50-78-2BSYNRYMUTXBXSQ-UHFFFAOYSA-NBSYNRYMUTXBXSQ-UHFFFAOYSA-N
AspirinAcetylsalicylic acid
Benzoic acid, 2-(acetyloxy)-
2-(ACETYLOXYBENZOIC) ACID
2-(Acetyloxy)benzoic acid
2-Acetoxybenzoic acid
2-Carboxyphenyl acetate
A.S.A. Empirin
Acenterine
Acetard
Aceticyl
Acetilum acidulatum
Acetisal
Acetonyl
Acetophen
Acetosal
Acetosalic acid
Acetosalin
Acetylin
Acetylsal
ACETYLSALICYLSAEURE
Acetyonyl
Acetysal
Acide O-acetylsalicylique
acido O-acetilsalicilico
Acidum acetylsalicylicum
Acimetten
Acylpyrin
Albyl E
Asaflow
Asagran
Asatard
Ascolong
Ascriptin
Aspalon
Aspergum
Aspirdrops
Aspirina 03
Aspirin-Direkt
Aspro Clear
Aspropharm
Asteric
Benaspir
Bialpirina
Bialpirinia
Cardioaspirina
Claradin
Colfarit
Contrheuma Retard
Coricidin
Coricidin D
Dolean pH 8
Dominal
Duramax
Easprin
Ecotrin
Empirin
Endosprin
Endydol
Entericin
Enterophen
Enterosarine
Entrophen
Gelprin
Globentyl
Globoid
Helicon
Idragin
Istopirin
Kapsazal
Magnecyl
Measurin
Medisyl
Melhoral
Micristin
Miniasal
Neuronika
NSC 27223
NSC 406186
Nu-seals
o-(Acetyloxy)benzoic acid
o-Acetoxybenzoic acid
O-acetylsalicylic acid
O-Acetylsalicylsaure
o-Carboxyphenyl acetate
Persistin
Polopiryna
Rheumintabletten
Rhodine
Rhodine 2312
Rhodine NC RP
Salacetin
Salcetogen
Saletin
Salicylic acid acetate
SALICYLIC ACID, ACETYL-
Salospir
Salycylacetylsalicylic acid
Solpyron
Temperal
Triple-sal
Trombyl
Zorprin
DTXSID502010815307-79-6KPHWPUGNDIVLNH-UHFFFAOYSA-MKPHWPUGNDIVLNH-UHFFFAOYSA-M
Diclofenac sodiumBenzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-, monosodium salt
[2-[(2,6-dichlorophenyl)amino]phenyl]acetate de sodium
[2-[(2,6-diclorofenil)amino]fenil]acetato de sodio
[o-(2,6-Dichloroanilino)phenyl]acetic acid sodium salt
{2-[(2,6-Dichlorophenyl)amino]phenyl}acetate de sodium
2-(2,6-Dichloroanilino)phenylacetic acid sodium salt
2-[(2,6-Dichlorophenyl)amino]benzene acetic acid monosodium salt
Acetic acid, [o-(2,6-dichloroanilino)phenyl]-, monosodium salt
Allvoran
Assaren
Benfofen
Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-, sodium salt (1:1)
Cataflam
Delphimix
Diacron
Dichronic
Diclobene
Diclobenin
Diclodyn
Diclofen SR 100
Diclofenac sodium salt
Diclofenac-Na Emulgel
Diclofenacsodium Emulgel
Diclokalium
Diclophenac sodium
Diclo-Phlogont
Diclo-Puren
Diclord
Diclorep
Dicloreum
Diklovit
Dolobasan
Duravolten
Dyloject
Effekton
Evofenac
Feloran
Fortfen
Hyanalgese D
Inflaban
Kriplex
N-(2,6-Dichlorophenyl)-o-aminophenylacetic acid sodium salt
Natrium-[2-[(2,6-dichlorphenyl)amino]phenyl]acetat
Neriodin
Novapirina
Orthofen
Orthophen
Primofenac
Profenac
Prophenatin
Rhumalgan
sodium [2-[(2,6-dichlorophenyl)amino]phenyl]acetate
Sodium [o-(2,6-dichloroanilino)phenyl]acetate
Sodium 2-(2,6-dichloroanilino)-phenyl-acetate
Sodium diclofenac
Sorelmon
Tsudohmin
Valetan
Voltaren
Voltaren Ophtha
Voltaren Ophtha CD
Voltarol
Voveran
DTXSID303720853-86-1CGIGDMFJXJATDK-UHFFFAOYSA-NCGIGDMFJXJATDK-UHFFFAOYSA-N
1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-Indole-3-acetic acid1H-Indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-
[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
1-(4-Chlorobenzoyl)-2-methyl-5-methoxyindole-3-acetic acid
1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid
1-(4-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
1-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid
1-(p-Chlorobenzoyl)-2-methyl-5-methoxyindole-3-acetic acid
1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid
1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
Artracin
Artrinovo
Artrivia
Bonidin
Bonidon Gel
Chibro-Amuno
Chrono-Indicid
Chrono-Indocid 75
Confortid
Dolcidium
Dolcidium PL
Dolovin
Durametacin
Elmetacin
Idomethine
Imbrilon
Indacin
Indocid
Indocin
Indocollyre
Indole-3-acetic acid, 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-
Indomecol
Indomed
Indomee
indometacin
indometacina
Indometacine
Indomethacine
Indomethine
Indomod
Indonol
Indo-Phlogont
Indoptic
Indoptol
Indo-Rectolmin
Indorektal
IndoRich
Indo-Tablinen
Indoxen
Inflazon
Infrocin
Innamit
Inteban
Inteban SP
Metacen
Metartril
Methazine
Metindol
Mezolin
Mikametan
Mobilan
N-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid
NSC 77541
Reumacide
Rheumacin LA
Sadoreum
Vital Vitacid
α-[1-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolyl]acetic acid
DTXSID902074022204-53-1CMWTZPSULFXXJA-VIFPVBQESA-NCMWTZPSULFXXJA-VIFPVBQESA-N
Naproxen2-Naphthaleneacetic acid, 6-methoxy-α-methyl-, (αS)-
(+)-(S)-Naproxen
(+)-2-(6-Methoxy-2-naphthyl)propionic acid
(+)-6-Methoxy-α-methyl-2-naphthaleneacetic acid
(+)-Naproxen
(S)-(+)-2-(6-Methoxy-2-naphthyl)propionic acid
(S)-(+)-Naproxen
(S)-(+)-Naproxene
(S)-2-(6-Methoxy-2-naphthyl)propanoic acid
(S)-2-(6-Methoxy-2-naphthyl)propionic acid
(S)-2-(6-Methoxynaphthalen-2-yl)propanoic acid
(S)-2-(6-Methoxynaphthalen-2-yl)propionic acid
(S)-6-Methoxy-α-methyl-2-naphthaleneacetic acid
(S)-Naproxen
(S)-α-Methyl-6-methoxynaphthalene-2-acetic acid
2-Naphthaleneacetic acid, 6-methoxy-α-methyl-, (+)-
2-Naphthaleneacetic acid, 6-methoxy-α-methyl-, (S)-
Apo-Naproxen
Aproxen
d-2-(6-Methoxy-2-naphthyl)propionic acid
Diocodal
d-Naproxen
Dysmenalgit
Equiproxen
Floginax
Laraflex
Naprium
Naprius
Naprosyn
Naprosyne
naproxene
naproxeno
Nycopren
Panoxen
Proxine
Veradol
DTXSID404068615687-27-1HEFNNWSXXWATRW-UHFFFAOYNA-NHEFNNWSXXWATRW-UHFFFAOYSA-N
IbuprofenBenzeneacetic acid, α-methyl-4-(2-methylpropyl)-
(.+-.)-2-(p-Isobutylphenyl)propionic acid
(.+-.)-Ibuprofen
(.+-.)-Ibuprophen
(.+-.)-α-Methyl-4-(2-methylpropyl)benzeneacetic acid
(4-Isobutylphenyl)-α-methylacetic acid
(RS)-Ibuprofen
2-(4-Isobutylphenyl)propanoic acid
2-(4'-Isobutylphenyl)propionic acid
2-(4-Isobutylphenyl)propionic acid
2-(p-Isobutylphenyl)propionic acid
4-Isobutylhydratropic acid
4-Isobutyl-α-methylphenylacetic acid
Actiprofen
Algi-Flanderil
Algiflex
Algofen
Amibufen
Anflagen
Antarene
Antiflam
Apo-Ibuprofen
Apsifen
Artofen
Balkaprofen
Betaprofen
Brufanic
Brufen Retard
Bruflam
Brufort
Buburone
Buluofen
Butacortelone
Butylenin
Codral Period Pain
Combiflam
Dansida
Dentigoa
Dibufen
dl-Ibuprofen
Dolgirid
Dolmaral
Dolocyl
Dolo-Dolgit
Dolofen
Dolofen F
Dolomax
Donjust B
Doretrim
Dorival
Easifon
Epobron
Femadon
Fenspan
Gynofug
Haltran
Hydratropic acid, p-isobutyl-
Ibosure
Ibu-Attritin
Ibuflamar
Ibugesic
Ibuleve
Ibulgan
Ibumetin
Ibupirac
Ibupril
Ibuprocin
Ibuprofene
ibuprofeno
Ibuprohm
Ibu-slow
Ibu-Tab
Inabrin
Iprogel
Lamidon
Librofem
Lidifen
Mensoton
Motrin IB
Mynosedin
Nagifen-D
Napacetin
Nobafon
Nobfelon
Noritis
Novogent
Novoprofen
NSC 256857
Nurofen
Optifen
Opturem
Ostarin
Ostofen
p-(2-Methylpropyl)-α-methylphenylacetic acid
Paduden
Panafen
Pantrop
Paxofen
Pediaprofen
Perofen
PHENYLACETIC ACID, 2-METHYL-4-(2-METHYLPROPYL)-
p-Isobutyl-2-phenylpropionic acid
p-Isobutylhydratropic acid
Proartinal
Proflex
Prontalgin
Quadrax
Ranofen
Recidol
Relcofen
Roidenin
Seclodin
Suspren
Syntofene
Tabalon
Tabalon 400
Tatanal
Trendar
Unipron
Uprofen
α-(4-Isobutylphenyl)propionic acid
α-Methyl-4-(2-methylpropyl)benzeneacetic acid
DTXSID5020732155569-91-8Emamectin benzoate4''-Epimethylamino-4''-deoxyavermectin B1a and B1b benzoates
Avermectin B1, 4''-deoxy-4''-(methylamino)-, (4''R)-, benzoate (1:1)
DTXSID0034566100-00-5CZGCEKJOLUNIFY-UHFFFAOYSA-NCZGCEKJOLUNIFY-UHFFFAOYSA-N
1-Chloro-4-nitrobenzeneBenzene, 1-chloro-4-nitro-
p-Chloronitrobenzene
4-Chloronitrobenzene
1-Chlor-4-nitrobenzol
1-cloro-4-nitrobenceno
1-Nitro-4-chlorobenzene
4-Chloro-1-nitrobenzene
4-Nitro-1-chlorobenzene
4-Nitrochlorobenzene
4-Nitrophenyl chloride
NSC 9792
P-CHLORNITROBENZOL
p-Nitrochlorobenzene
p-Nitrophenyl chloride
DTXSID5020281169590-42-5RZEKVGVHFLEQIL-UHFFFAOYSA-NRZEKVGVHFLEQIL-UHFFFAOYSA-N
CelecoxibBenzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-
4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
Celebra
Celebrex
Celecox
Celocoxib
DTXSID0022777112281-77-3LQDARGUHUSPFNL-UHFFFAOYNA-NLQDARGUHUSPFNL-UHFFFAOYSA-N
Tetraconazole1H-1,2,4-Triazole, 1-{2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl}-, (.+-.)-
DTXSID80349562058-46-0UBDNTYUBJLXUNN-IFLJXUKPSA-NUBDNTYUBJLXUNN-IFLJXUKPSA-N
Oxytetracycline hydrochloride2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-, (4S-(4.alpha.,4a.alpha.,5.alpha.,5a.alpha.,6.beta.,12a.alpha.))-
DTXSID5021097CHEBI:15551prostaglandin E2D007987Gonadotropin Releasing HormoneCHEBI:81568Luteinizing hormoneCHEBI:26764steroid hormoneCHEBI:581653',5'-cyclic AMP(1-)PR:000013427prostaglandin G/H synthase 1PR:000013428prostaglandin G/H synthase 2PCO:0000001population of organismsGO:0003707steroid hormone receptor activityGO:0023052signalingGO:0008315G2/MI transition of meiotic cell cycleGO:0022414reproductive processGO:0000003reproductionGO:0004666prostaglandin-endoperoxide synthase activityPCO:0000008population growth rate2decreased1increasedAceytlsalicylic acid2016-11-29T18:42:082016-11-29T18:42:08Diclofenac sodium2016-11-29T18:42:092016-11-29T18:42:09Indomethacin2016-11-29T18:42:172016-11-29T18:42:17Naproxen2016-11-29T18:42:202016-11-29T18:42:20Ibuprofen2016-11-29T18:42:262016-11-29T18:42:26Emamectin benzoate2016-11-29T18:42:262016-11-29T18:42:261-Chloro-4-nitrobenzene2016-11-29T18:42:262016-11-29T18:42:26169590-42-52016-11-29T18:42:262016-11-29T18:42:26Celecoxib2016-11-29T18:42:262016-11-29T18:42:263-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]-1H-pyrazole2016-11-29T18:42:262016-11-29T18:42:26Tetraconazole2016-11-29T18:42:262016-11-29T18:42:262058-46-02016-11-29T18:42:272016-11-29T18:42:27Oxytetracycline hydrochloride2016-11-29T18:42:272016-11-29T18:42:27Sodium (4-fluoro-2-{[(1S)-1-phenylpropyl]carbamoyl}phenyl)(quinolin-8-ylsulfonyl)azanide2016-11-29T18:42:272016-11-29T18:42:27WikiUser_22all speciesWikiUser_4Human, rat, mouseWCS_7957goldfishReduced, Prostaglandin E2 concentration, hypothalamusReduced, Prostaglandin E2 concentration, hypothalamusTissueUBERON:0001898hypothalamus2016-11-29T18:41:262017-09-16T10:15:57Reduced, Gonadotropin releasing hormone, hypothalamusReduced, Gonadotropin releasing hormone, hypothalamusTissueUBERON:0001898hypothalamus2016-11-29T18:41:262017-09-16T10:15:57Reduced, Luteinizing hormone (LH), plasma Reduced, Luteinizing hormone (LH), plasma TissueUBERON:0001969blood plasma2016-11-29T18:41:262017-09-16T10:15:57Reduced, Maturation inducing steroid, plasmaReduced, Maturation inducing steroid, plasmaTissueUBERON:0001969blood plasma2016-11-29T18:41:262017-09-16T10:15:57Reduced, Maturation inducing steroid receptor signalling, oocyteReduced, Maturation inducing steroid receptor signalling, oocyteTissueCL:0000023oocyte2016-11-29T18:41:262017-09-16T10:15:57Reduced, Meiotic prophase I/metaphase I transition, oocyteReduced, Meiotic prophase I/metaphase I transition, oocyteCellularCL:0000024oogonial cell2016-11-29T18:41:262017-09-16T10:15:57Increased, cyclic adenosine monophosphateIncreased, cyclic adenosine monophosphateTissue2016-11-29T18:41:262016-12-03T16:37:51Reduced, Reproductive SuccessReduced, Reproductive SuccessIndividual2016-11-29T18:41:262016-12-03T16:37:51Inhibition, Cyclooxygenase activityInhibition, Cyclooxygenase activityMolecular<p>Prostaglandin-endoperoxide synthase (PTGS; KEGG ID E.C. 1.14.99.1; <a rel="nofollow" target="_blank" class="external autonumber" href="http://www.genome.jp/dbget-bin/www_bget?ec:1.14.99.1">[1]</a>) is an enzyme that has two catalytic sites. Cyclooxygenase site (COX) catalyzes conversion of arachidonic acid into endoperoxide prostaglandin G2 (<a href="/wiki/index.php?title=Simmons_et_al.,_2004&action=edit&redlink=1" class="new" title="Simmons et al., 2004 (page does not exist)">Simmons et al., 2004</a>). Peroxidase active site converts PGG2 to PGH2 (KEGG reactions 1599, 1590, <a rel="nofollow" target="_blank" class="external autonumber" href="http://www.genome.jp/dbget-bin/www_bget?rn:R01599+R01590+R00073">[2]</a>). PGH2 is a precursor for synthesis of other prostaglandins (e.g., PGEs, PGFs; <a rel="nofollow" target="_blank" class="external autonumber" href="http://www.genome.jp/kegg-bin/show_pathway?scale=1.0&query=prostaglandin&map=map00590&scale=&auto_image=&show_description=hide&multi_query">[3]</a>), prostacyclin and thromboxanes (Simmons et al., 2004; Botting and Botting 2011). Two of the COX isoforms (COX-1 and COX-2) encoded by two different genes (ptgs1 and ptgs2) are well characterized. Ptgs1 is typically expressed constitutively and is involved in maintenance of homeostatic functions. Ptgs2 is largely inducible (e.g., by inflammation, during discrete stages of gamete maturation etc.), but can also be constitutively expressed (e.g., kidney; Green et al, 2012). In mammals, COX-3 (a splice of COX-1) has also been identified (Chandrasekharan et al., 2002), but its function is not well characterized and it is not likely to have prostaglandin producing capacity (Bacchi et al., 2012).
</p><p>Most COX inhibitors interfere with COX site via competitive inhibition (compete for active site with arachidonic acid), but some are capable of covalent modification of COX (Simmons et al., 2004; Willoughby et al., 2011). The inhibition of COX can lead to reduced efficiency of converting arachidonic acid to PGG2. Therefore inhibition of COX can decrease the rate of prostaglandin production (reviewed Simmons et al, 2004; Bacchi et al., 2012).
</p><p>Multiple methods have been developed to investigate inhibition of COX activity - the cyclooxygenase (COX) reaction can be monitored by measurement of oxygen consumption, peroxidase co-substrate oxidation or prostaglandin (PG) detection (e.g., Jang and Pezzuto, 1997; Cuendet et al., 2006). Commercial kits from many suppliers deploying a variety of methods are available for purchase (e.g., Cayman Chemicals, Ann Arbor, MI). Repeatability and reproducibility of these commercial assays is well documented – the data generated by assays is reproducible and interassay variation is typically below 5%. The preparation of fish ovarian tissue for COX activity assay is described by Lister and Van der Kraak (2008).
</p>
<ul>
<li>COX1 activity - US EPA ToxCast assay id: NVS_ENZ_oCOX1
</li>
<li>COX2 activity - US EPA ToxCast assay id: NVS_ENZ_oCOX2
</li>
</ul><p>There is a high level of conservation of this molecular target (i.e., COX), as well as its function, especially across vertebrates (Havird et al., 2008, 2015), indicating that many vertebrate taxa may be susceptible to COX inhibition. Typically, teleost fish genomes contain more than one COX-1 and/or COX -2 gene, likely a result of genome duplication after divergence of teleosts from tetrapods (e.g., Ishikawa et al., 2007; Havird et al., 2015). In invertebrates, COX is found in most crustaceans, the majority of molluscs, but only in specific taxa/lineages within Cnidaria and Annelida. COX genes are not found in Hemichordata, Echinodermata, or Platyhelminthes. Insecta COX genes lack in homology, but may function as COX enzymes based on structural analyses (Havird et al., 2015).
</p>CL:0000255eukaryotic cell<p>Bacchi, S., Palumbo, P., Sponta, A., & Coppolino, M. F. (2012). Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Inflammatory and Anti-Allergy Agents), 11(1), 52-64.
</p><p>Botting, R. M., & Botting, J. H. (2011). C14 Non-steroidal anti-inflammatory drugs. In Principles of Immunopharmacology (pp. 573-584). Birkhäuser Basel.
</p><p>Cao, H., Yu, R., Tao, Y., Nikolic, D., & van Breemen, R. B. (2011). Measurement of cyclooxygenase inhibition using liquid chromatography–tandem mass spectrometry. Journal of pharmaceutical and biomedical analysis, 54(1), 230-235.
</p><p>Chandrasekharan, N. V., Dai, H., Roos, K. L. T., Evanson, N. K., Tomsik, J., Elton, T. S., & Simmons, D. L. (2002). COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proceedings of the National Academy of Sciences,99(21), 13926-13931.
</p><p>Cuendet, M., Mesecar, A. D., DeWitt, D. L., & Pezzuto, J. M. (2006). An ELISA method to measure inhibition of the COX enzymes. Nature protocols,1(4), 1915-1921.
Green, T., Gonzalez, A. A., Mitchell, K. D., & Navar, L. G. (2012). The Complex Interplay between COX-2 and Angiotensin II in Regulating Kidney Function. Current opinion in nephrology and hypertension, 21(1), 7.
</p><p>Havird, J. C., Kocot, K. M., Brannock, P. M., Cannon, J. T., Waits, D. S., Weese, D. A., ... & Halanych, K. M. (2015). Reconstruction of Cyclooxygenase Evolution in Animals Suggests Variable, Lineage-Specific Duplications, and Homologs with Low Sequence Identity. Journal of molecular evolution, 1-16.
</p><p>Havird, J. C., Miyamoto, M. M., Choe, K. P., & Evans, D. H. (2008). Gene duplications and losses within the cyclooxygenase family of teleosts and other chordates. Molecular biology and evolution, 25(11), 2349-2359.
</p><p>Ishikawa, T. O., Griffin, K. J., Banerjee, U., & Herschman, H. R. (2007). The zebrafish genome contains two inducible, functional cyclooxygenase-2 genes.Biochemical and biophysical research communications, 352(1), 181-187.
</p><p>Jang, M. S., & Pezzuto, J. M. (1997). Assessment of cyclooxygenase inhibitors using in vitro assay systems. Methods in cell science, 19(1), 25-31.
</p><p>Kristensen, D. M., Skalkam, M. L., Audouze, K., Lesné, L., Desdoits-Lethimonier, C., Frederiksen, H., ... & Leffers, H. (2011). Many putative endocrine disruptors inhibit prostaglandin synthesis. Environmental health perspectives, 119(4), 534-41.
</p><p>Liedtke, A. J., Crews, B. C., Daniel, C. M., Blobaum, A. L., Kingsley, P. J., Ghebreselasie, K., & Marnett, L. J. (2012). Cyclooxygenase-1-selective inhibitors based on the (E)-2′-des-methyl-sulindac sulfide scaffold. Journal of medicinal chemistry, 55(5), 2287-2300.
</p><p>Lister, A. L., & Van Der Kraak, G. (2008). An investigation into the role of prostaglandins in zebrafish oocyte maturation and ovulation. General and comparative endocrinology, 159(1), 46-57.
</p><p>Simmons, D. L., Botting, R. M., & Hla, T. (2004). Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacological reviews,56(3), 387-437.
</p><p>Willoughby, D. A., Moore, A. R., & Colville-Nash, P. R. (2000). COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. The Lancet, 355(9204), 646-648.
</p>2016-11-29T18:41:222017-09-16T10:14:42Decrease, Population growth rateDecrease, Population growth ratePopulation<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">A population can be defined as a group of interbreeding organisms, all of the same species, occupying a specific space during a specific time (Vandermeer and Goldberg 2003, Gotelli 2008). As the population is the biological level of organization that is often the focus of ecological risk</span> <span style="color:black">assessments, population growth rate (and hence population size over time) is important to consider within the context of applied conservation practices.</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">If N is the size of the population and t is time, then the population growth rate (dN/dt) is proportional to the instantaneous rate of increase, r, which measures the per capita rate of population increase over a short time interval. Therefore, r, is a difference between the instantaneous birth rate (number of births per individual per unit of time; b) and the instantaneous death rate (number of deaths per individual per unit of time; d) [Equation 1]. Because r is an instantaneous rate, its units can be changed via division. For example, as there are 24 hours in a day, an r of 24 individuals/(individual x day) is equal to an r of 1 individual/(individual/hour) (Caswell 2001, Vandermeer and Goldberg 2003, Gotelli 2008, Murray and Sandercock 2020). </span></span></span></span></p>
<p style="margin-left:144px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Equation 1: r = b - d</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">This key event refers to scenarios where r < 0 (instantaneous death rate exceeds instantaneous birth rate).</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Examining r in the context of population growth rate:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A population will decrease to extinction when the instantaneous death rate exceeds the instantaneous birth rate (r < 0). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black"> ● The smaller the value of r below 1, the faster the population will decrease to zero. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A population will increase when resources are available and the instantaneous birth rate exceeds the instantaneous death rate (r > 0)</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black"> ● The larger the value that r exceeds 1, the faster the population can increase over time </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A population will neither increase or decrease when the population growth rate equals 0 (either due to N = 0, or if the per capita birth and death rates are exactly balanced). For example, the per capita birth and death rates could become exactly balanced due to density dependence and/or to the effect of a stressor that reduces survival and/or reproduction (Caswell 2001, Vandermeer and Goldberg 2003, Gotelli 2008, Murray and Sandercock 2020). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Effects incurred on a population from a chemical or non-chemical stressor could have an impact directly upon birth rate (reproduction) and/or death rate (survival), thereby causing a decline in population growth rate. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Example of direct effect on r: Exposure to 17b-trenbolone reduced reproduction (i.e., reduced b) in the fathead minnow over 21 days at water concentrations ranging from 0.0015 to about 41 mg/L (Ankley et al. 2001; Miller and Ankley 2004). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Alternatively, a stressor could indirectly impact survival and/or reproduction. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Example of indirect effect on r: Exposure of non-sexually differentiated early life stage fathead minnow to the fungicide prochloraz has been shown to produce male-biased sex ratios based on gonad differentiation, and resulted in projected change in population growth rate (decrease in reproduction due to a decrease in females and thus recruitment) using a population model. (Holbech et al., 2012; Miller et al. 2022)</span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Density dependence can be an important consideration:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● The effect of density dependence depends upon the quantity of resources present within a landscape. A change in available resources could increase or decrease the effect of density dependence and therefore cause a change in population growth rate via indirectly impacting survival and/or reproduction. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● This concept could be thought of in terms of community level interactions whereby one species is not impacted but a competitor species is impacted by a chemical stressor resulting in a greater availability of resources for the unimpacted species. In this scenario, the impacted species would experience a decline in population growth rate. The unimpacted species would experience an increase in population growth rate (due to a smaller density dependent effect upon population growth rate for that species). </span> </span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Closed versus open systems:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● The above discussion relates to closed systems (there is no movement of individuals between population sites) and thus a declining population growth rate cannot be augmented by immigration. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● When individuals depart (emigrate out of a population) the loss will diminish population growth rate. </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Population growth rate applies to all organisms, both sexes, and all life stages.</span></span></span></span></p>
<p> </p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Population growth rate (instantaneous growth rate) can be measured by sampling a population over an interval of time (i.e. from time t = 0 to time t = 1). The interval of time should be selected to correspond to the life history of the species of interest (i.e. will be different for rapidly growing versus slow growing populations). The population growth rate, r, can be determined by taking the difference (subtracting) between the initial population size, N</span><sub><span style="font-size:9pt"><span style="color:black">t=0 </span></span></sub><span style="color:black">(population size at time t=0), and the population size at the end of the interval, N</span><sub><span style="font-size:9pt"><span style="color:black">t=1 </span></span></sub><span style="color:black">(population size at time t = 1), and then subsequently dividing by the initial population size. </span></span></span></span></p>
<p style="margin-left:96px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Equation 2: r = (N</span><sub><span style="font-size:9pt"><span style="color:black">t=1 </span></span></sub><span style="color:black">- N</span><sub><span style="font-size:9pt"><span style="color:black">t=0</span></span></sub><span style="color:black">) / N</span><sub><span style="font-size:9pt"><span style="color:black">t=0</span></span></sub></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">The diversity of forms, sizes, and life histories among species has led to the development of a vast number of field techniques for estimation of population size and thus population growth over time (Bookhout 1994, McComb et al. 2021). </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● For stationary species an observational strategy may involve dividing a habitat into units. After setting up the units, samples are performed throughout the habitat at a select number of units (determined using a statistical sampling design) over a time interval (at time t = 0 and again at time t = 1), and the total number of organisms within each unit are counted. The numbers recorded are assumed to be representative for the habitat overall, and can be used to estimate the population growth rate within the entire habitat over the time interval. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● For species that are mobile throughout a large range, a strategy such as using a mark-recapture method may be employed (i.e. tags, bands, transmitters) to determine a count over a time interval (at time = 0 and again at time =1). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Population growth rate can also be estimated using mathematical model constructs (for example, ranging from simple differential equations to complex age or stage structured matrix projection models and individual based modeling approaches), and may assume a linear or nonlinear population increase over time (Caswell 2001, Vandermeer and Goldberg 2003, Gotelli 2008, Murray and Sandercock 2020). The AOP framework can be used to support the translation of pathway-specific mechanistic data into responses relevant to population models and output from the population models, such as changing (declining) population growth rate, can be used to assess and manage risks of chemicals (Kramer et al. 2011). As such, this translational capability can increase the capacity and efficiency of safety assessments both for single chemicals and chemical mixtures (Kramer et al. 2011). </span></span></span></span></p>
<p style="text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">Some examples of modeling constructs used to investigate population growth rate:</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A modeling construct could be based upon laboratory toxicity tests to determine effect(s) that are then linked to the population model and used to estimate decline in population growth rate. Miller et al. (2007) used concentration–response data from short term reproductive assays with fathead minnow (<em>Pimephales promelas</em>) exposed to endocrine disrupting chemicals in combination with a population model to examine projected alterations in population growth rate. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A model construct could be based upon a combination of effects-based monitoring at field sites (informed by an AOP) and a population model. Miller et al. (2015) applied a population model informed by an AOP to project declines in population growth rate for white suckers (Catostomus commersoni) using observed changes in sex steroid synthesis in fish exposed to a complex pulp and paper mill effluent in Jackfish Bay, Ontario, Canada. Furthermore, a model construct could be comprised of a series of quantitative models using KERs that culminates in the estimation of change (decline) in population growth rate. </span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● A quantitative adverse outcome pathway (qAOP) has been defined as a mathematical construct that models the dose–response or response–response relationships of all KERs described in an AOP (Conolly et al. 2017, Perkins et al. 2019). Conolly et al. (2017) developed a qAOP using data generated with the aromatase inhibitor fadrozole as a stressor and then used it to predict potential population‐level impacts (including decline in population growth rate). The qAOP modeled aromatase inhibition (the molecular initiating event) leading to reproductive dysfunction in fathead minnow (Pimephales promelas) using 3 computational models: a hypothalamus–pituitary–gonadal axis model (based on ordinary differential equations) of aromatase inhibition leading to decreased vitellogenin production (Cheng et al. 2016), a stochastic model of oocyte growth dynamics relating vitellogenin levels to clutch size and spawning intervals (Watanabe et al. 2016), and a population model (Miller et al. 2007).</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Dynamic energy budget (DEB) models offer a methodology that reverse engineers stressor effects on growth, reproduction, and/or survival into modular characterizations related to the acquisition and processing of energy resources (Nisbet et al. 2000, Nisbet et al. 2011). Murphy et al. (2018) developed a conceptual model to link DEB and AOP models by interpreting AOP key events as measures of damage-inducing processes affecting DEB variables and rates.</span></span></span></span></p>
<p style="margin-left:48px; text-align:start"><span style="font-size:medium"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><span style="color:black">● Endogenous Lifecycle Models (ELMs), capture the endogenous lifecycle processes of growth, development, survival, and reproduction and integrate these to estimate and predict expected fitness (Etterson and Ankley, 2021). AOPs can be used to inform ELMs of effects of chemical stressors on the vital rates that determine fitness, and to decide what hierarchical models of endogenous systems should be included within an ELM (Etterson and Ankley, 2021).</span></span></span></span></p>
<p> </p>
<p>Consideration of population size and changes in population size over time is potentially relevant to all living organisms.</p>
Not SpecifiedUnspecificNot SpecifiedAll life stagesHigh<ul>
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2016-11-29T18:41:242023-01-03T09:09:064cf67904-71fb-42c7-82e4-95d6059e0c640c95bfd7-b34c-42fc-b03a-b0d3a44d55592016-11-29T18:41:342016-12-03T16:37:590c95bfd7-b34c-42fc-b03a-b0d3a44d5559ee714eaa-f652-46ce-8923-b0feead66b3b2016-11-29T18:41:342016-12-03T16:37:59ee714eaa-f652-46ce-8923-b0feead66b3b41ed7064-efd0-4f41-811b-b9d6e55669de2016-11-29T18:41:342016-12-03T16:37:5941ed7064-efd0-4f41-811b-b9d6e55669def1f245b5-c632-4d37-a6bd-65cfbe8c6bdf2016-11-29T18:41:342016-12-03T16:37:59f1f245b5-c632-4d37-a6bd-65cfbe8c6bdfb0314602-cff8-4e58-b4fa-22b608a890212016-11-29T18:41:342016-12-03T16:37:59b0314602-cff8-4e58-b4fa-22b608a89021f6bdb8a5-e2ce-45f7-8e41-e7bd0bef799f2016-11-29T18:41:342016-12-03T16:37:59f6bdb8a5-e2ce-45f7-8e41-e7bd0bef799f31741691-03d8-4653-bdde-bcf47882aa2a2016-11-29T18:41:342016-12-03T16:37:5931741691-03d8-4653-bdde-bcf47882aa2a4e42b4e2-9b18-48da-afb6-589dc82873fa2016-11-29T18:41:342016-12-03T16:37:594e42b4e2-9b18-48da-afb6-589dc82873fa623031c3-fb36-45e8-a128-1095dcd4b5852016-11-29T18:41:342016-12-03T16:37:59Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transitionCyclooxygenase inhibition 4<p>Dalma Martinovic-Weigelt</p>
Under Development: Contributions and Comments WelcomeUnder Development1.29<p>Non-steroidal anti-inflammatory drugs have been specifically designed to inhibit cyclooxygenase active site of PTGS; these mechanisms of inhibition are well characterized (Simmons et al, 2004). NSAIDs interfere with COX site via multiple mechanisms including competitive inhibition (most NSAIDs compete for active site with arachidonic acid) and covalent modification (irreversible acetylation) of COX (e.g., aspirin) (Simmons et al., 2004; Willoughby et al., 2011). NSAIDs display different levels of selectivity for the COX-1 vs. COX-2 isoforms (Simmons et al., 2004). Majority of NSAIDs inhibit both isoforms (with variable levels of selectivity for COX-1 vs. COX-2), but several have been designed to preferentially inhibit COX-2 (Bacchi et al., 2012). Recently, COX-1 specific inhibitors have been developed and their therapeutic potential is being explored (Liedtke et al., 2012). Most extensive evidence regarding chemical initiation of this event comes from the mammalian literature and relates to NSAIDs.
</p><p>In addition to NSAIDs, common environmental contaminants of diverse chemical structures and uses (e.g., parabens, phthalates, benzophenones) have been postulated to inhibit prostaglandin synthesis via COX inhibition (Kristensen et al., 2011). U.S. EPA’s high throughput screening program (ACToR, epa.gov) indicated COX as a frequent contaminant target - 61% of 143 tested chemicals inhibited COX-1 and 59% of 106 inhibited COX-2 activity. Several chemicals were either similar in potency (e.g., monobutylphthalate) or more potent than NSAIDs (e.g., insecticide emamectin benzoate and industrial intermediary 1-Chloro-4-nitrobenzene were more potent inhibitors of COX2 than NSAID celecoxib, which was specifically designed to inhibit COX-2). Mechanisms of inhibition for these chemicals are not well elucidated.
</p><p>Maintenance of sustainable fish and wildlife populations (i.e., adequate to ensure long-term delivery of valued ecosystem services) is a widely accepted regulatory goal upon which risk assessments and risk management decisions are based.</p>
adjacentLowModerateadjacentLowHighadjacentModerateHighadjacentLowHighadjacentLowHighadjacentLowModerateadjacentLowHighadjacentLowHighadjacentLowModerateHighFemaleHighAdult, reproductively matureNot SpecifiedLow2016-11-29T18:41:162023-04-29T16:02:57