 7.86(↑14)

1.31 16.69 16 10.59*

(↑54)

1.77 16.73

A 16 6.90 0.294 NA 16 6.71 0.295 NA 15 7.83

(↑13)

0.304 NA 16 10.58*

(↑53)

0.294 NA

R 16 4.54 0.28 6.25 16 4.66 0.37 7.93 15 5.29*

(↑18)

0.33 6.28 16 7.18*

(↑58)

0.52 7.28

Kidneys

(g)

U 16 1.28 0.12 9.66 16 1.26 0.16 12.49 15 1.33 0.18 13.44 16 1.34 0.22 16.05

A 16 1.29 0.038 NA 16 1.26 0.038 NA 15 1.33 0.039 NA 16 1.34 0.038 NA

R 16 0.85 0.06 7.31 16 0.88 0.04 4.75 15 0.90*

(↑6)

0.05 6.07 16 0.91*

(↑7)

0.07 7.21

Pituitary

(mg)

U 16 8.1 0.9 11.3 16 7.2 1.1 15.2 15 7.3 1.1 14.8 16 7.6 1.6 21.1

A 16 8.1 0.29 NA 16 7.2 0.29 NA 15 7.3 0.30 NA 16 7.6 0.29 NA

R 16 5.3 0.7 13.4 16 5.0 0.5 10.3 15 4.9 0.6 12.6 16 5.1 0.7 12.9

Adrenals

(mg)

U 16 38.7 8.3 21.4 16 37.8 7.1 18.9 15 41.7 4.8 11.6 16 41.9 7.7 18.4

A 16 38.7 1.63 NA 16 38.0 1.63 NA 15 41.5 1.69 NA 16 41.9 1.63 NA

R 16 25.5 4.9 19.2 16 26.4 4.1 15.7 15 28.3 2.6 9.2 16 28.5 3.5 12.4

Ovaries

(mg)

U 16 57.4 8.6 15.0 16 57.0 9.6 16.8 15 57.2 9.6 16.7 16 54.5 17.9 32.8

A 16 57.5 2.92 NA 16 57.2 2.93 NA 15 57.0 3.02 NA 16 54.5 2.92 NA

Uterus, wet

(mg)

U 16 333.5 120.4 36.1 16 279.8 158.9 56.8 15 271.7 105.3 38.8 16 265.7 109.4 41.2

A 16 333.8 30.80 NA 16 281.5 30.81 NA 15 269.9 31.82 NA 16 265.4 30.80 NA

Uterus, 

blotted

(mg)

U 16 307.1 63.7 20.7 16 249.1 92.8 37.3 15 245.0 73.7 30.1 16 254.5 97.2 38.2

A 16 307.2 20.60 NA 16 249.9 20.61 NA 15 244.1 21.29 NA 16 254.4 20.60 NA

Thyroid, 

fixed

(mg)

U 16 8.7 1.5 17.2 15 8.9 1.4 15.8 15 10.3*

(↑18)

2.0 19.9 16 11.1*

(↑28)

1.9 17.1

A 16 8.8 0.39 NA 15 8.9 0.40 NA 15 10.2*

(↑16)

0.40 NA 16 11.1*

(↑26)

0.39 NA

a Data were obtained from page 58 of the study report. Percent differences from controls, calculated by the reviewers, are 

included in parentheses.

U Unadjusted for body weight on PND 22

A Adjusted for body weight on PND 22

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

R Organ-to-body weight ratio (relative to body weight) 

* Significantly different from controls at p<0.05.

E. ESTROUS CYCLICITY: Estrous cycle data are provided in Table 4. Administration of 

pronamide did not change the day of first estrus compared to the vehicle control group. The 

mean age at first estrus was PND 34.5 in control animals compared with PND 35.4, 34.7, and 

35.0 in the 25, 100 and 300 mg/kg/day pronamide groups, respectively. The age at vaginal 

estrus excluded values from the three high-dose animals that failed to achieve VO. Animals 

exhibited similar cycle lengths and regularity. The majority of females in the 300 mg/kg/day 

group were in diestrus at necropsy.

Page 232 of 285
Female Pubertal Assay (2012) / Page 11 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

TABLE 4. Estrous Cyclicitya

Treatment 

Groups N

Mean Age at 

First Vaginal 

Estrus (PND)

Mean Cycle 

Length 

(days) b

Cycling 

(%)

Regularly 

Cycling 

(%)

Cycle Status at Necropsy (# Females)

Diestrus Proestrus Estrus

Not 

Cycling

Vehicle Control 16 34.5 4.7 (n=15) 93.8 93.8 7 2 7 0

Pronamide

(25 mg/kg/day)

16 35.4 4.9 (n=13) 100.0 81.3 13 0 3 0

Pronamide

(100 mg/kg/day)

15 34.7 4.9 (n=12) 86.7 80.0 14 1 0 0

Pronamide

(300 mg/kg/day)

13 35.0 5.4 (n=10) 84.6 69.2 9 0 4 0

a Data were obtained from page 56 of the study report. Percent differences from controls, calculated by the reviewers, are 

included in parentheses.

b Cycle length was determined only for regularly cycling animals; the actual number of regularly cycling animals in each 

group is shown in parentheses. 

N Number of animals

F. CLINICAL CHEMISTRY AND HORMONE LEVELS: Mean hormone and clinical 

chemistry levels are presented in Table 5. Rats administered 300 mg/kg/day had a treatment 

related lower mean alkaline phosphatase activity (p≤0.05). Rats administered 100 or 300 

mg/kg/day had treatment-related higher mean phosphorus concentrations, which is a nonadverse effect as there were no corresponding histopathological alterations in the kidneys of 

rats administered 300 mg/kg/day. Rats administered 300 mg/kg/day had a statistically 

significant higher mean albumin concentration. 

There were dose-dependent decreases (p<0.05) in serum T4 at all dose levels of pronamide 

and corresponding increases in serum TSH, which were significant for the 100 and 300 

mg/kg/day dose groups. In the 25, 100 and 300 mg/kg/day groups, serum T4 levels were 

decreased by 25, 42, and 48%, respectively, and serum TSH levels were increased by 69, 

123 and 338%, respectively. 

The results for serum T4 in the control group were within the acceptable range of the 

performance criteria provided in the Guideline (890.1450). 

Page 233 of 285
Female Pubertal Assay (2012) / Page 12 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

TABLE 5. Hormone Levels and Clinical Chemistrya

Parameter

Evaluated

Vehicle Control Pronamide

(25 mg/kg/day)

Pronamide

(100 mg/kg/day)

Pronamide

(300 mg/kg/day)

N Mean SD

CV 

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%)

Hormones

Serum T4, 

Total

(μg/dL)

16 4.02 0.77 19.11 16 3.02*

(↓25) 0.36 11.92 15 2.34*

(↓42) 0.40 17.03 16 2.09*

(↓48) 0.20 9.74

Serum TSH

(ng/mL) 16 2.6 1.2 45.5 16 4.4(↑69) 4.7 107.1 15 5.8*(↑123) 2.1 37.1 16 11.4*(↑338) 4.1 35.7

Clinical Chemistry

Creatinine

(μmol/L) 16 0.14 0.05 35.6 16 0.18 0.04 22.2 15 0.17 0.06 34.3 16 0.16 0.05 32.8

Serum urea

nitrogen

(mg/dL)

16 15 2 17 16 15 3 18 15 15 3 21 16 15 3 17

Alkaline

phosphatase

(μ/L)

16 260 56 22 16 233 52 22 15 224 42 19 16 207*

(↓20) 47 23

ALT (μ/L) 16 48 10 22 16 51 6 12 15 52 8 15 16 54 14 26

AST (μ/L) 16 96 7 8 16 96 15 16 15 100 12 12 16 98 14 15

GGT (μ/L) 16 1.5 0.0 0.0 16 1.7 0.6 35.6 15 1.7 0.5 32.0 16 1.8 0.7 38.6

Albumin

(g/dL) 16 4.2 0.3 6.1 16 4.2 0.2 3.7 15 4.3 0.1 2.8 16 4.4*(↑5) 0.2 3.5

A/G Ratio 16 3.4 0.3 8.8 16 3.4 0.5 15.9 15 3.6 0.5 13.9 16 3.5 0.5 14.4

Cholesterol

(mg/dL) 16 87 17 20 16 88 18 21 15 84 18 21 16 88 20 23

Globulin

(g/dL) 16 1.3 0.1 8.6 16 1.3 0.2 13.5 15 1.2 0.2 13.9 16 1.3 0.2 14.7

Total

bilirubin

(mg/dL)

16 0.05 0.00 0.00 16 0.05 0.00 0.00 15 0.05 0.00 0.00 16 0.05 0.00 0.00

Total 

protein

(g/dL)

16 5.5 0.3 5.6 16 5.5 0.2 2.9 15 5.6 0.2 3.5 16 5.7 0.3 5.3

Sodium

(mmol/L) 16 143 1 1 16 143 1 1 15 143 2 1 16 143 2 1 

Potassium

(mmol/L) 16 4.9 0.4 7.5 16 4.9 0.4 7.3 15 5.1 0.5 8.9 16 4.9 0.5 9.2

Chloride

(mmol/L) 16 100 1 1 16 100 2 2 15 100 2 2 16 100 2 2 

Calcium

(mg/dL) 16 11.3 0.3 3.1 16 11.4 0.4 3.2 15 11.5 0.4 3.1 16 11.5 0.4 3.3

Phosphorus

(mg/dL) 16 8.8 0.7 7.7 16 8.9 0.6 6.7 15 9.5*(↑8) 0.7 7.8 16 9.6*(↑9) 0.9 9.1

a Data were obtained from page 57 of the study report. Percent differences from controls, calculated by the reviewers, are 

included in parentheses.

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from controls at p<0.05.

Page 234 of 285
Female Pubertal Assay (2012) / Page 13 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

G. HISTOPATHOLOGY: No treatment-related gross pathological alterations were observed 

at necropsy. The incidences of histopathological findings of the thyroid gland are presented 

in Table 6. Rats administered 300 mg/kg/day pronamide had treatment-related (p<0.05) 

decreases in follicular colloid area (Grades 2-3) compared to the control and the low- and 

mid-dose animals (Grades 3-5). Follicular cell height was also increased (p<0.05; Grades 3-

4) in the 300 mg/kg/day group compared to the vehicle control and the other pronamidetreatment groups (Grades 1-3). 

TABLE 6. Incidence of Histopathological Lesions of the Thyroid Glanda

Treatment Groups

Parameter Evaluated

Colloid Area Follicular Cell Height 

Gradeb Incidence Grade Incidence

O E O E

Vehicle Control

1 0 16 1 7 16

2 0 16 2 7 16

3 2 16 3 2 16

4 7 16 4 0 16

5 7 16 5 0 16

Pronamide

(25 mg/kg/day)

1 0 16 1 5 16

2 0 16 2 9 16

3 2 16 3 2 16

4 9 16 4 0 16

5 5 16 5 0 16

Pronamide

(100 mg/kg/day)

1 0 15 1 2 15

2 0 15 2 7 15

3 6 15 3 6 15

4 7 15 4 0 15

5 2 15 5 0 15

Pronamide

(300 mg/kg/day)

1 0 16 1 0* 16

2 7* 16 2 0* 16

3 9* 16 3 9* 16

4 0 16 4 7* 16

5 0 16 5 0 16

a Data were obtained from page 64 of the study report.

b Thyroid histopathology is graded 1-5 Follicular cell height, 1 = lowest, 5 = highest, and colloid area, 1 = most colloid 

5 = least colloid. 

See OECD No. 82 for reference.

O Number Observed

E Number Examined

* Significantly different from controls at p. < 0.05

The incidence of histopathological findings of the ovaries, uterus, and kidneys are presented 

in Table 7. There were no treatment-related findings in the kidneys, and no significant 

differences were observed in the ovaries or uterus, although at the high-dose, the ovaries of 

several animals (4/16) were slightly juvenile in appearance and there was a slight decrease 

in uterus size for 2/16 animals. However, a significant effect was observed on adrenal 

histology in both the mid- and high-dose groups. There was a very slight increase in 

hypertrophy of the zona fasciculate region and an increase in cortex vacuolization, with the 

incidence of both effects increasing with dose. 

Page 235 of 285
Female Pubertal Assay (2012) / Page 14 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

TABLE 7. Incidence of Histopathological Lesions of the Ovaries, Uterus and Kidneysa

Findings

Dose Level (mg/kg/day)

Vehicle Control Pronamide (25) Pronamide (100) Pronamide (300)

# Obs. # Exam. # Obs. # Exam. # Obs. # Exam. # Obs. # Exam.

Ovaries

Within Normal Limits 16 16 16 16 15 15 12 16

Juvenile Appearance (slight) 0 16 0 16 0 15 4 16

Uterus

Within Normal Limits 16 16 16 16 15 15 14 16

Decreased size (slight) 0 16 0 16 0 15 2 16

Kidney

Within normal limits 2 16 -- 0 -- 0 5 16

Degeneration; tubule; focal 

(very slight) 1 16 -- 0 -- 0 0 16

Degeneration; tubule; multifocal 

(very slight) 12 16 -- 0 -- 0 11 16

Cyst; cortex; tubule; focal 1 16 -- 0 -- 0 1 16

Inflammation; chronic; interstitium; 

multifocal (very slight) 2 16 -- 0 -- 0 1 16

Adrenal Glands

Within normal limits 12 16 10 16 2 15 0 16

Hypertrophy; zona fasciculate; 

(very slight) 0 16 1 16 5* 15 12* 16

Vacuolization; increased; cortex 

(very slight) 4 16 5 16 12* 15 16* 16

a Data were obtained from page 65 of the study report.

* Treatment-related

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS’ CONCLUSIONS: Based on the lack of significant changes in 

puberty onset, estrous cycle and reproductive organ weights, there was little evidence of 

altered estrogen status in this study, although three females in the 300 mg/kg/day group 

exhibited delayed development (delayed VO). Decreased T4, increased TSH, increased 

thyroid weights and altered thyroid histopathology (300 mg/kg/day only) suggest altered 

thyroid function at 100 and 300 mg/kg/day. Given the increase in relative liver weights at 

100 and 300 mg/kg/day and previous mode-of-action work, it is likely that pronamide is 

enhancing T4 clearance and thereby stimulating the hypothalamic-pituitary-thyroid axis. 

There were stress-mediated changes in adrenal histopathology at both the mid-and high-dose 

of pronamide. There was no evidence of endocrine activity for pronamide at 25 mg/kg/day. 

B. AGENCY COMMENTS: All rats survived the 21-day test period with the exception of 

one animal in the mid-dose group. This animal appeared dehydrated, had urine soiling, soft 

feces, decreased activity and partially closed eye lids on PND 23, and died spontaneously on 

PND 24. Tissues from this animal were moderately autolytic at necropsy, and the probable 

cause of death could not be determined. Given the lack of a dose-response relationship and 

previous toxicity data for pronamide, this death was not considered treatment related. 

No treatment-related effects were observed on body weights, body weight gains, age of 

attainment of VO or weight at day of attainment at any dose. Three high-dose animals 

failed to achieve VO by PND 42; whereas, all other study animals achieved VO during the 

monitoring period. Decreased body weights/body weight gains may have contributed to the 

Page 236 of 285
Female Pubertal Assay (2012) / Page 15 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

delays in VO because the three affected animals weighed 19-38% less on PND 34 than the 

mean control body weight at the time of VO. 

Administration of pronamide did not change the day of first estrus compared to the vehicle 

control group. Animals exhibited similar cycle lengths and regularity. The majority of 

females in the 300 mg/kg/day group were in diestrus at necropsy. 

There were dose-dependent increases in all liver weight parameters at 100 and 300 

mg/kg/day, with the increases being significant for all liver weight parameters at 300 

mg/kg/day and for relative liver weight at 100 mg/kg/day. Relative kidney weights were

also significantly increased at 100 and 300 mg/kg/day; however, neither absolute nor 

adjusted kidney weights were statistically different. Given the minimal change in absolute 

weights and the lack of associated histopathological changes in the kidney, the toxicological 

significance of the increase in kidney weights is unclear. For thyroid, both absolute and 

adjusted weights were significantly increased in the mid-and high-dose groups in a dosedependent manner. These increases in thyroid weight are consistent with the observed 

increases in serum TSH levels and are considered treatment related. There were no other 

significant, treatment-related on organ weights at any dose of pronamide. 

There were dose-dependent decreases (p≤0.05) in serum T4 at all dose levels of pronamide 

and corresponding increases in serum TSH at all doses, with the increases being significant 

at the mid- and high-dose levels. At 25, 100 and 300 mg/kg/day, serum T4 levels were 

decreased by 25, 42 and 48%, respectively, and serum TSH levels were increased by 69 

(NS), 123 and 338% respectively. Although serum T4 levels were significantly decreased at 

25 mg/kg/day, the effect is not considered toxicologically significant because there was no 

significant increase in TSH or thyroid weights, and no altered histopathology at this dose 

level. 

In addition, at the 300 mg/kg/day dose, there were treatment-related (p<0.05) decreases in 

follicular colloid area (Grades 2-3) and increases in follicular cell height (Grades 3-4), 

compared to the control as well as the low- and mid-dose groups. The combination of these 

thyroid effects indicates a change in thyroid function in response to treatment with 

pronamide. 

Pronamide treatment also had a significant effect on adrenal histology. In both the mid- and 

high-dose groups, there was a very slight increase in hypertrophy of the zona fasciculate 

region and an increase in cortex vacuolization, with the incidence of both effects increasing 

with dose. No significant differences were observed in the ovaries or uterus, although at the 

high-dose, the ovaries of several animals (4/16) were slightly juvenile in appearance and 

there was a slight decrease in uterus size for 2/16 animals. These findings in the ovaries and 

uterus were almost exclusively associated with the three high-dose animals that did not 

attain VO during the study. 

The large increases in liver weight (53-58%) and the histological changes noted in the 

adrenal glands of the animals in the 300 mg/kg/day group indicate that the high-dose was an 

adequate level to challenge the animals. 

Page 237 of 285
Female Pubertal Assay (2012) / Page 16 of 16

PRONAMIDE / 101701 OCSPP 890.1450/ OECD None

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

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

• No Certificate of Analysis was provided for pronamide. 

• The photoperiod was 12 hrs light/12 hrs dark instead of the Guideline recommendation 

of 14 hrs light/10 hrs dark. 

Page 238 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE)

Study Type: OCSPP 890.1500, Male Pubertal Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 3-28-2012 (MRID 48688001) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

CSS-Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

Rebecca L. Bryan, B.S. Date: 10/19/2012

Secondary Reviewer Signature:

Scott D. Studenberg, Ph.D., D.A.B.T. Date: 10/24/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 10/29/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 10/29/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 239 of 285
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 240 of 285
PRONAMIDE I 101701 

Male Pubertal Assay (2012) I Page 1 of 19 

OCSPP 890.1500 I OECD None 

DATA EVALUATION RECORD 

STUDY TYPE: Male Pubertal Assay; OCSPP 890.1500 

PC CODE: 101701 DP BARCODE: D405597 

TXR#: 0056255 CAS No: 23950-58-5 

TEST MATERIAL (PURITY): Pronamide (96.2% .a.i.) 

SYNONYMS: 3,5-dichloro-N-(l , l-dimethyl-2-propynyl)benzamide; Propyzamide 

CITATION: Marty, M.S., Andrus, A.K., Thomas, J. (2012). Pronamide: Pubertal 

Development and Thyroid Function in Intact Juvenile/Peripubertal Male Cr!: 

CD(SD) Rats. Toxicology and Environmental Research and Consulting, The 

Dow Chemical Company, Midland, MI. Laboratory Project Study ID No.: 

111081 ; August 31 , 2012. MRID 48688001. Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, Indiana 

TEST ORDER#: CON-101701-37 

EXECUTIVE SUMMARY: In two Male Pubertal Assays (MRID 48688001 ), 15 or 16 

Sprague Dawley Crl:CD(SD) male rats/dose group were treated daily via oral gavage with 

pronamide (96.2% purity, Lot No. XG 1088R301) in 0.5% aqueous methylcellulose from postnatal day (PND) 23 to 53 . The test doses included 0 (vehicle), 25, 100, and 300 mg/kg/day for 

Study 1 and 0 (vehicle), 2.5, 10, and 25 mg/kg/day for Study 2. Animals were examined for 

preputial separation (PPS) daily beginning on PND 30, and age and body weight on the day of 

attainment was recorded. Following sacrifice on PND 53, blood was collected for clinical 

chemistry and hormone analyses. Total serum testosterone, thyroxine (T4), and thyroid 

stimulating hormone (TSH) levels were analyzed by radioimmunoassay or chemiluminescent 

immunoassay. Liver, pituitary, adrenal and urogenital organs were weighed and examined 

macroscopically, and microscopic examinations were performed on the testes, epididymides, 

thyroid, and kidneys. 

All animals survived until scheduled termination. No treatment-related clinical signs of toxicity 

were observed in animals for any dose groups. During Study 1, the terminal body weights were 

significantly decreased by 11-12% for the 100 and 300 mg/kg/day dose groups, indicating overt 

toxicity at these dose levels. Therefore, the male pubertal assay was repeated with lower 

pronamide doses (:S25 mg/kg/day). For inter-study comparison, the data from the 25 mg/kg/day 

group from Study 1 was included in the study report; however, detailed data from the 100 or 300 

mg/kg/day groups were not reported. 

Page 241 of 285
Male Pubertal Assay (2012) / Page 2 of 19

PRONAMIDE / 101701 OCSPP 890.1500 / OECD None

In the 25 mg/kg/day group in Study 1, two animals did not achieve PPS. Terminal body weights 

were decreased by 7%, and body weight gain for PND 23 to 53 was decreased by 11% (no 

statistical analyses were conducted for Study 1 data). Adjustment for liver weight did not affect 

terminal body weight or body weight gain. The age at PPS was delayed by 4.7 days, compared 

to the control, and this increase is considered treatment-related and biologically relevant, as body 

weight at PPS was also increased by 9%. Relative liver weight was increased by 11% and 

absolute pituitary weight was decreased by 14%. Absolute thyroid weight was increased by 7%, 

but was within historical control range, and not considered treatment related. The absolute 

weights of the seminal vesicle + coagulating glands (with and without fluid) were decreased by 

38% and 26%, respectively, compared to the control. Absolute ventral prostate, dorsolateral 

prostate, and levator ani-bulbocavernosus muscle complex (LABC) weights were also decreased 

by 25, 23, and 20%, respectively, and absolute weights for the left and right epididymides were 

decreased by 11% and 12%, respectively. Serum testosterone was increased by 86%; however, 

the control testosterone value was atypically low compared to the historical control range, and 

the difference was reported as incidental. T4 concentration was decreased by 32% and TSH was 

increased by 46%. Cholesterol levels were also decreased by 14%, but there were no doserelated effects for the other measured clinical chemistry parameters. There were no dose-related 

effects on the weights of kidneys, adrenals, or testis. No treatment-related changes were 

observed in the histopathology of the thyroid, right testes, right epididymides, or kidneys. 

In Study 2, no treatment-related effects were observed on body weight, body weight gain, or age 

and weight at PPS at any dose of pronamide (up to 25 mg/kg/day; high dose). There were 

increases (p≤0.05) in absolute, adjusted and relative liver weights (↑10-14%) at 25 mg/kg/day. 

Absolute and adjusted thyroid weights at 10 and 25 mg/kg/day were increased (not significant, 

NS) by 5 and 12%, respectively. There were no significant, treatment-related effects on kidneys, 

adrenals or accessory sex tissue weights at any dose of pronamide. However, minor decreases of 

4-6% (NS) were noted in four of the androgen sensitive tissues in the 25 mg/kg/day group, with 

no effect on serum testosterone concentration. Serum T4 concentrations in the 10 and 25 

mg/kg/day dose groups were decreased (p≤0.05) by 13 and 23%, respectively. In addition, 

serum TSH was increased by 25% (NS) and 62% (p≤0.05) at 10 and 25 mg/kg/day, respectively. 

Thyroid histopathology showed a slightly higher incidence of taller follicular epithelial cells 

(Grade 4) with corresponding smaller colloid areas (Grade 2) at the high dose compared to 

control (5 to 1, respectively). Serum albumin was increased (p≤0.05) by 5% and cholesterol was 

decreased (p≤0.05) by 15% at 25 mg/kg/day, with no dose-related effects for the other clinical 

chemistry parameters. No treatment-related changes were observed in the histopathology of the 

right testes, right epididymides, or kidneys. 

The effects observed in both studies on T4 and TSH concentrations, and thyroid histopathology 

in Study 2, indicate a change in thyroid function in response to treatment with pronamide at 

25 mg/kg/day. Although the 25 mg/kg/day dose group tested in Study 2 did not reproduce the 

effects on age and body weight at PPS, or accessory sex tissue weights observed at 25 mg/kg/day 

during Study 1, liver weight changes at 25 mg/kg/day were consistent between both studies. 

The 25 mg/kg/day dose (Study 1 low dose; Study 2 high dose) was considered an adequate high 

dose based on the ≥10% increase in liver weights in Study 2, and because the next highest-tested 

dose (100 mg/kg/day) yielded >10% decreases in terminal body weight in Study 1. 

Page 242 of 285
Male Pubertal Assay (2012) / Page 3 of 19

PRONAMIDE / 101701 OCSPP 890.1500 / OECD None

The assay satisfies the EDSP Tier 1 Test Order requirements for a Male Pubertal Assay (OCSPP 

890.1500). 

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

Assurance statements were provided. 

Page 243 of 285
Male Pubertal Assay (2012) / Page 4 of 19

PRONAMIDE / 101701 OCSPP 890.1500 / OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Toxicology and Environmental Research and Consulting

Location: Midland, MI. 

Study Director: A.K. Andrus

Other Personnel: M.S. Marty, Lead Scientist

J.Thomas, Pathologist

Study Period: July 1, 2011 to August 31, 2012

2. Test Substance: Pronamide (Propyzamide)

Description: Not reported (CoA not provided)

Source: Dow AgroSciences, LLC, Indianapolis, IN

Lot #: XG1088R301, TSN003588-0004 (Expiration date not reported)

Purity: 96.2%

Stability: Not reported

CAS #: 23950-58-5

Structure:

Cl

Cl

O

N

H

CH3

CH3 CH

3. Vehicle: Aqueous Methylcellulose (0.5%)

4. Test Animals:

Species:

Rat (males only)

Strain:

Sprague Dawley Crl:CD(SD)

Age/Weight at Study 

Initiation:

PND 23/ 37.4 – 64.9 g 

Source: Charles River Laboratories, Inc., Portage, MI

Housing: 2 animals/cage in plastic solid bottom cages with heat-treated, aspen wood shavings (Harlan 

Laboratories, Inc., Indianapolis, IN)

Diet: Teklad Diet #2016 (Harlan Laboratories, Inc.), ad libitum

Total genistein equivalents <325 μg/g diet

Water: Deionized water, ad libitum

Environmental 

Conditions: Temperature:

Humidity:

Air changes:

Photoperiod:

22±1°C (with a permissible excursion of ±3)

40–70% 

10–15 times/hr

12-hr light/dark (with exception of unverified dates June 7 and June 

29-July 10, 2011) 

B. STUDY DESIGN

1. In-Life Dates: Study 1: Start: July 2-3, 2011 End: August 1-2, 2011 

 Study 2: Start: February 27-28, 2012 End: March 28-29, 2012 

Page 244 of 285
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2. Mating: Time-mated pregnant nulliparous dams were received from the supplier on 

Gestation Day 5-10 and allowed to deliver their pups naturally. Litters with more than 10

pups were standardized by culling on PND 4 to 10 pups per litter with equal numbers of 

males and females whenever possible. 

3. Animal Assignment: Animals were weaned on PND 21 and weighed. Animals were 

assigned to dose groups such that the mean body weights (and variances) were similar 

among the test groups noted in Table 1, and the assignment of littermates to the same 

treatment group was avoided. During Study 1, overt toxicity occurred at 100 and 300 

mg/kg/day based on decreased terminal body weights (↓11-12%). A second test, Study 2, 

was conducted at lower test concentrations.

TABLE 1. Study Designa

Test group Dose (mg/kg/day) # of Males

Study 1

Control 0 15

Low 25 15

Mid 100b 15

High 300b 15

Study 2

Control 0 16

Low 2.5 16

Mid 10 16

High 25 16

a Data were obtained from page 21 of the study report.

b Results for the 100 and 300 mg/kg/day dose groups were not included with this report.

4. Dose Selection Rationale: The dose levels were selected based on the results from a 

screening study, a dietary study, a probe study, a Hershberger assay and an uterotrophic 

assay. In a screening study, rats were treated for 3 days by oral gavage with pronamide 

doses of 0, 25, 100 or 400 mg/kg/day in 0.5% methylcellulose1

. Liver-to body weight ratios 

were increased in both sexes at the high dose. In a 2-week dietary study, pronamide was 

found to be an inducer of cytochrome P450 enzymes at 239.3 mg/kg/day2. In a probe study, 

male rats were given 0 to 1000 mg/kg/day pronamide by gavage for 15 days from PND 30-

44 (48673401.DER). Terminal body weights were decreased by 12-15% at pronamide 

doses ≥600 mg/kg/day without a strong dose-response relationship. There were marked 

increases in absolute and relative liver weights at doses ≥100 mg/kg/day, which partially 

masked body weight decreases. In the uterotrophic assay (48619108.DER), groups of 6 

immature female rats were exposed to 0, 25, 100 or 400 mg/kg/day pronamide from PND 

19-21. There were significant decreases in terminal body weights at all doses of pronamide. 

Body weight gains in pronamide-treated animals were decreased; however, there were no 

treatment-related effects on wet or blotted uterine weights at any dose level.

 

1 Deckert, F. W. and Steigerwalt, R. B. (1979). KERBTM: Screening for hepatic enzyme induction via in vitro para-nitroanisole 

demethylation after 3 day oral pretreatment of rats. Report of Toxicology & Environmental Research and Consulting, The Dow 

Chemical Company, Midland, Michigan. 2 Harada, T. (1996). Propyzamide: Hepatic drug-metabolizing enzyme induction study in mice and rats. Report of Toxicology & 

Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan.

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Based on the probe study a high dose of 300 mg/kg/day was selected for Study 1 of the male 

pubertal assay as this dose was expected to cause a statistically significant reduction in 

terminal body weight gain relative to the control animals, but not exceed a 10% change in 

terminal body weight. 

However, overt toxicity occurred during Study 1 based on reductions of 11-12% in terminal 

body weight at 100 and 300 mg/kg/day, compared to the control. The test concentrations 

were reduced during Study 2 and included 2.5, 10, and 25 mg/kg/day dose groups. Data 

from the 25 mg/kg/day dose group of Study 1 are also included in the results. 

5. Dose Preparation and Analysis: Dose formulations were prepared by mixing appropriate 

amounts of test substance with 0.5% aqueous methylcellulose. Homogeneity (top, middle, 

bottom) and achieved concentrations were tested for the low- and high-dose formulations. 

The stability of pronamide in 0.5% aqueous methylcellulose at 0.250, 2.50 and 250 mg/mL 

was determined in a previous study for 12 days3. 

Results of Dose Analysis 

Homogeneity (% R.S.D.): 1.3 to 1.5% 

Stability: Stable for ≥12 days (data not provided) 

Concentration (% nominal): 93.0 to 102.8% 

The analytical data indicated that the mixing procedure was adequate and that the variation 

between nominal and actual dosage to the animals was acceptable. 

6. Dosage Administration: All doses were administered once daily by gavage, from PND 23 

through PND 53, in a volume of 4 mL/kg of body weight. Dose volumes were adjusted 

based on the individual daily body weights.

7. Statistics: Mean values were presented with standard deviations and coefficient of 

variation. The following statistical scheme was used:

Classification Procedure

Body weight

Body weight gain

Clinical chemistries

Age at PPS

Body weight at PPS

Organ weights

Organ-to-body weight ratios (liver, kidney, adrenal 

and pituitary weights)

Serum hormones

A Bartlett’s test was conducted to check for 

homogeneity of variance (p=0.01). 

Two-way analysis of variance (ANOVA) with block 

and treatment as main effects was performed.

When significant dose effects were determined in the 

two-way ANOVA at p = 0.05, then individual dose 

groups were compared to controls with Dunnett's test 

at p = 0.05 (experiment-wise error).

 

3 Dryzga, M. D., and Yano, B. L. (2005). Pronamide Technical: 28-Day dermal toxicity, study in F344/DuCrl rats. Report of 

Toxicology & Environmental Research and, Consulting, The Dow Chemical Company, Midland, Michigan.

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Classification Procedure

Age and body weight at PPS

Organ weights

A Bartlett’s test was conducted to check for 

homogeneity of variance (p=0.01). 

Analysis of covariance (ANCOVA) was conducted 

with body weight on PND 23 as the covariate. 

When the dose effect was significant at p = 0.05, least 

square means with a Dunnett’s correction was used to 

determine differences (experiment wise p = 0.05). 

When the ANCOVA was not statistically significant, 

a Dunnett’s test was performed.

Specific histopathologic observations Pair-wise Chi-square test with Yates' continuity 

correction (alpha = 0.05, two-sided)

Statistical outliers were identified by a sequential test (p = 0.02). Outliers and questionable 

data points (i.e., values due to technical errors) were excluded only for documented 

scientifically sound reasons. Histopathology results were not subjected to outlier tests. The 

statistical analyses were considered adequate.

C. METHODS

1. Mortality and Clinical Examinations: All animals were examined cage-side at least twice 

daily for mortality, morbundity, availability of food/water, and clinical abnormalities. In 

addition, clinical, hand-held examinations with each animal were conducted daily post-dose. 

2. Body Weight: Animals were weighed prior to allocation to dose groups (PND 21) and

daily prior to dosing. Body weights determined prior to dosing on PND 53 were used as the 

terminal body weights. Body weights were statistically analyzed on PND 21, 23, 26, 30, 37, 

42, 45, and 53; body weight gains were statistically analyzed beginning with the PND 23-26 

interval, followed by subsequent intervals, in addition to the entire dosing period (PND 23-

53). Body weights and body weight gains were adjusted for liver weights to remove the 

contribution of the pronamide-induced increases in liver weights.

3. Preputial Separation (PPS): Beginning on PND 30, all animals were examined daily for 

onset of PPS. Age and weight on the day of completion of PPS were recorded. 

Examination for the onset of puberty ceased with acquisition or on PND 53 if PPS was not 

yet acquired. If PPS was not acquired by PND 53, then PND 54 is used for the calculation 

of mean age of puberty onset. 

4. Sacrifice and Pathology: Animals were moved to the necropsy holding room on the 

afternoon of PND 52. All surviving animals were anesthetized with 5% isoflurane 

approximately 2 hours after the final dose (starting at approximately 0800 hours) on 

PND 53. Blood was collected immediately into serum separation tubes after cardiac 

puncture. Blood samples for hormone analysis were kept on ice, or refrigerated, until 

centrifugation, and stored at −80°C until subsequent hormone evaluations. Animals were 

euthanized by exsanguination, followed by decapitation. 

Groups were counter-balanced during necropsy, and necropsies were completed by 

1300 hours. A complete necropsy was performed on all animals. Page 247 of 285
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a. Hormone Analysis: Samples were sent on dry ice to WIL Research Laboratories, LLC 

(Ashland, OH) for analysis. TSH concentrations were analyzed by radioimmunoassay, and 

chemiluminescent immunoassays were used for total T4 and testosterone analyses. 

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 X Total cholesterol

X Potassium X Globulins

X Sodium Glucose

ENZYMES X Total bilirubin

X Alkaline phosphatase (ALP/also ALK) X Total protein

Cholinesterase (ChE) Triglycerides

Creatine phosphokinase Serum protein electrophoresis

Lactic acid dehydrogenase (LDH) X A/G ratio

X Alanine aminotransferase (ALT/also SGPT)

X Aspartate aminotransferase (AST/also SGOT)

Sorbitol dehydrogenase (SDH)

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. The (XX) organs, in addition, were subjected to histological 

examination.

UROGENITAL OTHER

XX Testes (left and right separately)*+ XX Thyroid*+

XX Epididymides (left and right separately)*+ 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*

XX Kidneys (paired)*+

* Weights required based on Guideline 890.1500

+ Histopathological examination required based on Guideline 890.1500

All organs except the thyroid/trachea and pituitary were weighed prior to fixation. The 

paired kidneys and adrenals were weighed together. The seminal vesicle with coagulating 

glands was weighed. After each side was cut sagittally to allow removal of the fluid in the 

lumen (blotted weight), the seminal vesicle was weighed again.

The gross lesions, adrenals, dorsolateral prostate, kidneys, levator ani-bulbocavernosus 

muscle, liver, pituitary, seminal vesicle with coagulating glands, thyroid, and ventral 

prostate were fixed in 10% phosphate-buffered formalin prior to embedding. After fixation, 

the thyroid was dissected from the trachea and weighed. All collected tissues were routinely 

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processed into paraffin blocks, sectioned, stained with hematoxylin and eosin, and examined 

microscopically. 

The testes and epididymides were placed in Bouin’s fixative for 24–72 hours, rinsed with 

50% ethanol, and stored in 70% ethanol prior to embedment in paraffin. For the qualitative 

assessment of the spermatogenesis stages, a cross-section from the center of the testes was 

embedded in paraffin, and stained with PAS/hematoxylin. The histopathological 

examination of the testes included a qualitative assessment of the stages of spermatogenesis; 

a qualitative assessment of the relationships between spermatagonia, spermatocytes, 

spermatids, and spermatozoa seen in cross sections of the seminiferous tubules; and 

identification of any degenerative changes (e.g., vacuolation of the germinal epithelium, a 

preponderance of Sertoli cells, sperm stasis, inflammatory changes, mineralization, and 

fibrosis). Examination of the intact epididymis included the caput, corpus, and cauda, 

accomplished by evaluation of a longitudinal section, and was conducted in order to identify 

such lesions as sperm granulomas, leukocytic infiltration (inflammation), aberrant cell types 

within the lumen, or the absence of clear cells in the cauda epididymal epithelium.

Two sections of each of the two 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. Other histopathological findings were graded as very slight, 

slight, moderate, or severe. 

For Study 1, the thyroid, right testes, and right epididymis of the control and 25 mg/kg/day 

groups and the right and left kidneys from the control animals were processed for 

histopathology findings. For Study 2, right and left kidneys, right testes, and right 

epididymis of the control and 25 mg/kg/day groups were processed for histopathology 

findings. The thyroids from all dose groups were processed in Study 2. 

II. RESULTS

A. MORTALITY: All animals survived until scheduled termination. 

B. CLINICAL SIGNS OF TOXICITY: No treatment-related clinical signs of toxicity were 

observed in animals for any dose groups. At 25 mg/kg/day in Study 1, one animal had

dermatitis (PND 53) and one animal had a muzzle laceration (PND 32-34). These 

observations were considered isolated and not related to treatment. 

C. GENERAL GROWTH AND PREPUTIAL SEPARATION: Body weight, body weight 

gain, age of attainment of PPS, and weight at day of PPS are presented in Tables 2a and 2b 

for Study 1 and 2, respectively. 

In the 25 mg/kg/day group in Study 1, two animals did not achieve PPS, and body weight at 

PND 23 was increased by 11% compared to control. Terminal body weights were 

decreased by 7%, but were within the historical range, and body weight gain for PND 23 to 

53 was decreased by 11%. The terminal body weights adjusted for liver weights were 

decreased by 7%, and body weight gains adjusted for liver weights were decreased (p<0.05) 

by 11%. The age at PPS was increased by 4.7 days compared to the control, and body 

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weight at PPS was increased by 9%. However, the data for age at PPS, and body weight at 

PPS for Study 1 were not statistically analyzed. 

In Study 2, no treatment-related effects were observed on body weight, body weight gain, or 

age and weight at PPS at any dose. 

The mean age at PPS, body weight at PPS, weanling weight, and final body weight in the 

control group were within the acceptable range of the performance criteria provided in the 

Guideline; however, the % CV for weight at PPS (Study 2) and final body weights (Studies 

1 and 2) were outside the acceptable range, as follows: 8.47% CV for weight at PPS in 

Study 2 (maximum 7.57%), 10.33% CV for final body weight in Study 1 (maximum 7.47%) 

and 8.74% CV for final body weight in Study 2 (maximum 7.47%). 

TABLE 2a. Study 1 General Growth and Preputial Separation (PPS) a

Parameter Evaluated

Vehicle Control Pronamide 

(25 mg/kg/day)

N Mean SD N Mean SD

Initial body weight

(PND 23; g) U 15 50.5 8.4 15 56.1 (↑11) 5.2

Body weight at PPS

(g)

U 15 195.8 14.8 13 212.9 (↑9) 18.3

A 15 NR NR 13 NR NR

Final body weight

(PND 53; g)

U 15 273.1 28.2 15 254.9 (↓7) 29.3

A 15 NR NR 15 NR NR

L 15 273.1 27.0 15 254.4 (↓7) 27.4

Body weight gain

(final – initial; g)

U 15 222.6 23.4 15 198.7 (↓11) 27.2

A 15 NR NR 15 NR NR

L 15 222.6 22.3 15 198.3* (↓11) 25.3

Age at PPS

(PND)

U 15 43.4 2.2 15 48.1 (↑11) 3.2

A 15 NR NR 15 NR NR

Proportion unseparated (#/N) 0/15 2/15

a Data were obtained from Tables 7, 9, 11, and 13 on pages 65, 67, 69, and 71 of the study report. No statistical 

analysis was performed. Percent differences from controls, calculated by the reviewers, are included in 

parentheses.

SD Standard deviation 

U Unadjusted for body weight on PND 23

A Adjusted for body weight on PND 23

L Adjusted for liver weights

N Number of animals examined 

NR Not reported

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TABLE 2b. Study 2 General Growth and Preputial Separation (PPS) a

Parameter Evaluated

Vehicle Control Pronamide

(2.5 mg/kg/day)

Pronamide

(10 mg/kg/day)

Pronamide

(25 mg/kg/day)

N Mean

SD/ 

SEb

CV 

(%) N Mean

SD/ 

SEb

CV 

(%) N Mean

SD/ 

SEb

CV 

(%) N Mean

SD/ 

SEb

CV 

(%)

Initial body weight

(PND 23; g) U 16 56.5 4.84 8.57 16 56.0 4.16 7.44 16 56.1 4.01 7.15 16 56.31 4.92 8.74

Body weight at PPS

(g)

U 16 201.6 17.1 8.47 16 198.8 10.7 5.38 16 198.1 20.0 10.1 16 204.7 15.7 7.68

A 16 201.2 3.66 NA 16 199.2 3.66 NA 16 198.3 3.66 NA 16 204.6 3.66 NA

Final body weight

(PND 53; g)

U 16 286.3 25.0 8.74 16 281.5 20.0 7.11 16 285.1 20.2 7.07 16 275.9 28.5 10.3

A 16 285.4 4.34 NA 16 282.4 4.34 NA 16 285.6 4.34 NA 16 275.5 4.34 NA

L 16 286.3 23.6 NR 16 281.9 18.9 NR 16 284.7 19.0 NR 16 274.6 27.0 NR

Final body weight

(% of control)

U 16 NA NA NA 16 98.3 7.0 7.1 16 99.6 7.0 7.1 16 96.4 9.9 10.3

A 16 NA NA NA 16 NR NR NR 16 NR NR NR 16 NR NR NR

Body weight gain

(final – initial; g)

U 16 229.9 21.2 9.21 16 225.6 18.0 7.96 16 229.0 18.5 8.07 16 219.6 25.1 11.4

A 16 NR NR NR 16 NR NR NR 16 NR NR NR 16 NR NR NR

L 16 229.9 19.7 NR 16 226.0 16.9 NR 16 228.6 17.3 NR 16 218.3 23.6 NR

Age at PPS

(PND)

U 16 43.2 1.3 3 16 43.1 1.5 3.4 16 43.2 1.6 3.6 16 44.3 1.7 3.8

A 16 43.2 0.32 NA 16 43.0 0.32 NA 16 43.2 0.32 NA 16 44.3 0.32 NA

Proportion unseparated 

(#/N) 0/16 0/16 0/16 0/16

a Data were obtained from Tables 12 and 14 on pages 70 and 72 of the study report. 

b Standard deviation (SD) reported for unadjusted values and standard error of the mean (SE) reported for adjusted values. 

U Unadjusted for body weight on PND 23

A Adjusted for body weight on PND 23

L Adjusted for liver weights

N Number of animals examined

CV Coefficient of Variation

NA Not applicable

NR Not reported

D. ORGAN WEIGHTS: Organ weights at necropsy from Studies 1 and 2 are presented in 

Tables 3a and 3b, respectively. 

In Study 1, organ weights were not statistically analyzed. However, relative liver weight 

was increased by 11% and absolute pituitary weights were decreased by 14% at 25 

mg/kg/day. In addition, the absolute weights of the seminal vesicle + coagulating glands 

(with and without fluid) were decreased by 38% and 26%, respectively. Absolute ventral 

prostate, dorsolateral prostate, and LABC weights were also decreased by 25%, 23%, and 

20%, respectively. Absolute weights for the left and right epididymides were decreased by 

11% and 12%, respectively. Absolute thyroid weights were increased by 7%, but were 

within historical control range. There were no dose-related effects on the weights of 

kidneys, adrenals, or testes. 

In Study 2, there were significant increases (p≤0.05) in absolute, adjusted and relative liver 

weights (↑10-14%) at 25 mg/kg/day. All liver weights at 2.5 and 10 mg/kg/day were similar 

to the control. Absolute and adjusted thyroid weights at 10 and 25 mg/kg/day were 

increased (NS) by 5 and 12%, respectively. There were no other significant, treatmentrelated effects on organ weights at any dose of pronamide. However, minor decreases of 4-

6% (NS) were noted in four of the androgen sensitive tissues. 

The unadjusted values for all organ weights in the control group were within the acceptable 

range of the performance criteria provided in the Guideline (890.1500) with the following 

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exceptions: (i) CV for seminal vesicles in Study 1 (32.78%; maximum 21.06%); (ii) mean 

thyroid weight in Study 1 (11.5 mg; acceptable range 14-26 mg); (iii) mean kidney weight 

in Study 1 (1.97 g; acceptable range 2.242-3.050 g); (iv) mean thyroid weight in Study 2 

(11.3 mg; acceptable range 14-26 mg); and (v) mean kidney weight in Study 2 (1.93 g; 

acceptable range 2.242-3.050 g) 

TABLE 3a. Study 1 Organ Weights at Necropsya

Organ Vehicle Control Pronamide 

(25 mg/kg/day)

N Mean SD N Mean SD

Liver (g) U 15 12.19 1.33 15 12.63 2.06

R 15 4.46 0.23 15 4.93 (↑11) 0.31

Kidneys (g) U 15 1.97 0.22 15 1.92 0.23

R 15 0.72 0.04 15 0.75 0.02

Pituitary (mg) U 15 10.0 1.1 15 8.6 (↓14) 1.2

R 15 3.7 0.3 15 3.4 0.2

Adrenals (mg) U 15 45.0 5.1 15 42.4 6.3

R 15 16.5 1.7 15 16.8 2.6

Seminal vesicles + coagulating glands, with

fluid (mg) U 15 467.3 153.2 15 288.6 (↓38) 102.0

Seminal vesicles + coagulating glands, without 

fluid (mg) U 15 222.8 54.8 15 165.1 (↓26) 48.5

Ventral prostate (mg) U 15 222.2 38.3 15 167.0 (↓25) 42.5

Dorsolateral prostate (mg) U 15 169.0 28.1 15 130.5 (↓23) 33.9

LABC (mg) U 15 487.0 74.5 15 388.0 (↓20) 85.5

Epididymis, left (mg) U 15 209.9 22.0 15 185.8 (↓11) 27.2

Epididymis, right (mg) U 15 216.1 25.4 15 189.8 (↓12) 26.7

Testis, left (mg) U 15 1435.9 172.8 15 1359.9 192.7

Testis, right (mg) U 15 1438.7 147.9 15 1356.2 192.9

Thyroid, fixed (mg) U 15 11.5 1.9 15 12.3 (↑7) 2.0

a Data were obtained from Table 17 on pages 78-79 of the study report. Adjusted organ weights were not reported. No 

statistical analysis was performed. Percent differences from Text Tables 6-9 on pages 42-46 are included in parentheses. 

The pituitary percent difference was calculated by the reviewers.

SD Standard deviation

U Unadjusted for body weight on PND 23

R Organ-to-body weight ratio (relative to body weight, g/100g bodyweight) 

N Number of animals examined

TABLE 3b. Study 2 Organ Weights at Necropsya

Organ

Vehicle Control Pronamide

(2.5 mg/kg/day)

Pronamide

(10 mg/kg/day)

Pronamide

(25 mg/kg/day)

N Mean

SD/ 

SEb CV 

(%) N Mean

SD/ 

SEb CV 

(%) N Mean

SD/ 

SEb CV 

(%) N Mean

SD/ 

SEb CV 

(%)

Liver

(g) U 16 13.2 1.61 12.2 16 12.8 1.25 9.79 16 13.6 1.34 9.82 16 14.5*(↑10) 1.75 12.0

A 16 13.1 0.31 NA 16 12.9 0.31 NA 16 13.6 0.31 NA 16 14.5*

(↑10) 0.31 NA

R 16 4.60 0.25 5.4 16 4.54 0.2 4.46 16 4.77 0.25 5.31 16 5.26*

(↑14) 0.31 5.88

Kidneys

(g)

U 16 1.93 0.21 10.7 16 1.95 0.23 11.7 16 2.02 0.15 7.61 16 1.98 0.22 10.9

A 16 1.92 0.04 NA 16 1.96 0.04 NA 16 2.02 0.04 NA 16 1.98 0.04 NA

R 16 0.67 0.03 4.86 16 0.69 0.05 7.39 16 0.71 0.05 7.4 16 0.72 0.06 7.73

Pituitary

(mg)

U 16 10.1 0.7 7.4 16 10.0 1.3 13.3 16 9.5 0.7 7.8 16 9.7 1.5 15.1

A 16 10.1 0.27 NA 16 10.0 0.27 NA 16 9.5 0.27 NA 16 9.7 0.27 NA

R 16 3.6 0.4 10.1 16 3.5 0.4 11.4 16 3.4 0.3 8.8 16 3.5 0.3 9.5

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TABLE 3b. Study 2 Organ Weights at Necropsya

Organ

Vehicle Control Pronamide

(2.5 mg/kg/day)

Pronamide

(10 mg/kg/day)

Pronamide

(25 mg/kg/day)

N Mean

SD/ 

SEb

CV 

(%) N Mean

SD/ 

SEb

CV 

(%) N Mean

SD/ 

SEb

CV 

(%) N Mean

SD/ 

SEb

CV 

(%)

Adrenals

(mg)

U 16 43.3 6.1 14.2 16 40.7 9.3 22.8 16 42.8 7.3 17.2 16 42.0 5.9 14.1

A 16 43.2 1.83 NA 16 40.8 1.83 NA 16 42.8 1.83 NA 16 42.0 1.83 NA

R 16 15.1 2.1 13.6 16 14.4 3 20.5 16 15 2.2 14.7 16 15.3 2.3 15

Seminal vesicles + 

coagulating glands, 

with fluid (mg)

U 16 625.7 91.5 14.6 16 627.6 136 21.6 16 604.8 121 19.9 16 599.9

(↓4) 161 26.8

A 16 623.3 31.0 NA 16 629.8 31.0 NA 16 606.0 31.0 NA 16 598.9 31.0 NA

Seminal vesicles + 

coagulating glands, 

without fluid (mg)

U 16 342 70.2 20.5 16 333.7 56.2 16.8 15 319.6 49.6 15.5 16 319.9

(↓6) 64.1 20

A 16 341.8 15.3 NA 16 334.1 15.3 NA 15 319.5 15.7 NA 16 319.9 15.2 NA

Ventral prostate

(mg) U 16 227.9 38.6 16.9 16 220.7 39.3 17.8 16 212.7 29.5 13.9 16 213.1(↓6) 45.9 21.6

A 16 227.2 9.32 NA 16 221.4 9.32 NA 16 213.0 9.31 NA 16 212.8 9.31 NA

Dorsolateral prostate

(mg) U 16 154 24.1 15.6 16 157.2 30.2 19.2 16 144.7 27.3 18.9 16 147(↓5) 33.6 22.8

A 16 153.1 6.27 NA 16 158.0 6.27 NA 16 145.2 6.27 NA 16 146.6 6.27 NA

LABC

(mg) U 16 517.8 50.5 9.8 16 536.7 70.9 13.2 16 512.5 59.3 11.6 16 497.7(↓4) 100 20.1

A 16 515.6 15.7 NA 16 538.7 15.7 NA 16 513.6 15.7 NA 16 496.8 15.7 NA

Epididymis, left

(mg)

U 16 211.9 16.8 7.9 16 212.5 27.2 12.8 15 217.6 17.1 7.8 16 211.4 19.3 9.2

A 16 211.6 5.04 NA 16 212.8 5.04 NA 15 217.6 5.20 NA 16 211.3 5.04 NA

Epididymis, right

(mg)

U 16 212.1 20.6 9.7 16 217.8 28.4 13.0 16 218.2 15.2 7 16 204 21.4 10.5

A 16 211.7 5.30 NA 16 218.1 5.30 NA 16 218.4 5.29 NA 16 203.8 5.29 NA

Testis, left

(mg)

U 16 1429 87.6 6.1 16 1443 74.9 5.2 16 1449 122.3 8.4 15 1415 106.4 7.5

A 16 1426 24.4 NA 16 1443 24.4 NA 16 1448 24.4 NA 15 1418 25.3 NA

Testis, right

(mg)

U 16 1453 130 8.9 16 1465 93.2 6.4 16 1457 109.5 7.5 16 1427 97.2 6.8

A 16 1450 26.0 NA 16 1467 26.0 NA 16 1458 26.0 NA 16 1426 26.0 NA

Thyroid, fixed

(mg) U 16 11.3 2 17.3 16 11.3 1.9 16.5 16 11.9(↑5) 1.8 15.1 16 12.6(↑12) 2.1 16.2

A 16 11.3 0.48 NA 16 11.3 0.48 NA 16 11.9

(↑5) 0.48 NA 16 12.6(↑12) 0.48 NA

a Data were obtained from Table 18 on pages 80-82 of the study report. Percent differences from Text Tables 6 and 9 on 

pages 42 and 46 are included in parentheses.

b Standard deviation (SD) reported for unadjusted values and standard error of the mean (SE) reported for adjusted values.

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)

N Number of animals examined

NA Not applicable

CV Coefficient of Variation

* Significantly different from controls at p≤0.05.

E. CLINICAL CHEMISTRY AND HORMONE LEVELS: Mean hormone and clinical 

chemistry concentrations for Studies 1 and 2 are presented in Tables 4a and 4b, respectively. 

In Study 1, data for hormone and clinical chemistry concentrations were not statistically 

analyzed. Serum testosterone at 25 mg/kg/day was increased by 86%; however, the control 

testosterone value was atypically low compared to the historical control range, and the 

difference was reported as incidental. At 25 mg/kg/day, T4 was decreased by 32% and TSH 

was increased by 46%. No clinical chemistry changes were observed, except for a 14% 

decrease in cholesterol at 25 mg/kg/day. 

Page 253 of 285
Male Pubertal Assay (2012) / Page 14 of 19

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In Study 2, no dose-dependent treatment effects were observed on serum testosterone. 

However, serum T4 concentrations in the 10 and 25 mg/kg/day dose groups were 

significantly decreased (p≤0.05) by 13 and 23%, respectively, and serum TSH was increased 

by 25% (NS) and 62% (p≤0.05) at 10 and 25 mg/kg/day, respectively. At 25 mg/kg/day, 

albumin was increased (p≤0.05) by 5% and cholesterol was decreased (p≤0.05) by 15%. No

dose-related effects were observed for the other measured clinical chemistry parameters. 

Historical control values were not provided for either the hormone or clinical chemistry 

parameters.

The mean serum T4 and TSH in the control group were within the acceptable range of the 

performance criteria provided in the Guideline; however, the mean testosterone (Study 2) 

was 4.368 ng/mL was outside the acceptable range (0.260-3.96 ng/mL) and the 74.14% CV 

for TSH (Study 1) was outside the acceptable range (maximum 58.29%). 

TABLE 4a. Study 1 Hormone Levels and Clinical Chemistrya

Parameter

Evaluated

Vehicle Control Pronamide 

(25 mg/kg/day)

N Mean SD N Mean SD

Hormones

Serum T4, Total (μg/dL) 15 5.40 0.441 15 3.65 (↓32) 0.474

Serum TSH (ng/mL) 15 9.09 6.74 15 13.26 (↑46) 5.48

Serum testosterone (ng/mL) 15 2.47 1.10 15 4.59 (↑86) 3.89

Clinical Chemistry

Urea nitrogen (mg/dL) 15 15 2 15 14 2

ALT (U/L) 15 54 8 15 55 7

ALP (U/L) 15 286 46 15 293 56

AST (U/L) 15 86 9 15 92 13

Total protein (g/dL) 15 5.4 0.1 15 5.3 0.2

Albumin (g/dL) 15 3.8 0.1 15 3.9 0.1

Globulin (g/dL) 15 1.6 0.1 15 1.4 0.2

Albumin/ globulin ratio 15 2.4 0.3 15 2.8 0.3

Cholesterol (mg/dL) 15 88 15 15 76 (↓14) 16

Total bilirubin (mg/dL) 15 0.05 0.00 15 0.05 0.00

Creatinine (μmol/L) 15 0.1 0.0 15 0.1 0.0

GGT (U/L) 15 1.5 0.0 15 1.5 0.0

Calcium (mg/dL) 15 11.1 0.2 15 10.9 0.3

Phosphorus (mg/dL) 15 8.7 0.7 15 8.6 0.6

Sodium (mmol/L) 15 143 2 15 144 1

Potassium (mmol/L) 15 5.4 0.2 15 5.3 0.4

Chloride (mmol/L) 15 102 1 15 103 1

a Data were obtained from Table 15 on pages 73-75 of the study report. No statistical analysis was performed. 

Percent differences from controls, calculated by the reviewers, are included in parentheses.

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

Page 254 of 285
Male Pubertal Assay (2012) / Page 15 of 19

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TABLE 4b. Study 2 Hormone Levels and Clinical Chemistrya

Parameter

Evaluated

Vehicle Control Pronamide 

(2.5 mg/kg/day)

Pronamide 

(10 mg/kg/day)

Pronamide 

(25 mg/kg/day)

N Mean SD

CV 

(%) N Mean SD

CV

(%) N Mean SD

CV 

(%) N Mean SD

CV 

(%)

Hormones

Serum T4, Total 

(μg/dL) 16 5.04 0.479 9.51 16 4.95 0.653 13.2 16 4.36*(↓13) 0.656 15.0 16 3.86*(↓23) 0.414 10.7

Serum TSH 

(ng/mL) 16 10.6 4.07 38.3 16 10.8 4.51 41.7 16 13.2(↑25)b 6.67 50.5 16 17.2*(↑62) 7.73 45.0

Serum testosterone 

(ng/mL) 16 4.37 2.13 48.9 16 3.4 1.70 50.0 16 4.16 2.32 56.0 16 4.86 2.30 47.3

Clinical Chemistry

Creatinine

(μmol/L) 16 0.2 0 0 16 0.2 0 0 16 0.2 0 22.8 16 0.2 0 22.2

Serum urea

nitrogen (mg/dL) 16 16 2 11 16 14 2 12 16 15 2 14 16 15 2 12

Alkaline

phosphatase (μ/L) 16 325 49 15 16 314 57 18 16 317 45 14 16 300 49 16

ALT (μ/L) 16 47 7 15 16 48 6 12 16 51 9 17 16 52 8 15

AST (μ/L) 16 104 17 16 16 108 15 14 16 108 19 17 16 108 14 13

GGT (μ/L) 16 1.5 0 0 16 1.5 0 0 16 1.5 0 0 16 1.5 0 0

Albumin (g/dL) 16 4 0.2 3.8 16 4 0.1 3.2 16 4.1 0.2 4.4 16 4.2*

(↑5) 0.1 3.1

A/G Ratio 16 2.7 0.3 10.9 16 2.8 0.3 9.9 16 3.1 0.4 12.2 16 3.4 0.5 13.5

Cholesterol

(mg/dL) 16 88 11 12 16 88 11 13 16 84 14 16 16 75*(↓15) 12 16

Globulin (g/dL) 16 1.5 0.1 9.9 16 1.5 0.1 8.3 16 1.3 0.1 10.1 16 1.3 0.2 12.6

Total bilirubin

(mg/dL) 16 0.05 0 0 16 0.05 0 0 16 0.05 0 0 16 0.05 0 0 

Total protein

(g/dL) 16 5.5 0.2 4.1 16 5.5 0.2 3.1 16 5.4 0.2 3.4 16 5.5 0.2 3.9

Sodium (mmol/L) 16 145 1 1 16 145 1 1 16 145 2 1 16 145 1 1

Potassium

(mmol/L) 16 5.3 0.3 6.1 16 5.2 0.3 5.3 16 5.3 0.3 6.1 16 5.2 0.4 8.5

Chloride (mmol/L) 16 99 1 1 16 100 1 1 16 100 1 1 16 100 1 1

Calcium (mg/dL) 16 11.4 0.3 2.6 16 11.3 0.3 2.8 16 11.5 0.3 2.5 16 11.2 0.2 2.1

Phosphorus

(mg/dL) 16 8.8 0.7 7.4 16 8.9 0.5 5.8 16 9.2 0.8 8.2 16 8.8 0.5 5.5

a Data were obtained from Table 16 on pages 76 and 77 of the study report. Percent differences from controls, calculated by 

the reviewers, are included in parentheses.

b Not significant

N Number of animals examined

SD Standard Deviation

CV Coefficient of Variation

* Significantly different from controls at p≤0.05.

F. GROSS PATHOLOGY: No treatment-related effects were observed on gross pathology. 

Diagnoses of inflammation in the neck (one animal, Study 1, 25 mg/kg/day) and hiatal 

hernia (one animal, Study 1, 25 mg/kg/day, and three animals, Study 2, 2.5, 10 and 25 

mg/kg/day) were considered to be unassociated with exposure. 

G. HISTOPATHOLOGY: The incidences of histopathological findings of the thyroid gland 

for Studies 1 and 2 are presented below in Table 5. In Study 1, no significant treatmentrelated changes in thyroid histopathology were observed. In Study 2, there was a slightly 

higher incidence of taller follicular epithelial cells (Grade 4) with corresponding smaller 

Page 255 of 285
Male Pubertal Assay (2012) / Page 16 of 19

PRONAMIDE / 101701 OCSPP 890.1500 / OECD None

colloid areas (Grade 2) in the 25 mg/kg/day group compared to the controls (5 to 1, 

respectively, for each comparison).

TABLE 5. Thyroid Gland Follicular Cell Height and Colloid Area a

Treatment Groups

Parameter Evaluated

Colloid Area Follicular Cell Height

Gradeb Incidence Grade Incidence

Observed Examined Observed Examined

Study 1

Vehicle Control

1 0 15 1 0 15

2 1 15 2 10 15

3 4 15 3 4 15

4 10 15 4 1 15

5 0 15 5 0 15

Pronamide 

(25 mg/kg/day)

1 0 15 1 1 15

2 1 15 2 9 15

3 4 15 3 4 15

4 9 15 4 1 15

5 1 15 5 0 15

Study 2

Vehicle Control

1 0 16 1 0 16

2 1 16 2 9 16

3 6 16 3 6 16

4 9 16 4 1 16

5 0 16 5 0 16

Pronamide 

(2.5 mg/kg/day)

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

Pronamide

(10 mg/kg/day)

1 0 16 1 1 16

2 2 16 2 8 16

3 5 16 3 5 16

4 8 16 4 2 16

5 1 16 5 0 16

Pronamide

(25 mg/kg/day)

1 0 16 1 0 16

2 5 16 2 7 16

3 4 16 3 4 16

4 7 16 4 5 16

5 0 16 5 0 16

a Data were obtained from Tables 21 and 22 on pages 93 and 94 of the study report.

b Thyroid histopathology is graded 1–5. Follicular cell height: 1 = lowest, 5 = highest; and Colloid area: 1 = most colloid, 5 = 

least colloid.

The incidence of histopathological findings of the testes, epididymides and kidneys for 

Studies 1 and 2 are presented in Table 6. No treatment-related findings were observed in the 

right testes, right epididymides, or kidneys at any pronamide dose. 

Immature spermatic elements were noted in the right epididymis for both studies; however, 

these effects were not dose-dependent and are consistent with the juvenile age of the 

animals. 

Page 256 of 285
Male Pubertal Assay (2012) / Page 17 of 19

PRONAMIDE / 101701 OCSPP 890.1500 / OECD None

TABLE 6. Incidence of Histopathological Lesions of the Testes, Epididymides and Kidneya

Findings

Dose Level (mg/kg/day)

Vehicle Control Pronamide (25)

# Observed # Examined # Observed # Examined

Study 1

Testes

Within Normal Limits 15 15 15 15

Epididymides

Within Normal Limits 0 15 0 15

Decreased spermatic elements, slight 0 15 2 15

Immature spermatic elements, very slight 15 15 14 15

Immature spermatic elements, slight 0 15 1 15

Study 2

Testes

Within Normal Limits 16 16 15 16

Degeneration, seminiferous tubule, multifocal, very 

slight 0 16 1 16

Multinucleated spermatids, seminiferous tubule, 

focal, very slight 0 16 1 16

Epididymides

Within Normal Limits 0 16 0 16

Aggregates of mononuclear cells, focal, very slight 1 16 0 16

Immature spermatic elements, very slight 16 16 16 16

Kidney

Within Normal Limits 1 16 1 16

Cyst, cortex, unilateral 1 16 1 16

Cyst, medulla, unilateral 1 16 2 16

Degeneration, tubule, focal, very slight 14 16 15 16

Dilatation, tubule, focal, very slight 3 16 2 16

Dilatation, tubule, multifocal, very slight 1 16 0 16

Inflammation, subacute to chronic, interstitum; focal, 

very slight 6 16 5 16

Inflammation, subacute to chronic, interstitum; 

multifocal, very slight 4 16 1 16

a Data were obtained from Tables 23 and 24 on pages 95-97 of the study report.

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: There was an indication of potential 

antiandrogenic effects at 25 mg/kg/day pronamide in Study 1 (delayed age and increased 

body weight at PPS, and decreased weight of androgen-sensitive tissues and epididymal 

weights), which was not reproducible in Study 2. Decreases in body weight and body 

weight gain also were seen in Study 1, but not in Study 2. In Study 2, there was evidence of 

potential thyroid perturbations at 25 mg/kg/day, including decreased T4, increased TSH and 

thyroid histopathology. Although consistent changes in thyroid hormones (T4 and TSH) 

were seen in Study 1, there was no associated thyroid histopathology, thereby indicating a 

lack of sustained changes in thyroid function. In addition, previous pronamide mode-ofaction studies have shown hepatic enzyme induction and enhanced testosterone metabolism 

and thyroxine metabolism/clearance, which support an indirect mode-of-action for effects 

on androgen and thyroid-sensitive endpoints. There were no effects on androgen- or 

thyroid-sensitive endpoints at pronamide doses <10 mg/kg/day. 

Page 257 of 285
Male Pubertal Assay (2012) / Page 18 of 19

PRONAMIDE / 101701 OCSPP 890.1500 / OECD None

B. AGENCY COMMENTS: All animals survived until scheduled termination. No 

treatment-related clinical signs of toxicity were observed in animals for any dose groups. 

During Study 1, terminal body weights were significantly decreased by 11-12% for the 100 

and 300 mg/kg/day pronamide dose groups. Therefore, a repeated male pubertal 

developmental assay was conducted with pronamide at 0, 2.5, 10, and 25 mg/kg/day (Study 

2). The data from the 25 mg/kg/day group from Study 1 were reported for comparison with 

data from Study 2; however, detailed data from the 100 and 300 mg/kg/day groups was not 

reported. 

In the 25 mg/kg/day group from Study 1, two animals did not achieve PPS. Terminal body 

weights for this group were decreased by 7%, compared to control, but were within the 

historical range, and body weight gains for PND 23 to 53 were decreased by 11%. When 

adjusted for liver weight, the terminal body weights and body weight gains were decreased 

by 7 and 11% (p<0.05), respectively. The age at PPS was delayed by 4.7 days, compared to 

the control, and is considered treatment-related and biologically relevant as body weight at 

PPS was increased by 9% in the 25 mg/kg/day group compared to the control. Relative liver 

weight was increased by 11% and absolute pituitary weights were decreased by 14%. 

Although statistical analyses were not report, decreases of 11 to 38% were observed in the 

absolute weights of the seminal vesicle + coagulating glands (with and without fluid), 

absolute ventral prostate, dorsolateral prostate, and LABC, and absolute left and right 

epididymides. Absolute thyroid weights were increased by 7%, but were within historical 

control range, and the effect was not considered treatment related. There were no doserelated effects on the weights of kidneys, adrenals, or testis. Serum testosterone in the 

25 mg/kg/day animals was increased by 86% compared to the control; however, the control 

testosterone value was atypically low compared to the historical control range. Mean T4

was decreased by 32% and mean TSH was increased by 46%. No clinical chemistry

parameters were affected, except for mean cholesterol that was decreased by 14%. No 

treatment-related changes in histopathology for thyroid, right testes, right epididymides, or 

kidneys were observed in the 25 mg/kg/day group. 

In Study 2, no treatment-related effects were observed on body weight, body weight gain, or 

age and weight at PPS at any dose of pronamide. Significant increases (p≤0.05) were 

observed in absolute, adjusted and relative liver weights (↑10-14%) in the 25 mg/kg/day

group. All liver weights at pronamide doses of 2.5 and 10 mg/kg/day were similar to 

control. Absolute and adjusted thyroid weights at 10 and 25 mg/kg/day were increased (NS) 

by 5 and 12%, respectively. There were no other significant, treatment-related effects on 

organ weights at any dose of pronamide. However, minor decreases of 4-6% (NS) were 

noted in four of the androgen sensitive tissues in the 25 mg/kg/day group. No dosedependent treatment effects were observed on serum testosterone. Mean serum T4 

concentrations in the 10 and 25 mg/kg/day dose groups were decreased (p≤0.05) by 13 and 

23%, respectively, and mean serum TSH in the 25 mg/kg/day group was increased (p≤0.05) 

by 62%. For thyroid histopathology, there was a slightly higher incidence of taller follicular 

epithelial cells (Grade 4) with corresponding smaller colloid areas (Grade 2) in the 

25 mg/kg/day group compared to control (5 to 1, respectively). Also at 25 mg/kg/day, 

albumin was increased (p≤0.05) by 5% and cholesterol was decreased (p≤0.05) by 15%. No 

dose-related effects were observed for the other measured clinical chemistry parameters. No 

significant treatment-related changes were observed in the histopathology for the right 

testes, right epididymides, or kidneys. 

Page 258 of 285
Male Pubertal Assay (2012) / Page 19 of 19

PRONAMIDE / 101701 OCSPP 890.1500 / OECD None

The effects observed in both studies on T4 and TSH levels, and thyroid histopathology in 

Study 2, indicate a change in thyroid function in response to treatment with pronamide at 

25 mg/kg/day. Although the 25 mg/kg/day dose group in Study 2 did not reproduce the 

effects on age and body weight at PPS, or accessory sex tissue weights observed in the 25 

mg/kg/day group from Study 1, the liver weight changes at 25 mg/kg/day were consistent 

between both studies. The reviewers agree with the study investigator conclusion that 

despite the poor reproducibility between the first and second male pubertal study regarding 

the effects observed in the 25 mg/kg/day animals, the findings should be considered. 

 

Based on the >10% decreased in terminal body weight at 100 mg/kg/day in Study 1 and the 

≥10% increase in liver weight at 25 mg/kg/day in Study 2, an adequate dose for testing was 

reached at 25 mg/kg/day. 

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 genistein-equivalent content of the laboratory diet (Teklad Diet #2016) was 

reported as <325 μg/g; Guideline states that the content should be ≤300 μg/g.

• A 12:12 hour light:dark photoperiod was used instead of a 14:10 hour period. 

• A CoA for pronamide was not included in the study report. 

• Control CV for Study 2 body weight at PPS (8.47%) exceeded the performance criteria 

(maximum 7.57%) 

• Control CV for Study 1 final body weight (10.33%) exceeded the performance criteria

(maximum 7.47%) 

• Control CV for Study 2 final body weight (8.74%) exceeded the performance criteria

(maximum 7.47%) 

• Control CV for Study 1 seminal vesicles (32.78%) exceeded the performance criteria

(maximum 21.06%) 

• Control mean for Study 1 thyroid weight (11.5 mg) was below the performance criteria

(acceptable range 14-26 mg)

• Control mean for Study 2 thyroid weight (11.3 mg) was below the performance criteria 

(acceptable range 14-26 mg)

• Control mean for Study 1 kidney weight (1.97 g) was below the performance criteria

(acceptable range 2.242-3.050 g) 

• Control mean for Study 2 kidney weight (1.93 g) was below the performance criteria

(acceptable range 2.242-3.050 g) 

• Control CV for Study 1 TSH (74.17%) exceeded the performance criteria (maximum 

58.29%)

• Control mean for Study 2 testosterone (4.368 ng/mL) exceeded the performance criteria 

(maximum 3.96 ng/mL). 

Page 259 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE) 

Study Type: OCSPP 890.1550, Steroidogenesis Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 2-19-2012 (MRID 48619107) 

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: 2/16/2012

Secondary Reviewer Signature:

Michael E. Viana, Ph.D., D.A.B.T. Date: 2/28/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 3/02/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 3/02/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 260 of 285
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 261 of 285
PRONAMIDE I 101701 

Primary Reviewer: =Kh=in;;:......::0--=o'""--"-'M"""'.=D;...:.. _______ _ 

Health Effects Division 

Secondary Reviewer: John Liccione, Ph.D. 

Health Effects Division 

Steroidogenesis Assay (2011) I Page I of 13 

OCSPP 890.1550/ OECD None 

Signature: ---"-=-"------

Date: ~'-j;:~-'-4----=-"-='"---

S i gnat u re: --,,,;,.p;-_~--....,c--

Da te: ----¥+-=-"-#~'---

DATA EVALUATION RECORD 

STUDY TYPE: Steroidogenesis Assay (H295R Cells); OCSPP 890.1550 

PC CODE: 101701 DP BARCODE: D398506 

TXR#: 0056255 CAS No.: 23950-58-5 

TEST MATERIAL (PURITY): Pronamide (96.2% a.i.) 

SYNONYMS: 3,5-dichloro-N-(1 , l-dimethyl-2-propynyl)benzamide; Propyzamide 

CITATION: LeBaron, M.J. ; Kan, H.L; Perala, A.W. (2011) Evaluation ofpronamide in 

the in vitro steroidogenesis assay. Toxicology & Environmental Research 

and Consulting, The Dow Chemical Company, Midland, Ml. Laboratory 

StudyNo.: 101181 , December20, 2011. MRID48619107. Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 

TESTORDER#: CON-101701-37 

EXECUTIVE SUMMARY: In a steroidogenesis assay (MRID 48619107), H295R cells 

cultured in vitro in 24-well plates were incubated with pronamide (96.2% purity, Lot# 

XG 1088R301) at serial log concentrations of 10- 10 to 10-4 M for 48 hours in triplicate for three 

independent experiments. Dimethyl sulfoxide (DMSO) was used as the vehicle, at a final 

concentration in the assay of 0.1 %. 

Testosterone and estradiol levels were measured using LC-APPi-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. The positive controls included a known inhibitor (prochloraz) and a known inducer 

(forskolin) of estradiol and testosterone production. 

Guideline acceptability recommendations and requirements were generally met, including 

adequate production of testosterone and estradiol, acceptable reproducibility (low %CV), and 

appropriate induction and inhibition with positive controls. Departures from the Guideline 

included: (i) the required concentration for estradiol (25 pg/mL) was not met in in Run 1 for the 

solvent control (SC) well (22.1 - 24.3 pg/mL); (ii) two runs were slightly outside the criteria for 

prochloraz inhibition of estradiol production (0.6-fold vs 0.5-fold); and (iii) the between plate 

CV in the SC was 33 .5% for testosterone, rather than ::;30%. As the positive controls 

approximated the expected responses on both testosterone and estradiol concentrations, these 

Page 262 of 285
Steroidogenesis Assay (2011) / Page 2 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

departures from Guideline recommendations were considered minor and were not expected to 

affect the scientific integrity of these studies. 

Precipitation of pronamide and cytotoxicity were not reported at any concentration. No effect 

was observed on testosterone concentrations. Decreases (p≤0.05) of 20% in testosterone levels 

relative to DMSO-treated cells were observed in Run 2 at the lowest concentration and in Run 5 

at 1 μM. These effects were neither concentration-dependent nor reproducible. 

A treatment-related effect was observed on estradiol concentrations. A decrease (p≤0.05) of 

10% was noted at 1 μM in one run, but this effect was neither concentration-dependent nor 

reproducible. However, reproducible increases (p≤0.05) were noted at the highest concentration 

(100 μM), with estradiol concentrations increased 1.2-, 1.4-, and 1.9-fold that observed in the 

DMSO treated cells in the three runs.

Based on the hormone responses in each of the three independent runs, pronamide treatment 

resulted in statistically significant and reproducible increases in estradiol production. Pronamide 

treatment did not result in statistically significant and reproducible alterations in testosterone 

production. 

The assay satisfies the EDSP Tier 1 Test Order requirements for a Steroidogenesis Assay 

(OCSPP 890.1550). 

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

Confidentiality statements were provided. 

Page 263 of 285
Steroidogenesis Assay (2011) / Page 3 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Toxicology & Environmental Research and Consulting

Location: Midland, MI

Study Director: H. L. Kan

Other Personnel: M. J. LeBaron, lead scientist

A. W. Perala, analytical chemist

B. B. Gollapudi, technical reviewer

Study Period: Not provided

2. Test Substance: Pronamide

Description: White to off-white powder

Lot # (expiration date): XG1088R301 (not provided)

Purity: 96.2%

Solubility: Soluble in DMSO up to 0.1 M; insoluble in water

Vapor pressure: 4.97 Pa

Stability: 2 year shelf life

Storage conditions: Ambient

CAS #: 23950-58-5

Molecular weight: 256.1

Structure:

3. Positive Control: Forskolin

Description (molecular weight): White powder (410.50)

Source: Sigma-Aldrich (St. Louis, MO)

Batch # (expiration date): 097K50653 (not provided)

Purity: 99%

Solubility (in solvent): Soluble in DMSO up to 0.01 M

Storage conditions: Ambient

CAS #: 66575-29-9

4. Negative Control: Prochloraz

Description (molecular weight): Off-white powder (376.67)

Source: Sigma-Aldrich (St. Louis, MO)

Batch # (expiration date): SZE6220X (not provided)

Purity: 99.1%

Solubility (in solvent): Soluble in DMSO up to 0.01 M

Storage conditions: Ambient

CAS #: 67747-09-5

Page 264 of 285
Steroidogenesis Assay (2011) / Page 4 of 13

PRONAMIDE / 101701 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): 38096HK and 108K0186 (not provided)

Purity: >99.9%

Storage conditions: Ambient

CAS #: 67-68-5

Justification for choice of 

solvent:

Not provided. DMSO is a Guideline recommended solvent in which pronamide is 

reasonably soluble.

Final concentration in assay: 0.1% v/v

6. Stock Medium: Dulbecco’s modified Eagle’s medium/Ham’s F12 nutrient 

mixture

Source: Sigma-Aldrich (St. Louis, MO) 

Lot # (expiration date): RNBB 0035 (not provided)

Sodium bicarbonate: Component of stock medium

Nu-Serum: 2.5%, BD Biosciences; Lot # 81515; tested for background hormone 

concentrations by performing laboratory

ITS+premix: BD Biosciences; Lot # 75382

Other components: 2.5 mM L-glutamine (Life Technologies, GIBCO, Grand Island, New York), 

and penicillin/streptomycin (25 IU/mL/25 μg/mL) (GIBCO).

7. Test Cells: H295R human adrenocortical carcinoma cells (ATCC CLR-2128; Batch # not 

provided) at passage 5.5 – 7.5 were incubated in the stock medium. Incubation conditions 

were at approximately 37 °C with 5% CO2 for approximately 24 hours prior to exposure. 

The following performance criteria were met (indicated by an “x”):

X Cell passage identifier. Cell Passage #: 5.5 – 7.5

X Cells frozen down at passage 5

X Frozen cells cultured for 4 additional passages

X Total number of passages does not exceed 10

B. METHODS

1. Pre-Test Information 

a. Hormone Assay Interference Test: A separate chemical interference assay was not 

performed, as LC/APPI-MS/MS was used along with internal spike-in controls to measure 

extraction and quantitation efficiency. 

b. Hormone Extraction: Briefly, standards and samples were vortexed with methylene 

chloride containing both testosterone and estradiol internal standards, and the resulting 

organic phases were transferred to clean vials. The aliquots were evaporated to dryness, and 

the final residue in each vial was derivatized with dansyl chloride. Samples were subjected 

to LC/APPI-MS/MS analysis. 

Page 265 of 285
Steroidogenesis Assay (2011) / Page 5 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

c. Laboratory Proficiency Test: The Sponsor stated that Laboratory proficiency assays were 

performed to optimize and validate the H295R steroidogenesis assay. These non-GLP, 

unpublished experimental results with positive control chemicals demonstrated laboratory 

proficiency and validation and are reported separately (data not presented and report not 

cited).

2. Test Solutions: Pronamide, forskolin, and prochloraz were dissolved in DMSO and diluted 

1:1000 in the final treatment medium. 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 10−4, 10−5, 10−6, 10−7, 10−8, 10−9, and 10−10 M for pronamide. The selected 

concentrations of the test material in the dosing solutions used for the treatment in a 

definitive assay (generally the first assay) were verified analytically. The final 

concentration of DMSO in the medium was held constant at 0.1% (v/v). 

3. Cell Plating and Preincubation: Cells were maintained in the stock medium described 

above. The hormone concentrations in undiluted Nu-Serum were 974 pg/mL for 

testosterone and 681 pg/mL for estradiol. H295R cells were grown for five passages, frozen 

in liquid nitrogen, then thawed and cultured for five to seven additional passages prior to use 

in the assay. The cells were plated into wells of a 24-well cell culture plate at a density of 

approximately 200,000 – 300,000 cells in 1 mL (50 – 60% confluency). The cells were then 

placed into an incubator (approximately 37 °C/5% CO2) for approximately 24 hours prior to 

chemical exposure. After a 24-hour pre-incubation, the cells were checked microscopically 

for good attachment and proper morphology. 

4. Exposure: The medium was removed from the cells and replaced with 1 mL of medium 

containing concentrations of pronamide (or solvent) in triplicate, according to the schematic 

presented in Table 1. 

TABLE 1. Dosing Schematic for the Exposure of H295R Cells to Pronamide (Final Concentrations in M).a

1 2 3 4 5 6

A DMSO DMSO DMSO 10−7 10−7 10−7

B 10−4 10−4 10−4 10−8 10−8 10−8

C 10−5 10−5 10−5 10−9 10−9 10−9

D 10−6 10−6 10−6 10−10 10−10 10−10

a Data were obtained from pages 17 and 18 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 266 of 285
Steroidogenesis Assay (2011) / Page 6 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

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 Blank + methanolc Blank + methanol Blank + methanol

B DMSO DMSO DMSO DMSO + methanol DMSO + methanol DMSO + methanol

C Forskolin 

1 μM

Forskolin 

1 μM

Forskolin 

1 μM

Prochloraz 

0.1 μM

Prochloraz 

0.1 μM

Prochloraz 

0.1 μM

D Forskolin 

10 μM

Forskolin 

10 μM

Forskolin 

10 μM

Prochloraz 

1 μM

Prochloraz 

1 μM

Prochloraz 

1 μM

a Data were obtained from page 16 of the study report. 

b Blank wells received medium only.

c Methanol (MeOH) was added after the exposure was terminated and the medium was removed.

Following dosing, the plates were incubated for approximately 48 hours under the 

conditions previously described. After the incubation period, two aliquots of medium were 

collected and frozen at −80°C until further processing. 

5. Cell Viability/Cytotoxicity Assay: The cell viability/cytotoxicity testing was conducted in 

the QC plate and in the test chemical exposure plate immediately after termination of the 

exposure experiments. In addition to viability/cytotoxicity testing, cells were checked for 

the degree of confluence, homogeneity from well-to-well, and any signs of cytotoxicity or 

altered morphology. A subjective parallel visual assessment of each well was conducted. 

The CellTiter 96 Aqueous One Solution Cell Proliferation Assay kit (Madison Wisconsin, 

Cat# G3580) was used for assessment of cell viability testing, as per manufacturer’s 

instructions. This cell proliferation assay kit is a colorimetric modified MTT cell viability 

assay, containing a tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5(3-

carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron 

coupling reagent (phenazine ethosulfate; PES). The quantity of formazan product as 

measured by the amount of 490 nm absorbance is directly proportional to the number of 

viable cells in culture. The minimum cell viability required per well was ≥80%; wells with 

lower viability were excluded in the final data analysis. 

6. Hormone Measurement System: The concentration of each hormone (testosterone and 

estradiol) was evaluated in triplicate in the culture medium. Hormones were extracted from 

the samples with methylene chloride, derivatized with dansyl chloride, and analyzed by 

LC-APPI-MS/MS. The lower limit of quantification (LLQ) for this measurement system 

was 25 pg/ml for testosterone and 10 pg/ml for estradiol. 

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)

X Solvent control within 75% range below maximum response on standard curve

NA Test compound tested for interference with measurement system

C. DATA ANALYSIS: To evaluate the relative increase or decrease of hormone production 

after test chemical exposure, the results were normalized to the mean SC value for each 

assay and results were expressed as fold-change relative to the SC in each exposure plate. 

All data were expressed as mean ± standard deviation (SD) and concentrations that 

exhibited cytotoxicity ≥20% were omitted from further evaluation. Relative changes were 

calculated as follows:

Page 267 of 285
Steroidogenesis Assay (2011) / Page 7 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

Relative Change = hormone concentration in each well ÷ mean hormone concentration of 

solvent (vehicle) control 

Prior to conducting statistical analyses, the assumptions of normality and variance 

homogeneity were evaluated. Homogeneity of variance were evaluated by Bartlett’s test 

and normality by Shapiro-Wilk’s test at alpha = 0.01. If the data were not homogeneous or 

normally distributed, then the data were transformed to approximate homogeneity or a 

normal distribution. If the data were homogeneous and approximately normally distributed, 

differences between chemical treatments and SC were analyzed using a parametric analysis 

of variance followed by Dunnett’s test, if significant. If the data were not homogeneous or 

normally distributed, a non-parametric test was used (Kruskal Wallis) and if significant, was 

followed by the Wilcoxon rank sum test with a Bonferroni-Holm correction. Differences 

were considered significant at p ≤0.05. These statistical analyses were considered 

appropriate. 

II. RESULTS

A. TEST COMPOUND: Precipitation of pronamide was not reported at any concentration. 

Cytotoxicity was not observed at any tested concentration. The %CVs were 4.0–10.2% for 

absolute testosterone concentrations in the solvent control replicate wells within a plate. 

The %CVs were 3.1-4.8% for absolute estradiol concentrations in the solvent control 

replicate wells within a plate. The between plate CVs for solvent controls were 34.1% for 

testosterone and 26.0% for estradiol. The inter- and intraplate variability was within the 

guideline recommendation of ≤30%, except for the between plate CV for testosterone which 

was slightly high.

No effect was observed on testosterone levels (Table 3). Decreases (p≤0.05) of 20% in 

testosterone levels relative to DMSO-treated cells were observed in Run 2 at the lowest 

concentration and in Run 5 at 1 μM. These effects were neither concentration-dependent 

nor reproducible. The effects on testosterone and estradiol are illustrated in Figures 1 and 2. 

An effect was observed on estradiol levels. A decrease (p≤0.05) of 10% was noted at 1 μM, 

but this effect was neither concentration-dependent nor reproducible. However, 

reproducible increases (p≤0.05) were noted at the highest concentration (100 μM), where 

estradiol levels were determined to be 1.2-, 1.4-, and 1.9-fold that observed in the DMSO 

treated cells in the three runs. 

The Sponsor stated that Run 3 was analyzed, but not included for data analysis due to an 

insufficient inhibition of E2 production in response to 1 μM prochloraz, i.e., the assay varied 

considerably from the quality control criteria. Run 4 was not included for analysis as one of 

the replicate cell culture wells for 1 μM pronamide administration was contaminated, hence 

the samples were not analyzed. 

Page 268 of 285
Steroidogenesis Assay (2011) / Page 8 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

TABLE 3. Mean (±SD) Hormone Concentrations Following Treatment with Pronamide for 48 Hours.a

Nominal 

Concentration 

(μM)

Run 1 Run 2 Run 5 Run 1 Run 2 Run 5 Mean ± SD Statistical 

Significance b 

Testosterone (pg/mL) Fold Difference

DMSO 913.3 634.3 460.3 — — — — — —

0.0001 893.3 527.0 426.3 1.0 0.8 0.9 0.9 0.1 Run 2

0.001 914.0 627.0 475.7 1.0 1.0 1.0 1.0 0.0 —

0.01 847.3 558.3 427.3 0.9 0.9 0.9 0.9 0.0 —

0.1 931.3 577.0 465.3 1.0 0.9 1.0 1.0 0.1 —

1 944.7 636.7 370.3 1.0 1.0 0.8 0.9 0.1 Run 5

10 785.3 548.7 404.0 0.9 0.9 0.9 0.9 0.0 —

100 1010.0 648.3 486.0 1.1 1.0 1.1 1.1 0.0 —

Estradiol (pg/mL) Fold Difference

DMSO 23.1 33.0 39.6 — — — — — —

0.0001 24.4 35.3 36.3 1.1 1.1 0.9 1.0 0.1 —

0.001 25.4 34.1 38.5 1.1 1.0 1.0 1.0 0.1 —

0.01 24.2 34.1 37.4 1.0 1.0 0.9 1.0 0.1 —

0.1 23.6 34.5 38.3 1.0 1.0 1.0 1.0 0.0 —

1 22.6 32.4 34.5 1.0 1.0 0.9 0.9 0.1 Run 5

10 24.6 33.4 37.6 1.1 1.0 0.9 1.0 0.1 —

100 43.5 45.9 47.6 1.9 1.4 1.2 1.5 0.4 Runs 1, 2, 5

a Data were obtained from page 31 of the study report. The lower limit of quantification (LLQ) was 25 pg/mL for 

testosterone and 10 pg/mL for estradiol.

b p ≤ 0.05

Page 269 of 285
Steroidogenesis Assay (2011) / Page 9 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

FIGURE 1. Change in Testosterone Production Relative to Pronamide Concentration.

Page 270 of 285
Steroidogenesis Assay (2011) / Page 10 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

FIGURE 2. Change in Estradiol Production Relative to Pronamide Concentration. 

B. CYTOTOXICITY: Pronamide was not cytotoxic to the H295R cells (Table 4). Viability 

in each run ranged from 103–140% relative to solvent controls. In the quality control plate, 

viability in each run ranged from 91–142% relative to the SC, except in the methanol-treated 

cells which had viabilities of 17.7–23.7%. 

Page 271 of 285
Steroidogenesis Assay (2011) / Page 11 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

TABLE 4 . Mean (±SD) MTT Cell Viability Results after Treatment with 

Forskolin, Prochloraz, or Pronamide for 48 Hours. a

Compound Concentration

(μM)

Cell Viability

Mean SD

Media NA 95.0 4.56

Media + Methanol NA 20.0 3.21

DMSO + Methanol NA 20.1 1.89

Forskolin 1 128.3 15.02

Forskolin 10 116.0 10.54

Prochloraz 0.1 104.7 1.95

Prochloraz 1 102.8 7.18

Pronamide 0.0001 118.1 8.50

Pronamide 0.001 115.0 6.27

Pronamide 0.01 112.1 0.93

Pronamide 0.1 104.8 2.08

Pronamide 1 118.4 4.51

Pronamide 10 115.7 6.30

Pronamide 100 131.3 7.17

a Values were calculated by the reviewers from data obtained from page 43 of the study report. 

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 

± 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 for testosterone, except in Run 5 for the SC well (433 pg/mL). The 

required concentration for estradiol was only met in in Run 5 for the SC well; other estradiol 

concentrations ranged from 26.7–39.2 pg/mL. Forskolin at 10 μM induced testosterone an 

average of 3.1-fold and estradiol 18-fold over the SC. Prochloraz at 1 μM inhibited 

concentrations of testosterone and estradiol by 0.3- to 0.6- fold compared to SC. Two runs 

were slightly outside the criteria for prochloraz inhibition of estradiol production (0.6-fold 

vs 0.5-fold). Criteria for the QC plate were generally met for induction and inhibition. 

The variability (%CV) between the runs (calculated by the reviewer) based on the absolute 

hormone concentrations in the SC were 33.5% for testosterone and 26.6% for estradiol; the 

CV for testosterone was slightly greater than the guideline criteria of ≤30% for the assays. 

The %CVs within each run for the QC plates were 4.2-9.0% for testosterone and 3.1-5.9% 

for estradiol, which were within the guideline criteria (≤30%).

Page 272 of 285
Steroidogenesis Assay (2011) / Page 12 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

TABLE 5 . Mean (±SD) Hormone Concentrations Following Treatment with Forskolin or Prochloraz for 

48 Hours.a

Concentration 

(μM)

Run 1 Run 2 Run 5 Run 1 Run 2 Run 5 Mean ± SD

Testosterone (pg/mL) Fold Difference (Relative to DMSO)

Blank 1240 691 543 — — — — —

DMSO 840 575 433 — — — — —

1 μM Forskolin 1680 1233 964 2.0 2.1 2.2 2.1 0.1

10 μM Forskolin 2750 1620 1333 3.3 2.8 3.1 3.1 0.2

0.1 μM Prochloraz 578 357 385 0.7 0.6 0.9 0.7 0.1

1 μM Prochloraz 252 165 132 0.3 0.3 0.3 0.3 0.0

Estradiol (pg/mL) Fold Difference (Relative to DMSO)

Blank 26.8 33.2 39.2 — — — — —

DMSO 26.7 34.6 45.6 — — — — —

1 μM Forskolin 383.0 312.0 259.0 14.3 9.0 5.7 9.7 4.3

10 μM Forskolin 687.0 612.0 483.0 25.7 17.7 10.6 18.0 7.6

0.1 μM Prochloraz 22.9 24.9 33.1 0.9 0.7 0.7 0.8 0.1

1 μM Prochloraz 13.5 20.7 28.5 0.5 0.6 0.6 0.6 0.1

a Data were obtained from pages 32 of the study report. The lower limit of quantification (LLQ) was 25 pg/mL for 

testosterone and 10 pg/mL for estradiol. ALQ indicates the concentration was above the limit of quantification (>2000 

pg/mL).

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: It was concluded that pronamide treatment 

resulted in a statistically significant increase in estradiol production at the assay limit 

concentration of 100 μM (10−4 M), while no effects on estradiol production were seen at 

lower concentrations. There were no effects on testosterone production at any concentration 

of pronamide. The slight increases in estradiol production (1.2-fold, 1.4-fold, and 1.9-fold) 

did not reproducibly meet the 1.5-fold cut-off criteria established in the validation program 

for this assay and hence was not interpreted to be biologically relevant. 

B. AGENCY COMMENTS: Guideline acceptability recommendations and requirements 

were generally met for the following: lack of cytotoxicity, adequate production of 

testosterone, acceptable reproducibility (low %CV), and appropriate induction and 

inhibition with positive controls. Departures from the Guideline included: (i) the required 

concentration for estradiol (25 pg/mL) was not met in in Run 1 for the SC well (22.1–24.3 

pg/mL); (ii) two runs were slightly outside the criteria for prochloraz inhibition of estradiol 

production (0.6-fold vs 0.5-fold); and (iii) the between plate CV in the SC was 33.5% for 

testosterone rather than ≤30%. As the positive controls approximated the expected 

responses on both testosterone and estradiol concentrations, these departures from Guideline 

recommendations were considered minor and were not expected to affect the scientific 

integrity of these studies. 

Precipitation of pronamide was not reported at any concentration. Cytotoxicity was not 

observed at any tested concentration. The %CVs were 4.0–10.2% for absolute testosterone 

concentrations in the solvent control replicate wells within a plate. The %CVs were 3.1-

4.8% for absolute estradiol concentrations in the solvent control replicate wells within a 

plate. The between plate CVs for solvent controls were 34.1% for testosterone and 26.0% 

for estradiol. 

Page 273 of 285
Steroidogenesis Assay (2011) / Page 13 of 13

PRONAMIDE / 101701 OCSPP 890.1550/ OECD None

No effect was observed on testosterone levels. Decreases (p≤0.05) of 20% in testosterone 

levels relative to DMSO-treated cells were observed in Run 2 at the lowest concentration 

and in Run 5 at 1 μM. These effects were neither concentration-dependent nor reproducible. 

An effect was observed on estradiol levels. A decrease (p≤0.05) of 10% was noted at 1 μM, 

but this effect was neither concentration-dependent nor reproducible. However, 

reproducible increases (p≤0.05) were noted at the highest concentration (100 μM), where 

estradiol levels were determined to be 1.2-, 1.4-, and 1.9-fold that observed in the DMSO 

treated cells in the three runs. 

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: 

• Stability of pronamide in the test system was not reported.

• There were minor departures from the Guideline: (i) the required concentration for 

estradiol (25 pg/mL) was not met in in Run 1 for the SC well (22.1–24.3 pg/mL); (ii) 

two runs were slightly outside the criteria for prochloraz inhibition of estradiol 

production (0.6-fold vs 0.5-fold); and (iii) the between plate CV in the SC was 33.5% 

for testosterone rather than ≤30%.

• Proficiency assays 2 and 3 found that the EC-50 concentrations for testosterone with 

the inhibitor prochloraz were 0.58 μM and 0.26 μM respectively (expected range is 

0.01 – 0.1) 

Page 274 of 285
DATA EVALUATION RECORD

PRONAMIDE (PROPYZAMIDE)

Study Type: OCSPP 890.1600, In Vivo Uterotrophic Assay 

EPA Contract No. EP10H001452 

Task Assignment No. 2-19-2012 (MRID 48619108) 

Prepared for

Health Effects Division

Office of Pesticide Programs

U.S. Environmental Protection Agency 

2777 South Crystal Drive 

Arlington, VA 22202 

Prepared by

CSS-Dynamac Corporation

1910 Sedwick Road, 

Building 100, Suite B 

Durham, NC 27713 

Primary Reviewer Signature:

Rebecca L. Bryan, B.S. Date: 2/15/2012

Secondary Reviewer Signature:

Ronnie J. Bever Jr., Ph.D., D.A.B.T. Date: 2/27/2012

Program Manager: Signature:

Jack D. Early, M.S. Date: 2/27/2012

Quality Assurance: Signature:

Jack D. Early, M.S. Date: 2/27/2012

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

signing by CSS-Dynamac Corporation personnel. 

Page 275 of 285
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 276 of 285
PRONAMIDE/101701 

In Vivo Uterotrophic Assay (2011) I Page I of9 

OCSPP 890.1600/ OECD 440 

DATA EVALUATION RECORD 

STUDY TYPE: Uterotrophic Assay (Rat); OCSPP 890.1600; OECD 440 

PCCODE: 101701 DP BARCODE: D398506 

TXR#: 0056255 CAS#: 23950-58-5 

TEST MATERIAL (PURITY): Propyzamide (96.2% a.i.) 

SYNONYMS: Pronamide; KERBTM Technical; 3,5-Dichloro-N-(l ,1-dimethyl-2-

propynyl)benzamide 

CITATION: Marty, M.S., Brooks, K.J. and Jeong, Y.C. (2011). Pronamide: Uterotrophic 

assay in the immature female CrL:CD(SD) rat. Toxicology & Environmental 

Research and Consulting, The Dow Chemical Company, Midland, MI. 

Laboratory Project Study ID: 101145, October 19, 2011. MRID 48619108. 

Unpublished. 

SPONSOR: Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 

TEST ORDER#: CON-101701-37 

EXECUTIVE SUMMARY: In a uterotrophic assay (MRID 48619108) conducted to screen for 

potential estrogenic activity, pronamide (96.2% a.i., lot# XG 1088R301) in 0.5% aqueous 

methylcellulose was administered daily via oral gavage to groups of 6 immature female, 

Sprague-Dawley rats at dose levels of 0 (vehicle), 25, 100, or 400 mg/kg/day on postnatal days 

(PND) 19-21. A positive control group was treated with 17a-ethynyl estradiol (EE) in com oil 

by gavage at a dose level of 10 μg/kg/day. All animals were terminated and necropsied 

approximately 24 hours after the final dose on PND 22 to determine wet and blotted uterine 

weights. 

All animals survived until scheduled termination. No clinical signs of toxicity were observed in 

animals for any pronamide treated groups, and no precocious vaginal opening was observed in 

the pronamide-treated females. The body weights and overall body weight gain were decreased 

in all pronamide-treated groups. Body weights were decreased (p<0.05) at 25 mg/kg/day O 11 %, 

Day 4), 100 mg/kg/day (l 7-8%, Days 3-4), and 400mg/kg/day(l10-25%, Days 2-4). Overall 

body weight gains were also decreased (p<0.05) for the 25, 100 and 400 mg/kg/day groups by 

58, 38, and 112%, respectively. Uterine weights in the pronamide-treated groups were 

comparable to the controls. Absolute wet and blotted uterus weights for the positive control EE 

group were increased (p<0.05) by 797% and 423%, respectively, as expected. 

Page 277 of 285
In Vivo Uterotrophic Assay (2011) / Page 2 of 9 

PRONAMIDE/101701 OCSPP 890.1600/ OECD 440

Dosing for the assay (high dose of 400 mg/kg/day) was adequate based on decreased body 

weight observed at all doses. 

No statistically significant changes were seen in uterine weight in this assay. Pronamide is 

negative in the uterotrophic assay. 

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

890.1600). 

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

Assurance statements were provided. 

Page 278 of 285
In Vivo Uterotrophic Assay (2011) / Page 3 of 9 

PRONAMIDE/101701 OCSPP 890.1600/ OECD 440

I. MATERIALS AND METHODS

A. MATERIALS

1. Test Facility: Toxicology & Environmental Research and Consulting

Location: Midland, MI

Study Director: K. J. Brooks

Other Personnel: M. S. Marty, lead scientist

J. A. Wachner, animal technician

H. M. Mahan, quality assurance

L. G. McFadden, data analyses

J. W. Lacher, laboratory veterinarian

J. R. McFadden, analytical analyses

Study Period: Not provided

2. Test Substance: Pronamide

Description: Molecular weight = 256.1 g/mol

Source: Dow AgroSciences LLC (Indianapolis, IN)

Lot #: XG1088R301, TSN003588-0004

Purity: 96.2%

Stability: Stable in 0.5% methylcellulose for up to 12 days; temperature of stability determination 

not reported

CAS #: 23950-58-5

Structure:

Cl

Cl

O

N

H

CH3

C

CH3 CH

3. Reference Estrogen: 17α-ethynyl estradiol (EE)

Supplier: Sigma Aldrich (St. Louis, MO)

Lot #: 028K1411

Purity: 98%

CAS # : 57-63-6

4a.Solvent/Vehicle Control

for Test Chemical: Methylcellulose

Supplier: The Dow Chemical Company (Midland, MI)

Lot #: WD14012N13

Rationale (if other than water): Selected due to the solubility properties of the test substance and lack of toxicity

Final concentration: 0.5% aqueous

4b.Solvent/Vehicle Control 

for Positive Control: Corn Oil

Supplier: Sigma Aldrich (St. Louis, MO)

Lot #: MKBC6753

Rationale (if other than 

water):

Selected due to the solubility properties of the test substance without estrogenicity or 

toxicity

Final concentration: Not applicable

Page 279 of 285
In Vivo Uterotrophic Assay (2011) / Page 4 of 9 

PRONAMIDE/101701 OCSPP 890.1600/ OECD 440

5. Test Animals:

Species: Rats (immature, female only)

Strain: Sprague-Dawley (Crl:CD[SD])

Age/weight at dose initiation: Post-natal day (PND) 19; 41.5-49.0 g

Source: Charles River Laboratories (Portage, MI)

Housing: Rats were housed 6 per cage in solid bottom cages with paper pulp bedding with 

low phytoestrogen content (7089 Tekland Diamond Soft bedding, Harlan 

Laboratories, Inc., Indianapolis, IN) 

Diet: Teklad Diet #2016 (Harlan Laboratories, Inc., Indianapolis, IN), ad libitum (low 

phytoestrogen rodent diet, total genistein equivalents <325 μg/g)

Water: Tap water, ad libitum 

Environmental conditions: Temperature:

Humidity:

Air changes:

Photoperiod:

22 ± 3 oC

40-70% 

12-15 times/hour (average)

12 hrs light/12 hrs dark

Acclimation period: 8 days; immature females housed with their dam

B. METHODS 

1. In-Life Dates: Dates not provided 

2. Study Design: Following an 8-day acclimation period, intact, immature female rats were 

administered the test substance by oral gavage once daily from PND 19-21. A positive 

control group of six rats were given 17α-ethynyl estradiol (EE) daily by gavage at 10 

μg/kg/day. 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 using a computer program designed to increase the probability 

of uniform group mean weights and standard deviations on Day 1. Statistical analysis 

indicated that there were no significant differences in group means at study initiation. 

TABLE 1. Study Design a

Test Group Dose (mg/kg/day) # of Females b

Estrogen Agonist Assay

Vehicle Control 0 6

Low 25 6

Mid 100 6

High 400 6

17α-ethynyl estradiol (EE), Reference 

Estrogen 10 μg/kg/day 6 

a Data were obtained from Text Table 1 on page 15 of the study report.

4. Dose Selection Rationale: In a screening study examining hepatic enzyme induction, rats 

(6/sex/dose) were treated for 3 days by oral gavage with pronamide at doses of 0, 25, 100 or 

400 mg/kg/day in 0.5% methylcellulose. Liver-to-body weight ratios were increased in both 

sexes at the high dose and in vitro p-nitroanisole O-demethylase activity was increased at 

doses of 100 and 400 mg/kg/day pronamide. In a 2-week dietary study in Crl:CD rats, 

pronamide was found to be a mixed inducer of cytochrome P450 enzymes at 239 

mg/kg/day. Liver weights, microsomal protein levels, and microsomal enzyme activities 

were increased. Male rats were administered the test substance via gavage at doses of 0, 25, 

100, 250, 500, 600, 800 or 1000 mg/kg/day for 15 days from PND 30. Decreased body 

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weight gains were observed at the ≥500 mg/kg/day dose groups, and terminal body weights 

were decreased in the ≥600 mg/kg/day dose groups. The absolute and relative liver weights 

were increased in the ≥100 mg/kg/day dose groups. Relative kidney and adrenal weights 

were increased at 1000 mg/kg/day. Based on these results, the dose levels selected for this 

study were ≤ 400 mg/kg/day. 

5. Dose Preparation: Dose formulations were prepared by mixing appropriate amounts of 

test substance with 0.5% methylcellulose, such that a dose volume of 4 mL/kg BW yielded 

the target dose. Pronamide dosing solutions were prepared once at the beginning of the 

study in accordance with established stability limits. Dose volumes were adjusted daily

based on individual body weight measurements. Prior to dose administration, samples of 

pronamide dose formulations from all three dose levels were analyzed for achieved 

concentration and samples from the low and high dose formulations were tested for 

homogeneity. Samples were taken from the top, middle, and bottom of the container after 

stirring overnight. In a previous study,1

 pronamide was determined to be stable in 0.5% 

aqueous methylcellulose for up to 12 days at concentrations ranging 0.250-250 mg/mL 

(temperature not specified).

Results of Dose Analysis 

Homogeneity (%RSD): 0.6-0.9% 

Stability: Stable in 0.5% methylcellulose for up to 12 days; temperature of stability 

determination not reported (Dow Chemical Company, 2005) 

Concentration (% of nominal): 86.3-101.0%

The analytical data indicated that the mixing procedure was adequate and that the variation 

between nominal and actual dosage to the animals was acceptable. 

6. Dosage Administration: Animals were administered the pronamide formulations, positive 

control (EE) or vehicle control daily via gavage for three consecutive days in a dose volume 

of 4 mL/kg body weight. Dose volumes were adjusted daily based on the concurrent body 

weight measurement.

7. Statistics: Body weights and body weight gains were analyzed by a forced parametric test. 

The blotted and wet uterine weights were first analyzed by Bartlett’s test for homogeneity of 

variance. A log transformation was performed when data variance was not homogeneous. 

Analysis of covariance (ANCOVA) was performed with terminal body weight as the 

covariate. If the ANCOVA was significant (p≤0.05), either one-sided least square means 

with Dunnett’s correction was performed. Significance was denoted at p≤0.05. The 

assumptions of parametric testing (homogeneity of variance and normal distribution) should 

be confirmed prior to using parametric testing, and non-parametric testing is performed 

when these assumptions are not met.

 

1 Dryzga, M.D. and Yano, B.L. (2005). PronamideTechnical: 28-Day dermal toxicity study in F344/DuCrl rats. 

Report of Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, 

Michigan.

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C. METHODS

1. Clinical Examinations: Cage-side checks for mortality, moribundity and clinical signs of 

toxicity were conducted at least twice daily. 

On PND 22 prior to necropsy, all animals were examined for vaginal patency. 

2. Body Weight: Animals were weighed at randomization, daily throughout the dosing period 

and at termination.

3. Food Consumption (Optional): Food consumption was not determined. 

4. Necropsy and Measurement of Uterine Weight: On PND 22 (approximately 24 hours 

after final administration of the test substance), all surviving animals were anesthetized by 

CO2, euthanized 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 nicked three times and gently blotted with moist filter paper to remove the luminal 

fluid, and the blotted uterus was weighed. Uterine desiccation was avoided. After 

weighing, the uteri were fixed in 10% neutral phosphate-buffered formalin for potential 

future examination. 

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: No clinical signs of toxicity were observed in animals for any 

dose groups. 

No precocious vaginal opening was observed in the pronamide treated groups or vehicle 

control. One animal exhibited precocious vaginal opening in the positive control group 

(EE).

B. BODY WEIGHT AND WEIGHT GAIN: Body weight and body weight gain data are 

presented in Table 2. The body weights and overall body weight gain were decreased in all 

pronamide treated groups. Body weights were decreased (p<0.05) at 25 mg/kg/day (↓11%, 

Day 4), 100 mg/kg/day (↓7-8%, Days 3-4), and 400 mg/kg/day (↓10-25%, Days 2-4). 

Overall body weight gains were decreased (p<0.05) for the 25, 100 and 400 mg/kg/day by 

58, 38, and 112%, respectively. 

In the positive control group (EE), body weights on Day 4 were decreased (p<0.05) by 14%, 

and overall body weight gains decreased (p<0.05) for Days 1-4 (↓58%).

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TABLE 2. Group Body Weights and Cumulative Body Weight Gains (g) in the Estrogen Agonist Assay a

Study Day

#

Dose Group (mg/kg/day)

Vehicle Control Pronamide

(25)

Pronamide

(100)

Pronamide

(400)

Estrogen, EE

(10 μg/kg/day)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

1 6 44.1 2.2 6 45.1 2.3 6 44.3 2.1 6 44.4 1.7 6 43.8 2.0

2 6 48.3 2.4 6 47.6 2.2 6 45.6 2.4 6 43.5*

(↓10) 1.7 6 46.1 2.2

3 6 53.3 2.7 6 52.5 2.3 6 49.4*

(↓7) 2.0 6 41.5*(↓22) 2.0 6 50.3 2.7

4 6 57.0 2.9 6 50.5*

(↓11) 2.5 6 52.3*(↓8) 2.1 6 42.9*(↓25) 4.2 6 49.2*(↓14) 2.1

BWG

Days 1-4 6 12.9 1.2 6 5.4*(↓58) 0.8 6 8.0*(↓38) 1.0 6 -1.6*(↓112) 5.2 6 5.4*(↓58) 0.8

a Data were obtained from Table 3 on page 29 of the study report. 

N No. of animals in the group

SD Standard Deviation

* Significantly different from vehicle control at p < 0.05.

C. FOOD CONSUMPTION (OPTIONAL): Food consumption was not determined. 

D. PATHOLOGY

1. Uterine Weights: Uterine weight data are presented in Table 3. Uterine weights in the 

pronamide treated groups were comparable to the controls.

Absolute wet and blotted uterus weights for the positive EE group were increased (p<0.05) 

by 797% and 423%, respectively. These wet and blotted uterine weights increased as

expected.

Imbibed and blotted weights in the vehicle group were within the range of historic control 

values 0.0234 – 0.0318 g (0.0259± 0.0032 g) and 0.0209-0.0308 g (0.0240±0.0037 g), 

respectively, in the corn oil vehicle-control animals in six studies. Mean imbibed and 

blotted uterine weights in untreated control animals in four other studies (historical control 

data) were (0.0254±0.0032 g and 0.0235±0.0022 g) similar to the weights seen in the 

current methylcellulose vehicle controls. It was concluded that there was no estrogenic 

potential from the vehicle used in this study. 

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TABLE 3. Uterine Weights (g) from Estrogen Agonist Assay in SD Rats a

Parameter

Dose Group (mg/kg/day)

Vehicle Control Pronamide

(25) 

Pronamide 

(100) 

Pronamide

(400) 

Estrogen, EE 

(10 μg/kg/day)

N Mean SD N Mean SD N Mean SD N Mean SD N Mean SD

Terminal BW (g) 6 57.0 2.9 6 50.5*

(↓11) 2.5 6 52.3*(↓8) 2.1 6 42.9*(↓25) 4.2 6 49.2*(↓14) 2.1

Wet, absolute (g) 6 0.0250 0.0033 5 0.0239 0.0031 6 0.0205 0.0028 6 0.0181 0.0025 5 0.2243*

(↑797) 0.0377

Wet, 

relative (%) c 6 0.044 0.006 6 0.047 0.004 6 0.039 0.006 6 0.042 0.004 6 0.455 0.079

Blotted, absolute 

(g) 6 0.0231 0.0040 6 0.0189 0.0057 6 0.0198 0.0015 6 0.0162 0.0036 6 0.1208*(↑423) 0.0157

Blotted, relative 

(%) c 6 0.040 0.006 6 0.037 0.011 6 0.038 0.004 6 0.038 0.009 6 0.246 0.031

a Data were obtained from Table 4 on page 30 of the study report. Percent difference from controls (calculated by reviewer) 

is presented in parentheses.

b Two wet uterine weights were excluded from analysis, one from 25 mg/kg/day (0.0228 g) and one from EE group (0.1428 

g). 

c Relative wet and blotted uterine weights were calculated by the reviewer from the individual data (Appendix Table 2, pages 

35-36). 

BW Body weight

N No. of animals in the group

SD Standard Deviation 

* Significantly different from vehicle control at p < 0.05. 

2. Microscopic Examination (Optional): No microscopic examinations were conducted. 

III. DISCUSSION AND CONCLUSIONS

A. INVESTIGATOR’S CONCLUSIONS: There was no animal mortality or treatmentrelated clinical signs observed in this study. All pronamide-dosed animals had significantly 

decreased body weight gains throughout the study period. At study termination, pronamidetreated animals at dose levels of 25, 100, and 400 mg/kg bw/day exhibited 11.4%, 8.3%, and 

24.7% decreases in body weight gains, respectively, compared to the vehicle-control 

animals. Significant body weight decreases were observed in the 400 mg/kg bw/day 

pronamide group (TD 2-4) and in the 100 mg/kg bw/day pronamide group (TD 3-4). 

However, there were no treatment-related increases in mean uterine weights (wet or blotted) 

in immature rats treated with ≤400 mg/kg bw/day pronamide. Neither the vehicle control 

animals nor the pronamide-treated animals had precocious vaginal opening. The EE 

positive-control group had a 13.7% decrease in terminal body weight compared to the 

vehicle-control group. In contrast to the body weight decrease, the positive-control group 

animals had 797.2% and 422.9% increases in imbibed and blotted uterine weights, 

respectively. One rat in the EE positive-control group exhibited precocious vaginal 

opening. Uterine weights of the vehicle-control animals met the performance criteria 

outlined in the applicable test guidelines, indicating acceptable assay sensitivity. 

Overall, under the conditions of this study, there was no indication of estrogenicity in 

immature female rats at doses ≤400 mg/kg bw/day pronamide, the highest dose level tested 

in female immature rats.

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B. AGENCY COMMENTS: All animals survived until scheduled termination. No clinical 

signs of toxicity were observed in animals for any pronamide treated groups, and no 

precocious vaginal opening was observed in the treated females. The body weights and 

overall body weight gain were decreased in all pronamide treated groups. Body weights 

were decreased (p<0.05) for 25 mg/kg/day (↓11%, Day 4), 100 mg/kg/day (↓7-8%, Days 

3-4), and 400 mg/kg/day (↓10-25%, Days 2-4). Overall body weight gains were decreased 

(p<0.05) for the 25, 100 and 400 mg/kg/day by 58, 38, and 112%, respectively. Uterine 

weights in the pronamide treated groups were comparable to the controls. Absolute wet and 

blotted uterus weights for the positive EE group were increased (p<0.05) by 797% and 

423%, respectively, as expected. 

Dosing for the assay (high dose of 400 mg/kg/day) was adequate based on decreased body 

weight observed at all doses. 

No statistically significant changes were seen in uterine weight in this assay. Pronamide is 

negative in the uterotrophic 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 temperature at which the test substance was found to be stable in 0.5% 

methylcellulose was not reported. 

• Six immature females were housed per cage; three/cage is recommended.

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