??? ??????

??? ???? ??	?????? ?????????? ? ?????? ? ??? ???????
??????	???? ????
????	cardiotoxicology (en)
???????	?????

??? ??????? ?? ??? ?? ??? ??????? ????????? ????? ???????? ???? ?????? ????? ?????? ?????????? ??? ????? ???????? ????? ?????? ??????? ??? ??? ???????? ???? ???? ??? ?????? ?????? ?????? ???????? ?????? ?????????? ??? ???????? ????? ???????? ???? ?????? ??? ?????? ?????????? ?????? ???????? ???? ???? ??? ??????? ???? ?????? ?????? ????? ?? ??? ?????? ??????.

???? ??? ?????? [ ??? ]

?????? ???????? ?????????? (Dioscorides) ?? ??? ?? ???? ????? ???????? ??? ????????? ?????? ?????????. ??? ????? ??? ????? ?? ?????? ?? ????? ?????? ?? ?????? ????????. ????? ????? ??????? (Mathieu Orfila) ???? ?????? ???? ?????? ??? ???? ??? ????? ???? ??????? ??? 1813? ?? ????? ???? ????? (Traite des poisons). ?? ??? 1850 ??? ??? ???? (Jean Stas) ?????? ??? ?? ???????? (de Bocarme Hypolyte Visart) ??? ???? ?? ???? ?????? ?????????? . ?????????? ??????? (Theophrastus Phillipus Auroleus Bombastus von Hohenheim) ???? ??? ??? ???? (1493?1541?) ???? ????? ??? ???? ??????. ???? ?? ????? ?????? ≪?? ??????? ???? ??? ???? ??? ???? ????? ????? ?????? ?? ?? ???? ??????? ??? ????≫. ?????? ??? ??????? ??? ≪?????? ???? ??????≫.

’’’??????? ??? ?????? ?????? ??? ?????? ????’’’ ???? ????? ??? ???? ????? ???? ?? ??? ??????. ??????? ??????? ???? ????? ????? ???? ???????? ?? ?????? (???? ?????? ??????). ?? ?????? ????? ???? ?? ?????? ????????. ???? ??????? LD50 ??? ?????? ?? ?????? ?????? ???? ???? 50% ?? ?????? ?????? ????? (????? ?? ???? ????? ?? ????? ???? ????? ????? ???????? ??????? ??? ???????).

?????????? (Dioscorides) ???? ?? ??? ?????? ?? ???? ?????????? ???????? (????)? ??? ????????? ?????? ?????? ???????? ????? ?????????? ???????? ???????. ^[1] ??? ( ??? ????? ) ?????? ???? ?? ?????? ?? ????? ?????? ??????? ????????. ^[2]

??? ?????? ????? ??????? ???? ?????? ???? ??????? ??? ????? ??????? ???? ????????? ??????? ?? ??? 1813 ?? ????? (Traite des poisons)? ???? ???? Toxicologiegenerale.????? ???? ??? ?????? ?????.. ^[3]

?? ??? 1850? ???? ??? ???? ^[??????????] ??? ??? ???? ???? ?????? ???????? ?? ??????? ???????? ???? ???? ?? ?????? ??? ????????? ????? ???? ?? ???? ??? ?????? ???????? ?????? ?????? ??????? ?????? ?????? ???????? ???????? ?????? ?? ???????" Hippolyte Visart de Bocarme ^[??????????]" ???? ?? ?????.

??? ?????? ?????????? ??? ????????? "Theophrastus PhillipusAuroleusBombastus von Hohenheim " 1493- 1541 (???? ???? ???? ? ??????????? ≪ ?????????? ≫? ???? ???? ??????? ??? ??????? ???? ??? ?? ?? ???? ????? ?????? "Celsus"- ??? ???? ?????? ?? ????? ?????)???? ???? ??????. ????? ???? ????? ????????? ??????? ?? ??? ??????:"Alle Dinge sind Gift und nichtsistohne Gift; allein die Dosismacht, dassein Ding kein Gift ist " ????? ??? ??????? ????: ?? ??????? ????? ?? ???? ??? ??? ???? ?? ??????? ??? ?????? ?? ???? ???? ??? ????? ??????? ?? ??. ?????? ?? ????? ??? ??????? ????? ??????????:"Sola dosisfacitvenenum" ?????? ????: ?????? ???? ????????. ^[4]:30

??????? ?? ??? ?????? [ ??? ]

??? ????? ???????: ?? ????? ??????? ??????? (??????) ????? ??. ^[5] ??????? ?????? ????? ??? ?????? ????????: 1.????? ?????? ?????? (???????) (?? ???? ????? ?????????? ?? ?????) 2.?????? (????? ???????? ?????? ??). ???????? ????? ??? ??? ?????? ?????? ???? ??????. ^[6] ???? ???????? ?????? ?????? ?? ??????? ?????? ???? ?? ???? ?????? ????? ???????? ?????? ????? ???? ???????. ^[6]

??????? ???? ???? ???????? ?????????? [ ??? ]

??????

??? ????? ??? ????????: ?????? ????? ????? (????)? ??????? ??????? ????? ????? (?????).

????? ?????? ??????:

??????? ?? ???? ?????????? ?? ?? ???? ?????? ?????.

????? ????:
?????
?????
?????
?????
??????
????? ?????

??? ???????? [ ??? ]

??????? ???? ???? ???????? ?? ????? ??? ???? ??? ?????? ???? (??????? ?? ???????)? ?? ???? ??? ?????? ???? (?????? ??? ????? ?? ????? ??????)? ?? ???????? (??? ?????? ?????????). ^[7]

??? ??????? ??? ????????? [ ??? ]

?????? ????????? ??????? ?? ??? ??????: ?? ???????? ??? ?????????.. ^[4] ??? ??? 2014? ???? ??????? ??? ????????? ????????? ???? ?? ??? ??????? ???????? ?????? ?? ???? ??? ??? ?????? ?? ?????? ????. ^[8]

??? ???????? ??????? [ ??? ]

????? ???? ??????? ??? ????????? ?? ???? ????? ?????? ??????? ??? ???????? ???? ????? ??????? ?????? ???? ????? ???????? ??? ?????????. ^[9] ?? ????? ?? 1950? ??? ???? ??? ?????? ??? ??????? ?? ?????? ??? ??????? ??? ????????? ??? ?????: ≪?? ????? ???????≫ ?? "three R's"? ????? ??? ??????? ??? ????????? ???? ?????? ?? ???????? ????? ??????? ??? ??????? ????? ??? ?????? ??? ?????????? ???????? ??????? ???? ???? ???? ?????? ???? ??????? ??????? ?? ??????? ????? ?????? ?????? ????? ??? ??? ??? ?????. ^[10]^[11] ?? ??? ???????? ?? ??????? ?? ????? ???????? ??? ????????? ????? ??????? ?? ???????? ??? ??? 2013? ??? ??????? ???????? ???? ????? ??????? ??? ????????? ??? ??? ?????? ???????? ???????. ^[12]

??????? ??????? ????????? ?? ???? ??? ??? ???????? ???????? ???????? ??? ??????? ?????? ?????????? ???????????? ???? ????? ?? ????? ????? ????? ?? ??????? ??? ???? ?? ????? ?????? ?????????? ???? ?????? ???????? ????????? ?? ?????????? ??? ??????? ????????. ^[13] ??? ????? ????? ???? ?? ????? ???????? ?????????? ???????? ??? ???? ???? ?? ???????? ???????? ???? ??????. ^[13]

??? ?????? ??????? [ ??? ]

???? ??? ?????? ??????? ???? ???? ????? ??????? ?????? ????? ??? ?????????? ???? ???? ???? ??????? ?????????? ?????? ?????? ??????? ?? ???????? ??????? ???????????. . ^[14] ??? ????? ??? ?????? ?? ????? ?????? ???????? ^[15]^[16] ?? ????? "deep neural network" ? "Random Forest" ? Support vector Machines" " ????? ??????? ???? ???? ??????? ????? ???? ?? ??? ???? ???? ??????? ?? ???????.

??? ?????? ????? [ ??? ]

???? ?????? ?? ?????? ?? ??? ??????? ?? ?????? ?? ????? ?? ?????? ????? ???? ?? ????? ??????? ???????? ????????? ??????? ??????? ????? ????? ?????. ????? ????? ?? ??????? ??? ????? ?? ???? ??? ???? ?? ??? ?????? ?? ???? ?????? ???? ?? ??????? ? ?? ???????? ?? ???????? ??????? ? ????? ?????? ???? ?????? ?? ???????? ????????? ?? ????? ????? ???????? ?? ???????? ??????????? ??? ??????? ????????? ????????? ?????? ????? ????????? ???????????? ???????? ??? ??????? ?????? ??????? ?????????? ?????????. ???????? ??? ??? ?????? ???? ?????? ?? ???????? ?? ???? ??? ?????? ????? ???? ?????? ????? ????????? ?????? ?? ??? ???????. ???: ?????? ?????? ??? ???????toxicogenomics ???? ?????? ??????? Aquatic toxicology) ???? ?????? ????????? (?????????) (Chemical (pharmaceutical) toxicology) ?Ecotoxicology ???? ?????? ?????? ((Environmental toxicology ???? ?????? ?? ???? ?????? (Forensic toxicology) ???? ?????? ??????? (Nanotoxicology) ???? ?????? ????? Medical toxicology))

??? ?????? ????????? (?????????) [ ??? ]

????? ???? ????? ??????? ????? ????? ???????? ???????? ????? ????? ????????. ????? ??????? ??????? ????? ?????? ?????? ???????? ?? ??? ???????. ??????? ?? ??? ?????? ?????? ???????? ???? ???? ??? ???? ???: ???????? ????????? (computational chemistry), ????????? ????????? (synthetic chemistry), ??????? ??????? (drug discovery), ????? ??????? ??????? (drug metabolism), ????? ????? (mechanisms of action).

????????? [ ??? ]

??? ?????? ????? ????? ?? ?????? (???? ?? ??? ??????)? ??? ????? ?? ???? ??? ???? ?? ??? ?????? ?? ???? ?????? ???? ?? ???????? ?? ???????? ?? ???????? ???????. ????? ???? ??????????? ???? ??????? ????????? ?????? ??????? ???????? ??? ?????? ??? ???????? ???????? ??? ????? ???????≪??????????≫? ??? ??????. ??? ???????? ?? ???????? ????????? ????? ??????? ???? ?????? ????????? ??? ??????? ?????? ????? ??? ?????? ???????? ????????? ??????? ????? ???? ???????? ?????? ?????? ??? ?????? ??????? ????? ???????? ???????? ?? ????? ???????? ????? ???? ?????? ??? ?????? ?? ?????. ???? ????? ??? ?????? ^[??????????] (???)? ??? ?????? ????? ?? ??????? ??? ?? ??????? ???????? ?? ??????? ???? ?? ???? ???? ????????? ?? ??? ?????? ?????? ?? ????? ????? ????????? ?? ???????. ???????? ????? ???? ????? ?? (???) ????? ?????? ???????? ???? ????? ?? ??????? ??????????? ???????? ???? ???? ?? ?????????? ?? ???? ????? ??????? ??????? ????? ??? ??????? ????????.

???????? [ ??? ]

???? ???? ?????? ??????? ?? ????????? ?? ????? ??????? ??????????? ????????? ??? ??????? ????????? ????????? ????? ????? ????????? ??????????? ??????? ??????? ???????? ????????. ??? ???? ????? ???? ?????? ?????? ????? ??????? ?? ??? ????? ?????? ???? ?????? ??????????. ??? ??????? ????? ?? ????? ?????? ??????? ?????? ????? ???? ?? ???? ????? ???????? ???????? ????? ????? ?? ???? ??????? ??? ???????? ???? ???? ???? ??????? ?????. ?? ?????? ???????? ??????? ?? ????? ???? ???????? ?????? ??? ??????? ?????? ??? ??????? ???? ??????? ?????? ???????? ????????? ?? ???????? ??????????? ?? ??? ?? ?? ???????? ???????? ?????? ?????? ?? ????? ????? ?????? ?????????? ??? ?????? ???? ???????? ?????? ??????? ??????? ?? ????? ????????? ??? ??????? ????????? ??? ???? ??????: ?? ???? ????? ?????? ???????? ????? ?????? ??? ?????? ?????? ?? ???? ???????? ????? ????? ?????? ??????? ????? ?????? ?????? ????? ??????? ?? ?????? ???????.

??????? [ ??? ]

??????? ??????? ?? ??? ??????? ????? ??? ??? ?????: ???? ??????? ??????? ?????? ???????? ??????? ???????. ????? ?????? ???????? ???????? ????? (BLS)? ?? ??????? ??????? ??????????? ????? ???? ??? ???? ????? ??????? ?? ??????? ?? ????? ????? 21% ??? ???? 2008 ? 2018. ??? ????? ?? (BLS)? ?? ??? ??????? ?? ???? ???? ????? ???????? ?? ???? ??????????? ???????? ???????? ??? ?????? ??????? ?????? ?????? ????????? ?? ?????? ????????.

???? ?????? ??????? ?? ????? ????? ???? ????? [ ??? ]

?????? ?? ?????? ???? ????? ???? ???? ??????? ????? ???? ??? ?????. ????: ??????? ?? ????????? ????? ???? ????? ?? ???? ????? ??? ??????????? ???? ???????? (formaldehyde and formic acid) ?????? ???????? ??? ????? ?? ????? ????? ??????. ??????? ???????? ?????? ?? ??????? ????? ??? ???? ?? ?????? ???? ??? ??? ???????????? (???????????) ????? ??? ??????? ???????? ??? ??????. ?????????? ??????? ?? ??? ??????? ????? ???? ?????? ???? ??? ?????? ????? ?? ??? ????. ??? ??????? ???? ???? ??? ????? ?? ????? ????. ???? ????? ???? ??? ????????? ?? ??? ?????? ?????: ?????? ??? ??????? ????? ???? ???? ?????? ??? ??? ??? ?? ????? ??? ??????? ???? ?? ??? ??? ?? ?? ????? ???? ??? ??????.

???????? ??? ??? ?????? [ ??? ]

???? ?????? ?? ???????? ?? ???? ??? ?????? ????? ???? ?????? ????? ????????? ?????? ?? ??? ???????. ???:

????? ?????? ??? ??????? toxicogenomics
??? ?????? ??????? Aquatic toxicology)
??? ?????? ????????? (?????????) (Chemical (pharmaceutical) toxicology)
Ecotoxicology
??? ?????? ?????? ((Environmental toxicology
??? ?????? ?? ???? ?????? (Forensic toxicology)
??? ?????? ??????? (Nanotoxicology)
??? ?????? ????? Medical toxicology))

??? ?????? ????????? (?????????) [ ??? ]

?? ??? ???? ????? ??????? ????? ????? ???????? ???????? ????? ????? ????????. ????? ??????? ??????? ????? ?????? ?????? ???????? ?? ??? ???????. ??????? ?? ??? ?????? ?????? ???????? ???? ???? ??? ???? ???: ???????? ????????? (computational chemistry), ????????? ????????? (synthetic chemistry), ??????? ??????? (drug discovery), ???? ??????? (drug metabolism), ????? ????? (mechanisms of action).

???? ???? [ ??? ]

????? [ ??? ]

^ Hodgson? Ernest (2010). A Textbook of Modern Toxicology . John Wiley and Sons. ?. 10 . ISBN : 0-470-46206-X .
^ Levey? Martin (1966). Medieval Arabic Toxicology: The Book on Poisons of ibn Wahshiyya and its Relation to Early Native American and Greek Texts .
^ "Biography of Mathieu Joseph Bonaventure Orfila (1787?1853)" . U.S. National Library of Medicine. ????? ?? ????? ?? 2019-04-04.
^ ^? ^? Ottoboni? M. Alice (1991). The dose makes the poison : a plain-language guide to toxicology (?. 2nd). New York, N.Y: Van Nostrand Reinhold. ISBN : 0-442-00660-8 .
^ Committee on Risk Assessment of Hazardous Air Pollutants, Commission on Life Sciences, National Research Council (1994). Science and judgement in risk assessment . The National Academic Press. ?. 56. ISBN : 978-0-309-07490-2 . {{ ??????? ????? }}: ????? ?????????: ????? ??????: ????? ???????? ( link )
^ ^? ^? "Human Health Toxicity Assessment" . United States Environmental Protection Agencies. ????? ?? ????? ?? 2014-12-09.
^ Bruin? Yuri.? ?????? (2009). "Testing methods and toxicity assessment (Including alternatives)". Academic Press . ELSEVIER: 497?514. DOI : 10.1016/B978-0-12-373593-5.00060-4 . {{ ??????? ?????? ????? }}: Explicit use of et al. in: |?????= ( ?????? )
^ "The importance of animal in research" . Society of Toxicology. 2014. ????? ?? ????? ?? 2016-01-26.
^ "Existing Non-animal Alternatives" . AltTox.org. 8 ?????? 2011. ????? ?? ????? ?? 2014-04-28.
^ "Alternative toxicity test methods: reducing, refining and replacing animal use for safety testing" (PDF) . Society of Toxicology. ????? ?? ????? (PDF) ?? 2016-03-04.
^ Alan M. Goldberg. The Principles of Humane Experimental Technique: Is It Relevant Today? Altex 27, Special Issue 2010 ???? ?????? 2016-03-04 ?? Wayback Machine
^ Adler. S.? ?????? (2011). "Alternative (non-animal)methods for cosmetic testing: current status and future prospects - 2010". Arch Toxicol . Springer-Verlag. ?. 85 ?. 1: 367?485. DOI : 10.1007/s00204-011-0693-2 . {{ ??????? ?????? ????? }}: Explicit use of et al. in: |????= ( ?????? )
^ ^? ^? Leeuwen van.C.J., Vermeire T.G. (2007). Risk assessment of chemicals: An introduction . New York: Springer. ?. 451?479. ISBN : 978-1-4020-6102-8 .
^ Reisfeld? B? Mayeno? A. N. (2012). "What is Computational Toxicology?". Computational Toxicology . Methods in Molecular Biology. ?. 929. ?. 3?7. DOI : 10.1007/978-1-62703-050-2_1 . ISBN : 978-1-62703-049-6 . PMID : 23007423 .
^ Hartung? T (2009). "A toxicology for the 21st century--mapping the road ahead" . Toxicological Sciences . ?. 109 ?. 1: 18?23. DOI : 10.1093/toxsci/kfp059 . PMC : 2675641 . PMID : 19357069 .
^ Berg? N? De Wever? B? Fuchs? H. W.? Gaca? M? Krul? C? Roggen? E. L. (2011). "Toxicology in the 21st century--working our way towards a visionary reality". Toxicology in Vitro . ?. 25 ?. 4: 874?81. DOI : 10.1016/j.tiv.2011.02.008 . PMID : 21338664 .

Amdur MO, Doull J, Klaassen, CD. 1993. Cassarett and Doull's Toxicology: The Basic Science of Poisons. New York: McGraw-Hill, Inc.
Gilbert SG. A Small Dose of Toxicology ? The Health Effects of Common Chemicals . CRC Press, Boca Raton, February 2004 , p 266. ? see web site http://www.asmalldoseof.org/
Hodgeson E, Levi PE. 1987. A Textbook of Modern Toxicology. New York: Elsevier Science Publishing Co., Inc.

????? ?????? [ ??? ]

?? ????? ??? ?????? ??: ??? ??????

[1] Hodgson? Ernest (2010). A Textbook of Modern Toxicology . John Wiley and Sons. ?. 10 . ISBN : 0-470-46206-X .

[2] Levey? Martin (1966). Medieval Arabic Toxicology: The Book on Poisons of ibn Wahshiyya and its Relation to Early Native American and Greek Texts .

[3] "Biography of Mathieu Joseph Bonaventure Orfila (1787?1853)" . U.S. National Library of Medicine. ????? ?? ????? ?? 2019-04-04.

[Ottoboni-4] ? ^? Ottoboni? M. Alice (1991). The dose makes the poison : a plain-language guide to toxicology (?. 2nd). New York, N.Y: Van Nostrand Reinhold. ISBN : 0-442-00660-8 .

[5] Committee on Risk Assessment of Hazardous Air Pollutants, Commission on Life Sciences, National Research Council (1994). Science and judgement in risk assessment . The National Academic Press. ?. 56. ISBN : 978-0-309-07490-2 . {{ ??????? ????? }}: ????? ?????????: ????? ??????: ????? ???????? ( link )

[d1-6] ? ^? "Human Health Toxicity Assessment" . United States Environmental Protection Agencies. ????? ?? ????? ?? 2014-12-09.

[a1-7] Bruin? Yuri.? ?????? (2009). "Testing methods and toxicity assessment (Including alternatives)". Academic Press . ELSEVIER: 497?514. DOI : 10.1016/B978-0-12-373593-5.00060-4 . {{ ??????? ?????? ????? }}: Explicit use of et al. in: |?????= ( ?????? )

[8] "The importance of animal in research" . Society of Toxicology. 2014. ????? ?? ????? ?? 2016-01-26.

[9] "Existing Non-animal Alternatives" . AltTox.org. 8 ?????? 2011. ????? ?? ????? ?? 2014-04-28.

[b1-10] "Alternative toxicity test methods: reducing, refining and replacing animal use for safety testing" (PDF) . Society of Toxicology. ????? ?? ????? (PDF) ?? 2016-03-04.

[11] Alan M. Goldberg. The Principles of Humane Experimental Technique: Is It Relevant Today? Altex 27, Special Issue 2010 ???? ?????? 2016-03-04 ?? Wayback Machine

[12] Adler. S.? ?????? (2011). "Alternative (non-animal)methods for cosmetic testing: current status and future prospects - 2010". Arch Toxicol . Springer-Verlag. ?. 85 ?. 1: 367?485. DOI : 10.1007/s00204-011-0693-2 . {{ ??????? ?????? ????? }}: Explicit use of et al. in: |????= ( ?????? )

[c1-13] ? ^? Leeuwen van.C.J., Vermeire T.G. (2007). Risk assessment of chemicals: An introduction . New York: Springer. ?. 451?479. ISBN : 978-1-4020-6102-8 .

[Reisfeld2012-14] Reisfeld? B? Mayeno? A. N. (2012). "What is Computational Toxicology?". Computational Toxicology . Methods in Molecular Biology. ?. 929. ?. 3?7. DOI : 10.1007/978-1-62703-050-2_1 . ISBN : 978-1-62703-049-6 . PMID : 23007423 .

[Hartung2009-15] Hartung? T (2009). "A toxicology for the 21st century--mapping the road ahead" . Toxicological Sciences . ?. 109 ?. 1: 18?23. DOI : 10.1093/toxsci/kfp059 . PMC : 2675641 . PMID : 19357069 .

[Hartung2011-16] Berg? N? De Wever? B? Fuchs? H. W.? Gaca? M? Krul? C? Roggen? E. L. (2011). "Toxicology in the 21st century--working our way towards a visionary reality". Toxicology in Vitro . ?. 25 ?. 4: 874?81. DOI : 10.1016/j.tiv.2011.02.008 . PMID : 21338664 .

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???????	????? ??? ??????? ??????? ?????? ??? ??????? ??????? ????? ??????? ?????? ??????? ???? ????????? ??????? ?????? ?????????? ?????? ??????? ?????? ??????? ???? ????? ??????? ?????? ????? ??????/????? ?????? ??????? ?????? ????? ??? ??????? ??????? ???? ??????? ?????? ???? ??????? ?????? ??????? ??? ???????? ?????? (??????) ?????? ????
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